INTESTINAL ANGIOEDEMA – A RARE COMPLICATION OF ACEI THERAPY

Abhinav Agarwal, MD, Associate, Rajika Munasinghe, MD, Fellow, Department Of Medicine, Sinai Grace Hospital, WSU/DMC, Detroit, MI

Introduction – ACEI are commonly prescribed for the treatment of hypertension and congestive heart failure with significant beneficial effects on morbidity and mortality. Peripheral angioedema occurs in about 0.1-0.2% of cases and is clinically apparent on presentation. Less frequent, however, is intestinal angioedema, which is often misdiagnosed or detected late after repeated radiological studies, endoscopic evaluations and at times after surgical exploration.

Case Presentation – We present the case of an 80-year old Caucasian woman who presented over the course of 8 months with 4 episodes of lower abdominal pain, nausea and vomiting. At each visit, her examination was significant only for mild lower abdominal tenderness. She was investigated with three abdominal CTs, one EGD, two colonoscopies, stool studies as well as blood and urine labs. Gastroenterology and surgical consults were also obtained. She was diagnosed with and treated for sigmoid diverticulitis at her first visit (due to clinical and CT findings), acute pancreatitis at her second (due to elevated lipase) and Clostridium difficile colitis at her third (due to positive stool studies). At her fourth hospitalization, the persistence of small bowel thickening and intraperitoneal fluid on prior CT scans and the recurrent nature of her symptoms were taken into consideration and a diagnosis of lisinopril induced intestinal angioedema was entertained. The drug was withdrawn, resulting in symptomatic improvement and the patient was discharged home on a calcium channel blocker without any subsequent complaints.

Discussion – Intestinal angioedema also referred to as visceral angioedema is an infrequent complication of ACEI therapy so far reported in only about 17 patients with a strong predilection for females (16 patients). In at least 3 patients the diagnosis was made after surgery. The index of suspicion should be high in a patient (especially women) on ACEI therapy presenting with abdominal symptoms and imaging studies showing intestinal edema or thickening. Due to the widespread use of these medications, healthcare personnel should be aware of this presentation as early detection will reduce unnecessary testing and decrease the physical and psychological impact on the patient, as also as the economic burden of this entity.

 

 

 

 

COMPARISION OF UNFRACTIONATED HEPARIN (UFH) TO LOW MOLECULAR WEIGHT HEPARIN (LMWH) IN VENOUS THROMBOEMBOLISM (VTE) PROPHYLAXIS AFTER ACUTE ISCHEMIC STROKE

Abhinav Agarwal, MD, Associate, Rajika Munasinghe, MD, Fellow, Department Of Medicine, Sinai Grace Hospital, WSU/DMC, Detroit, MI

Background – Acute ischemic stroke has a prevalence of about 5.5million (2.6% of US population) with 700,000 new/recurrent cases every year. 20-50% of stroke patients experience DVT and 2% PE. Prophylaxis is recommended to reduce the morbidity, mortality and cost associated with VTE in these patients.

 

Methods – A literature search of MEDLINE, Pubmed, Cochrane library and the Stroke Trials Registry was undertaken to identify studies comparing different anticoagulants for VTE prophylaxis in patients with acute ischemic stroke. Twelve clinical trials were identified (11 completed and 1 ongoing), with seven double-blinded randomized controlled trials. The agents studied included LMWH with placebo (2 trials), warfarin with placebo (1 trial), heparinoids with UFH (2 trials) and LMWH with UFH (2 trials). Since heparinoids are not available in the US anymore, the 2 trials with a head-to-head comparison of LMWH and UFH were selected for analysis.

Results – The Prophylaxis of thromboembolic events with certoparin trial (PROTECT, n=545) compared 12-16 days of treatment with certoparin 3000U SC QD to UFH 5000U SC q8h. The difference in primary endpoints (DVT, PE or death related to VTE during treatment) was 18(6.6%) for certoparin and 24 (8.8%) for UFH, p=0.0008. The risk of bleeding complications in both groups was 10 (3.7%), with a lower incidence of major bleeding in the certoparin arm. The other trial by Hillbom et al (n=212) compared 8-12 days of treatment with enoxaparin 40 mg SC QD to UFH 5000U SC q8h. The endpoint (DVT, PE, death from any cause, clinically significant bleeding) was 40 (37.7%) for enoxaparin and 54 (49.1%) for UFH, p=0.127. Hemorrhagic transformation of the ischemic zone occurred in 14 (13.2%) patients in the enoxaparin and 20 (18.9%) in the UFH arm.

Conclusions – Current best evidence suggests increased efficacy and safety of LMWH compared to UFH for VTE prophylaxis. The PROTECT trial demonstrated a statistically significant advantage, and Hillbom et al a nonsignificant trend towards superiority. Major stroke trials and several meta-analyses have shown increased efficacy of both forms of heparin over placebo without any comparison between them. More head-to-head trials are needed to provide a definite answer.

 

 

 

 

 

A rare case of Duodenal MALToma presenting with obstructive jaundice

Li Ding, MD (Associate), Saad Usmani, MD (Associate), Husain Saleh, MD, Mohamed Siddique MD FACP

Department of Internal Medicine, Detroit Medical Center/Wayne State

University, Sinai Grace Hospital, Detroit MI.

 

Introduction

Mucosa-associated lymphoid tissue (MALT) makes up to 5% of all NHL cases. The most common site for MALT lymphomas is stomach, followed in incidence by the small intestine, ileocecal area, colon and the esophagus. We are reporting a rare case of duodenal MALT lymphoma presenting with obstructive jaundice.

 

Case report

A 57-year-old male presented with complaint of nausea, vomiting and right upper quadrant abdominal pain for 2 weeks.  Physical examination revealed scleral icterus and right upper quadrant tenderness. Laboratory studies showed normocytic anemia, direct bilirubinemia, elevated alkaline phosphatase and aminotransferases. CT of abdomen and pelvis showed a large mass in the right anterior para-renal space. EGD revealed evidence of mucosal abnormality around the second portion of duodenum. Biopsy histopathology was consistent with MALT lymphoma and Helicobacter pylori was not seen. A common bile duct stent was placed under endoscopic retrograde cholangiopancreatography (ERCP).  However, patient developed contrast-induced nephropathy, acute pancreatitis, aspiration pneumonia, and ARDS. Patient was admitted to the ICU but his condition continuously deteriorated. The patient expired on the 47th day of admission while in the ICU.

Discussion and Conclusion

This is the first reported case of duodenal MALT presenting with obstructive jaundice. A thorough literature search revealed only 19 reported cases of duodenal MALT with median age of presentation being 52 years. Unlike gastric MALT, there is not sufficient evidence of chronic Helicobacter pylori infection being associated with duodenal disease. Duodenal MALT is an aggressive disease and the response to H. pylori eradication therapy in the reported patients has been variable. We are presenting this case to alert internist about this disease in the differential diagnosis of obstructive jaundice and its overall poor prognosis. 

 

 

 

 

 

BLEEDING RISK IN TRANSBRONCHIAL LUNG BIOPSY IN PATIENTS TAKING ANTIPLATELET MEDICATIONS

Li Ding, MD, Associate, Department of Medicine, Sinai-Grace Hospital/Detroit Medical Center, Wayne State University, Detroit, MI.

INTRODUCTION: Antiplatelet agents (APA) are wildly used in primary and secondary prevention for coronary heart disease, cerebral vascular accident and peripheral artery diseases. The aim of this project is to study the safety of patients taking APA while undergoing transbronchial lung biopsy (TBLB).

METHODS: A comprehensive literature review was done using PubMed, Ovid Medline and Cochrane library databases. Keywords used were bronchoscopy, transbronchial lung biopsy, aspirin, clopidogrel, antiplatelet therapy, bleeding, invasive procedure and surgery. The results of relevant articles were then compared.

STUDY SELECTION CRITERIA: Prospecitve or retrospective cohort study, meta-analysis and randomized controlled trials published during the past ten years were selected.

SEARCH RESULTS: Of the few relevant studies, this project reviews mainly three studies, two of which are prospective cohort studies and the third one is a meta-analysis.

RESULTS: The first study showed that there was no significant difference in post TBLB bleeding rate between aspirin group (3.5%) and control group (5%). The second study compared the bleeding events in TBLB among the patient taking clopidogrel or without taking clopidogrel. They found that bleeding rate is 3.4% in control group, 88% in clopidogrel alone group and 100% in clopidogrel + aspirin (P<0.001). This result indicated that clopidogrel use greatly increases the risk of bleeding in TBLB, and aspirin exacerbates this bleeding effect. The meta-analysis compared all the studies on bleeding risk of patients who taking aspirin and undergoing different invasive procedures or non-cardiac surgeries. This study showed that aspirin increased the rate of bleeding complication by a factor of 1.5. However, aspirin did not lead to a high level of the severity of bleeding complications.

CONCLUSION: TBLB can be safely performed on patients taking aspirin on standard doses. However, clopidogrel increases the bleeding rate of TBLB and aspirin will exacerbate this risk.

 

 

 

 

 

Chronic myeloid leukemia-what have genes got to do with it?

Gana Doronina, MD, Saad Usmani, MD, Joel Appel, MD FACP.

Department of Internal Medicine, Detroit Medical Center/Wayne State

University, Sinai Grace Hospital, Detroit MI.

 

Introduction:

Chronic myeloid leukemia is a clonal myeloproliferative disorder characterized on the molecular level by the BCR-ABL gene fusion. The use of cytogenetics and fluorescent in-situ hybridization (FISH) analysis in CML patients have identified atypical inversions/translocations of the Philadelphia chromosome in less than 5% of cases. Their role in prognostication is still controversial. We present a case of CML that presented with a unique fusion gene along with inversion of chromosome 9.

Case Report:

67 year old woman with past medical history of gastro-esophageal reflux disease and mitral valve replacement was admitted to hospital with acute onset of left-sided chest discomfort and recent history of recurrent epistaxis. Physical exam revealed hepatomegaly and an abdominal bruit. Laboratory work-up showed elevated white cell count. Myocardial ischemic and septic work-up was negative. Peripheral smear showed marked leucocytosis with increased bands, myelocytes and metamyelocytes, basophillia and eosinophilia with no increase in blast count. CT of the abdomen showed hepatomegaly and mediastinal lymphadenoapthy. Bone marrow aspiration showed myeloid hyperplasia with left shift, increased megakaryocytes consistent with chronic myelogenous leukemia. Cytogenic analysis was positive for Ph chromosome. FISH analysis revealed the presence of single fusion pattern of BCR-ABL along with pericentric inversion of chromosome 9. Patient was started on Imatinib mesylate (Gleevac) and has reached complete hematological response.

Discussion & Conclusion:

Our understanding of hematological malignancies in general and CML specifically has evolved with the insight into cancer genomics.  Fusion pattern of BCR-ABL along with variant inversions, such as in our patient, have been observed to have quick progression to blast phase and variable response to Imatinib mesylate. Our patient has shown excellent response to standard CML therapy, achieving complete hematological response. We are presenting this case to highlight the emerging role of molecular genetics in CML therapy and the unanticipated response to therapy in our patient.

 

 

 

 

 

Treatment of Venous Tromboembolism in Patients with Cancer.

Ganna Doronina Gramling, MD, Associate, Department of Medicine, Wayne State University/Detroit Medical Center (Sinai-Grace Hospital) Program, Detroit, MI.

Introduction: Association between cancer and venous thromboembolism (VTE) is well established. Challenges of VTE in cancer patients compared to non-cancer patients include increased recurrence and bleeding rates during warfarin therapy. 

Methods: I performed literature search for clinical evidence in support of therapy alternative to warfarin. I used Pubmed, Ovid Medline and Cochrane as search engines. My key words were: cancer, tromboembolism, and warfarin.

Results: The CLOT trial was a randomized, open-label trial comparing dalteparin and warfarin in the prevention of recurrent VTE in 672 patients with acute VTE and cancer. The cumulative rate of recurrent VTE at 6 months was significantly higher, at 17,4%, in the warfarin group than in the dalteparin group (8.8%). There was no statistically significant difference in the rate of bleeding between two groups.

The post-hoc analysis of the CLOT data showed that the survival in the dalteparin group at 1 year was higher than in warfarin group in patients without metastasis (P=0.03). There was no statistically significant difference in 1-year survival in patient with advanced cancer.

In randomized, open-label, French trial enoxaparin at fixed dose and warfarin were compared in 146 patients with acute VTE and cancer.  Major bleeding or/and recurrent VTE was the measured outcome. During the 3-months treatment period, 21.1% of patients receiving warfarin and 10,5% receiving enoxaparin experienced recurrent VTE and/or major bleeding. The difference was not statistically significant (P=0.09).

Conclusion: Low-molecular-weight heparin is more effective than warfarin in reduction of the risk of recurrent thromboembolism without increasing risk of bleeding. Use of low-molecular-weight heparin is associated with higher rate of survival in patients with cancer without metastasis.      

 

 

 

 

 

The utilization of the right internal jugular vein in left ventricular lead placement.

Adriss Faraj, MD,MRCP, Associate,Rajika Munasinghe, MD, Fellow, Mukkaram Siddiqui, MD, Department of Medicine, Sinai Grace Hospital,Wayne State University , Detroit, MI.

Background:Biventricular pacing has emerged as a novel therapeutic option for those patients who continue to be symptomatic despite optimum medical therapy.Cannulating the coronary sinus in order to place the left ventricular placing lead can be challenging due to anatomical variation .Herein we describe a case of implantable defibrillator(ICD)upgrade to biventricular pacemaker using right internal jugular venous route for left ventricular pacing lead implantation.Case report:We report a case of a 64 years old female patient with a history of advanced heart failure who continue to be symptomatic on maximum medical therapy and identified as a candidate for cardiac resynchronization therapy. The patient has previous defibrillator implanted via the left subclavian route.During this procedure placement of the left ventricular(LV) pacing lead was unsuccessful due to difficulty in cannulating the coronary sinus.Procedure:The coronary sinus was cannulated via the right jugular vein.The posterolateral branch of the coronary sinus was found to originate from a separate ostium at the posterior septal aspect of the tricuspid annulus. Venous access was later obtained via the left axillary vein and Rapido advance system was introduced into the vein in an effort to cannulate the coronary sinus. Notwithstanding, the cannulation of the coronary sinus was proved to be unattainable despite the use of different catheters .Considering the fact, that coronary sinus was successfully cannulated by the jugular approach.The right jugular vein was re-cannulated and the coronary sinus was easily identified.A posterolateral epicardial  venous branch was chosen as an appropriate vein  and the left ventricular pacing lead advanced with ease.The lead was  anchored and tunneled across the chest to the left side and connected to the new pacing generator.The postoperative course was unventful.

Discussion:Our case illustrate that the right internal jugular vein can be utilized as an alternative route for coronary sinus cannulation.This is particularly valid in instances where it is difficult to access the coronary sinus via the traditional left cephalic-axillary-subclavian route due to variation in the anatomy as evident in this case.

 

 

 

 

UNILATERAL EXUDATIVE PLEURAL EFFUSION DUE TO PULMONARY TOXICITY FROM AMIODARONE.

Salah Fares , MD (Associate), Rajika L. Munasinghe, MD, Fellow, Sinai-Grace Hospital/Wayne State University, Detroit, Michigan

INTRODUCTION:

Amiodarone is a very effective antiarrhythmic drug  that has been associated with multi –organ toxicity. Pulmonary toxicity is reported in approximately 5-7% of patients treated with amiodarone. We present an unusual case of unilateral exudative pleural effusion induced by amiodarone.

CASE REPORT: A 88-year-old Caucasian woman with a known history of atrial fibrillation treated with 200 mg of amiodarone since 2004, presented with shortness of breath since June-2005. Chest X-ray showed a right pleural effusion and air space disease that was confirmed by chest CT. The patient underwent a diagnostic thoracentesis, and pleural fluid analysis demonstrated an exudative effusion with no evidence of infection or malignancy. The patient had been treated empirically with multiple courses of antibiotics without a significant improvement in her condition. In October-2005 a follow up chest X-ray showed a persistent moderate right-sided pleural effusion with basilar pulmonary infiltrates. High resolution chest CT scan showed a small right pleural effusion with calcification within the inner and outer aspect of the pleura in the right lower chest. Atelectasis and infiltrate in the right lower lobe was also present. Drug induced lung disease was suspected and Amiodarone was discontinued. The patient was followed with serial chest X-rays that showed a gradual decrease in the amount of pleural effusion and the most recent chest X-ray in August-2006 showed no evidence of pleural or pulmonary pathology.

DISCUSSION & CONCLUSION: 

Although pulmonary toxicity induced by amiodarone has been well described in the medical literature, our case is unique from other cases because pulmonary toxicity was associated with a relatively lower dose of amiodarone (200 mg) and the co-existence of an exudative plural effusion. Previous case reports of pulmonary toxicity have been associated with amiodarone doses between 400mg-1600mg. Amiodarone-induced pleural effusion is rare with only seven prior cases reported in the literature. Unless this diagnosis is entertained early, patients may be subjected to unnecessary interventions and a reversible cause of exudative pleural effusion overlooked.

 

 

 

 

 

What Is The Usefulness Of Brain Natriuretric Peptide In Predicting The Prognosis In Patients With Acute Pulmonary Embolism ?

Salah Fares , MD (Associate)

Sinai-Grace Hospital/Wayne State University, Detroit, Michigan

 

Introduction: Recently the accuracy and usefulness of brain natriuretric peptide (BNP) in the diagnosis and assessment of patients with left ventricular dysfunction has been already established.

Clinical Question: How useful are BNP values in predicting right ventricular dysfunction and prognosis in patients with Acute Pulmonary Embolism (PE)?

Methods: Literature search was conducted utilizing Medline Ovid (1966-2006), Medline PubMed and Cochrane library with PE, and BNP used as key words.

Study Selection Criteria: Randomized trials, Prospective studies, Sample size.

Search Results: Only three prospective trials were selected.

Discussion/Results: In the first study , a BNP level <85 pg/ml was highly accurate in excluding right ventricular (RV) dysfunction with 100% negative predictive value. Also, BNP represented a powerful predictor of in-hospital clinical deterioration, with 487 pg/ml being the cutoff. In the second study , a BNP level > 90 pg/mL had a sensitivity rate of 64% and a specificity rate of 94% for detecting RV dysfunction when left ventricular (LV) systolic function was normal, BNP levels were not predictive of mortality or in-hospital complications. In the third

study, in 27% patients with adverse events, median BNP was higher than

in patients with a benign course;( P <0.001). Three patients with adverse outcomes had low BNP levels on admission.  The value of BNP 90 pg/mL as a cutoff for absence of adverse outcomes had high sensitivity and high negative predictive values of 85% and 94% respectively.

Conclusions: The measurement of BNP levels in acute PE is very promising in predicting the RV dysfunction in patients with normal LV function.  There is not enough data to confirm the role of high BNP levels in predicting the outcome in patients with PE. Randomized studies should be done before suggesting any guidelines for BNP use in PE.

 

 

 

 

 

A Case of Myelodysplastic Syndrome , Refractory Anemia With Ringed     Sideroblasts  And Thrombocytosis

Zartash Gul, MD,( Associate); Doina David,MD ; Leopoldo Eisenberg, MD, FACP.

Department of Internal Medicine & Pathology , Sinai-Grace Hospital/Detroit Medical Center, Wayne State University, Detroit, Michigan.

Introduction:

Myelodysplastic syndrome includes a heterogeneous group of bone marrow disorders characterized by ineffective erythropoiesis. Majority of the patients are anemic at diagnosis, 40 % are neutropenic and 30- 45% are thrombocytopenic. Thrombocytosis is an unusual finding in myelodysplastic syndrome mainly associated with refractory anemia with ringed sideroblasts(RARS) and 5q- syndrome.. Patients with myelodysplastic syndrome and thrombocytosis not carrying the diagnosis of 5q- are rare and raise questions about their diagnosis and prognosis. This finding is not classifiable under any of the current classification systems being used.

Case:

This is a case of 56 years old African American man with a history of Diabetes Mellitus and Hypertension. He was found to have thrombocytosis of 635,000 , anemia of 12.8g/dl with a white count that was normal. Peripheral  smear revealed tear drop cells.Rest of the hematological work up was negative except for an elevated ferritin.Bone marroe biopsy  and aspirate showed a hypercellular bone marrow ,dysplastic and binucleatic red blood cell morphology as well as dysplastic megakaryocytes and 10% ringed sideroblasts..Subsequently,the platelet count increased to more than a million and he was started on Anagrelide to which he responded, but required increasing doses of Angrelide with better response. However he started to complain of palpitations, therefore he was switched to Hydroxyurea and is currently maintained on it.

Discussion:

Thrombocytosis is a prominent feature of myeloproliferative disorders and is rare in myelodysplastic syndrome.While the WHO classification describes the mixed myeloproliferative and myelodysplastic disorders and 5q- as separate entities ,Refractory anemia with ringed sideroblats with thrombocytosis (>600,000) is not classified and data regarding these patients’ treatment and prognosis remains scarce.

Conclusion:

This case emphasizes the need for further evolution in the classification of Myelodysplastic syndrome.

 

 

 

 

 

CASE REPORT: MEGALOBLASTIC ANEMIA PRESENTING AS ANASARCA

Zartash Gul MD (Associate), Shireen Jindani MD (Associate), Zarnab Sajjad MD(Associate), Leopoldo Eisenberg MD FACP.

Wayne State University Siani Grace Hospital,Detroit MI

INTRODUCTION:

This is the case report of a patient who presented with anasarca and was found to have megaloblastic anemia secondary to Vitamin B12 deficiency due to pernicious anemia. While there are numerous cases with neurological manifestations of B12 deficiency and B12 deficiency secondary to intestinal malabsorption what makes this case unique is B12 deficiency leading to intestinal malabsorption with subsequent albumin deficiency leading to malabsorption manifesting as anasarca.

BACKGROUND:

B12 deficiency due to pernicious anemia combines the general features of megaloblastic anemia and features specific for B12 deficiency .The disease is easily missed because of its insidious onset and many atypical presentations.1

Intestinal disorders leading to B12 deficiency are extensive resection of ileum 2

regional ileitis,3 lymphoma radiation damage 4certain drugs and sprue.B12 deficiency in itself leads to gastric and intestinal mucosal atrophy as reported in literature 5 but pernicious anemia leading to malabsorption to the extent that it manifests as anasarca being a rare occurrence.

CASE

47-year-old African American gentle man admitted in hospital for progressive generalized swelling and weakness for past 3 months. Patient was diagnosed 3 years ago with macrocytic anemia suspected of being megaloblastic but refused treatment. Prior to 3 years patient was healthy. He denied any history of alcohol or drug abuse. Physical exam demonstrated significant anasarca, profound pallor of mucosa and conjunctiva. He also had difficulty maintaining balance on walking. On admission anemia was detected at Hgb 3.5 gm/dl,macrocytic,MCV at 111 fl ,white cell 4200K/mm3 and a thrombocytopenia of 40,000. Peripheral smear showed drastic megaloblastic changes with significant macro-ovalocytes, hypersegmention of neutrophils and decreased platelets. LDH was in the range of 700 and albumin in the range of 2.5gm/dl.

Diagnosis of megaloblastic anemia was established and confirmed by bone marrow studies as well as Methyl Malonyl Co A levels of 129 micromole/litre. Repeated B12 levels twice were less than 100pg/ml on two occasions, normal folate, elevated gastrin levels and positive anti- parietal cell antibody. As part of work up for hypoalbuminemia and B12 deficiency LFTs and viral studies were ordered and found to be normal. Upper and lower GI endoscopy failed to reveal any evidence of H.pylori , IBD or colitis .Initial treatment included transfusion therapy, gentle diuresis, respiratory and nutritional support as well as B12 administration.

Within 3-4 months of diagnosis patient returned to normal blood count , normal weight and complete functional status with only residual peripheral neuropathy secondary to B12 deficiency.

Conclusion

We report a unique case of pernicious anemia presenting with anasarca secondary to profound gastric and intestinal mucosal atrophy with resolution with appropriate therapy. Our literature search did not reveal such a presentation of pernicious anemia.

 

 

 

 

 

ASSOCIATION OF JAK2 MUTATION IN MDS  PATIENTS WITH MYELOFIBROSIS

Zartash Gul M.D, Shireen Jindani M.D ,N Galili PhD,A Raza M.D

University of Massachusetts ,Worcester Massachusetts

Wayne State University Siani Grace Hospital,Detroit MI

Introduction: JAK2 the primary kinase gene activated by erythropoietin and  essential for erythropoiesis is found to be mutated in several myeloproliferative disorders including polycythemia vera,essential thrombocythemia and myelofibrosis.In addition some reports suggested that V617F mutation in JAK 2 in MDS/MPD cases is infrequent. In a recent issue of Leukemia Ohyashiki et al.described the presence of JAK2 mutation in 2 out of 6 cases of MDS with myelofibrosis.However ,this mutation was not detected in cases of MDS without myelofibrosis. This is a single center study of 19 patients to discover if JAK 2 mutation might play a role in patients who have MDS leading to myelofibrosis.

Methods :DNA samples of 19 patients who had MDS with subsequent myelofibrosis were isolated for this study.Genomic DNA was isolated using DN easy tissue kit(Qiagen).This genomic DNA was then amplified by PCR.After confirmation of DNA presence on 1 % agarose gel and purification using QIA quick PCR purification kit (Qiagen) sequencing was done .This sequencing was then analyzed using Finch TV for G to T mutation in JAK2.

Results: None of the 19 patients included in this study showed evidence of JAK2 mutation.

Discussion: JAK 2 mutation is a major advance in our understanding of various classical Myeloprolferative disorders.It was worth investigating if JAK 2 had any role in pathogenesis of myeloproliferative disorders steming from prior MDS. Reports in Leukemia,by Ohashiki et al apperared promising in this respect. However the ensuing debate and articles in subsequent issues of Leukemia  showed lack of any relation

between JAK 2 and MDS patients with subsequent myelofibrosis .The 2 studies quoted so far consisted of 9 and 17 patients of MDS with myelofibrosis.Our cohort which consists of 19 patients also showed lack of evidence for any relation between JAK2 and MDS with myelofibrosis.

Conclusion: Our study shows that JAK 2 mutation has no role in pathogenesis of MDS with Myelofibrosis.

 

 

 

 

 

LEFT ATRIAL MYXOMA PRESENTING AS UNSTABLE ANGINA

Ruchika Jain, MD (Associate) Ashraf Ahmed, MD (Associate) Carlos Godoy, MD  (Member) Department of Medicine, Sinai-Grace Hospital, Detroit, Michigan

 

Background: The incidence of benign primary cardiac tumors is less than 0.1%.  Among these most common tumor is the left  atrial  myxoma. These tumors usually present with signs of mitral  valvular disease and congestive heart failure. We present a rare case of a left atrial  myxoma presenting as unstable angina.

Case Report: A forty-six-year-old female with a history of diabetes and hypertension presented to the Sinai-Grace emergency room with acute on chronic shortness of breath ,lower extremity swelling and left sided chest pressure radiating to her left arm and weight loss. Physical examination revealed a II/VI mid-diastolic low pitched sound over the precordium without radiation. A chest X-ray, EKG, and serial troponins were normal. Trans esophageal echocardiogram following a  trans thoracic echocardiography  revealed a left atrial myxoma 11.6 cm in diameter attached to the inter atrial septum.  The patient underwent resection of the myxoma  following negative coronary angiography . Gross examination revealed nodular mass with a glistening surface. Microscopic examination revealed small cords and spindle stellate cells in prominent myxoid stroma.  Tumor cells were positive for CD31, CD34, vimentin, and calretinin; and negative for monoclonal CEA. This immunostain pattern is consistent with cardiac myxomas. Pt showed significant clinical improvement after surgery.

Discussion:  Atrial myxomas may be symptomatic or an incidental finding.  Smaller friable or villous myxomas tend to present with systemic emboli. Larger smooth tumors are usually associated with cardiovascular symptoms related to mitral valve disease and left atrial hypertrophy. A classic tumor plop on auscultation is evident only in 15% of cases. Myxomas can be detected by TTE, TEE, CT, or MRI. Prompt resection is required to reduce the risk of embolization and cardiovascular complications. Patients need close follow up to detect recurrence.

Conclusion: Left atrial myxomas are rare benign primary cardiac tumors  which  usually present with mitral valve disease ,heart failure, and systemic emboli. But their presentation  as unstable angina is very rare  with unknown incidence. These patients need meticulous cardiac evaluation including echocardiography for diagnosis and follow up.

 

 

 

 

 

Association of  FLT-3 ITD Mutations with AML arising from MDS.

S Jindani M.D, Z Gul M.D, N Galili PhD, A Raza M.D

Department of Medicine Hematology section

University of Massachusetts, Worcester Massachusetts

 

Introduction: Receptor-tyrosine kinase genes play an essential role in hematopoiesis. Internal tandem repeats (ITD) of the FLT3 receptor-tyrosine kinase gene have been found in 20-27% of patients with de novo AML and correlates with poor prognosis. ITD mutations are rare in patients with MDS. Those that do harbor the mutation may have a higher risk of evolving to AML. We proposed to look for FLT-3 mutation in AML patients transformed from MDS as a possible contributory cause of this transformation.

Methods: Bone marrow samples of 16 patients with AML progressing from MDS were obtained. DNA was extracted ( DNeasy Tissue kit, Qiagen) and exons 11 - 12 and the intervening intron of the FLT3 gene were amplified from isolated DNA by PCR. Amplified products were electrophoresed through 1.8% agarose gels and visualized under UV light with ethidium bromide staining. ITD was recognized as an increase in the size of the PCR product which is normally 328 base pairs.

Results: Out of the 16 patient samples, only one sample was positive for FLT3/ITD mutation as recognized by increase in size of the PCR product

Discussion: The FLT3/ITD mutation has prognostic significance i.e with high risk of transformation to AML, rapid progression of AML, and poor survival in patients with MDS. However, in our cohort, the presence of this mutation is clearly not the major event leading to progression to AML  Similar to previous findings this one patient found to have the FLT3 mutation correlated clinically with rapid progression from MDS to AML with  a karyotype of triploidy (92,XXYY[13]/46,XY[7]).

Conclusion: The result of the current study demonstrates that in patients with MDS FLT3/ITD is associated with risk of transformation to AML. However for the vast majority of patients with AML arising from MDS other mechanisms precipitate transformation of MDS into AML.

 

 

 

 

 

Reversal of genetic abnormalities in Paroxysmal Nocturnal Hemoglobinuria (PNH) with Myelodysplastic syndromes (MDS): A Case Report

Shireen Jindani M.D,Associate, Leopoldo Eisenberg, M.D.Member Clinical Associate Professor of Medicine Wayne State University School of Medicine.

 

Background

PNH is a consequence of nonmalignant clonal expansion of hematopoitic stem cells that have acquired a somatic mutation. Progeny of affected stem cells are deficient in glycosyl phosphatidylinositol- anchored proteins (GPI-APs).Deficiency of GPI- anchored complement regulatory proteins CD55 and C59 accounts for the intravascular hemolysis. Bone marrow analysis and cytogenetics are used to determine if PNH occurs in association with specified bone marrow disorder. We report a case of PNH with MDS with reversal of genetic abnormalities.

Case:

In August 2000, 38 year old Caucasian Lady was referred for the evaluation of anemia and thrombocytopenia with symptoms of dizziness, ringing in ears, headache and fatigue. Past medical history is significant for hypertension. Laboratory data showed a Hb 5.5 gm/dl, MCV 101.9fl,Peripheral smear showed marked degree of Macrocytic anemia and megaloblastoid forms. Bone marrow revealed Sideroblastic erythropoises with 80% cellularity while cytogenetic were initially normal.Differential diagnosis at that point was B12, Folate deficiency versus Myelodysplastic syndrome. Patient was managed with transfusions and supplements but remained transfusion dependent and two months after presentation cytogenetics showed 13 q deletions, by then B12 and folate defieciency was ruled out. Patient then complained of passing dark coloured urine her haptoglobin was low with high lactate dehydrogenase and negative direct and indirect Coomb’s test, CD59 CD55 assay were negative with 7.3% and 2.1% of type II and III PNH cells respectively on flow cytometric analysis so patient had PNH with MDS. While awaiting bone marrow transplant she became transfusion independent. Cytogenetics were further changed with addition of 7 q partial deletion but patient was still transfusion independent so she did not get bone marrow transplant and remained transfusion independent for  some  time with  surprisingly reversal of her cytogenetics to normal in 2006.

Patient is now being considered to be a potential candidate for Eculizumab humanized monoclonal antibody against terminal complement protein C5.

Discussion

This case with follow up for past six years of a patient with Myelodysplasia with Paroxysmal Nocturnal Hematuria and cytogenetic changes with complete reversal provides a unique opportunity to scrutinize the dynamic interaction between myelodysplastic and PNH clones.

 

 

 

 

 

Valproic acid induced hyperammonemic encephalopathy in a patient with normal liver function.

Adedeji Karunwi, MD, Associate, Vikas Veeranna, M.D, Associate,

Department of Medicine, Sinai Grace Hospital/Wayne State University Detroit MI.

 

Introduction

Valproic acid is an anti-seizure medication used commonly as a first line or second line agent. Hyperammonemic encephalopathy is an unusual complication that has been reported with the use of valproic acid. Here we present a case with a patient having normal liver function.

Case report

A 43year old African American male with a history of seizure disorder, hyperlipidemia and bipolar disorder was on valproic acid, benztropine, clonazepam and quetiapine. He presented to the hospital with sudden onset intractable vomiting, progressive lethargy and increasing confusion of one day duration. Physical examination revealed stable vital signs and moderate dehydration. The patient was confused and agitated but no seizure activity was observed. No sign of liver failure was present.

Laboratory exam revealed normal liver functions, a high normal value of valproic acid 90mcg/ml, ammonia of 114µmol/L and metabolic acidosis. Urine drug screen and serum toxicology screen including alcohols were negative. CT scan of the brain was normal. EEG revealed generalized slow waves.

Valproic acid was stopped and therapy with carnitine was started. There was a complete but gradual improvement in his mental status with return of serum ammonia level to normal over 48hours.

Discussion

Valproic acid hyperammonemic encephalopathy is a rare disorder of uncertain etiology, characterized by vomiting, mental status change which ranges from confusion, seizure activity, agitation, drowsiness to coma. Elevated ammonia levels are found in these patients, more frequently in patients on polypharmacy with valproic acid and drugs like topiramate, phenobabitone, carbamazepine. Reversal of encephalopathy is seen in most cases once valproic acid is stopped.

Conclusion

Our case is unique because this patient presented with encephalopathy while on chronic valproic acid therapy and had normal liver functions. There was no adjustment in his medication dosages. Anti-psychotic medications could have contributed to this presentation. This stresses the need for serum ammonia monitoring in patients on valproic acid therapy.

 

 

 

 

 

Proton Pump Inhibitors for Stress Ulcer Prophylaxis in Low Risk Critically Ill Patients.

Adedeji Karunwi, MD, Associate,

Department of Medicine, Sinai Grace Hospital/Wayne State University Detroit, MI.

Research Question:

What are the advantages or risks in the use of proton pump inhibitors (PPIs)for stress ulcer prophylaxis in low risk critically ill patients?

Data Source:

Studies were identified by searching the Medline and Cochrane database for articles published in English Language from 1994-2006.

Search words include stress ulcer, PPIs, Gastro-intestinal bleed.

           

Study Selection:

Randomized controlled double blinded trials that were statistically significant with a p-value of <0.05 were selected. My literature review showed two studies that met the above criteria.

Results:

The first study “Risk Factors for Gastrointestinal Bleeding in critically Ill Patients” enrolled 2252 patients; the primary outcome of the study was clinically significant gastrointestinal bleed.

It revealed a bleeding of incidence of 0.1 %( 0.02-0.5% at 0.95 C.I) in the low risk group on stress ulcer prophylaxis when compared to placebo, the Number Needed to Treat (NNT) to avoid one bleeding episode was >900.

The second study “Stress Ulcer Prophylaxis in Critically Ill Patients” had 287 patients; the primary outcomes studied were clinically significant gastrointestinal bleeding and the risk of pneumonia.

It revealed a bleeding incidence of 1% in both the PPI group and the control group, with no reduction in mortality or hospital stay. There was a higher incidence of gastric colonization and nosocomial pneumonia with the PPI group when compared to Control (37% vs.17% p<0.001, 11% vs. 7% p<0.05 respectively).

  

Conclusion:

This review shows that the incidence of significant stress ulcer bleeding in low risk risk patient is too low to justify prophylaxis with PPIs, and it may predispose to the development of nosocomial pneumonia.

           

      

 

 

 

 

 

Miliary tuberculosis -  A Case Report

Zohra Khan MD, Associate, Shireen Jindani MD, Associate, Wasif Hafeez MD Member, Hassan Makki MD, Member,Department of Medicine, Sinai Grace Hospital Detroit Medical Center/Wayne State University.

Introduction

Miliary Tuberculosis is progressive disseminated hematogenous tuberculosis which can present as an acute infection with  typical tissue reaction or chronic prolonged illness with more subtle clinical / histopathological findings. We present a case of Miliary Tuberculosis with  more cryptic presentation in an elderly African American woman.

Case Report

A 74-year-old female with history of hypertension presented with progressive generalized weakness, progressively decreasing mentation, lower back pain, low grade fever, non productive cough, night sweats, malaise and weight loss for past five months. Physical exam showed significant lower extremity weakness with diminished reflexes. Chest X ray showed bilateral reticulo-nodular infiltrates. MRI of Spine showed compression fracture of L1 with abnormal signals involving T11-12 and Para-spinal abscess. AFB smear on sputum and broncho-alveolar lavage were consistently negative. Lung and bone-marrow biopsies showed multiple non-caseating granulomas with no evidence of malignancy or fungal infection. Spinal tap showed lymphocytic pleocytosis.

Patient was empirically treated with a four drug anti-tuberculosis regimen. Response to treatment was slow. Steroids were added after Lumber puncture studies were reviewed. Patient showed marked improvement. Neurosurgery evaluated patient and elected to continue with medical management alone. Lung tissue and Bone marrow cultures came back positive for Mycobacterium Tuberculosis after four weeks.

Discussion:-

 Miliary Tuberculosis is more frequently seen in older patients often with co-morbidies. It is an infection more commonly seen in minority racial groups and is associated with conditions like alcoholism, cirrhosis, cancers, pregnancy and rheumatological diseases. Patients can present with signs and symptoms involving CNS (meningitis), GI- tract (peritonitis) and lung involvement (typical-millet-seed like infiltrates on chest x-ray is seen in 90% cases). Symptoms duration can range from 2 weeks to 52 weeks. Sputum AFB smears are positive in one-third of cases. Bone marrow is positive in 20-40% cases and transbronchial biopsy is positive in 60-75%  cases. Treatment is best started based on strong clinical suspicion. Response may be prompt or take several weeks. Adjunctive steroids have been recommended in severe cases.

Conclusion;

Mortality of untreated Miliary tuberculosis is high. Early diagnosis requires high degree of clinical suspicion. Treatment is often started empirically. Response to treatment can be slow.

 

 

 

 

 

IgA Nephropathy:A Common disease with an uncommon presentation.

Gulnaz Khan, MD (Associate), Kavitha Potluri, MD (Associate), Dr.Krishnamoorthy, MD (Member), Irfan Omar, MD (Member), Sinai Grace Hospital / Wayne State University, Detroit, MI.

Introduction:  IgA Nephropathy is known to be the most common form of glomerulonephritis worldwide.In U.S, the incidence is approximately 4% of all renal biopsies and it is six times lower in African Americans than in Caucasians.The lower prevalence in African Americans is unexplained.

Case report: We are describing a case of 41 year old African American male with past medical history of hypertension and type II diabetes, who presented with worsening shortness of breath and bilateral leg swelling for 3 days. The patient was recently discharged from the hospital after being treated for pneumonia and review of the medical records revealed that he had a right leg DVT during the hospital stay. Physical examination revealed anasarca with prominent facial swelling and diffuse crackles on auscultation.Workup showed nephrotic range proteinuria with spot urine protein of 450mg/dl, serum creatinine of 0.5, hemoglobin of 7.7 and thrombocytosis. Work up for the nephrotic range protienuria including Hepatitis profile, HIV, ASO titers, ANCA levels and protein electrophoresis, were negative. Dilated fundoscopy did not show any evidence of diabetic retinopathy. CT guided renal biopsy was performed which showed immune complex mediated, IgA predominate; diffuse mesangial and segmental endocapillary proliferative glomerulonephritis. Patient’s symptoms improved with aggressive diuresis and he was discharged home on ACE inhibitors.

Discussion:  IgA Nephropathy is an immune complex mediated glomerulonephritis, occurring in all age groups.It is often progressive with 25% of the patients going to end stage renal disease over the course of 25 years. Asymptomatic microscopic hematuria is the most common presentation and less than 30% present with nephrotic range proteinuria. Although proteinuria at the time of biopsy, is a well known indicator of progressive renal disease in patients with IgA Nephropathy, our patient has stable renal function even after 2 years of follow up.

Conclusion:IgA nephropathy shows regional and racial variation,  diagnosed by renal biopsy.Ig A nephropathy is an important disease that should be considered in differential.

 

 

 

 

 

 

Purple urine bag syndrome (PUBS)** A Case Report and literature review

Gulnaz Khan MD,Associate,Irfan Hameed MD,Associate,Wasif Hafeez MD,Fellow,Wayne State University/Detroit Medical Center (Sinai-Grace Hospital) Porgram, Detroit, MI.

Purple urine bag syndrome (PUBS) is an interesting phenomenon of irresolute etiology first reported in 1978, associated with chronic urinary catheterization. This syndrome is more frequently observed in chronically catheterized constipated elderly women in geriatric wards or patients lived in nursing homes. We are describing a case report of PUBS in 80 year old male from home with a history of quadriplegia secondary to spinal abscess resulting in bed bound state and chronic indwelling catheter since last 10 years. Patient presented with abdominal distension, vomiting and chronic constipation. On presentation he was found to be hypotensive, lethargic and confused with distended abdomen. He also had supra pubic catheter for years secondary to repeated urinary tract infection. The catheter bag was filled with purple color urine which showed pH of >9.0, 3+ bacteria and leukocytes. Abdominal imaging was consistent with fecal impaction through out the colon. He was treated with intravenous fluid, cefepime and disimpaction. Urine culture grew multiple organisms. PUBS is characterized by the purple discoloration of the urine, collecting bag, and tubing. A number of factors are involved, but not always present, in its development including female sex, gram negative lower urinary tract infection, constipation, laxative suppository use, indicanuria, institutionalization, the use of a plastic (PVC) urinary catheter and alkaline urine. The etiology is still controversial but in the literature researched most authors believe that indigo, which is blue, and indirubin, which is red, are responsible for the colors obtained. Chronic constipation is commonly associated with bacterial overgrowth in the bowel in which tryptophan has been converted to idol and yields the high levels of indigo (blue) and indirubin (red) in urinary bags of patients with bacterial infection of the urine, because indigo-producing bacteria have indoxyl phosphatase or sulfatase that can produce indigo and indirubin. Despite multiple theories that involve the complex tryptophan metabolism to the tubing dye, the cause remains elusive. The common pathogens isolated from the urine samples are Escherichia coli, Providencia var. spp., Proteus mirabilis, Klebsiella pneumoniae and Pseudomonas Aeruginosa. The syndrome resolves usually after treatment of urinary tract infection or changing of the collecting bag.

 

 

 

 

What new pharmacological options are available for weight reduction and glycemic control in Type-II Diabetes Mellitus?

 

Zohra Khan MD Associate, Shireen Jindani MD Associate,Opada Alzohaili MD Member, Department of Medicine, Sinai Grace Hospital,Wayne State University,Detroit,Michigan.

Background :

Prevalence of obesity is  28% and 34% in men and women respectively.  Obesity is associated with over 100,000 excess deaths every year. It is predicted that in upcoming years Catastrophic impact of global obesity epidemic on rates of diabetes and cardiovascular disease.

Data Source;  Pub med , Ovid and Cochrane  databases were searched for all English language papers on new treatment options available for  weight reduction and glycemic  control.

Study Selection Only randomized double blind control trials with a P-value of <0.05 and that are statistically significant have been selected. My literature review was further filtered with limits of Randomized double blind control trials, Clinical phase three and phase four human trials.

Study Details

Out of several new pharmacologic therapies, Exanetide and Rimonabant are two new drugs that have been studied in clinical trials and  has  shown significant impact in diabetic control by causing significant decrease in HbA1c levels and control in type-2 diabetes and weight reduction.This is shown in AMIGO (AC2993: Diabetes Management for Improving Glucose Outcomes) studies phase 1,2 and 3 trials for Exanetide and RIO (Rimonabant In Obesity Program ) studies.

Rimonabant is  another new agent, there were seven clinical  trial program for the treatment of multiple cardiometabolic risk factors .Four  out of seven studies  were designed to evaluate its effect in Obesity which showed significant reduction in weight: thereby reducing incidence  of Metabolic Syndrome.2

Conclusion

Patients who can not achieve good glycemic control with mono or multi drug therapy for diabetes could get benefit from Exanetide and/or .Rimonabant  combined with diet in patients with obesity & cardiovascular co-morbidites  help in weight loss, better control of diabetes, lowers Lipid levels thereby decrease risk of Metabolic syndrome .

 

 

 

 

 

ARE THE NEWER INSULIN DERIVATIVES INSULIN GLARGINE AND LISPRO BETTER THAN PREMIXED NPH/REGULAR(70/30)FOR THE TREATMENT OF TYPE 1 DIABETES?

Gulnaz Khan,MD,Associate,Rajika L.Munasinghe ,MD,Fellow Sinai Grace Hospital / Wayne State University,Detroit,Michigan.

Background: DCCT and UKPDS confirmed the value of glycemic control in the prevention of complications of diabetes. This is achieved with regular insulin administered by either as continuous subcutaneous insulin(CSI) by pump or multiple daily injections( MDI ).The chief adverse event with intensive therapy was severe hypoglycemia.Insulin analogues are characterized by action profiles that afford more flexible treatment with a lower risk of the development of hypoglycemia.

 

Objective:To compare glargine + lispro with NPH + regular insulin and to suggest insulin regimen based on blood glucose profiles in patients with Type 1 diabetes.

Methods:Articles were identified through MEDLINE, PubMed, Cochrane library and Ovid. Five (relevant) randomized Multicenter controlled Trial in type 1 diabetes were identified.

Results: Three out of the 5 studies showed a statistically significant improvement in HbA1c in patients treated with Insulin Glargine and Lispro compared to NPH and Regular insulin. Fasting blood glucose values were significantly improved in 3 out of 5 trials for patients treated with Insulin Glargine and Lispro.Incidence of nocturnal hypoglycemia was significantly less with Glargine and Lispro in 4 trials. The remainder of the results  were non-significant. NPH/Regular insulin was not superior to Glargine/Lispro for the above outcome measures in any one of the trials.

Conclusion: Insulin analogues allow more accurate replication of the basal and prandial components of insulin replacement.Glycemic control is improved as measured by HbA1c,FBG,nocturnal hypoglycemia and postprandial hyperglycemia with no major differences in safety and efficacy profiles of two groups.New insulin preparations are more expensive and increased cost should be considered in deciding between different insulins. Recent studies have also shown that flexible insulin management can be cost effective and can be associated with an improvement in quality of life. Our literature review supports the use of insulin analogues to achieve recommended goals of glycemic control in patients with diabetes.

 

 

 

 

 

Signet Ring Cell Carcinoma of the Esophagus

Sabah Khokhar MD, Ashraf Ahmad MD, Melhem SOlh MD

Wayne State University/ Detroit Medical Center (Sinai-Grace)

INTRODUCTION: Signet cell carcinoma is an undifferentiated diffuse type with predilection for the submucosa. It commonly affects the younger population with a poor prognosis. Several cases of signet cell cancer have been reported in the stomach and colon; however esophageal involvment is rarely reported. Mucoepidermoid esophageal cancer with signet cell ring type is extremely rare with six reported cases in the literature. We hereby present a case of mucoepidermoid signet cell ring type cancer of the distal esophagus with extension into the proximal stomach.

CASE REPORT: A 57 yr old African American male presents with 4 weeks complaints of epigastric pain associated with  recurrent episodes of nausea and vomiting. The patient also complained of progressive dysphagia , and a 25 pounds weight loss during the last two months. The patient had a social history significant for heavy smoking and alcohol abuse. A Double-contrast upper GI study showed 3cm long, moderate stricture of the distal esophagus with dysmotility. EGD showed an ulcerated mass 2x3 cm in dimensions with focal area of diffuse signet cell infiltration of the lamina propria. CT abdomen and thorax showed dilated esophagus with distal esophageal mass extending into the proximal stomach with no evidence of lymphadenopathy or metastasis. Based on these findings, patient referred for neoadjuvant chemotherapy followed by surgical resection and primary anastomosis. The pathology of the resected specimen showed clear margins with no residual tumor cells after neoadjuvant chemotherapy.Patient is being followed in the outpatient oncology clinic with no residual symptoms or signs of recurrence.

DISCUSSION:

Signet-ring cell  mucoepidermoid tumor of the esophagus is a rare malignancy accounting for less than 0.5% of the esophageal tumors. It is thought to be an intermediate histology between squamous cell and adenocarcinoma,however; it is an extremely malignant tumor as it usually present at a late invasive stage. The only reported case of survival was a tumor confined to the submucosa whereas, the rest of the reported 6 cases were invasive with no response to neoadujant chemo or radiothearapy. The case we presented with an early stage signet-ring cell carcinoma with stomach involvement that showed significant response to chemotherapy followed by curative resection.

 

 

 

 

 

Anti Hypertensive Treatment In patients with Diabetic Nephropathy .

Saba Khokhar, MD (Associate)

Sinai-Grace Hospital/Wayne State University, Detroit, Michigan

 

Introduction: Both hypertension and microalbuminuria are risk factors for progression of chronic kidney disease. Uncontrolled blood pressure has a major role in the development of proteinuria. Current guidelines recommend blood pressure goal of 130/80 in diabetic patients with proteinuria less than 1g /24 hours urine.

Clinical Question: What are the best treatment options for control of hypertension in Type-2 diabetic patients with microalbuminuria ?

Methods: Literature search was conducted utilizing Medline Ovid (1966-2006), Medline PubMed and Cochrane library , Journal and Review articles.

Keywords: Antihypertensives, microalbuminuria, kidney disease, ACEIs. ARBS, CCBS,Thiazides.

Selection Criteria: Randomized controlled trials, Sample size.

Search results: Five randomized controlled trials were selected .

Discussion/Results: In the first trial 3557 type 2 diabetic patients included,SBP decreased by 1.92 mmHg in the rimapril group whereas increased by 0.55mmHg in the placebo group. In the second trial 43 hypertensive patients were randomized to either lisinopril or atenolol, Ambulatory BP  was lower in the ACEI group and had a greater decrease during follow up.In the the third trial, 77 type 2 diabetic patients were randomized to verapamil SR/trandolapril ( VT) 180/2   or losartan/hydrochlorothiazide (LH) 20/12.5 mg/day, overall BP significantly decreased.values by treatment were for VT 164.3  ± 18.5/ 87.2±10.7mmHg at baseline and 135.0±15.1/ 71.3±8.4 mmHg at conclusion, For LH 158±17.4/80.1±8.4 mmHg at baseline and 139.9±16.1/70.5±8.2 at conclusion. In the forth trial 590 diabetic hypertensive patients

were randomly assigned to receive placebo or isbesartan 150mg or 300 mg daily, The difference was not statistically significant between placebo and isbesartan 150  but it Was significant between placebo and isbesartan 300mg(P<0.001). In the fifth trial 1715 Patients were  randomly assigned to placebo,10mg amlodipine, or 300mg isbesartan.The MBP in the placebo group was 3.3 mmHg higher than in the active drug groups Throughout the study( P= 0.001), the difference in favor of isbesartan in reaching

The end point remained  significant even after statistical adjustment for BP differences.

Conclusion: we believe that drugs blocking the rennin-angiotensin system have an advantage that may apparent in clinical practice in terms of controlling BP and decreasing the progression of diabetic nephropathy.

 

 

 

 

 

PHYSICAL EXERCISE IN CHRONIC KIDNEY DISEASE: ASSOCIATION WITH DISEASE PROGRESSION AND OUTCOMES

Rama Nadella, MD 1, Xiaotong Zhang, MA 1, DNB2, Brenda M. Gillespie, PhD 1, F Finkelstein, MD3, George Eisele, MD4, Sanjay Rajagopalan, MD 2, Rajiv Saran, MD MRCP, MS 1,2

1 Kidney Epidemiology and Cost Center, Univ. of Michigan, Ann Arbor, MI; 2 Department of Internal Medicine, University of Michigan, Ann Arbor, MI; 3 Yale University, New Haven, CT; 4 Division of Nephrology, Department of Internal Medicine, Albany Medical Center, Albany, NY.

 

Introduction: Physical inactivity is a major modifiable cardiovascular risk factor, but its effect on progression of chronic kidney disease (CKD) is unknown. While there are studies showing therapeutic and psychological benefits of exercise in dialysis patients, there is little research exploring the potential benefits of exercise in those with CKD.

Methods: This study explored the benefits of self-reported exercise (ex) frequency in a cohort of stage III-V pre-dialysis CKD patients at 4 US sites and also addresses association between physical exercise and other Quality of Life parameters, time to ESRD and mortality. Ex frequency (6-level ordinal scale from never to daily), mental and physical component summary (MCS and PCS) scores and activities of daily living (ADL) score were derived from the KDQOL-SF36. Predictors of ex frequency and ADL score were assessed using multiple regression. Association of ex frequency with MDRD-GFR slope (ml/min/1.73m2/year) was examined using multiple regression, adjusting for age, race, body mass index, systolic blood pressure, proteinuria, angiotensin converting enzyme use, albumin and ADL score.

Results: In 639 patients at enrollment, mean age was 61+/-15yrs, 45% were female, 18% were African American, mean GFR was 24.1+/-10.2ml/min/1.73m2 and mean MCS and PCS scores were 50.3+/-10.3 and 37.5+/-11.5 respectively. Ex frequency was higher among men (p=0.075), white race (p=0.001) and in individuals with higher PCS (p<0.001), MCS (p<0.001) and ADL score (p<0.001). In the multivariable model, black race (p=0.003) and higher body mass index (p=0.057) were significantly associated with lower exercise frequency. Higher exercise frequency was associated with slower rate of decline in GFR in nondiabetics (p= 0.049) after adjusting for other predictors of GFR slope, but no similar association was seen in diabetic group and the overall cohort. Higher exercise frequency was significantly associated with lower ESRD events i.e. dialysis and transplant combined (p=0.064) and the combined outcome of death or ESRD events (p=0.022).

Conclusion: To the best of our knowledge, this study is the only prospective observational study examining self reported physical activity profiles and a variety of domains of self reported quality of life in a large sample of CKD patients and suggests that further investigation is necessary in this area.

 

 

 

 

Pulmonary Benign Metastasizing Leiomyoma presenting as multiple pulmonary nodules, and a cavitary lesion, case report.

 

George Nassif,MD , Hassan Makki,MD,

Department of internal medicine, Wayne State University ,Detroit Medical Center,Sinai-Grace Hospital.

Benign metastasizing leiomyoma (BML) is a rare entity with less than 100 documented cases (1). The condition is characterized by uterine leiomyoma associated with metastatic pulmonary lesions years later (2). The purpose of this presentation is to report a rare case of BML presenting as multiple pulmonary nodules and a cavitary lesion with hilar lymphadenopathy.

Case report

A 55-year-old African-American woman presented with shortness of breath and cough for one week. She denied any other symptoms. She had hysterectomy 20 years previously for a uterine leiomyoma. Her physical examination revealed scattered rhonchi.

Sputum specimens were negative for bacterial, fungal, and mycobacterium pathogens.  

CT and x-rays of the chest revealed multiple bilateral pulmonary nodules, a solitary left lower lung cavitary lesion, and left hilar lymphadenopathy. 

Pathological examination of lung sections revealed a well circumscribed nodule. It was composed of elongated spindle cells. Immunoperoxidase showed that the cells react to smooth muscle actin, estrogen, and progesterone receptors, but not to S-100, CD34, and Vimentin.

Discussion

BML is an uncommon cause of pulmonary nodules, affecting middle-aged women after hysterectomy for uterine myoma.

 Patient’s with BML are usually asymptomatic, although dyspnea, dry cough, or chest pain have been described. The most commonly affected organ is the lung, but lymph nodes, mesentery, bones, and the heart may be implicated (3).

The pathogenesis of BML is somewhat controversial, but hematogenous spread is the most commonly proposed mechanism (4).

 Typical radiographic findings of BML include multiple pulmonary nodules (5). BML has been found to express both estrogen and progesterone receptors. A radical surgical resection, such as extensive tumor debulking and oophorectomy, has been advocated as the treatment of first choice (6,7,8). Also, the use of hormonal therapy with long-acting GnRH analogs has been described with good results in several reports, but, the exact place for Aromatase inhibitors (AIs) and Raloxifene in the algorithmic treatment of BML is not known (4).

In summary, our case is unique not only for the rarity of pulmonary BML, but the presence of a cavitary lesion and hilar lymphadenopathy. BML should be considered in any asymptomatic patient presenting with multiple pulmonary nodules and a history of a uterine leiomyoma. 

References

1-Abramson S, Gilkeson RC, Goldstein JD, Woodard PK, Eisenberg R, Abramson N. Benign metastasizing leiomyoma: clinical, imaging, and pathologic correlation. AJR Am J Roentgenol  2001; 176:1409–13.

2-Goyle KK, Moore DF Jr, Garrett C, Goyle V. Benign metastasizing leiomyomatosis: case  Report and review. Am J Clin Oncol 2003; 26:473-6.

3-Esteban JM, Allen WM, Schaerf RH. Benign metastasizing leiomyoma of the uterus  histological and Immunohistochemical characterization of primary and metastatic lesions. Arch Pathol Lab Med 1999; 123:960–2.

4-Rivera JA,  Christopoulos S, Small D . Hormonal Manipulation of Benign Metastasizing Leiomyoma: Report of Two Cases and Review of the Literature. The Journal of Clinical Endocrinology & Metabolism 2004;Vol. 89, No. 7 3183-3188.

5-Camenzuli A, Twaite E, Huda B, Haqqani M, Warburton CJ, Curtis J. Cavitation in lung masses from benign metastizing leiomyomatosis. Clin Radiol Extra 2004; 59:83–5.

6-Banner AS, Carrington CB, Emory WB, Kittle F, Leonard G, Ringus J, Taylor P, Addington WW.  Efficacy of oophorectomy in lymphangioleiomyomatosis and benign metastasizing leiomyoma. N Engl J Med 1981; 305:204–209.

7-Evans AJ, Wiltshaw E, Koshanowski SJ, Macfarlane A, Sears RT. Metastasizing leiomyoma of the uterus and hormonal manipulations. Case report. Br J Obstet Gynaecol 1986; 93:646–648.

8-Uchida T, Tokumaru T, Kojima H, Nakagawaji K, Imaizumi M, Abe T. A case of multiple leiomyomatous lesions of the lung: an analysis of flow cytometry and hormone receptors. Surg Today 1992; 22:265–268.

 

 

 

 

 

WHOLE BLOOD ACCUMULATION OF ASYMMETRIC DIMETHYLARGININE

IN END-STAGE RENAL DISEASE

 

Raylene Platel (1), Scott Billecke (2), Steven Whitesall(2), Rachel L.Perlman(2), Kenneth A.Jamerson(2), Louis G. D’Alecy(2), Crystal A. Gadegbeku(2).

1. Wayne State University/Detroit Medical Center/Sinai Grace Hospital, Detroit, MI; 2.University of Michigan, Ann Arbor, MI

 

Plasma asymmetric dimethylarginine (ADMA) is significantly elevated in patients with renal disease and associated with cardiovascular mortality. Our recent animal model observations suggest that whole blood (WB) possesses large concentrations of protein-incorporated ADMA and the proteolytic machinery necessary for its release.  To explore the link between WB and plasma ADMA in humans, we compared plasma ADMA and WB free ADMA accumulation in subjects with and without end stage renal disease (ESRD).  Pre-dialysis blood samples were obtained from 13 ESRD patients receiving chronic outpatient hemodialysis and 13 subjects without kidney disease who were matched for age, gender, race and presence of diabetes and/or hypertension. ADMA plasma concentrations were measured at baseline and ADMA levels from WB supernatant (e.g. the soluble fraction of lysed WB) were quantified over a five hour ex vivo incubation. ADMA was measured by high-pressure liquid chromatography. Baseline values were compared using unpaired two sided t-tests. The slopes derived from WB ADMA accumulation were analyzed using a marginal effects linear regression model.  We observed that plasma ADMA levels in ESRD patients are greater than levels in matched controls (0.83±0.05 vs. 0.61±.06µM, p=0.05, respectively) while baseline WB ADMA levels only trended toward higher values in ESRD subjects (0.89±0.06 vs. 0.72±.07 µM, p=0.10).  Both groups showed significant increases in WB ADMA levels during ex vivo incubation.  However, ESRD population had a 47% greater rate of accumulation than matched controls (p=0.04).   These findings support the concept that blood components may contribute to pathophysiologic elevations of free plasma ADMA.

 

 

 

 

RHABDOMYOLYSIS AND ACUTE RENAL FAILURE IN A PATIENT WITH HYPOTHYROID

Rama Nadella MD, Associate, Prakash Vishnu MD, Associate, Muhammad Ahsan MD, Department of medicine, Sinai Grace Hospital, Wayne State University, Detroit, MI

Introduction:

Myopathy is frequently associated with hypothyroidism. Proximal muscle weakness, myalgias, cramps, delayed tendon jerk relaxation and moderate elevation of serum creatine kinase are the commonest features of hypothyroid myopathy. However, rhabdomyolysis due to hypothyroidism leading to acute renal failure is very rare.

Case Report:

A 39 year old man with a past medical history of hypertension diagnosed a year ago and hyperthyroidism treated with radioactive iodine ablation 20 years ago, was evaluated for elevated serum creatinine. He complained of muscle aches in his thighs and stated he had been exercising and lifting weights once or twice a week for many years. There was no history of strenuous exercise, trauma, recent infection, seizures or kidney disease. Alcohol and cocaine use was denied. On examination, there was no thyromegaly or muscle tenderness. Relaxation of deep tendon reflexes was delayed. His initial serum creatinine was 1.8 mg/dl and creatine kinase (CK) was 1,456 U/L. At three months follow up creatinine was 1.7mg/dl and CK went up to 1788U/L, 100% of it was CK-MM. Rhabdomyolysis secondary to hypothyroidism was suspected. Patient was advised to avoid weight lifting and strenuous exercise. His thyroid stimulating hormone (TSH) was 99.29 UIU/ml (n=0.2-4.7), total thyroxine < 1mcg/dl (n=5-12). Replacement with thyroxine was started at 100mcg/day with improvement of symptoms in four months. The repeat TSH came down to 17.494 UIU/ml, CK to 351U/L and creatinine to 1.2mg/dl.

Discussion:

This case illustrates that hypothyroidism can precipitate rhabdomyolysis which in turn can lead to acute renal failure. Other predisposing factors for rhabdomyolysis are strenuous exercise, alcohol ingestion, cocaine use, muscle compression, trauma or seizures. Although hypothyroid myopathy leading to rhabdomyolysis is rare, recognizing it is important to institute appropriate therapy thereby preventing permanent renal damage. Adequate therapy with thyroxine usually leads to complete recovery in such patients. In conclusion, patients presenting with myalgia, weakness, and unexplained elevated serum muscle enzymes should be evaluated for hypothyroidism.

 

 

 

 

 

Effectiveness of Exenatide Therapy In The Treatment of Type 2 Diabetes In Ambulatory Practice.

K.Ramesh, M.D, R.Munasinghe, M.D, O. Alzohaili, M.D, G.W.Edelson M.D,

Sinai-Grace Hospital, Wayne State University/ Detroit Medical Center.

 

Introduction:

Exenatide, an incretin mimetic and GLP-1 agonist improves glucose homeostasis and promotes weight loss by glucose dependent insulin release, regulation of glucogan secretion, delaying gastric emptying, and decreasing appetite. It is approved as adjunctive therapy for type 2 diabetes in conjunction with Metformin and/or sulfonylurea to improve glycemic control. Principal side effects are gastrointestinal manifestations such as nausea, vomiting and diarrhea. This study was conducted to evaluate the effectiveness of exenatide in two private endocrinology practices.

Method:

Medical records of 30 poorly controlled type 2 diabetic patients seen in office practice between Oct 2005 and August 2006 were reviewed. Exenatide was initiated at 5mcg twice daily and increased to 10mcg twice daily in 4 weeks. The change in HbA1c, lipid profile and body weight before and after initiation of exenatide were evaluated using paired Student’s t-Test. The prevalence of hypoglycemia and other major adverse effects of exenatide were also recorded. 

Result: The mean age of the study subjects was 54.7 years, 53.3% were female and 93% were white. Treatment prior to initiation of exenatide included oral hypoglycemic drugs [Metformin (22) +/- Sulfonylurea (18) +/- Thiazolidinedione (13)] with or without insulin (9). The mean duration of follow up was 15 weeks (range 8 to 28 weeks). The mean HbA1c of the study subjects declined from 7.80% to 7.32% (p <.0008) and the mean body weight decreased from 244.3 to 238.6 lbs (p <0.0004), an average loss of 5.7 lbs. There was no statistically significant change in total cholesterol, triglycerides, HDL, LDL, or in the cholesterol/HDL ratio. The majority (90%) of patients continued exenatide after the first follow up visit. Hypoglycemia was noted in 10% of patients while nausea and vomiting was reported by 31% of patients. Other gastrointestinal side effects were reported by 23% of patients.

Conclusion:

In typical ambulatory practice, exenatide is effective in improving glycemic control and promoting weight loss in poorly controlled type 2 diabetic patients on oral hypoglycemic therapy. Although a substantial number of patients reported gastrointestinal side effects, the majority of patients managed to remain on exenatide therapy.

 

 

 

 

 

Impact of baseline glycemic control on longitudinal blood pressure responses in drug-treated hypertensives ?

Krithi Ramesh, MD; Zongshan Lai, MS; Xuefeng Liu, PhD; Anupam Goel, MD; John Flack, MD, MPH

Wayne State University, Detroit, Michigan.

 

Background:  Most persons with diabetes have hypertension.   Glycemia, per se, has physiological effects such as vascular stiffening that might interfere with longitudinal blood pressure (BP) lowering in drug-treated hypertensive patients.

Objective:  To determine the BP response to antihypertensive drugs in a pharmacologically treated in a largely African American hypertensive cohort.  

Methods:  We performed a retrospective review in the Wayne State University Hypertension Clinic (WSUHC) between May 2001 and May 2006 of patients with at least two visits and one glycosylated hemoglobin (A1C) determination.  The outcome of interest was last available SBP.  We recorded age, sex, race, weight, A1C, chronic kidney disease staging and albuminuria.  A therapeutic intensity score (TIS), the patient’s daily medication dose over the maximum FDA approved dose of that medication for each drug, was calculated to determine therapeutic intensity of treatment.  We compared the fitting of two linear mixed models]) on last available SBP: a) Hemoglobin A1C alone versus b) Hemoglobin A1C with other covariates.

Results:  The average age in our cohort [N=146] was 61.0 years.  Most of the patients were female (101 [69.2%]) and 136 (93.2%) were African American. The average weight (lbs), hemoglobin A1C (%), and baseline SBP (mm Hg) were 213.3 pounds, 7.3, and 175.8 mm Hg, respectively.  Average baseline antihypertensive TIS was 2.0 (SD 1.2).   The average follow-up period was 18.1 months.  The average final antihypertensive TIS was 2.8 (SD 1.2) and the ending mean SBP was 145.3 mm Hg.  In the model including hemoglobin A1C alone, each 1% higher baseline hemoglobin A1C was associated with a 2.6 higher exit SBP (P=0.010).  In the multivariate mixed model for predicting final SBP including all baseline variables and time-dependent covariates such as antihypertensive TIS, the each 1% higher baseline hemoglobin A1C  was linked to 2.9 mm Hg higher SBP (P=0.008).   

Conclusions:  Baseline glycemic control has a very significant and negative impact on longitudinal SBP levels in a drug-treated hypertensive cohort with diabetes.  These data imply, though do not prove, that  better glycemic control will improve BP control in drug-treated hypertensive patients with diabetes. 

 

 

 

 

 

Oxaliplatin associated anaphylactic shock, immunological neutropenia and thrombocytopenia.

Syed Raza, MD, Saad Usmani, MD, Joel Appel, DO FACP

Department of Internal Medicine, Detroit Medical Center/Wayne State

University, Sinai Grace Hospital, Detroit MI.

 

Introduction:

Oxaliplatin is a platinum salt that has been used as a chemotherapeutic agent, specifically for gastrointestinal malignancies. We present a case of a patient who developed an uncommon but life-threatening anaphylactic reaction to this agent.

Case Report:

A 63 year old Caucasian female with past medical history of hypertension and hypothyroidism was diagnosed with Stage III A sigmoid cancer. She underwent colectomy and was started on adjuvant therapy with FOLFOX 4 regimen containing oxaliplatin, 5-flourouracil (5-FU) and leucovorin. She was asymptomatic after Cycle#1. On the second day of Cycle#2, she presented with fevers and chills at home. On physical examination, she was found to be hypotensive and had a generalized non-pruritic rash. Laboratory evaluation revealed neutropenia. She was treated for febrile neutropenia and was discharged after 6 days. While receiving oxaliplatin for the Cycle#3 a week later, she became diaphoretic, developed the same rash and went into shock. She was admitted to the ICU and treated for suspected septic shock with fluids, antibiotics and required vasopressor agents. Physical examination did not reveal a focus of infection and the septic work-up was negative. Blood counts, which were normal before Cycle#3, now showed profound neutropenia and thrombocytopenia. Patient made a quick recovery and was transferred to the general medical floor on day 2 of her second admission. She was later discharged on day 5 of her admission in a stable condition. Her shock was attributed to anaphylaxis to oxaliplatin.

Discussion and Conclusion:

Oxaliplatin induced anaphylactic shock is an unusual presentation with only one prior reported case. It is a Type 1 hypersensitivity reaction, possibly IgE mediated. Our patient developed shock while on oxaliplatin infusion and also developed immunological neutropenia and thrombocytopenia. A thorough review of the literature showed that three patients had type 3 hypersensitivity reactions with immunological thrombocytopenia.  Three cases of 5-FU anaphylaxis have been reported in the literature but the timeline in our case leads us away from incriminating this agent. We report this case to alert physicians to consider oxaliplatin anaphylaxis in the differential for patients on this agent who present with shock when other etiologies have been ruled out.

 

 

 

 

 

CIGARETTES AND ALCOHOL INCREASE THE RISK OF BREAST CANCER

Syed Raza MD. (Associate)

Detroit Medical Center/Wayne State University, Sinai Grace Hospital, Detroit MI.

 

Introduction:    Unlike the other established risks for developing breast cancer a greater amount of alcohol consumption and cigarette smoking also play a role in increasing this risk.

Clinical Question:    Along with other risk factors for breast cancer like family history, BRCA genes, does cigarette smoking and alcohol consumption play a role in increasing the risk for breast cancer?

Methods:     A literature search was done for epidemiological trials using key words like breast cancer/neoplasms, alcohol consumption and tobacco/cigarette smoking. The search was conducted on Medline Ovid, Medline Pubmed and Cochrane library.

Results:      There were 3 relevant studies found and were all cohort studies which showed that the relative risk estimate of any amount of alcohol consumption to no consumption was 1.5. Active smokers were at 32% greater risk than never smokers. Those who had a 40 pack year history or greater of smoking had an 83% risk and those with less amounts of smoking were at 60% risk and that smoking was an initiator not a promoter.

Conclusion:     Based on the evidence provided by these studies it can be concluded that women with greater amounts of alcohol consumption or those who smoked were at a higher risk of developing breast cancer. With a positive family history or other established risk factors their risk was increased. There is a need for further studies to give more accurate results for the degree of risks of developing different types of breast cancer with other substances which are potentially carcinogenic.

 

 

 

 

 

I can not walk, is it West Nile virus, HIV or Hepatitis C?

Zainab Shahid (Associate), Saad Usmani (Associate), Mark Wolfe (Infecious Diseases), Geetha Krishnamoorthy (Member)

Department of Medicine, Sinai-Grace Hospital/Wayne State University, Detroit, MI

Introduction:

West Nile virus (WNV) has become a re-emerging health problem in the United States with number of cases rising from 62 in 1999 to 9,862 in 2003. It usually manifests as a viral meningeo-encephalitis like picture. We present an unusual case of WNV infection presenting with acute onset lower extremity weakness.

Case Report:

47 year old woman with history of type II diabetes, chronic pancreatitis and intravenous drug use presented with sudden onset of inability to walk, lower back pain, fever and chills beginning 4 days prior to presentation. Patient had a 10 pound weight loss and loss of appetite in the last 2-3 weeks. On physical examination, temperature was 103.0 0F, there was point tenderness of spinal and paraspinal lumbar area, power was 0/5 in bilateral lower extremities along with areflexia and positive Babinski’s sign. Differential diagnosis at this point included spinal cord compression (due to osteomyelitis or epidural abscess) or an acute viral syndrome. Patient was started on IV antibiotics. Laboratory work-up showed leucocytes (12,400 cells/cumm, Normal 4,000-11,000/cumm) with leftward shift. Chest X-ray and MRI of the lumbosacral spine with contrast were also negative for any pathology. Serology was positive for HIV and HCV but negative for Lyme’s disease, HSV, CMV, EBV, and syphilis. Lumbar puncture showed normal opening pressure, 78 nucleated cells with lymphocytic predominance, high protein levels (89 mg/dl) and cerebrospinal fluid (CSF) serology positive for WNV IgM consistent with an acute WNV infection. Electrodiagnostic studies were consistent with demyelination pattern in lower extremities. Patient received supportive care with no improvement in her symptoms.

Discussion:

This case presents us with a diagnostic dilemma where the patient had acute flaccid paralysis (AFP) with at least two competing diagnoses. HIV can be associated with Guillian-Barre syndrome (GBS) but GBS usually presents 2-8 weeks after an acute infection without any fever or leucocytosis. Hepatitis C on the other hand presents as peripheral neuropathy in relation to mixed cryoglobulinemia. Review of literature showed that about 100 cases of acute flaccid paralysis due to WNV infections have been reported of which 77 cases involved all four extremities. Vast majority of cases had meningeoencephailits along with AFP. Our patient had evidence of fever, leucocytosis, lower extremity paralysis, high CSF protein and positive WNV IgM in CSF pointing towards a diagnosis of an acute WNV infection and away from GBS. We are reporting this case to alert internists regarding various presentations of West Nile virus and how to differentiate this entity from other etiologies of acute flaccid paralysis.

 

 

 

 

 

NEWER TESTS TO DIAGNOSE AND STRATIFY SEVERITY OF ACUTE PANCREATITIS

Abu Fazal Shaik Mohammed, MD (Associate),

Sinai-Grace Hospital/Wayne State University, Detroit, Michigan.

 

Introduction:   Acute Pancreatitis is a common condition with an outcome ranging from asymptomatic illness to severe pancreatitis which has a mortality of 20%. Hence diagnosing and furthermore stratifying the severity of acute pancreatitis at the earliest is of utmost importance. This study reviews the literature published on Urinary Trypsinogen Activation Peptide (TAP) and Urinary Trypsinogen, which are new urine dipstick tests, in diagnosing and assessing severity of acute pancreatitis respectively.

Methods:   A literature search was done looking effectiveness of TAP and Urinary Trypsinogen in comparison with serum Lipase, serum Amylase and abdominal CAT scans in diagnosis and assessing severity of Acute Pancreatitis. The search was conducted on Medline Ovid, Medline PubMed and Cochrane library using keywords Urinary trypsinogen, Acute Pancreatitis, Diagnoses of Acute Pancreatitis, Trypsinogen Activation Peptide and Severity of Pancreatitis.

Results:  The search yielded 4 studies with Urinary Trypsinogen 2 for diagnosing Acute Pancreatitis. The sensitivity of Urinary Trypsinogen 2 ranged from 68% to 95%, the specificity ranged from 86% to 95% (Both comparable to serum Lipase and serum Amylase), the Positive Likelihood Ratio >10 was found in 2 studies while the Negative Likelihood Ratio <0.1 also in 2 studies suggesting that it can be a quick screening test for diagnosing Acute Pancreatitis but not a confirmatory test.

  For assessing severity with TAP there were 5 studies. The Sensitivity ranged from 62% to 100%, The Specificity 73% to 92%, The Positive Likelihood ratio was <10 (2.3-6.7) while the Negative Likelihood Ratio was 0-0.52. Hence this test can quickly rule out a severe presentation of the illness.

Conclusions:  Based on the evidence provided by this study, it can be said that these test are comparable to conventional tests like serum Lipase and serum Amylase in diagnosing Acute Pancreatitis but also offer the added advantage of stratifying severity. Also these tests are urine dipstick tests hence they are faster to use and interpret.

 

 

 

 

 

Which one is it? Microangiopathic Hemolytic Anemia in Malignant Hypertension or Thrombotic Thrombocytopenic Purpura?

Abu-Fazal Shaikh Mohammad, MD, Saad Usmani,MD, Shehzad Rehman, MD, Pravit Cadnapaphornchai, MD

Department of Internal Medicine, Detroit Medical Center/Wayne State

University, Sinai Grace Hospital, Detroit MI.

 

Introduction:

Microangiopathic hemolytic anemia (MAHA) is a well known accompaniment of malignant hypertension. Thrombotic thrombocytopenic purpura (TTP) is a clinical syndrome that is associated with low levels of ADAMTS13. Both these conditions are associated with thrombotic microangiopathy (TMA) as histopathological manifestation. We present a patient who had confounding features of both these conditions.

Case Report:

43 year old woman with history of hypertension presented with elevated blood pressure, headaches, nausea and abdominal pain. Laboratory studies showed acute renal failure, thrombocytopenia, normocytic anemia, elevated LDH, low haptoglobin and acute renal failure. .Peripheral smear showed fragmented RBCs consistent with microangiopathic hemolytic anemia. Patient was started on plasmapharesis and IV steroids. Her blood pressure was controlled by 4 different agents. The renal function progressively deteriorated and she required hemodialysis. Immunological and serological work-up for ARF was negative. A renal biopsy was performed for definitive diagnosis and was consistent with thrombotic microangiopathy. Her platelet count improved on normal levels by 3 weeks of presentation. ADAMTS13 activity was normal along with undetectable ADAMTS13 inhibitor levels. The patient remained on hemodialysis for a year.

Discussion and Conclusion:

This is the second reported case of concomitant TTP and MAHA associated with malignant hypertension. Renal biopsy in our patient showed TMA which is again a feature of both these conditions. The presence of microangiopathic hemolytic anemia, thrombocytopenia and elevated LDH levels are sufficient in making a diagnosis of TTP. The specificity of ADAMTS13 activity is still considered controversial and clinical features along with simple blood tests are enough to proceed to plasmapharesis.  We report this case to alert internists about the challenges in diagnosing and managing patients who presented with clinical features of both TTP and microangiopathic hemolytic anemia of malignant hypertension.

 

 

 

 

 

Central nervous system (CNS) leukemia after imatinib mesylate therapy for chronic myelogenous leukemia (CML)

 

M.solh1, H. Kantarjian2, S. O'Brien2, F. Giles2, S. Faderl2, G. Garcia-Manero2, M. Rios2, J. Shan2, J. Cortes2, F. Ravandi-Kashani2;

1Internal Medicine, Wayne State University/Detroit medical center, Detroit, MI, 2Leukemia, University of Texas - M D Anderson Cancer Center, Houston, TX.

 

Background: Imatinib is the standard first line treatment for CML. Imatinib penetrates the CSF poorly. We examined the incidence and outcome of CNS disease in patients with CML treated with imatinib at our institution.

Methods: The clinical data for pts with early or late chronic phase and accelerated phase CML treated with imatinib between 1999 and 2006 were reviewed. Pts who were started on imatinib elsewhere and progressed to blast phase were also included. CNS disease was defined as a pathologically proven enhancing lesion (leptomeningeal or parenchymal) or presence of CSF leukemic cells.

Results: Nine hundred and ten pts with chronic or accelerated phase CML were treated with imatinib. Fifty five developed blast crisis while on imatinib; another 28 pts had blast transformation while receiving imatinib elsewhere, making up a total of 83 pts. At diagnosis, their median age was 51 yrs, median Hgb, WBC and PLT counts were 10.6 g/dl, 59.7 x 109/L and 307 x 109/L, respectively. Median time from diagnosis to starting imatinib was 45.4 mts and the median duration of imatinib therapy was 17.9 mts. Fifteen pts had achieved a complete cytogenetic response and 47 had a complete hematologic response before progressing to blast phase. Their median overall survival from diagnosis was 73.2 mts. Thirty pts developed extramedullary disease; they had similar baseline characteristics as the rest with a median survival of 68.3 mts. Fifteen pts developed CNS disease (5 leptomenigeal, 5 CSF, 3 parenchymal, and 2 spinal cord); 14 had concomitant medullary blast crisis. They had a statistically significant younger age at diagnosis (41.9 vs 52.4 yrs), lower platelet counts (186 vs 334 x 109/L), and shorter overall survival (66.7 vs 73.2 mts) compared to the other pts with blast phase.

Conclusions: CNS disease occurs infrequently in pts receiving imatinib for CML but should be suspected in pts with relevant symptoms. Pts developing CNS leukemia had a worse prognosis; this may be secondary to an inherently worse disease, poor CSF penetration of imatinib, and subsequent difficulty in eradicating CNS disease using available therapies. More potent tyrosine kinase inhibitors, such as nilotinib and dasatinib, and new agents with the ability to cross the blood-brain barrier should be evaluated in this setting.

 

 

 

 

 

Virtual Colonoscopy: A New Screening Tool for Colorectal Cancer

Melhem Solh MD

Wayne State University/Detroit Medical Center(Grace Hospital)

Introduction:Conventional colonoscopy (CC) is the best available method for detection of colorectal cancer, however, this invasive procedure carries significant potential for complications. CT colonoscopy or virtual colonoscopy(VC) has been reported in many studies to have comparable results with conventional colonoscopy in screening for colorectal cancer.

Clinical Question: In patients with low to moderate risk of colorectal malignancy, is Virtual Colonoscopy as effective as conventional colonoscopy in detecting colorectal cancer?

Methods:

Data Source: Ovid, Cochrane and Pubmed controlled trials from 1975 till September 2005. Prospective randomized trials that compared results of  conventional colonoscopy with virtual colonoscopy in average risk adult patients.

Outcome: sensitivity, specificity, positive and negative likelihood ratios in detecting colorectal cancer.

Results: 2 large studies by cotton et al (JAMA 2004) and Pickhardt et al (NEJM  2003) met the selection criteria to the clinical question mentioned above.

Each of  the above studies arrived at a different conclusion regarding the efficacy of virtual colonoscopy in detecting colorectal cancer. Cotton et al showed that VC is inferior to CC as far as polyp detection and cancer diagnosis, whereas, Pickhardt et al showed that VC is as sensitive and specific as CC with a nonsignificant superiority for polyp size of more than 6 mm.

Both studies are randomized multi-center that were published within a four month period from each other. Pickhardt studied VC under ideal conditions that involve electronic cleansing of the colon, 3-D reconstruction images, contrast administration, newly designed software and well trained radiologists whereas, Cotton et al studied the efficacy of VC under ordinarily conditions of 2-D images, no contrast and radiologists who are don’t have the special expertise of VC.

Conclusion: Both studies looked at the efficacy of VC in colorectal screening but under different conditions. VC is getting more available in many centers. The CT scan quality, radiologist expertise and the installed software are major determining factors in the efficacy of VC in colorectal screening. Pickhardt study suggests that the time for VC is soon whereas Cotton suggests it is not time yet.

 

 

 

 

 

CASEATING GRANULOMA CAUSING VERETBRAL CORD COMPRESSION

Shironda Stewart, MD, Associate, Cortney Jones, MD, Associate, Jennifer Holt, MD, Member, Department of Medicine, Sinai-Grace Hospital, Detroit, Michigan

A fifty-eight-year-old female with a history of asthma, hypertension, and chronic back pain presented with lower extremity weakness.  A review of systems was positive for a non-productive cough, pleuritic chest pain, night sweats, and weight loss. There was no travel history. A neurological exam revealed distal lower extremity weakness, decreased pinprick sensation at T4-T6 dermatome regions, depressed reflexes of the lower extremities, and decreased rectal tone.  Labs were normal.  An MRI of the spine revealed a compression fracture at the level of T5 with epidural, vertebral body, and soft tissue enhancement at the level of T4-T6.  The patient underwent a T4-T6 laminectomy with excision of the epidural mass. The mass was placed in formalin. A pathologic diagnosis of the bone and soft tissue revealed multiple caseating granulomas. There was no evidence of malignancy.  AFB and gram stains for fungus were negative.  The patient received antituberculosis therapy.  HIV serology was recommended.

The differential diagnosis of caseating granulomas includes tuberculosis, fungi, and necrotizing tumors.  In the United States, skeletal tuberculosis is rare and tends to occur among the immigrant population and immunocompromised.  Nevertheless, it is more likely to cause vertebral cord compression when compared to fungal infections.  A positive AFB stain and culture confirm a diagnosis; however, the sensitivity of these tests may be decreased if the tissue specimen is fixed in formalin.  This has been described in literature.  Skeletal tuberculosis was the most accurate diagnosis in this patient.  She completed three months of antituberculosis therapy and her neurological symptoms significantly improved. She will require close follow-up and a minimum of twelve months of antituberculosis therapy.

                                                                                               

Vertebral cord compression is a medical emergency that requires a multidisciplinary approach.  This entails proper imaging, a tissue biopsy with proper storage techniqus, and the correct interpretation of test results.     

 

 

 

 

 

MRI AS A BREAST CANCER SCREENING TOOL

Shironda Stewart, MD, Associate

Department of Medicine, Sinai-Grace Hospital, Detroit, MI.

Suppose a forty-year-old woman with a strong family history of breast cancer requests an MRI of the breast despite recent negative mammography.  Is there evidence supporting that an MRI is more useful than mammography in this setting?

The incidence of breast cancer has risen over the past two decades. In 2006, it is approximated to be 200,000. 41,000 deaths are predicted.  Despite an increase in mammography, breast cancer is the second leading cause of cancer deaths in females. Perhaps one explanation is that the false negative rate of screening mammography, 10-30%, prevents detection of slow growing tumors. Moreover, mammography is not a useful tool in women with radiologically dense breast tissue. However, yearly screening mammography has been proven to decrease breast cancer mortality in women forty and older. Contrast enhanced MRI is able to distinguish benign from malignant breast lesions. It is not limited by radiologically dense breast tissue; but may miss microcalcifications. 

The objectives of this literature search are to compare the sensitivity and specificity of mammography with contrast enhanced MRI for breast cancer screening.  Inclusion criteria require both modalities to be used on a patient. All studies must be prospective.  Search engines Ovid Medline, Pub Med, and Cochrane Library were used.  One hundred ninety two (192) studies were identified.  Five (5) studies qualified for this evidence based research.  Overall, the sensitivity of MRI was higher than mammography; however the specificity of MRI was less than mammography. 

The amount of studies pertaining to this literature search was inadequate.  Furthermore, the inclusion criteria varied among different studies.  At this point in time, there is insufficient evidence to conclude that MRI is a superior screening modality when compared to mammography.  

 

 

 

 

 

Spontaneous Tumor Lysis Syndrome in Stage IIA Colorectal Cancer- Halloween Horror with a Christmas ending.

Saad Usmani, MD, Zainab Shahid, MD, Husain Saleh,MD, Joel Appel MD, FACP

Department of Internal Medicine, Sinai-Grace Hospital/Wayne State University,Detroit,MI.

Introduction:

Spontaneous tumor lysis syndrome (STLS) is an oncological emergency that occurs at the onset of hematological malignancies without treatment. It has been rarely reported in solid tumors. We present the first reported case of limited stage colorectal cancer presenting with STLS perplexed by hemolytic anemia.

 

Case report:

60 year old woman with prior history of asthma and diverticulosis presented with 4 day history of diarrhea with blood clots and left sided abdominal pain. Physical examination showed stable vitals and left lower quadrant tenderness. Laboratory studies revealed microcytic anemia (10.4 gm/dl, MCV=64.5 fl), leucocytosis (44,100 cells/cumm, N=4,000-11,000) and thrombocytosis (619,000 plts/cumm, N=150,000-400,000). CT Scan of the Abdomen and Pelvis showed diffuse colitis suggestive of either ischemic colitis or inflammatory bowel disease. Patient underwent colonoscopy which showed a fungating mass obstructing the sigmoid colon. On Day 4 of admission, patient’s chemistry profile showed acute renal failure, hyperphosphatemia, hyperuricemia, hypocalcemia and hypokalemia. At the same time, patient’s hemoglobin and platelet counts plummeted with peripheral smear showed a microangiopathic picture, low haptoglobin (<6 mg/dl,N=16-200) and elevated serum LDH levels (2435 U/l,N=100-225). Patient was aggressively hydrated along with treatment with allopurinol. Patient underwent resection of distal colon, showing Stage IIA disease. Her renal function and blood counts started to improve on Day 9 of admission. Patient was discharged home on Day 14 in clinically stable condition.

Discussion:

This case depicts two highly unexpected events that made the management of this patient a challenging process. There are only 4 reported cases of STLS in solid tumors, all presenting with advanced disease stages. Our patient, on the other hand, was only Stage IIA when STLS occurred suggesting that this phenomenon may occur even with relatively low tumor burden. The simultaneous occurrence of microangiopathic hemolytic anemia confounded the diagnosis in our patient because tumor lysis itself can give elevated LDH levels. A thorough literature review did not reveal any association of tumor lysis with hemolysis. But circumstantial evidence shows that treating STLS led to resolution of the hemolytic picture. We report this case to alert internists to think of STLS in a patient with similar presentation when other plausible causes have been ruled out.

 

 

 

 

 

Paradoxical Embolism in A Young Male

Vikas Veeranna, Rashad H Khazi-Syed, Preeti Misra, Christopher Schooley.

Wayne State University/ Detroit Medical center, Sinai-Grace Hospital.

Introduction:

Paradoxical embolism (PDE) is a well know cause of systemic thromboembolism. We report a young patient who developed acute arterial occlusion from a presumed paradoxical embolism of a venous thrombosis through a patent foramen ovale (PFO).

Case report:

A 34 year old male was being evaluated for suspected bacterial endocarditis with a TEE, which showed a PFO with no vegetations or a thrombus. During his stay in the hospital he developed acute left lower limb ischemia. He underwent an angiogram which showed an acute thrombus in left common and the left external iliac arteries and complete occlusion of the left superficial femoral artery. Since the suspicion for PDE was high , venous duplex was performed which showed acute deep vein thrombosis of the right common femoral, right popliteal vein, the left popliteal and the left posterior tibial vein. The patient was treated with thrombolytics followed by stenting of the left common and the external iliac was performed with an inferior venacava filer placement. Subsequently, due to deterioration in the limb ischemia and gangrenous changes he underwent left above knee amputation.

Discussion:

Paradoxical embolism is the passage of venous thrombus into arterial circulation. Most common cause for this is an intracardiac defect at the level of atria. A presumptive diagnosis of PDE is made if there is a systemic arterial embolism in the  presence of right to left shunt at any level, venous thrombosis and / or pulmonary embolism, and with out any evidence of a left heart or proximal arterial thrombus. Literature review showed that the PFO is present in about 35% of the population. PDE should be suspected in the young and middle aged patients presenting with acute systemic thromboembolic events especially in the presence of simultaneous deep vein thrombosis.

 

 

 

 

 

Cryoplasty for Superficial Femoral Artery Stenosis: An Effective Strategy?

Vikas Veeranna, Rashad H. Khazi-Syed, Sabeeh A. Siddiqui, Geetha Krishnamoorthy, Rajika Munasinghe, Syed A. Mahmood,

Sinai-Grace Hospital ,Wayne State University/Detroit Medical Center, Detroit, MI

Background

Peripheral arterial disease [PAD] affects about 8 million Americans and is associated with significant morbidity and mortality. Femoropopliteal arteries are common sites of occlusion. We present a retrospective study on the efficacy of cryoplasty as a technique for superficial femoral artery stenosis revascularization.

Method

A retrospective study was done which involved 8 patients (10 arterial segments). Each patient had undergone cryoplasty of the superficial femoral artery [SFA]. A baseline Duplex ultrasound and ABI measurement was done. A follow-up Duplex ultrasound and ABI was done at less than a month and at > 6 months post procedure. The mean pre-procedural and follow-up ABI’s were compared using paired t-test.

Result

Of the 8 patients, 12.5% had diabetes mellitus, 62.5% had coronary artery disease, 62.5% had dyslipidemia and 50% were smokers. The mean age was 70.25 years. All patients were Rutherford classification stage 3 or 4. 70% of the patients had total occlusion. The mean lesion length was < or = 10 cm. Technical success was 100% defined by residual stenosis of <30% and no flow limiting dissection.

The mean ABI pre-procedure was 0.62 with standard deviation of 0.02. The mean ABI at follow up was 0.71 with standard deviation of 0.09. The mean duration at follow-up was 238.3 days. The change in ABI at > 6 months follow up was statistically significant with P <0.0065 indicating improved arterial patency. Two patients (2 segments) needed revascularization procedure for restenosis [20%].

Conclusion and Discussion

Cryoplasty is an effective method of intervention for SFA as evidenced by a significant change in ABI at > 6 months of follow-up with low restenosis rates. However, larger prospective and retrospective studies need to be done.

 

 

 

 

 

Bailout Cryoplasty in Iatrogenic Superficial Femoral Artery Dissection.

Vikas Veeranna, Rashad H. Khazi-Syed, Sabeeh A. Siddiqui, Geetha Krishnamoorthy, Thomas Matthys, Syed A. Mahmood,

Sinai-Grace Hospital, Wayne State University/Detroit Medical Center, Detroit, MI

Background

Superficial Femoral Artery [SFA] occlusion presents as difficult management problem to interventional cardiolovascular specialist because of several major technical challenges which include long lesions, significant calcifications, high rate of restenosis, and incidence of stent fractures. We present an observational study introducing the potential role of cryoplasty as a bailout strategy in wire induced vessel dissection during attempts at crossing the SFA occlusion.

Method

We report an observational study comprising 5 patients who underwent cryoplasty to the SFA. In all of these cases there was iatrogenic wire induced dissection of the SFA ranging from linear non flow limiting dissection to more complex dissection including one case of extravasation of radiocontrast dye. In all of these cases we were eventually able to cross the lesion and the distal intraluminal placement of the guide wire was confirmed by injecting radiocontrast dye in the distal SFA beyond the occluded segment using a 4 french angled glide catheter. A cryoplasty Polar Catheter was successfully used to seal this dissection and obtain good angiographic results.

Result

Of the five patients 20% had diabetes mellitus, 60% had coronary artery disease, 60% had hyperlipidemia and 60% were smokers. The lesions were long segments of severely calcified chronic occlusions. The lesion length ranged from 6 to 10 cm. Technical success was 100%, defined by < 30% residual stenosis and no flow limiting dissection.

Conclusion

We conclude that in cases of iatrogenic dissection of SFA, cryoplasty may be a viable bailout strategy. The mechanism behind this process needs to be further evaluated and merits a larger study.

 

 

 

 

 

Percutaneous CT guided Radiofrequency ablation for the treatment of Adrenal metastasis from melanoma

Malini Venkatram MD, Associate, Dept of Internal Medicine, Wayne state university, Sinai Grace hospital, Detroit, MI

Venkataramu N. Krishnamurthy MD, Clinical Asst professor, Dept of Radiology, University of Michigan, Ann Arbor, MI

 

Aim: To report Radiofrequency (RF) ablation as a treatment option for melanoma metastatic to the adrenal gland.

Case report: This is a 47 year old male with melanoma metastatic to bones, liver and right adrenal gland. He was treated with combination of Chemo-radiation, Interleukin-2 and interferon therapy for over 6 months with significant resolution of the disease. However CT scans showed continued growth of the right adrenal mass which increased from 3.6 cm x 5.2 cm to 4.4 cm x 6.8 cm in 6 weeks. RF ablation was performed under CT scan guidance under general anesthesia. Four overlapping ablation spheres were created using 5cm semi-flex ablation probe (RITA Medical Systems Inc. Fremont, CA). No procedure related complications were noted. At six weeks, follow up CT scan showed stable size of the mass with no enhancement.

Discussion: RF ablation is a technique in which alternating RF current produces agitation of ions and generates heat that causes tissue necrosis. RF ablation has been extensively used to treat liver, kidney and lung tumors. RF ablation has only recently been used to treat primary and metastatic adrenal tumors with only two published reports. Wood et al (Cancer 2003; 97:554-560) treated 15 adrenal tumors in 8 patients with a mean diameter of 4.3cm. Overall stability or regression of the disease was seen in 80% at a mean follow up of 10.3 months. Mayo-Smith et al. (Radiology 2004; 231:225–230) treated 13 adrenal tumors (average tumor size 3.9cm) including 11 metastases (5 from lung cancer, 4 from renal cell carcinoma, and 2 from melanoma). 85% were successfully treated without residual disease. Of the 2 patients with metastatic melanoma, 1 patient had residual disease, treated repeat ablation.

Conclusion: Percutaneous, CT guided RF ablation is a safe treatment option for adrenal neoplasms and it is effective for the short-term local control of disease. Limited experience has shown near complete tumor necrosis when tumor size is less than 5cm.  Aggressive local disease control may potentially influence survival as well. However, further study is required to evaluate efficacy and survival benefits of this new technique.

 

 

 

 

Propylthiouracil (PTU)induced severe hepatitis: A case report

Malini Venkatram MD, Associate, Dept of Internal Medicine, Wayne state university, Sinai Grace hospital, Detroit, MI

O Alzohaili, MD, Dept of Endocrinology, Wayne state university, Sinai Grace hospital, Detroit, MI

Venkataramu N. Krishnamurthy MD, Clinical Asst professor, Dept of Radiology, University of Michigan, Ann Arbor, MI

 

INTRODUCTION: Propylthiouracil (PTU) related symptomatic severe hepatitis is a rare occurrence seen in only 0.1-1.2% of the treated cases. Asymptomatic transient rise in liver enzymes can occur in 14-28% of cases. Thus far 85 cases of PTU related severe hepatitis have been reported in literature including fatality in 28 patients.

CASE REPORT: A 11 year old male presented with symptoms of hyperthyroidism such as palpitations, jitteriness, diaphoresis & was diagnosed to have Graves disease based on laboratory work up, ultrasound, thyroid scan & uptake studies. He was started on 200mg of PTU per day. He presented with lethargy, anorexia & nausea after 10weeks. He was found to be icteric & work up showed a bilirubin of 8.2 mg/dl with direct bilirubin of 6.2 mg/dl. ALT & AST were markedly elevated (1167 IU/ L, 733 IU/L respectively). His albumin, prothrombin times were normal. The work up for viral markers & autoimmune hepatitis were negative. He was diagnosed as PTU induced severe hepatitis & the drug was discontinued. The liver enzymes & bilirubin normalized in 4 weeks.

DISCUSSION: The diagnosis of PTU induced hepatitis is usually based on the occurrence of liver damage within few months of therapy, excluding other etiologies based on history, lab work, and recovery after discontinuation of PTU. Liver biopsy & lymphocyte stimulation test has been used in some cases to support diagnosis.

The pathophysiology of PTU induced hepatitis is multifactorial including liver congestion, increased liver oxygen consumption, reduced bile acid synthesis, & glucuronyl transferase inhibition. Histopathologic examination shows non specific changes including variable degree of liver necrosis, cellular infiltration, & cholestasis.

The mortality may be as high as 25 - 30% & so far 28 lethal cases have been reported in literature.

CONCLUSION: Although transient liver function abnormalities are often seen with PTU therapy, symptomatic severe hepatitis is a very rare entity. It can be associated with high mortality. This may warrant need for regular monitoring of liver function during the course of PTU treatment. Also early diagnosis and discontinuation of PTU is vital.

 

 

 

 

The role of ACE inhibitors & ARBs in the prevention of DM-2

Malini Venkatram MD, Associate, Dept of Internal Medicine, Wayne state university, Sinai Grace hospital, Detroit, MI

Venkataramu N. Krishnamurthy MD, Clinical Asst professor, Dept of Radiology, University of Michigan, Ann Arbor, MI

S Marur, Dept of Internal Medicine, Wayne state university, Sinai Grace hospital, Detroit, MI

Introduction: Other than life style modifications, no single drug has been shown to prevent diabetes mellitus type 2 (DM-2). We present an evidence based research to establish the role of ACE inhibitors & ARBs in the prevention of DM-2.

Methods:

Study Type: Evidence Based Medicine

Data source: COCHRANE, EMBASE, MEDLINE

Study selection: Randomized controlled trials and Meta analyses

Key words: Diabetes mellitus, ACE inhibitors, ARBs, glucose intolerance and impaired fasting glucose.

Inclusion Criteria: Studies examining the effects of any ACE inhibitor or ARBs on the incidence of DM-2

Exclusion Criteria: Studies in patients with preexisting Diabetes, use of drugs other than ACE inhibitors/ARBs

Results:

Search yield: 12 randomized controlled trials including 5 on ACE inhibitors & 7 on ARBs

DREAM trial: Compared Ramipril versus placebo in patients with Impaired glucose tolerance; Ramipril did not significantly reduce the incidence of DM-2 (18.1%) compared to placebo (19.5%) (p=0.001)

SOLVD trial: Compared enalapril versus placebo in patients with left ventricular dysfunction; enalapril significantly reduced the incidence of DM-2 (5.9%) compared to placebo (22.4%) (p<0.0001)

HOPE trial: Compared Ramipril versus placebo; Ramipril group had lesser incidence of DM-2 (3.6%) compared to placebo (5.4%) (p<0.001)

CAPPP trial:  Evaluated onset of DM-2 as a secondary outcome; captopril lowered incidence of DM-2 compared to conventional group (0.86; p=0.039)

ALLHAT trial: Evaluated onset of DM-2 as a secondary outcome; lisinopril had the least incidence of DM-2 (8.1%) compared to thiazide (11.6%) & amlodipine (9.8%).

CHARM trial: Compared candesartan versus placebo in patients with heart failure; candesartan reduced the incidence of DM-2 (6%) compared to placebo (7.4%) (p=0.020)

SCOPE trial: Compared candesartan versus placebo; candesartan group had lower incidence of DM-2 (4.3%) compared to placebo (5.3%) (p=0.09).

ALPINE trial: Compared candesartan versus thiazide; candesartan group had lower incidence of diabetes (4.1%) compared to thiazide (0.5%) (p=0.030).

VALUE trial: Compared valsartan versus amlodipine; valsartan lowered the incidence of DM-2 from 16 to 13%

ONTARGET & TRASCEND trials:  Evaluated incidence of DM-2 in patients taking telmesartan (an ARB) alone or with Ramipril; results pending

Conclusion

ACE inhibitors & ARBs either decrease or do not change the incidence of new onset DM-2.

 

 

 

 

PROFILING OF AUTO-ANTIBODIES AGAINST TUMOR-ASSOCIATED ANTIGENS FOR EARLY DIAGNOSIS OF ADENOCARCINOMA OF THE LUNG

Prakash Vishnu, MD 1, Guoan Chen, MD, PhD 2, Jianjun Yu 3, William Bigbee, PhD 4, Andrew C. Chang, MD 2, Mark B. Orringer, MD 2,  Arul M. Chinnaiyan, MD, PhD 3, and David G. Beer, PhD 2

1 Department of Medicine, Sinai Grace Hospital/Detroit Medical Center, Wayne State University, Detroit, Michigan

2 Section of Thoracic Surgery, Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan

3 Department of Pathology, University of Michigan Health System, Ann Arbor, Michigan

4 University of Pittsburgh Medical Center, Pittsburgh, Philadelphia

Background

Tumors are known to stimulate production of auto-antibodies against autologous cellular proteins, also called as tumor associated antigens (TAAs). Identification of these auto-antibodies against TAAs by screening phage-displayed cDNA libraries derived from cancer tissue could be utilized as a serological tool for early diagnosis of cancer.

Majority of lung cancers when first diagnosed are at a relatively advanced stage, 76% accounting for > stage III. New markers and approaches are essential to monitor patients at greater risk and identify cancer early. Here, we explore the potential of auto-antibody profiling for early diagnosis of lung adenocarcinoma.

Methods

A T7-phage display peptide library was constructed using cDNA from pooled lung cancer tissues. Four rounds of affinity enrichment (biopanning) using serum from lung cancer patients were performed to select the tumor-related epitopes. A 1,152 element phage-displayed peptide micro-array was constructed and screened for epitopic profiling of humoral immune response in 124 patient sera (62 lung adenocarcinomas and 62 non-cancer controls) obtained from University of Pittsburgh Medical Center. Two thirds of samples were used as training set and rest as validation set to define a combination of markers that were best able to distinguish patient from control samples.

Results

Leave-one-out-cross-validation (LOOCV) using support vector machine (SVM) model on the training and validation sets of samples identified a 40 phage-peptide signature pattern that could best distinguish serum samples of patients with lung adenocarcinoma from those of controls with a sensitivity of 80.60% and specificity of 81.70%.  This 40 phage-peptide signature pattern when used on an independent validation set of 44 samples (22 serum samples from lung adenocarcinoma patients; 22 matched controls) obtained from University of Michigan Health System had a sensitivity of 86.4% and a specificity of 86.4% in discriminating between the group with lung adenocarcinoma and the control group.

Conclusions

This study identifies new diagnostic biomarkers and indicates that epitopic profiling of humoral immune response against tumor-associated antigens may be used as serological markers for early detection of lung adenocarcinomas. Further studies to characterize the candidate clones will add to our understanding of regulation of these proteins in tumor vs. normal tissue.

 

 

 

 

 

AMYLOID (b) PEPTIDE-RELATED CEREBRAL ANGIITIS - A RARE CASE OF PRIMARY ANGIITIS OF CENTRAL NERVOUS SYSTEM (CNS) WITH CEREBRAL AMYLOID ANGIOPATHY

Pratik Bhattacharya (1), Prakash Vishnu (1), Scott Glickman (2), Sarmad Al-Mansour (3), William Kupsky (4)

1 Department of Internal Medicine, 2 Division of Neurosurgery, 3 Division of Rheumatology, 4 Department of Pathology

Detroit Medical Center / Wayne State University, Detroit, Michigan

Introduction

Cerebral amyloid angiopathy (CAA), seen in 30% of otherwise normal elderly subjects rarely evoke an inflammatory response in cerebral microcirculation. Very few cases of CAA-associated CNS vasculitis, also known as amyloid (b) peptide-related cerebral angiitis(ABRA) has been reported to-date. Diagnosing angiitis limited to CNS is particularly difficult because of nonspecific nature of cerebral angiography. Brain biopsy is, hence, considered the gold standard for diagnosis of primary angiitis of CNS (PACNS). We present a biopsy-proven case of ABRA, who showed a remarkable clinical improvement with immunosuppressive therapy.

Case report

LK, a 68 year old female with a past medical history of hypertension presented to our institute with sudden deterioration of pre-existing left-sided weakness. She had developed left hemi-paresis and encephalopathy two months earlier, which was provisionally diagnosed elsewhere as viral encephalitis and treated with acyclovir and steroids. CT scan of the brain showed low-attenuation area in right temporo-parieto-occipital lobe with significant edema and midline shift. Magnetic resonance (MR) imaging/angiography revealed intense signaling in the same area, with a normal intracranial vasculature. The distribution did not correspond to a major vascular territory. Allergy to dye precluded conventional cerebral angiography. Patient had no evidence of extra-cranial organ involvement. ESR was 76 mm/hr. Serology revealed IgG against measles and varicella. Anti-nuclear antibodies were absent. Histopathology of stealth-MRI assisted brain biopsy revealed extensive amyloid (b) peptide deposits with granulomatous and lymphocytic inflammation affecting small vessels, establishing the diagnosis of PACNS with CAA. AFB-stain was negative. She was started on oral Cyclophosphamide and Prednisone. Patient showed a complete resolution of left-sided weakness in six weeks following initiation of immunosuppressive therapy and physiotherapy. Repeat CT scan of the brain at six weeks showed resolution of edema and midline shift with decrease in ‘low-attenuation’ areas.

Discussion

Primary angiitis of CNS with CAA is a rare disease entity with varied neurological presentation and is quite challenging to diagnose. Given a low specificity of cerebral angiography, biopsy is the key step in making a firm diagnosis. Combined cortical and lepto-meningeal biopsy is most likely to be diagnostic, with results from angiography or MRI identifying the involved area.

 

 

 

 

 

CANDIDA GLABRATA PAROTITIS: UNUSUAL INFECTION IN AN UNUSUAL SITE - IS THIS A HARBINGER OF IMMUNOCOMPROMISED STATE ?

Prakash Vishnu, MD (Associate), Geetha Krishnamoorthy, MD (Member), Wasim Hafeez, MD (Fellow) Department of Medicine, Sinai Grace Hospital, Detroit Medical Center/Wayne State University, Detroit, Michigan

Introduction:

Candida glabrata, a yeast that forms part of normal microbial flora of digestive tract, skin and vagina, is known to cause superficial infection in immunocompetent hosts of all ages with a benign course and full recovery. However, in immunocompromised hosts, it can result in systemic illnesses, which is associated with high morbidity and mortality. We report a case of fungal parotitis caused by Candida glabrata.

Case report:

66-year-old female with a past medical history of hypertension and well controlled diabetes mellitus, presented to the primary care clinic with complaints of progressive painful swelling over right parotid area of 2 months duration. CAT scan of neck revealed an irregular contrast-enhancing lesion suggestive of neoplastic process vs. infection. FNAB/FNAC revealed chronic granulomatous inflammation in a purulent background. Fluid cultures grew Candida glabrata while concurrent blood cultures were sterile. Fluid culture for AFB was negative. CAT scan of thorax revealed no abnormality. Patient had no previous history of surgical intervention to right parotid gland. HIV testing was non-reactive. Patient was treated with IV caspofungin and was closely followed up in the outpatient clinic every two months. Patient’s clinical course was uneventful for next eighteen months, after which she presented with symptoms of dysphagia and altered voice. Chest x-rays revealed a mediastinal mass. CAT scan of the thorax revealed a large left mediastinal mass with multiple lung nodules. Biopsy of mediastinal mass revealed small cell carcinoma of the lung. Further workup revealed metastatic lesions in the liver. Patient underwent 5 cycles of VP-16 based chemotherapy with interval resolution in the size of mediastinal mass.

Discussion:

Systemic infection caused by Candida glabrata in an immunocompetent host is unusual. Theoretically, although any organ in the body can be affected, to date there has been no case report of parotitis caused by Candida glabrata. When an unusual organism is isolated from an unusual site causing infection, does it become pertinent to rigorously workup for co-morbid conditions that herald an underlying immunocompromised state? Will frequent clinical follow-up help in early detection of such conditions, thereby giving us a chance for early intervention? These questions still remain unanswered.

 

 

 

 

RADIATION PNEUMONITIS IN LUNG CANCER PATIENTS TREATED WITH CHEMOTHERAPY AND THORACIC RADIATION: RETROSPECTIVE ANALYSES OF PATIENTS TREATED AT A COMPREHENSIVE CANCER CENTER

Prakash Vishnu, MD, Sridhar Srinivasan, MD, Lance K. Heilbrun, PhD, Raghu Venkat, MS Antoinette Wozniak, MD, Ayman Soubani, MD, Shirish M. Gadgeel, MD

Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, Michigan

Background

Combined chemotherapy and thoracic radiation (TR) is the current standard for locally advanced non-small cell lung cancer (NSCLC) and SCLC. Severe RP, an important adverse effect of TR, is reported in clinical trials to occur in 10% of patients receiving chemotherapy and TR. The rate in routine care may be higher as patients are not selected based on pulmonary function. We conducted a retrospective study to assess the incidence of RP in lung cancer patients treated with chemotherapy and TR.

Methods

Retrospective identification of patients who underwent combined modality therapy (concurrent or sequential chemotherapy and TR) for lung cancer (NSCLC & SCLC) at our cancer center between January 2001 and December 2004. Demographic features, RP incidence and grade (RTOG criteria), hospitalization rate and overall survival (OS) were assessed.

Results

51 patients who met the selection criteria were analyzed. The demographic features were - males 61%; Caucasians - 53%; African Americans - 39%; history of pulmonary disorder - 45%; NSCLC - 82%; CT - 62% received Cisplatin/Etoposide, while 24% received Carboplatin/Paclitaxel; 92% received concurrent CT and TR. The median dose of TR was 5940 cGy. 20 patients (39%) developed RP; 13 (25%) had grade > 3 RP. Median time to development of RP was 4.4 months. Rate of RP in females and males was 50% vs. 32% (p=0.25). Rate of RP in patients with pulmonary disorder at baseline was 52% vs. 29% in others (p=0.15). 1 year hospitalization rate was 75% and 42% in RP and non-RP patients (p=0.025). For all 51 patients, the median overall survival (OS) was 16.4 months (95% CI 11.8 - 23.3). Length of OS did not differ significantly (p = 0.36) between the 20 patients who had RP vs. the 31 who had no RP (median OS: 22.2 vs. 14.5 months, respectively).

Conclusion

RP rate in lung cancer patients treated off-protocol with chemotherapy and TR is higher than that reported in clinical trials. The rate was higher in patients with history of pulmonary disorder. Despite higher morbidity (i.e. increased hospitalization) in patients with RP, overall survival did not differ significantly based on RP status.

 

 

 

 

CAN ANGIOTENSIN II RECEPTOR BLOCKERS (ARBs) BE USED IN PATIENTS WITH HISTORY OF ANGIOTENSIN CONVERTING ENZYME (ACE) INHIBITOR INDUCED ANGIOEDEMA ?

Prakash Vishnu, MD (Associate), Surendra Marur, MD (Member), Department of Medicine, Sinai Grace Hospital, Detroit Medical Center /Wayne State University, Detroit, Michigan

Introduction:

Angiotensin converting enzyme (ACE) inhibitors and Angiotensin II receptor blockers (ARBs) are widely used in the treatment of hypertension, chronic renal disease and congestive heart failure, and prevention of diabetic nephropathy. ACE inhibitors are associated with major side effects such as acute renal failure, hyperkalemia, cough and angioedema. Characterized by localized edema of the skin and/or subcutaneous tissue, angioedema is a potentially life-threatening side effect of ACE inhibitors. Incidence of angioedema with ACE inhibitors, which is considered a class related side effect, is estimated to be around 0.1 to 1.2%. Few cases of angioedema have also been reported with the use of ARBs.

Clinical Question: Is it safe to use ARBs in patients who have experienced ACE inhibitor induced angioedema ?

Search Strategy:

Data sources: MEDLINE and Cochrane Library (Jan 1991 - April 2006)

Key words: Angioneurotic edema, angioedema, angiotensin converting enzyme inhibitors, ACE inhibitors, AT-II receptor blockers, angiotensin receptor antagonists, and ARBs.

Results:

Results of retrospective analyses and placebo-controlled trials of ARBs demonstrate that a ‘small' proportion of patients with ACE inhibitor related angioedema continue with this symptom when switched to an ARB. 1. Cicardi et.al reported a retrospective analysis of 54 patients with ACE inhibitor induced angioedema who were switched to different treatment. 26 patients had switched to an ARB, and of these, angioedema persisted or recurred in 2 patients after switching to an ARB and disappeared upon its withdrawal. 2. CHARM-alternative trial, a large multi-center double-blinded randomized control trial described the effects of candesartan in congestive heart failure patients intolerant to ACE inhibitors. 3 out of 39 patients in candesartan group with a history of ACE inhibitors had recurrence of angioedema.

Conclusions/Recommendations:

Only a small proportion (7-8%) of patients with ACE inhibitor related angioedema develop or persist to have this symptom when switched to an ARB. The cardiovascular benefits and potential reduction in mortality from use of these drug classes are important and significant. Hence, a risk-benefit assessment should be considered when substituting ARBs in patients who develop angioedema from ACE inhibitors. 

 

 

 

 

 

CLEAR CELL SARCOMA OF THE ILEUM: A RARE TUMOR IN AN UNCOMMON LOCATION

Venkata Yalamanchili, MD, Associate, Melhem Solh, MD, Associate, Nevin Oskuz, MD, Medical Student, Geetha Krishnamoorthy, MD, Member

Department of Medicine, Wayne State University/Detroit Medical Center(Sinai Grace Hospital), Detroit, MI

Introduction: Clear cell sarcoma (CCS) is a rare malignant soft tissue neoplasm that commonly afflicts tendons and aponeuroses in adolescents and young adults. Primary CCS of digestive tract is exceedingly rare and only three cases of ileum involvement are reported, including only two cases with liver metastasis. We hereby report a patient with CCS of the ileum with liver metastasis presenting with abdominal pain and fever.

Case Report: A 40 year old African American woman with a history of appendectomy and cholecystectomy, presented with a two day history of lower quadrant abdominal pain and fever. No nausea, vomiting, change in bowel movements, burning micturition or vaginal discharge was reported. Physical exam revealed a fever of 100.7 F, bilateral lower abdominal and cervical motion tenderness. Laboratory data showed leucocytosis, negative urinalysis and pregnancy tests. Pelvic ultrasound showed a 7x7x4 cm mixed echogenic complex mass in the left adnexa. After 72 hours of empiric antibiotics for pelvic inflammatory disease, abdominal pain worsened and fever persisted. CT scan of the abdomen showed a 6 cm soft tissue mass engulfing the ileum. The patient underwent exploratory laparotomy with small bowel resection and anastomosis. Surgery revealed a 9.5 X 9.0 X 5.0 cm mass arising from the terminal ileum. The mass was focally ulcerated and infiltrating into the mesentery and the bladder. Pathology reported an epithelioid neoplasm, with small, oval nuclei surrounded by abundant clear cytoplasm and well defined cell membranes. On immunohistochemical examination, tumor cells were strongly immunoreactive for S-100. Slides were sent for further counseling at Memorial-Sloan Kettering Cancer Center and the final report was a CCS of the ileum with negative surgical margins. Follow up CT scan of the abdomen showed hepatic lesions, histologically consistent with CCS. The patient was started on palliative chemotherapy.

Discussion: This is the third reported case of ileal CCS with hepatic metastasis. Cytogenetics and KIT tyrosine kinase stains have a central role in the diagnosis as this highly malignant tumor can be mistakenly diagnosed as a gastro intestinal stromal tumor (GIST) or a melanoma. The outcome of metastatic CCS is dismal despite aggressive surgery and adjuvant therapy.

 

 

 

 

 

Asymptomatic Bacteriuria Associated with Indwelling Urinary Catheters in Patients with Neurogenic Bladder

 

Venkata Yalamanchili, MD, Associate, Department of Medicine, Wayne State University/Detroit Medical Center(Sinai Grace Hospital), Detroit, Michigan

 

Clinical Question: Should we treat asymptomatic antibiotic susceptible bacteriuria in patients with neurogenic bladder with an indwelling urinary catheter?

Background: Urinary tract infection is the second leading cause of death in patients with neurogenic bladder. Indwelling urethral catheters provides a direct access to the uroepithelium, making bacteriuria and subsequent infection inevitable.

Data Source: Medline (PubMed, Ovid), Cochrane Database (1975- August 2006)and references from relevant papers published in English were searched using Urinary Tract Infection, Neurogenic Bladder, Spinal Cord Injury, Quadriplegia, Paraplegia, Bacteriuria and Antimicrobials as search terms.

Selection Criteria: Randomized control trials done in patients with neurogenic bladder with an indwelling urinary catheter as a method of bladder management; the studies had to address antimicrobial treatment for asymptomatic bacteriuria and outcome measures include symptomatic urinary tract infection.

Results: An extensive literature search resulted in finding only one study which meets the selection criteria for the clinical question mentioned.

(Warren etal; JAMA 1982; 248:454-8)

Study Details. Randomized Controlled Trial (N=34, Treatment Group = 17, Control Group=18) comparing ten-day courses of cephalexin monohydrate repeated whenever a susceptible bacteriuria was present versus no treatment in patients with indwelling urinary catheter.

Study Results: There was no difference in the prevalence of bacteriuria and incidence of symptomatic urinary tract infections in both cephalexin treated group and the control group. However, the treatment group resulted in having a significantly higher proportion of cephalexin resisistant organisms at the end of the study.  The study concluded by recommending against the routine treatment with cephalexin for asymptomatic long-term catheterized patients, even when the cultures grew antibiotic susceptible organisms.

Conclusion: Asymptomatic bacteriuria associated with indwelling urinary catheters in patients with neurogenic bladder should not be treated based upon current evidence in the literature.This is true even in the presence of antibiotic susceptible bacteria in this patient population. Treatment should be reserved for symptomatic urinary tract infection to prevent emergence of antibiotic resistant bacteria.

   

 

 

 

 

 

BIOCHEMICAL ANALYSIS OF AMYLOID PROTEIN OF PERCUTANEOUS RENAL BIOPSIES

Ziad Zaky M.D. (Associate), Juris J. Liepnieks PhD, Merrill D. Benson M.D.

Department of Internal Medicine Sinai-Grace hospital/Wayne State University, Detroit, Michigan. Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana

 

Introduction

 Amyloidosis is characterized by the pathologic deposition of at least 20 different precursor proteins. Despite the differing chemical nature of these molecules, all forms of amyloid have identical tinctorial and ultrastructural features and, as a result, cannot be differentiated microscopically.

Objective

 To determine if sufficient tissue amyloid can be obtained by percutaneous renal biopsy to differentiate the type of amyloid protein, AL, AA, or hereditary. If successful, it would be recommended to do biochemical analysis for all renal biopsies with diagnosis of amyloid.

Methods

 Amyloid protein was isolated from sixteen percutaneous renal biopsies using microextraction techniques. Samples were analyzed on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE).  Separated proteins were electrophoretically transferred to Polyvinylidine Difluoride (PVDF) membrane for sequence analysis. A portion of isolated protein was digested with trypsin and fractionated by reverse phase high pressure liquid chromatography (HPLC). Samples were analyzed by Edman degradation technique.

Results

 Analysis of the pool on SDS PAGE of six patients showed bands at 14 and 20 KDa. One patient showed bands 14, 18, 20, 25, 30 and 40 KDa. The type of amyloid protein was as follows: &#955;VI  light chain was identified in three patients, &#1179; light chain in two patients and AA was identified in one patient. The results are still pending.

           

Discussion/Conclusion

 The type of amyloid often can be inferred from immunohistochemical analyses or immunologic assays, but, the results may be inconclusive owing to the lack of appropriate antisera. Thus, to establish unequivocally the nature of the amyloid protein, it is essential that the material be extracted from the specimen and analyzed chemically.  The ability to diagnose precisely the type of amyloid protein has become increasingly important given the development of specific therapies. These include high-dose chemotherapy and organ transplantation for AL and transthyretin (ATTR), respectively, as well as the use of inhibitors of fibril formation, amyloidolytic drugs. Recently, active or passive immunotherapy has been used to prevent pathologic fibrillar deposits. Thus, to provide optimal patient care, we recommend that pathologists not only establish a diagnosis of amyloidosis but also to ascertain the type of protein that is deposited as amyloid.

 

 

 

 

 

LAMBDA II IMMUNOGLOBULIN LIGHT CHAIN A PRECURSOR PROTEIN OF PRIMARY LOCALIZED RECTAL AMYLOIDOSIS

Ziad S. Zaky, M.D. (Associate), Juris J. Liepnieks,Ph.D., Douglas K. Rex, MD, F.A.C.G., Oscar W.Cummings,M.D.,Merrill D. Benson,M.D.

Introduction

 Localized amyloidosis is limited to the involved organ and does not become systemic. Localized rectal amyloidosis is a rare entity, and, to the best of our knowledge, there were less than ten cases reported in the literature.

Case description

 A 61-year-old Caucasian male, with no significant past medical history, was admitted to hospital for screening colonoscopy. The patient was asymptomatic. Physical examination was non impressive with no evidence of systemic amyloidosis. Colonoscopy revealed a 3 cm sessile smooth mass 10 cm from the anal verge and two small polyps. Biopsy of the mass revealed amyloidosis and the polyps were hyperplastic but without evidence of malignancy.Workup to exclude systemic amyloidosis was done and found to be negative.

 Amyloid fibrils were isolated from amyloid laden tissue and characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The isolated protein was transferred to Polyvinylidine Difluoride (PVDF) for sequence analysis. Edman sequence analysis was applied before and after Tryptic digestion showed that the protein belongs to immunoglobulin light chain (Ig LC) &#955;II subgroup

Discussion/Conclusion

 

 Rectal involvement is usually a part of systemic amyloidosis. However, localized rectal amyloidosis is a rare entity. We present a case of asymptomatic localized rectal amyloidoma. To our knowledge, this is the first reported case to isolate the amyloid fibrils and analyze using SDS-PAGE and amino acid sequence from a localized rectal amyloidoma.

 

 In our case the isolated fibril subunit protein proved to be derived from a &#955; II immunoglobulin light chain. There were a few cases of localized amyloidosis of the rectum and colon reported in the literature, amyloid fibrils identified by immunohistochemistry in the described cases was AL type. In contrast to systemic amyloidosis, local resection is the preferred treatment and this small subset of patients does not need chemotherapy for a plasma cell dyscrasia

 Currently, the type of amyloid often can be determined by immunohistochemical analyses or immunologic assays. However, the results may be inaccurate and ambiguous, due to failure to react with the specific antiserum. Thus, extraction and unequivocal biochemical characterization of the amyloid protein will add to the management of amyloid patients.