Myeloid sarcoma presenting as acute renal failure and bilateral ureteral obstruction- a very rare presentation.

Saad Usmani, MD (Associate); Kamal Nasser, MD (Associate); Husain Saleh, MD; Joel Appel, MD, FACP.

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

INTRODUCTION:

Myeloid sarcoma (MS), historically known as chloroma or granulocytic sarcoma, is a very rare disease. It is an extramedullary accumulation of myeloblasts that either presents with acute myeloid leukemia (AML) or presents as relapse of AML. The most common sites include the small intestine, skin, bone and lymph nodes. We present a very unusual case of MS presenting with acute renal failure and bilateral ureteral obstruction without florid AML.

CASE REPORT:

51-year-old previously healthy post-menopausal female presented with ascites, worsening bilateral lower extremity edema and decreasing urinary output for three weeks. Lab results showed normocytic anemia, hyperkalemia and acute renal failure (ARF). She was started on hemodialysis and workup of acute renal failure was initiated. Transabdominal and transvaginal ultrasounds showed bilateral hydronephrosis and a large pelvic mass displacing the uterus. CT Scan of thorax, abdomen and pelvis showed mediastinal lymphadenoapthy in addition to the above findings. Retrograde pyelogram and bilateral ureteral stenting were done but renal function did not improve.  Fine needle aspiration results of the pelvic mass were suspicious for hematopoietic malignancy with inconclusive immunostaining. An exploratory laparotomy and pelvic mass biopsy were done for a definitive diagnosis. Histopathology showed fibroadipose tissue with diffuse neoplastic cell infiltration and immunostaining was positive for leukocyte common antigen (LCA) and myeloperoxidase. Bone marrow biopsy revealed 63% myeloblasts. These findings were found to be consistent with myeloid sarcoma. Chemotherapy was started but the patient developed pancytopenia, septicemia, and acute respiratory distress. Patient expired on seventeenth day of induction therapy.

DISCUSSION & CONCLUSION:

Myeloid sarcomas rarely have their initial presentation in the lower urinary tract. We came across only four cases in English literature that presented with ARF. Two cases had tumors originating from the prostate, one from the urinary bladder and one from the uterine cervix. To our knowledge, this case is the first description of myeloid sarcoma presenting with ARF and bilateral ureteral obstruction not originating from urogenital system. Physicians should consider possible hematological malignancies in patients with similar presentation. 

 

 

 

Carcinoid tumourlet presenting as ectopic Cushing's syndrome.

P Misra MD, Z Shahid MD, R Thirumala MD, B Dalal MD, O Alzohaili MD, Department of Internal Medicine, Sinai-Grace hospital/ Wayne State University, Detroit, MI.

 

Introduction: Bronchial carcinoid tumours are rare, low-grade malignant neuroendocrine tumours accounting for 2.5% of all lung tumours & 12-15% of carcinoid tumours. We report a case of carcinoid tumourlet presenting as ectopic Cushing’s syndrome.

Case report: An 80-year old African American female with a history of CHF was found to have persistent severe hypokalemia. Basic lab work revealed a normal serum aldosterone with extremely high renin and serum cortisol. On further investigation of her hypercortisolism, a low dose dexamethasone suppression test was done that failed to suppress the cortisol. Subsequently, a high dose dexamethasone suppression test also failed to suppress the cortisol. Further, the serum ACTH was found to be very high. A search for the source of her high ACTH with a CT abdomen revealed bilateral adrenal hyperplasia. An MRI brain did not reveal any pituitary adenoma. This entire constellation of findings favored an ectopic  source of high ACTH. To differentiate between a pituitary micro adenoma and an ectopic source of high ACTH, a petrosal venous sampling with CRH stimulation was performed. It did not reveal a gradient between the central and peripheral serum ACTH levels, which confirmed an ectopic source of ACTH. Therefore, a CT chest was done which showed bilateral small ground glass appearance more on the right. Bronchoscopy and BAL were negative for malignant cells. Subsequently, a right open lung biopsy revealed carcinoid tumorlet that was weakly positive with ACTH immunostaining. The patient’s serum FSH, LH and TSH were also inappropriately suppressed while serum prolactin and IGF-1 were normal. But the patient’s respiratory condition deteriorated and the patient died a couple of months after initial presentation.

Discussion: Our case report highlights the following facts: 1) Only 2% of carcinoid tumours present as Cushing’s syndrome. 2) Unusual clinical presentation of bronchial carcinoid tumour at this age group. 3) High serum cortisol can cause feedback suppression on FSH and LH. 4) The approach to determine the etiology of Cushing’s syndrome. The drawback in our case is our inability to rule out tumour/metastasis at other sites by tissue biopsy, which might have explained the rapid deterioration in this case.

 

 

 

The Role of Monocyte Chemoattractant Protein-1 (MCP-1) in Motility and Bone Homing of Prostate Cancer Cells

Asmita Patel, MD (Associate), Sinai Grace Hospital, Wayne State University, and Kenneth J. Pienta, MD (Member), University of Michigan

Background:

The propensity of prostate cancer cells to metastasize to bone is leading to a design of novel therapies targeting both the cancer cells as well as the bone microenvironment. MCP-1 is a member of CC chemokine family and is known to act as a potent chemotactic factor for myeloma cells as well as certain epithelial cells. The role of MCP-1 in prostate cancer metastasis has not been investigated. Some preliminary data has shown that human bone marrow endothelial (HBME) cells secrete significantly higher levels of MCP-1 compared to human aortic endothelial cells (HAEC) and human dermal microvascular endothelial cells (HDMVEC). These data suggest that HBME cells are a major source of MCP-1. We sought to determine if MCP-1 stimulation of VCaP and PC-3 cells (two bone derived prostate cancer cell lines) results in a dose dependent cell proliferation and motility.

Method:

1) To assess the ability of MCP-1 to stimulate prostate cancer cell motility, PC-3 and VCaP cells were plated in a transwell plate at 1 X 105 cells/mL in the upper chamber. Increasing concentrations of MCP-1 were plated in the bottom chamber. Cells were incubated for 24 hours. The number of cells per 100X objective field were quantified and analyzed.

2) To determine the role of MCP-1 in prostate cancer cell growth, PC-3 cells were seeded at a density of 4 X 103 cells/well in a 96 well plate in regular media. Increasing concentrations of MCP-1 were added to these plates in the presence or absence of P13k inhibitor (LY294002). Cell growth was determined at 24, 48, and 96 hours after seeding using WST-1 assay.

Results:

MCP-1 stimulated PC-3 and VCaP cell motility in a concentration dependent fashion (1 ng/ml to 100 ng/mL). It also shows a dose dependent proliferation of PC-3 cells via activation of the P13kinase/Akt signaling pathway.

Conclusion:

MCP-1 is a potent regulator of prostate cancer motility and proliferation at the site of the bone microenvironment. This suggests that it may contribute to prostate cancer metastasis and act as a chemoattractant for prostate cancer cells. Chemotaxis and motility are essential components of tumor cell trafficking and metastasis. Identifying the key components linking the connection between the chemoattractant-activated receptor and cytoskeletal reorganization is an important part of understanding tumor biology and may lead to the identification of novel therapeutic targets.

 

 

 

Angiotensin Converting Enzyme inhibitors (ACE inhibitors), Angiotensin Receptor Blockers (ARBs) or combination in heart failure patients, an evidence based medicine review.

Ziad S. Zaky, M.D. (Associate)

Department of Internal Medicine, Sinai Grace Hospital, Detroit, Michigan.

 

Introduction: ACE inhibitors improve morbidity and mortality in chronic heart failure (CHF) and after myocardial infarction (MI).This occurs through the inhibition of angiotensin II production. This inhibition is incomplete with ACE inhibitors. Therefore, a selective angiotensin II antagonist could provide better protection than ACE inhibitors. Our clinical question is: in elderly males, with history of hypertension, MI and presenting with CHF (NYHA class≥II, ejection fraction ≤ 30%), is the substitution of ACE inhibitors by ARBs or the addition of ARBs to ACE inhibitors of any clinical benefit?

Methods: Our literature search included database from Pubmed, Ovid, ACP Journal club and ACP Pier. Keywords were males, ACE inhibitors, ARBs, CHF, randomized controlled clinical trial, meta-analysis. Studies selected were comparing ARBs vs. placebo, ARBs vs. ACE inhibitors and ARBs+ACE inhibitors vs. ACE inhibitors. The outcome was all-cause mortality and CHF hospitalization with follow-up duration > 4 weeks. The ARBs studied were losartan, candesartan, valsartan, eprosartan, irbesartan and telmisartan.

Results: Our search resulted in 24 studies. Meta-analysis of 9 studies comparing ARBs vs. placebo included 4623 patients. CHARM-Alternative study contributed most of data. This revealed a significant reduction in all-cause mortality (odds ratio (OR) 0.83 [95% confidence interval (CI), 0.69 to 1.00] P= 0.048) and reduction in CHF hospitalizations (OR 0.64 [CI, 0.53 to 0.78]). Meta-analysis of 8 studies comparing ARBs vs. ACE inhibitors, including 5201 patients, revealed no difference in all-cause mortality (OR 1.06 [CI, 0.9 to 1.26]) and no difference in CHF hospitalizations (OR 0.95[CI, 0.8 to 1.13]). ELITE II study contributed most of data. Meta-analysis of 7 studies comparing ARBs+ACE inhibitors vs. ACE inhibitors ,including 8260 patients, revealed no difference in all-cause mortality (OR 0.97 [CI, 0.69 to 0.87]). Combination therapy was associated with adverse effects, e.g. hypotension and renal impairment.Val-HeFT and CHARM-Added were the most contributing studies.

Conclusion: Use ACE inhibitors in all patients with CHF regardless of functional class except in patients with a history of angioedema. Consider using ARBs in patients who cannot tolerate ACE inhibitors. The combination of ARBs and ACE inhibitors does not have any additional benefit and may have more deleterious effects.

 

 

 

Quinine Enhances the Antiproliferative Effect of Vitamin D3 or EB 1089 in Breast Cancer Cell Lines.

Melhem Solh , M.D(1)., Catherine Lobocki, M.S.(2), Linda Dubay M.D. FACS(2), Vijay Mittal, M.D., FACS(2)

1-Department of Internal Medicine, Wayne State University/Detroit Medical Center(Sinai Grace)

2-Department of Surgery, Providence Hospital- St John Health System

Objectives: Vitamin D3 and quinine have been considered modulators of cell differentiation and proliferation, as well as inducers of apoptosis.  In vivo studies investigating Vitamin D3 and its analogues for breast cancer treatment have been faced with the side effect of hypercalcemia. The purpose of this study was to examine the growth inhibitory and cellular differentiation effects of 1,25-dihydroxyvitamin D3 and EB1089 (a Vitamin D3 analog) alone and in combination with quinine on four breast cancer cell lines (MCF7, T-47D, SKBR3 and BT474).

Methods:  Growth inhibition was determined using the colorimetric MTT assay after 4 and 7 days of drug treatment.  Lipid visualization using the Oil Red O stain was used to assess cellular differentiation.Cells containing 10 or more lipid droplets were considered differentiated, and were counted in a blinded-fashion. Data from MTT assays are the average of 3 separate experiments.

Results:  Both time and dose dependent effects were demonstrated. The IC50’s for MCF7, T-47D and SKBR3 were:  3 – 5 x 10-8 M and 14 – 29&#61549;M for 1,25-D3 and quinine, respectively.  EB1089 was significantly more potent with an IC50 of 2 – 3 x 10-9 M.  The BT474 cell line was relatively resistant to all drugs tested.  The combination of drugs showed a significant decrease in growth (p < 0.02), as well as a dramatic increase in lipid staining after 4 or 7 days of treatment compared to single agents.

Conclusion: 1,25-D3 and EB1089 can cause cell death and induce differentiation in breast cancer, and when combined with quinine, a better growth inhibitory response is achieved.  The combination may allow for a dose reduction of Vitamin D3 or its analogue, and potentially reduce the risk of hypercalcemia in patients.

 

 

 

SPORADIC VON HIPPEL-LINDAU DISEASE PRESENTING WITH BILATERAL RENAL CELL CARCINOMA - A RARE ENTITY

Prakash Vishnu, MD (Associate), Saad Usmani, MD (Associate), Ulka Vaishampayan, MD, FACP (Fellow)

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

INTRODUCTION

von Hippel-Lindau disease (VHL disease) is a rare hereditary syndrome with an autosomal dominant inheritance pattern. Patients usually present with cerebellar hemangiomas, pancreatic cysts and/or renal cell carcinoma between 20-40 years of age. We report a rare case of late onset VHL disease presenting as bilateral clear cell renal carcinoma with multiple pancreatic cysts and left cerebellar hemangioblastoma.

CASE REPORT

A 51-year-old Caucasian female was referred for management of bilateral renal masses, which were found when she underwent a CT scan of the abdomen as a part of workup for refractory anemia of six months’ duration. CT scan revealed complex cystic and predominantly solid renal masses in both kidneys. Multiple cystic lesions in the pancreas were also noted. CT guided core biopsy of each renal mass suggested a histopathological diagnosis of clear cell renal cell carcinoma. Patient underwent a two-stage nephron sparing surgery - right partial nephrectomy followed by left radical nephrectomy. One month following the surgery, patient developed complaints of persistent nausea, vomiting and recurrent headaches. CT scan of the brain revealed a mass lesion in left cerebellar hemisphere. Gadolinium enhanced MRI defined the lesion as nodulo-cystic, the nodular component measuring 60 mm in diameter and the cyst, 40 mm. She underwent a craniotomy and excision of the nodulocystic lesion. Histopathology showed the lesion to be hemagioblastoma, thereby establishing the diagnosis of VHL disease. Pedigree analysis was negative for VHL lesions or disease in the family and the patient has no children. 

DISCUSSION AND CONCLUSION

Sporadic VHL is rare and occurrence of bilateral renal cell carcinoma is even rarer. The late age of onset in this case is unusual considering that most patients present between 20-40 years of age. With a clinical presentation of bilateral renal cancer of clear cell histology, the possibility of VHL should be considered despite the older age of the patient. Because of increased survival with VHL related tumors, patients need a long-term clinical follow-up and surveillance for onset of new tumors in other organ systems particularly retina. Genetic evaluation is indicated to identify and start early screening for family members at high risk.

 

 

 

Hypothyroidism Refractory to Oral Thyroid Hormone Supplementation.

K. Ramesh, MD, A. Reddy, MD, O.Alzohaili, MD, Department Of Internal Medicine, Sinai Grace Hospital, Detroit Medical Center, Wayne State University, Detroit, Michigan.

Hypothyroidism is well controlled in compliant patients with adequate doses of oral thyroid hormone replacement. In a minority of patients, an adequate response to this is not observed. Here we present one such unusual case of hypothyroidism where oral levothyroxine therapy failed.

A 34-year-old African American female with a history of hypothyroidism on very high doses of oral Synthroid (300micrograms per day), was seen for persistent symptoms of hypothyroidism. She had Thyroidectomy for goiter in the past. Physical exam revealed central obesity and acanthosis nigricans. Labs showed a high TSH of 58.8 and a low Free T4 of <0.2 (after >4weeks of therapy). Trials were done in the office with different formulations - Synthroid, Levoxyl and also single high dose Levothyroid 1000mcg orally on different occasions. Free T4 level was measured at one, two, three and four hours. Free T4 remained undetectable. Since levothyroxine failed, trials with oral T3, cytomel, thyrolar, armour thyroid were done. These also failed to suppress TSH and raise serum thyroid hormone levels. A workup for malabsorption syndromes done in the Primary care physician’s office was also negative. The probable explanation for this was the patient’s inability to absorb oral thyroid hormones. Irrespective of the formulary chosen, the problem with absorption persisted.

 

Clinically overt ‘Celiac Disease’ (CD) has been suggested as a possible cause for many of the cases of replacement failures. Apart from ‘CD’, ‘Pseudo-Malabsorption’ (Factitious and Munchausen’s) and drug interference with intestinal absorption, particularly with calcium salts have been reported. Our patient was compliant and took the thyroid replacement on an empty stomach with no interference from other drugs. She had no absorption problems for any of her medications for hypertension and hypercholesterolemia (showed appropriate response). She appeared to have a selective intestinal malabsorption for thyroid hormone preparations.

This is thus far the second known case of selective thyroid hormone malabsorption in the absence of CD, Factitious Disorder and drug interference. A good response to parenteral thyroid replacement was documented in that particular case. Our clinical scenario also calls for parenteral forms of thyroid replacement. Arrangements are currently made to initiate this therapeutic process.

 

 

 

Asystole During Dipyridamole Administration

Vikas Veeranna MD, Kavitha Potluri MD, Syed Mahmood MD, Lawrence MacDonald, MD, FACP.

Department Of Internal Medicine, Sinai Grace Hospital, Detroit Medical Center, Wayne State University, Detroit, Michigan.

 

Introduction

Dipyridamole is an indirect coronary vasodilator which works by increasing intravascular adenosine levels, causing functional ischemia in susceptible individuals. This is the basis for its use in pharmacologic stress testing. We report a case of asystole which occurred after the administration of dipyridamole.

Case report

A 67-year-old African American female underwent elective dypiridamole stress testing as an outpatient. She had presented after experiencing dyspnea on exertion. She took a beta blocker (metoprolol 50 mg once daily) for hypertension. During the infusion of dypiridamole she experienced nausea, dizziness and loss of consciousness. Electrocardiographic monitoring during the procedure demonstrated asystole for 20 seconds coincident with these symptoms. No other dysrhythmias were noted. This spontaneously resolved, with return of consciousness and hemodynamic stability. Theophylline was administered, and was associated with a brief period of atrial fibrillation. After transfer to our institution she underwent further workup for coronary artery disease. There was no EKG or enzymatic evidence of myocardial infarction. No significant epicardial coronary artery disease was noted on angiogram. Echocardiography showed normal cardiac function. No further episodes of asystole were noted.

Discussion

Dipyridamole has been noted to have an indirect inhibitory effect on cardiac conduction. This is felt to be mediated by adenosine. This may be potentiated by beta blockade. In our patient, no other cause for asystole was noted. Specifically, myocardial ischemia was excluded by the normal cardiac catheterization.

Conclusions

We feel that dipyridamole is the probable cause of asystole in this individual. Beta blocking agents have an inhibitory effect on cardiac conduction and impulse generation and may have contributed.

Recommendations

In patients with underlying conduction abnormalities, bradycardia or concomitant beta blocker administration, caution should be exercised before administration of dipyridamole.

 

 

 

Effects of Thiazolidinedione on Reactive Oxygen Species in Mesangial Cells

Ramesh Kotihal, MD, Associate, Sinai-Grace Hospital, Wayne State University, Detroit; Frank.C.Brosius III, MD, Member, University of Michigan, Ann-Arbor.

Background:

Diabetes is the most common cause of renal failure in the United States. Oxidative stress has been known to play an important role in the development and progression of diabetic nephropathy. High glucose induces intracellular reactive oxygen species (ROS) directly via glucose metabolism and auto-oxidation and indirectly through the formation of advanced glycation end products (AGE). Elevated levels of ROS in glomerular mesangial cells are responsible for mesangial expansion, thus causing diabetic nephropathy. We sought to determine the usefulness of Thiazolidinediones (TZD) in reducing the accumulation of ROS and thus ameliorating features of diabetic nephropathy.

Methods:

We utilized differentiated mesangial cultures exposed to normal and high glucose to determine the levels of accumulation of reactive oxygen species. Normal mesangial cells were obtained from c57/B6 mice. Transgenic mouse lines overexpressing GLUT1 were used to obtain GLUT1 overexpressed mesangial cells. Mesangial cells that stably overexpress GLUT1 represent the diabetic models.

ROS accumulated in mesangial cells were measured using the cell permeant 5-(and-6- )-chloromethyl-2, 7-dichlorodihydrofluorescein diacetate ( CM-H2DCFDA). ROS levels in both normal and GLUT1 overexpressing mesangial cells were compared. The mesangial cultures were later treated with rosiglitazone and the accumulated ROS were measured.

Results:

There were higher levels of ROS in GLUT1 overexpressing mesangial cells as compared to normal mesangial cells. Treating both groups of mesangial cells with rosiglitazone was associated with reduction in the levels of ROS. The reduction was more in the GLUT1 overexpressing group as compared to the normal mesangial cells.

Conclusion:

Thiazolidinedione compounds have antioxidant properties in glomerular mesangial cells and further studies to determine there usefulness in ameliorating diabetic nephropathy should be conducted.

 

 

 

Fatal spontaneous massive hemorrhage in SLE (Systemic Lupus Erythematosis)

Fatal spontaneous massive hemorrhage in SLE (Systemic Lupus Erythematosis)

Fatal spontaneous massive hemorrhage in SLE (Systemic Lupus Erythematosis

Shireen jindani, MD, Associate, Glen cipullo, MD, Member, Thomas Piskowroski,Member, Department of Medicine,  Wayne State University/Detroit Medical Center, Sinai GraceHospital.Detroit,MI.

SLE is an autoimmune disease mediated by autoantibodies and immune complexes. 90% of patients are women of childbearing age. The highest prevalence of SLE in United States is among African Americans.We report a rare case of fatal spontaneous hemorrhage of the breast in a patient with SLE.

55-year-old African American woman with past medical history significant for Diabetes, Hypertension, ESRD on Hemodialysis and SLE was admitted for neuroglycopenic symptoms of hypoglycemia. Patient was treated for her symptoms and on day 5 of hospital stay developed sudden chest pain with hypotension that required cardiopulmonary resuscitation. ACLS protocol was followed leading to intubation and transfer to ICU. During resuscitative efforts a hematoma was found in left chest wall. Patient was found to have coagulopathy,(PTT, PT, INR >200, 35.9, 3.55 respectively) acute on chronic anemia,(hemoglobin from 10 gm/dl to 2.5 gm/dl) and thrombocytopenia (platelet count dropped from 114,000/cmm to 75,000/cmm). Peripheral blood smear did not reveal any schistocytes and was negative for any evidence of microangiopathy . Work up for acute coronary syndrome was negative. Complement levels CH50 was found to be very low and anticardiolipin antibody was negative. Patient was aggressively treated with Packed Red Blood Cells, Frozen Plasma, and Cryoprecipitate and given vitamin K. Uncontrolled bleeding of left breast required embolization of feeding branches of subclavian artery. Although hemostasis was achieved, patient died on hospital day 9 due to VDRF (Ventilator Dependent Respiratory Failure) and Multiple Organ Failure. Post mortem revealed left breast   hematoma ( 30cm x20 cm x15 cm). Microscopy shows fibrinoid necrosis of vessels consistent with SLE

This acute and fatal presentation of massive hemorrhage is unique. An extensive review of literature reveals that bleeding complications are rare with SLE and typically present with  pulmonary hemorrhage and Intra cranial bleed.Our case is first reported case of subclavian artery hemorrhage as  bleeding complication of SLE.

 

 

 

Actinomyces meyeri Bacteremia: Presenting as Pneumomediastinum and Myocarditis, A Case Report

Irfan Hameed,MD,Associate, Asadulla Mohammad MD, Mark Wolf MD,

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

 

Introduction: Actinomycosis is a relatively rare infection, caused by Actinomyces species, a commensal in humans . A. Israeli (85%) is the most common pathogen. Dentogingival disease and alcoholism are risk factors for acquiring A. meyeri, which is more commonly reported in pulmonary infections.

Case Report: We are describing a case report of a patient who is a 21-year-old male with no significant past medical history presented with pleuritic chest pain, shortness of breath and palpitations for one week, anorexia, nausea, fatigue and profound weight loss since five months. Physical examination revealed a cachectic man with hypotension and subcutaneous emphysema. Workup showed pre-renal azotemia and pneumomediastinum but CT scan of the chest and esophagogram did not show any perforation at the time of presentation. Later patient developed fever and worsening chest pain with elevated troponin. An EGD was performed and a large ulcer at the gastroesophageal junction was found with suspected perforation. He underwent surgical exploration of chest and abdomen which showed large fundic gastric ulcer but no evidence of perforation. Echocardiogram of the heart showed global hypokinesia with ejection fraction of 15%. Alpha-1 antitrypsin level was normal. Blood culture grew Actinomyces Meyeri for which he was treated with Unasyn. Repeated echocardiogram showed ejection fraction of 55%. Patient had an extensive workup in the search for the site of local infection which was negative.

Discussion: Actinomycosis is a chronic disease, most commonly involving the cervicofacial, thoracic, abdominopelvic and CNS regions. A break in the mucosa of the GI tract is often the portal of entry. In tissues it is associated with a chronic inflammation with granulation tissue, fibrosis and sinus tract formation. Diagnosis is best made by growing it in culture. Penicillin is the drug of choice and treatment duration is usually prolonged. Our case appears to be the result of a gastroesophageal tear. Whether cardiac involvement occurred as a result of hematogenous spread from gastroesophageal tear or from aspiration with subsequent spontaneous resolution of the pulmonary site is unknown. This patient demonstrated a globally decreased EF which improved after antibiotic course. This supports previous reports of cardiac involvement by actinomyces.

 

 

 

Idiopathic pericardial tamponade in an AIDS patient on HAART

Akintayo Sokunbi, MD,  Department of Medicine, Sinai Grace hospital /DMC/Wayne state University,Detroit MI.

 

Idiopathic Pericardial effusion/ tamponade are a recognized presentation of advanced HIV/AIDS. However, the influence of HAART on the development of this life threatening complication has not been explored.

We report the case of a 44yr old man with a history of AIDS well controlled on HAART who presented with a progressively worsening chest pain of one week duration. He was initially diagnosed with HIV in 2002 in view of Cryptococcus meningitis and a history of intravenous drug abuse.  He however has been stable on Zerit,Viread and kaletra with his most recent viral load of less than 2 months ago being undetectable and CD4 count of 361cell/cumm.

His blood pressure at the time of presentation was 130/86mmhg, pulse rate 108bpm, respiratory rate 20cpm, and temperature 99.2F.  Pulse ox 94% on room air. Chest examination revealed a displaced PMI.

2D echocardiography showed a large pericardial effusion with evidence of a swinging heart and right ventricular diastolic collapse and ejection fraction of 55-60. He subsequently had pericardial window placement and drainage of 1000mls of serosanguinous fluid. Biopsy and fluid analysis showed non specific acute and chronic inflammation but negative for malignancy and granulomas. Fluid culture and gram stain were negative for bacteria including mycobacterium and anaerobes. Fungal culture and special stains were negative.  Viral culture was also negative for echo, CMV, Coxsackie’s etc. Both troponins and blood culture were negative. Serum BUN and creatinine was 5mg/dl and 0.8mg/dl respectively. Serum albumin was normal at 4.8g/dl. TSH was within normal limits. Clotting profile was also within normal limits. Amylase and lipase were not elevated. WBC was 8.5cell/cumm, Hb 10.2g/dl, platelet count 581cells/cumm and UDS was negative. He was continued on his medications and continuous pericardial tube drainage via mechanical suction. After eight days of drainage the pericardial tube was removed without any complications. He developed septic thrombophlebitis of the right cubital fossa which was treated successfully.

This case illustrates the fact that idiopathic pericardial effusion/tamponade can occur in patients whose HIV infection is well controlled on HAART. Hence, prospective studies to explore the influence of HAART on this dreaded complication will be needed now.

 

 

 

A CASE OF MYELODYSPLASTIC SYNDROME, REFRACTORY ANEMIA WITH SIDEROBLASTS AND THROMBOCYTOSIS

Zartash Gul, MD (Associate), Irfan Hameed, MD (Associate), Leopoldo Eisenberg, MD (Member)

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

 

INTRODUCTION: Mylelodysplastic syndrome includes a heterogenous group of bone marrow disorders characterized by ineffective production of normal mature blood cells. Majority of patients are anemic at diagnosis,40 percent are neutropenic and 30 –45 percent are thrombocytopenic. Thrombocytois 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 (myelodysplastic versus myeloproliferative) and prognosis. This finding is not classifiable under any of the current classification systems being used.

CASE: 56 year old African American man with history of Diabetes Mellitus and Hypertension for 10 years presented with a sensation of pain in lower extremities on exertion and tingling in upper extremities. On investigation he was found to have thrombocytosis (platelet count 635,000/cmm), hemoglobin of  12.8g/dl and a normal white count  with peripheral smear showing  teardrop cells .Rest of the hematological work up was negative except for a raised ferritin.  Bone marrow biopsy showed a hyper cellular bone marrow and 10 percent ringed sideroblasts suggestive of myelodysplasia. The patient, however, could not be placed under any of the prevalent classification systems.

Subsequently his platelet count increased to more than a million and he was started on anagrelide to which he responded initially and then relapsed.  Increasing doses of anagrelide did show response.  However, he started complaining of palpitations because of which 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 syndromes. While the WHO classification describes mixed myeloproliferative and myelodysplastic disorders and 5q- as separate entities, RARS 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 syndromes.

 

 

 

A RETROSPECTIVE REVIEW OF ANAL SQUAMOUS CELL CARCINOMA IN HIV POSITIVE AND HIV NEGATIVE PATIENTS

Jayasree Grandhi, MD, Associate, Department of Medicine, Wayne State University/ Detroit Medical center(Sinai-Grace Hospital), Detroit, MI Philip A. Philip, MD, PhD, Tara Washington, MD, Anthony Shields, MD, PhD, Ulka Vaishampayan, MD, Lance K. Heilbrun, PhD, Raghu Venkatramanamoorthy, MS, Basil El-Rayes, MD, Department of Hematology-Oncology, Barbara Ann Kamanos Cancer Institute/ Wayne State University, Detroit, MI

Background: The incidence of invasive anal cancer is 120 times higher in the HIV infected patients than in the general population. The outcome of anal cancer in HIV infected patients has not been evaluated in prospective trials and the published literature is limited to small retrospective case series. The aim of this study is to describe the outcome, tolerability, event free survival, and overall survival in patients with squamous cell carcinoma of anal canal (SCCAC) with and without HIV infection treated at Karmanos Cancer Institute/ Wayne State University from 1991 to 2005.

Methods: We performed a retrospective chart review. Patients were identified using the SEER database. We collected data regarding HIV status, demographics (age, gender, race), stage at diagnosis, treatment, response to treatment, toxicity and survival.

Results: Forty patients with SCCAC were identified, of which 13 were HIV positive and 27 were HIV negative. The HIV-positive and HIV-negative groups differed by mean age (44 vs. 55 years), male gender (100 vs. 37 percent), and African American race (92 vs. 59 percent). There were no differences in stage at diagnosis, type of chemotherapy received. HIV positive population received reduced chemotherapy (67 vs. 8 percent), and RT  (22 vs. 7 percent) dosage. The major toxicities observed in HIV positive and negative patients were mucositis (23% vs. 29%), neutropenia (8% vs. 33%) and skin toxicity (46% vs. 55%) secondary to radiotherapy. Only 61 percent of HIV-positive patients were disease free vs. 60 percent of HIV-negative patients.

Conclusions: We found that HIV positive patients received lower doses of chemo-radiotherapy. Patients with HIV tolerated the lower dose chemoradiotherapy and had a similar toxicity profile to the HIV negative patients. No major difference in the risk of recurrence between HIV positive and negative patients was observed.

 

 

 

Hereditary Hemorrhagic Telangiectasia (HHT) – A Case Report

Anupam Gupta, M.D., Asadullah Mohammed, M.D.,

Department of Internal Medicine, Sinai-Grace Hospital/DMC, Wayne State University, Detroit, Michigan

 

Background: HHT or Osler-Weber-Rendu syndrome is a autosomal dominant disorder characterized by epistaxis, cutaneous telangiectasia and visceral arteriovenous malformations. It is estimated that half a million population worldwide have HHT.

Case Report: We describe a 37 year old female with a long standing history of migraine, multiple transient ischemic attack (TIA) in the past, irritable bowel syndrome with GI bleed, recurrent pulmonary symptoms and epistaxis during pregnancy. The onset of her symptoms was at an early age of 8-9 years when she started having repeated attacks of headache, weakness and numbness of right side of the body, decreased vision. During that time, CT of the head was negative and she was diagnosed with migraine headache and TIA. At age 17, she started to develop pulmonary symptoms like dyspnea and tiredness after exertion, severe chest pain. X-Ray/ CT scan results were negative.  Ten years later, she was admitted for pneumonia and at that time X-Ray/CT scan results showed minor left PAVM. No treatment was suggested until she became pregnant two years later and the chest pain / dyspnea got worse. CT scan and MRA showed enlargement of PAVM with a risk of bleeding and she was treated with embolization and coils. She was eventually appropriately diagnosed to have HHT at 31 years of age.  Her mother had a history of migraine headache and facial telangiectasia and her brother died of a stroke at age 12. After her HHT diagnosis, her five children were screened and all of them meet 2-3 HHT criteria out of 4.  

Discussion: HHT has long been viewed as rare condition. However, this disorder is now considered to be more common than previously thought. The overall incidence of HHT in North America is estimated to be about 1:10,000; however, it is likely that this represents an underestimation because of underdiagnosis of the condition.    

Conclusion: This report serves to remind clinicians about the early detection of HHT to prevent any major complications. This case also illustrates the importance of hereditary counseling for patient and to suggest HHT screening in patient’s relatives.

 

 

 

MEDIASTINAL CASTLEMAN DISEASE ASSOCIATED WITH LUNG CANCER

 

Mohammad Rezvani, MD (Associate), Arvind Reddy, MD, MPH (Associate), Geetha Krishnamoorthy,MD (Member),Surendra Marur,MD(member) Sinai-Grace Hospital, Wayne State University, Detroit

 

Introduction

Castleman Disease (CD) is a rare non malignant lymphoprolipherative disease, with unknown etiology and 95% of cases presenting as a localized mediastinal lymph node enlargment. Histopathologically,It has two major variants: hyaline vascular and plasma cell types, which former comprises 90% and latter 10% of cases.We are presenting the Plasma cell type of CD that was associated with Squamous cell cancer of Lung. As per our literature review, this is the second reported case of concurrent mediastinal CD and squamous cell lung Cancer.

Case

A 54 year old African American male, heavy smoker,was admitted with chest and neck pain with hoarseness of voice lasting over 2 months. He also reported a 30 lb wt loss and weakness. On Physical Exam, he had a diffuse swelling of the right side of neck and supra clavicular region. The remaining physical exam was unremarkable.Chest X-ray revealed a moderate-sized mass in the upper part of right mediastinum which was described by CT-thorax as a large, irregular, heterogeneous mass measuring 9x 6x 7 cm with necrotic areas,compressing the trachea and superior vena cava (SVC). A satellite nodule measuring 13 mm was located in the superior segment of right lower lobe of lung. With high index of suspicion for a metastatic lung cancer, a Mediastinoscopic biopsy of this mass was performed that showed a plasma cell variant of Castleman disease.He was HIV negative. Resection of the lung nodule was then performed that showed a 1 cm poorly differentiated squamous cell carcinoma,staged as T4N2Mx. Radiation therapy was started and was continued after discharge. Patient reported significant improvement in his symptoms after radiation.

Discussion

CD associated with lung cancer is rare and must be considered in patients who present with a disproportionately large mediastinal lymphadenopathy. This can possibly avoid overstaging of cancer. it is,also, important to exclude other possible concomitant pathologies (Squamous cell lung CA) for an atypical finding in CD (lung nodule).

 

 

 

INTERPLAY OF NF&#61547;B & RHOC GTPASE IN INFLAMMATORY BREAST CANCER

Saad Z. Usmani MD1 (Associate), Sofia D. Merajver MD PhD2

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

2 University of Michigan Comprehensive Cancer Center, Ann Arbor, MI.

 

BACKGROUND:

NF&#61547;B is a sequence-specific transcription factor that activates multitude of immunologic and angiogenic molecules. It has been found to have increased activity in several cancers including breast cancer. RhoC, a member of the Rho family GTPases, is implicated in the pathogenesis of inflammatory breast cancer. It has been shown that Rho family GTPases can activate and be activated by &#61518;F&#61547;&#61506;&#61486; We hypothesize that NF&#61547;B is involved with activation of RhoC GTPase.

MATERIALS & METHODS:

LifeSeq databases were searched to identify RhoC cDNAs (complementary DNA) with the longest 5'-end extensions. The cDNA was subsequently mapped to the human genome. A 10 kb genomic region upstream of the cDNA start site was analyzed with the Transplorer 1.4 software.  A genomic fragment upstream of the ATG translation initiation site of RhoC GTPase containing the putative promoter and transcriptional start site will be amplified. Primer 3 software will be used in constructing 20-21 b primers for gene amplification. Truncated clones containing those sites will be used in cell-based assays of luciferase to observe expression of RhoC mediated by TNF or IL-1 activation of NF&#61547;B.

RESULTS:

A putative RhoC GTPase promoter was identified starting at -3647 with a transcriptional start site at -2478 using the Transplorer software. It was observed that this promoter region has multiple transcription factor binding sites, including c/EBP, SP1 and NF&#61547;B. Gene amplification of a 5 kb was attempted using cDNA but yielded a very low DNA concentration. Bacterial Artificial Chromosome (BAC) clones were then employed in an attempt to isolate 1 kb segments and subsequently anneal the 5kbp fragment. We have isolated the first 1 kb segment.

CONCLUSION:

Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer. RhoC plays a pivotal role in IBC by promoting angiogenesis. It is known that NF&#61547;B and Rho family have multiple interlinked pathways in tumor angiogenesis. We have thus far identified multiple NF&#61547;B binding sites in the RhoC promoter region. Gene amplification using cDNA did not give an adequate DNA concentration for further experiments but employing BAC clones has provided an alternative way of amplifying the require genomic segment. The final data from our experiments may help in creating biological agents for targeted cancer therapy.

 

 

 

Gastric Pacing for Treatmnet of Morbid Obesity

Arwa Laheri,MD, Resident PGY1, Sinai Grace Hospital/Wayne State University(WSU), Rajika Munasinghe,MD, Attending/Faculty Physician, Sinai Grace Hospital/WSU.

Abstract: Gastric Pacing for Treatment of Morbid Obesity

Introduction: Obesity has become an escalating epidemic worldwide. It is associated with a number of medical conditions like insulin resistance, diabetes, hypertension, CAD, cancers, sleep apnea and GERD. It is the second leading preventable cause of death after smoking. Medical therapies are often ineffective and surgical treatments have significant risk. Implantable Gastric Stimulation (IGS) offers a novel approach to weight loss. Methods: Only randomized controlled trials or multi-center studies were selected. Literature search was from Ovid Medline, Pub med and Cochrane Library. Ovid Medline and Cochrane Library yielded 698 and 3 hits, respectively, but were non relevant. Pub med yielded 7 results, 5 were relevant and 3 studies met my criteria: 1) US O-01 trial:  a multi-center, randomized, double blinded, placebo controlled trial, involving 103 morbidly obese patients. 2) DIGEST (Dual- lead implantable gastric electrical stimulation trial): a prospective, open label, trial involving 30 morbidly obese patients. Patients were followed for complications, post-operative untoward effects, and weight loss. In the DIGEST trial patient's satiety, appetite and quality of life were also assessed before and after implantation. These studies were same in many respects except a few differences, which led to a significant difference in results. The DIGEST trial was unique in 3 ways: a) it used two leads and the lead parameters were individualized, b) it excluded binge eaters from the study, c) it gave behavioral support and dietary advice to patients at each visit. A preoperative Screening Algorithm (SA)(Age, BMI, and patient’s perception of his/her emotional and physical health) was applied to both these trials retrospectively as they thought some patients responded better to IGS than others. 3) LOSS (Laparoscopic obesity stimulation survey): a multi-center, prospective clinical trial, involving 69 patients in 5 European countries. Here the patients were followed for complications and weight loss.

Results: In US O-01, at 7 months there was no significant difference in weight loss between the study and control groups. However, at 29 months, the mean excess weight loss (EWL) was 20%. With DIGEST, EWL was 23% after only 16 months. With the application of SA, almost 40% EWL was achieved for selected patients in both trials. LOSS trial showed EWL of 21 % at 15 months. There were no major peri-operative complications seen in all the three trials. The SHAPE (Screened Health Assessment and Pacer Evaluation) trial is currently ongoing to prove if combining preoperative screening algorithm and IGS yields significant benefits.

Conclusion: IGS holds promising results for morbidly obese patients, especially for those who are not candidates for or willing for surgery.

 

 

 

COUGH, TESTICULAR MASS, LOSS OF CONSCIOUNESS AND BLURRY VISION: COULD THAT BE A PRESENTATION OF SARCOIDOSIS?

S. Rajaguru, M.D (Associate), J. Gowda, M.D (Associate), V. Nayak, M.D (Associate), Lackey Lawrence S Jr. MD (Member), Department of Medicine, Sinai Grace Hospital/Wayne State University, Detroit, Michigan.

Introduction: Sarcoidosis is a multisystem disease of undetermined etiology, which is characterized by noncaseating granulomas. The most common sites of involvement of the disease are lungs and thoracic lymph nodes. However any organ system can be involved.

Case report: A 32 year old African American male with no significant past medical history presented to Sinai Grace emergency department with a history of loss of consciousness and fall. He also complained of early morning headache, blurry vision, productive cough and night sweat for past 2- 3 weeks duration. Also he noted 60 pounds of weight loss over 2-3 months. Other than a 0.5 cm non-tender firm left testicular nodule revealed in testicular examination the rest of the physical examination was unremarkable. CAT scan of thorax revealed extensive thoracic and upper abdominal adenopathy, patchy air space disease of upper lobe of left lung, pleural based mass and multiple small parenchymal nodules. MRI of head showed a large mass involving middle cranial fossa that extends to the right orbit. USS of testis revealed a 6mm solid nodule in left testis. Histopathology of brain mass and lung tissue showed noncaseating granuloma.

Discussion: Sarcoidosis presents with broad range of physical symptoms. However the manifestation of central nervous and urogenital system as initial presentation of the disease is rare. Since sarcoidosis is a multisystem disease and can be indolent, rarely it could present initially as combination of symptoms. Therefore along with the other possible diagnoses like metastatic testicular cancer, lymphoma and tuberculosis sarcoidosis also should be considered in high-risk patients with the above-mentioned presentation.

Conclusion: Here we would like to announce a rare presentation of multisystem involvement in sarcoidosis.

 

 

 

USE OF CANNABIS AND CANNABINOIDS FOR TREATMENT AND PREVENTION OF CHEMOTHERAPY INDUCED NAUSEA AND VOMITING

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

INTRODUCTION

Marijuana (Cannabis sativus) also known as ‘Indian hemp’, is one of the oldest psychoactive plants known to humans. Historically, based on its putative analgesic, anti-inflammatory, antispasmodic, antiasthmatic and anticonvulsant properties, it was used for a variety of conditions. In the current era of medical therapeutics, marijuana in its natural form is not approved by the Food and Drug Administration (FDA), though the synthetic derivative of one of its psychoactive ingredients - delta-9-tetrahydrocannabinol (THC) has been approved for treatment of breakthrough chemotherapy induced nausea and vomiting (CINV) and AIDS-related wasting syndrome.

OBJECTIVE

To review the anti-emetic efficacy of cannabis and cannabinoids for treatment of chemotherapy induced nausea and vomiting

DATA SOURCES

MEDLINE, Cochrane Central Register of Control Trials, manual search of Journals and reference lists.

RESULTS

27 randomized trials could be retrieved. The studies compared the efficacy of cannabinoids vs. placebo, prochlorperazine, chlorpromazine, thiethylperazine, haloperidol, alizapride, metoclopramide +/- dexamethasone and ondansetron. The cannabinoids tested were synthetic THC compounds (dronabinol and nabilone), administered orally or inhaled. There were no studies comparing the efficacy of oral vs. smoked THC. Cannabis or naturally occurring cannabinoids were not used in any of the studies.

DISCUSSION AND CONCLUSION

Studies are heterogeneous in terms of the age of sample population (5 to 78 years), as well as the malignancies treated and chemotherapeutic regimens used. The homogenous studies are too small and lack statistical power. THC controlled nausea and vomiting better than placebo. Against the conventional antiemetics, efficacy of THC was either same or slightly better, whereas the side effects such as dysphoria, lightheadedness and orthostatic hypotension were more frequent and severe. Of note was the differential efficacy of cannabinoids in different chemotherapeutic regimens. While cannabinoids were more effective against the moderately emetogenic drugs, they were not so effective against low and high risk emetogenic agents. The incidence of severe degree of side effects and modest therapeutic efficacy compared to the conventional antiemetics would limit its wide spread use as an antiemetic in the treatment of CINV.  Large homogenous randomized studies are needed.

 

 

 

A RARE PRESENTATION OF NON SECRETORY MULTIPLE MYELOMA FOLLOWING A SOLITARY PLASMACYTOMA

Saad Z. Usmani MD (Associate), Ashraf Ahmed MD (Associate), Leopoldo Eisenberg MD FACP.

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

 

INTRODUCTION:

Multiple myeloma accounts for 1% of all malignant diseases and10% of all hematological malignancies. The median age of onset is 65 years with men affected more than women. Patients presenting without monoclonal proteins in their serum or urine make up hardly 1% of the cases. We present such a case of a patient with history of plasmacytoma who progressed to a non-secretory multiple myeloma.

CASE REPORT:

57 years old female presented with 20-pound weight loss over 3 months, fatigue, anorexia, back and neck pain refractory to analgesics for four weeks. The past medical history was significant for frontal sinus plasmacytoma treated with surgery and radiation therapy in 2004. Physical examination showed hyperreflexia and sensorimotor deficits in all extremities. She had MRI Thorax and pelvis, which showed lytic lesions in the T 7, 8, 9, 10 and L1 as well as the right 8th rib. MRI of the cervical region showed a lytic lesion in C3 compressing the cord. Bone survey confirmed multiple lytic lesions. The serum calcium level was mildly elevated (10.3 mg/dl), normal serum albumin (3.9 gm/dl), normal serum creatinine (0.6 mg/dl), and normal blood counts. The urine and serum immunoelectrophoresis was normal without monoclonal spike. Bone marrow biopsy showed only 4% plasma cells. MRI guided biopsy of the lytic lesions showed rare plasmacytes and lymphoplasmacytoid lymphocytes. The cytogenetic studies were normal. She was started on IV steroids and had radiation therapy with improvement in her symptoms. She is currently on thalidomide and steroids and being evaluated for autologous stem cell transplant.

DISCUSSION:

This case is a unique presentation of non-secretory multiple myeloma following a solitary plasmacytoma. Monoclonal protein spikes in urine or serum accompany most solitary plasmacytomas. Such cases can progress to florid multiple myeloma on further follow-up. Our patient shows multiple osteolytic lesions without evidence of systemic manifestations or bone marrow involvement.  High dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) is the therapy of choice in eligible patients. There a tendency of better survival in non-secretory multiple myeloma in comparison to secretory disease with HDCT/ASCT. The purpose of this report to alert physicians that patients with solitary plasmacytomas can present with non-secretory disease and have a better prognosis than secretory multiple myeloma.

 

 

 

Predicting cardiovascular outcomes -postprandial blood glucose or HbA1C?

P Misra MD, S Marur MD. Department of Internal medicine, Sinai Grace hospital/Wayne state university. Detroit MI

 

Background: Currently we use HbA1C as an index of glycemic control and a predictor of microvascular complications of diabetes. There is a controversy as to the role of PP2BS (2 hour post prandial blood sugar) in predicting cardiovascular outcomes. There is a direct relation between PP2BS and increased vascular tone and endothelial damage. Postprandial hyperglycemia promotes production of adhesion molecules and inflammatory markers, which along with hyperlipidemia promote atherosclerosis. The aim of this study was to analyze the efficacy of PP2BS as an effective predictor of cardiovascular events.

Methods: Extensive literature search was carried out using pubmed and Ovid as the search engines. Search words used were PP2BS, HbA1C, and cardiovascular events. Selection criteria were cohort, retrospective or prospective studies of adequate sample size assessing the relationship between PP2BS and cardiovascular events. Statistical significance was evaluated using hazards ratio, odds ratio, relative risk or a p value of less than 0.05.

Search results: 8 studies showed direct evidence linking PP2BS with cardiovascular events while 5 studies were found to have indirect evidence for the above.

Study conclusion: Epidemiological data suggest that HbA1C alone is not a good predictor for cardiovascular events. When supplemented with postprandial blood sugars, they both give a better prediction for cardiovascular events. The limitation of the above analysis was that there is no study comparing head to head HbA1C and PP2BS in the context of cardiovascular events in diabetics. In addition, most of the data was observational.

Discussion & Conclusion: If PP2BS were a more reliable predictor of cardiovascular risks this would have implications both in the treatment (for example using short acting pre-prandial agents like alpha glucosidase inhibitors, meglitinides, analog insulin) and the timing of monitoring of glycemic events. We look forward for answers to the HEART2D study (Hyperglycemia and its effect after acute myocardial infarction in cardiovascular outcomes in patients with Type 2 diabetes mellitus) for determining the effect of PP2BS control on cardiovascular outcomes in type 2 diabetics keeping a target of HbA1C of less than 7% in both of the 2 randomized groups.

 

 

 

TRICUSPID VALVE ENDOCARDITIS CAUSED BY STREPTOCOCCUS AGALACTIAE POST VOLUNTARY TERMINATION OF PREGNANCY

Ziad S. Zaky, MD (Associate); Padmaja Naidu, MD (Associate), Oronde White, MD (Member), Surendra Marur, MD (Member), Mark Wolf, MD

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

 

Group B streptococcus (GBS; streptococcus agalactiae) is a common cause of sepsis and meningitis in the neonates. Adult GBS infections are less known with reported annual incidence 4 to 6 per 100.000. The typical host is elderly with underlying disease. Diabetes, malignancy, HIV infection, alcoholism, cardiovascular diseases, and advanced hepatic and renal disease are risk factors for invasive GBS infection. Approximately; two to nine percent of GBS bacteremia develops endocarditis. GBS endocarditis involves left sided valves more commonly than right sided. The incidence of infective endocarditis after obstetric and gynecologic procedures is low, ranging between 0.03 to 0.14 per 1000 deliveries. The incidence is especially lower after abortions, about one per million abortions.

We report a case of a 28 year old African American female who presented with fever and chills four weeks after an elective abortion. Workup revealed a positive blood culture for GBS, right lower lobe pneumonia and bilateral pleural and pericardial effusions.  Transvaginal ultrasound and CT abdomen was negative for any retained products of conception or abscess.  Despite resolution of pneumonia both clinically and radiologically, daily fever spikes persisted.  A transesophageal echo (TEE) was performed and revealed tricuspid valve endocarditis with a vegetation measuring 1.2 x 1.7cm involving the septal leaflet. The patient was started on vancomycin 1.5gm Q8h for 6 weeks and gentamycin 140mg Q12h for 2 weeks. Fever resolved and the patient underwent tricuspid valve replacement with bioprosthetic valve. One month later, at the time of follow up, the patient was doing well. All repeat blood cultures were negative.

Our patient presents a rare case of subacute GBS endocarditis involving native tricuspid valve following an elective abortion. The patient was young, with no underlying disease and no history of drug abuse. The overall mortality rate of GBS endocarditis is lower with combined medical and surgical strategy than with medical therapy alone (range of 20% vs. 40% - 50%). Fevers post voluntary termination of pregnancy should prompt a full work up including a TEE if no other focus is found.

 

 

 

A rare presentation of pulmonary sarcoidosis

Asmita Patel, MD, Associate, Ramesh Kotihal, MD, Associate, Mohammed Asadulla, MD, Member, Department of Internal Medicine, Sinai-Grace Hospital, Wayne State University, Detroit, Michigan

 

Introduction: Sarcoidosis is a systemic disorder of unknown cause characterized by the presence of noncaseating granulomas. It has a variety of pulmonary manifestations including the nodular or infiltrative form. However, primary cavitary form is rare. We report a rare case of sarcoidosis presenting as primary acute pulmonary cavitation.

Case Report: A 31 year old African American female presented to the emergency room with sharp retrosternal chest pain of one month duration. Patient also complained of cough productive of clear sputum for a month, not associated with hemoptysis. She also complained of shortness of breath on exertion. Patient denied any history of travel or any sick contacts. She did admit to smoking half pack of cigarettes a day for 16 years. Her last tuberculin test, one year ago, was negative.

Chest roentgenogram done at the time of admission revealed multiple cavitary lesions in the right and left upper lung fields measuring 3.5 cm to 3.9 cm in diameter. Air-fluid levels were not demonstrated in the cavities. Computed tomography of the thorax was done which confirmed these findings and showed hilar adenopathy, few nodular densities and pleural thickening.  Pulmonary function tests revealed mild restrictive ventilatory defect along with decreased diffusion capacity. Bronchoscopy along with transbronchial biopsy was performed, and the histology revealed non-necrotizing granulomas consistent with sarcoidosis. Corticosteroid therapy (prednisolone 40 mg/day) resulted in reduction of the cavitary lesions and improvement in patient’s symptoms in a few days.

Discussion:  Primary acute pulmonary cavitation is a rare presentation of sarcoidosis. English literature has described only five cases of similar presentation. The cavities range in size from 3-8 cm and are usually thick walled. Patients may be asymptomatic, but life threatening hemoptysis has been reported. The cavitation probably results from ischemic necrosis of the granulomas, though others have postulated infarction secondary to a granulomatous angiitis. It is important to distinguish cavitary sarcoidosis from cavitary infections, cystic bronchiectasis, and mycetoma formation, which are common complications of pulmonary sarcoidosis. This distinction is important since the treatment of cavitary sarcoidosis is corticosteroids.

 

 

 

Blood Pressure Response to Renal Angioplasty in African Americans with Renal Artery Stenosis.

Kavitha Potluri,MD(Associate); Rekha Galla,MD(Associate); Zongshan Lai, Suzanne Ohmit, Peter Dews, Delair Gardi, John M Flack, MD,MPH(Member); Wayne State University, Detroit, MI

Background: Atherosclerotic renal artery stenosis is the most common form of secondary hypertension and percutaneous transluminal angioplasty (PTA) with stenting is the most common therapeutic intervention.Randomized controlled clinical trials are not available and data on African Americans with critical renal artery stenosis is sparse.

Objectives: To characterize blood pressure (BP) and kidney function response to renal angioplasty and stent placement, and to examine attainment and persistence of Joint National Committe(JNC)-7 BP goals before and after revascularization.

Population: Fourteen patients who underwent PTA with stenting for critical renal artery stenosis, were identified from Medtrace electronic medical records. All were African Americans, mean age was 70 years (range: 57-85), and all had difficult to control hypertension.

Methods: Data considered included patient demographics, diabetes status and measures of kidney function, BP recordings, medication use, and results of duplex/MRA/angiography procedures. Mean pre- and post-intervention BP and kidney function values were calculated and BP responses determined. SBP and DBP responses to revascularization were examined in random coefficient mixed models adjusted for patient age, sex, weight, estimated glomerular filtration rate (EGFR), diabetes status, and treatment with antihypertensive and statin drugs.

Results: Mean BP averaged 168/87 mm Hg pre-intervention and 147/75 mm Hg at the first visit post-revascularization (P<0.005, both SBP and DBP). In the adjusted mixed models, mean BP declined by 19/7 mm Hg following revascularization (P< 0.003, both SBP and DBP). Prior to revascularization, BP was below JNC-7 BP goal levels at only 9.2% of visits compared to 37.3% of visits post-revascularization (P=0.008). Mean pre- and post-revascularization EGFR was nearly identical (57.8 vs. 57.7 ml/min/1.73m2, P=0.39); mean post-revascularization serum creatinine increased from pre-revascularization values (1.3 v. 1.6 mg/dL, P=0.35); and median spot urine albumin:creatinine ratio values declined following revascularization (37.9 vs. 32.3, P=0.25).

Conclusion: Renal artery revascularization with stenting lowered BP and significantly improved attainment of and persistence below JNC-7 BP goals in an older African American cohort with critical renal artery stenosis.

 

 

 

Small Cell Carcinoma of the Esophagus: A Rare Tumor

Arwa Laheri MD (Associate), Saad Z. Usmani MD (Associate), Geetha Krishnamoorthy MD (Member)

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

 

INTRODUCTION:

Small cell carcinoma of the esophagus is a rare and aggressive tumor with early widespread dissemination. . It has a high incidence of metastatic disease at presentation and a poor overall prognosis. We present such a case.

CASE REPORT:

A 70-year-old man presented with an episode of generalized grand-mal seizures. He also complained of chest discomfort, dysphagia, and odynophagia and had a 15-pound weight loss four weeks prior to presentation. Past medical history was significant for gastroesophageal reflux disease. Physical examination revealed bilateral submandibular adenopathy and a small left axillary lymph node. His initial laboratory work up was normal. The CT scan of the head showed evidence of multiple metastases, later confirmed by MRI of the brain. The CT scan of the abdomen and pelvis revealed widespread metastasis to liver, spleen, bilateral adrenal glands, and retroperitoneal lymph nodes and left pubic bone. Bone scan was done which was negative. He underwent esophago-gastro-dudenoscopy for dysphagia, which showed a midesophageal mass. The biopsy of this mass revealed small cell cancer. Biopsy of the lymph node was also consistent with small cell cancer. He received palliative chemotherapy with carboplatin and etoposide.

DISCUSSION:

The current case joins the almost 200 reported cases of small cell esophageal cancer. This is a rare tumor with early systemic metastasis and generally poor prognosis. Unfortunately, optimal treatment has not been defined yet but chemotherapy and radiotherapy combined with surgery has been used in early stage disease. So far only one case has been reported to be a long-term survivor of this disease (96 months) with the above modality of treatment. The objective of this report is to inform physicians of this disease and its dismal prognosis.

 

 

 

Multiple Daily Injections or Continuous Subcutaneous Insulin Infusion for better Glycemic control in Type 1 Diabetes

K Ramesh MD,S Marur MD, Department of Internal Medicine, Sinai Grace Hospital, Detroit Medical Center, Wayne State University,Detroit, Michigan.

Introduction:

1 out of 800 people in the United States have Type 1 Diabetes. The Diabetes Complications and Control Trial (DCCT) was a Randomized Controlled Clinical Trial that studied the relation between Glycemic control and vascular complications in Type 1 Diabetes. DCCT concluded that intensive therapy of Diabetes decreased the complications significantly. Intensive therapy is possible with either Multiple Daily Injections (MDI) of Insulin or Continuous Subcutaneous Insulin Infusion (CSII). This literature review analyzes the various studies comparing CSII and MDI for glycemic control.

Methods:

 Articles were searched in Ovid, PubMed and Cochrane. The search criteria used were CSII and MDI. The search yielded 31, 61 and 5 articles in Ovid, PubMed and Cochrane respectively. Articles in English with comparison between CSII and MDI, in adults with Type 1 diabetes were considered relevant. Articles dealing with non comparison on glycemic control between CSII and MDI, those dealing with children, pregnancy or Type 2 Diabetes were considered as not relevant. This filtering yielded 7, 11 and 0 relevant articles in Ovid, PubMed and Cochrane.

Results:

Many articles were common in the search results .The study by Hissa MN et al had a P value of <0.05 for HbA1c compared to baseline. The study by Hanaire-Broutin H et al using lispro had P value for HbA1c as < 0.001.The metanalysis by Retnakaran etal showed P=0.002 for interaction between baseline HbA1c and treatment modality. The Randamized Controlled Trial by Hoogma RP et al had P<0.001. The study by Tsuii et al had a P >0.1.Other 6 studies reviewed showed better glycemic control with CSII.

Conclusion:

All of the above, except one concluded that CSII was better than MDI for lowering the HbA1c. The exception showed no difference between CSII and MDI. However, not all these studies considered the other aspects like hypoglycemia, incidence of DKA, dose and weight changes with either of them. Best results with CSII, needs patient education on how to maintain the pump and importance of blood sugar monitoring. Hence, though CSII appears to offer better glycemic control, this treatment modality needs to be individualized to each patient.

 

 

 

Synchronous Versus Metachronous Breast Cancer:Charecteristics of The Second Tumor.

Melhem Solh, MD(1), Hanadi Bu Ali, MD(2),Vijay Mittal, MD, FACS(2).

1-Department of Internal Medicine(Sinai-Grace hospital)Wayne State University/Detroit Medical Center.

2-Department of Surgery, Providence Hospital And Medical Centers

 

Introduction: Synchronous cancer is defined as a tumor diagnosed simultaneously or within a period of three months of diagnosis of the first tumor whereas a metachronous cancer was defined as a tumor diagnosed after this three month period. Synchronous breast cancer has an incidence ranging from 0.3% to 12%.Despite this high incidence, there is no clear consensus whether synchronous tumor represents one disease entity as the primary,or it is an independent second primary that shares some biologic features with the other tumor.

Objective:To foresee any similarities and differences between patients with synchronous versus metachronous breast cancer. To check whether synchronous breast cancer represents one disease entity or is an independent tumor than the primary.

Methods: A retrospective analysis of all patients with synchronous or metachronous breast cancer treated at a single institution between January 1991 and March 2004. Patients were compared regarding demographic features, menopausal status, age at menarche, age at diagnosis, number of children , breast feeding and hormonal intake.Tumors were evaluated regarding clinicopathologic status and response to treatment.

Results: Both groups were similar regarding age, ethnicity, menopausal status and number of children. Metachronous cancer group were more likely to have a first degree relative with breast cancer( 77% vs 22%). Ductal adenocarcinoma was the most common tumor in both groups whereas the Synchronous group tend to have a higher incidence of LCIS (16% vs 4% p<0.05). 46% of the synchronous group tumors were poorly differentiated vs 23% of the metachronous group. There was no statistical difference between the behavior of the first and second tumor in each group as far as histologic subtype, receptor status, stage and grade. The average life time survival from the day of diagnosis for the synchronous group was 4.7 years( range 0-14 years) whereas the metachronous average life time survival was 12.5 years (range 2-25 years) with a p value<0.005.

Conclusion: synchronous breast cancer tends to be more aggressive than metachronous breast cancer, and has a poorer outcome. Moreover, the concordance between different tumors within the same patient , in particular for histology, grade, stage and receptor status support the hypothesis of monoclonal origin of bilateral breast cancer.

 

 

 

ARE WE THERE YET? – USE OF 16 SLICE CT SCANNERS IN DIAGNOSIS OF CORONARY ARTERY DISEASE.

Vikas Veeranna MD, Surendra Marur MD, Department Of Internal Medicine, Sinai-Grace Hospital, Wayne State University, Detroit, Michigan.

Introduction Coronary artery disease [CAD] is the single leading cause of death with a prevalence of 13 million in the United States. About 1.5 million undergo diagnostic cardiac catheterization with coronary angiography each year. Computed tomography is a new diagnostic tool in the diagnosis of coronary stenoses [block >50%], especially multi slice CT scanners [MSCT]. This study reviews the literature published on the use of 16 Slice CT for diagnosis of CAD.

Methods A literature review was done on the effectiveness of MSCT angiography in comparison with interventional coronary angiography in diagnosis of CAD in native vessels. The search included all articles published between July 1998 and July 2005 with a focus on 16 slice scanners. Pubmed, Ovid Medline and Cochrane were searched, yielding 137 results. 121 of these were exclude as they did not meet inclusion criteria [humans, Comparison with Coronary Angiography, native coronary vessels] or MSCT for screening or used calcium score for diagnosis. This yielded 13 studies. Cost was not a factor.

Results Most 16 slice CT scanners had small groups with definite inclusion criteria. All the study group individuals had undergone or underwent invasive coronary angiography, which was the measure of comparison. In most studies patients were placed on Beta blockers to reduce the heart rate and ECG gating used to improve image quality. The sensitivity of the tests ranged from 63% to 95%, indicating a high level of false negatives. Specificity range was 80% to 98%. Positive likelihood ratio of >10 was found in 10 studies, while negative likelihood was < 0.1 in only 5 studies, suggesting that MSCT angiography may be useful to detect the disease and increase post test probability but not rule out the disease.

Conclusion Based on the literature review it can be concluded that 16 slice CT angiography do not have a better ability to diagnose CAD compared to invasive coronary angiography. A substantial number of patients would be missed [false negatives] hence not receiving adequate or early treatment. Invasive coronary angiography is still recommended.

 

 

 

SCREENING FOR LUNG CANCER:EVIDENCE BASED

Zartash Gul, MD (Associate),Sinai Grace Hospital-Wayne State University, Detroit, Michigan.

 

Introduction:Lung cancer is the leading cause of cancer related deaths in United States.While cancers with a lesser disease burden have screening guidelines,there is no suitable screening test for lung cancer that can detect the disease at a treatable stage.Chest X rays,CT scans,and sputum cytology are few of the common screening options.Therefore a search was conducted to find evidence in favour of or against screening for lung cancer.Ovid,Pubmed,and Cochrane were the the databases searched.Cochrane was finally selected as the basis of this search.

Methods:Search terms used were Pulmonary neoplasms,Lung cancer,NSCL cancer,Small cell lung cancer,Lung Tumor,Screening,CT scan,Chest Xray,

Mass screening for lung cancer.An effort was made to select large,prospective,randomized,control trials .Blinding was also present except in one of the trials.Trails selected were Kaiser,Czech,North London,Mayo,John Hopkins and Sloan Kettring trials.In Mayo,John Hopkins and Sloan Kettring trials male smokers  more than 45 years of age were selected.A chest Xray was done at baseline and then they were randomized to two arms. In the intervention arm chest Xray and sputum exam was done at 4 month intervals while in the other arm chest Xray was done yearly.In North London,Kaiser and Czech studies the subjects in the intervention arm underwent chest Xray more frequently as compared to less frequent chest Xray or no chest Xray(Czech and Kaiser)in the non-intervention arm.

Results:The results from all the trials gave a relative risk of death from lung cancer that was considered as statistically insignificant(0.88-1.36).

Discussion:Majority of the studies reflected an increase in survival time

for intervention arms.However this conclusion could not be accepted on its face valve because of the issue of inherent bias in these studies.These were over diagnosis,lead time and length time bias.Because of these the conclusions drawn from these studies failed to show a mortality benefit to those undergoing intervention.

Conclusion:Therefore, based on the above evidence screening for lung cancer cannot be justified now till further evidence proves it otherwise.

 

 

Adenocystic Breast Cancer:

A Case Report And Review Of The Literature

 

Melhem Solh, MD (1), Mubashir Sabir, MD (2), Linda Dubay, MD, FACS (2),

 Farooq  Minhas, MD (2).

1-Wayne State University/DMC(sinai Grace Hospital) DePARTMNET OF INTERNAL MEDICINE.Detroit-Mi

2-PROVIDENCE Hospital, Department Of Surgery. Southfield-Mi

 

A 65 year old female gravida 5, para 3, presented with a lump in her left breast. She had no history of breast diseases, breast discoloration, breast discharge or any change in the size of the recently palpated lump.Upon physical examination, she had a 3 cm lump located in the left breast at 5-6 o'clock, hard and movable.No axillary or supraclavicular lymph nodes.

             An ultrasonogram showed 2.5 cm solid mass at 6 o'clock of the left breast.An excisional biopsy was performed. Pathologic slides were sent to new York Presbyterian Hospital for consultation.The result was an adenocystic carcinoma, predominantly low grade, with a high grade component.After extensive literature review,the decision was to do a lumpectomy.The permanant pathology report was confirmatory with the above result of fine needle aspiration.

Discussion

            Adenocystic carcinoma of the breast is a rare pattern of invasive breast carcinoma.It accounts for less than one-percent of all primary carcinomas of the breast.It typically presents in the postmenopausal age group (6th and 7th decades).The most frequent clinical presentation is a palpable mass usually detected by self examination. The mean tumor size is l.9 cm.A subareolar location was reported in 50% of the cases with the same incidence in both right and left breasts.

            It is mainly diagnosed based on morphologic features.This tumor is characterized by the presence of cribrose structures that are formed by multiple pseudocysts filled with amorphous substance.Diagnosis of the tumor should be based on strict criteria because it carries a very good prognosis.  Estrogen receptor positivity range between 24% and 46%.  Grading of the tumor has been proposed on the same basis as it is graded in other locations.It is considered a benign disease and its treatment is still an era of debate. Treatment of the tumor included lumpectomy, MRM, total mastectomy and total mastectomy with axillary lymph node dissection.The incidence of axillary lymph node metastasis is almost nil (0-5 %).

            The outcome of treatment for the tumor is excellent, with five-year overall survival of 85-90%, and five year disease free survival almost 100% .The prognosis was found to be independent of histologic grading, nuclear grading,proliferative activity or the type of procedure done , whether it is lumpectomy, total mastectomy or modified radical mastectomy and whether there was axillary lymph node dissection.

 

 

Jejunal-Ileal Diverticulitis

Melhem Solh MD(1), Kongkrit Chaiyasate, MD(2),  and Vijay Mittal, MD, FACS(2).

1-department of internal medicine, Wayne State University/DMC (Sinai Grace Hospital).

2-Department of surgery, Providence Hospital and Medical center

A 68 year old gentleman presented to the hospital with diffuse abdominal pain for 24 hour. The pain was located mostly in his lower abdomen, and was associated with nausea and vomiting. Physical examination revealed fever and peritoneal signs associated with leukocytosis. Diagnosis of peritonitis was entertained. During abdominal exploration, there was a necrosis of segment of bowel identified as jejunal diverticulitis (figure 1). The affected part of small bowel was resected with a primary anastomosis. The patient was discharged home on postoperative day 6 without complication.

Jejunoileal diverticula are estimated to occur in 1-5% of the population. They are pulsion diverticula thought to be the result of intestinal dyskinesia. Eighty percent of jejunoileal diverticula are localized to the jejunum, 15% to the ileum, and 5% to both1. Diverticula in the jejunum tend to be large and multiple, whereas those in the ileum are small and solitary. Complication occurs in 6-10% of the patients ranging form acute problems including acute obstruction and massive bleeding, to chronic problems which can produce a significant diagnostic and therapeutic dilemma. One should entertain the diagnosis of jejunoileal diverticulitis whenever a patient present with 1) unexplained intestinal obstruction, 2) unexplained gastrointestinal bleeding, 3) an unexpected cause of acute abdomen, 4) chronic abdominal pain, 5) anemia, or 6) malabsorbtion2. Asymptomatic jejunoileal diverticula should be managed conservatively. When surgical therapy is indicated intestinal resection with primary anastomosis is the preferred treatment.

 

 

MANAGEMENT OF PATIENTS WITH ASYMPTOMATIC PATENT FORAMEN OVALE

AKINTAYO SOKUNBI M.D. SINAI GRACE/WAYNE STATE UNIVERSITY, DETROIT, MICHIGAN

Background: Patent foramen ovale is seen in about 25 % of the normal population. It is usually asymptomatic. However, several medical conditions which include cryptogenic stroke,  paradoxical thromboembolism,  migraine with aura and the platypnea-orthodeoxia syndrome has been linked to a patent foramen ovale.

Method: Electronic search of the MEDLINE database with PubMed, Ovid, and Cochrane library for relevant articles was done. This was supplemented with manual search of secondary sources including selected references from the primary articles. Search terms included: patent foramen ovale, combined with various words including, treatment, asymptomatic, stroke, migraine, risk and prevention.

Results:  In the absence of controlled trials, identified articles were systematically screened for the following inclusion criteria: a study cohort with primary prevention of complications attributable to a patent foramen ovale, minimum of 10 patients per cohort and mean duration of follow up of at least 5yrs.

There were no studies found in the literature to support any form of primary prevention of complications in asymptomatic patient with patent foramen ovale. However there are many on going studies for the management of complications secondary to this common congenital defect.

Conclusion: Patent foramen ovale is common enough in the general population to be considered a variant of normal and until there are appropriate studies to measure the impact of any form of intervention, asymptomatic patent foramen ovale will continue to be observed as a variant of normal.

 

 

 

BORDETELLA PERTUSSIS INDUCED ACUTE RESPIRATORY DISTRESS SYNDROME IN AN ADULT MALE.

Platel R, MD, MPH (Associate); Wolf M, MD; Dalal B, MD, (Associate).  Sinai-Grace Hospital, Wayne State University, Detroit, Michigan. Detroit, MI

Introduction: We are reporting a case in which Bordetella Pertussis was responsible for Acute Respiratory Distress in an Adult.

Case Report: A 55-year-old male health worker, with a recent diagnosis of Autoimmune Hepatitis and on steroid therapy was admitted to the hospital with the complaints of leg pain and weight loss. On day 3 of hospitalization he developed shortness of breath, had a chest x-ray showing interstitial infiltrate suggestive of pulmonary edema or congestion. The patient worsened clinically even with diuretics, repeat chest radiograph showed bilateral air space or alveolar infiltrates. Transferred to the ICU on day 5 and broad-spectrum antibiotics initiated. The relevant lab work up and investigations were sent. On day 13 the patient deteriorated with a PO2 of 50%, and was intubated. The patient was maintaining a PO2>90% only with 90-100% of FiO2. A bronchoscopy and subsequently a lung biopsy were performed. Previously sent results sera came back positive for Chlamydia pneumoniae (IgG) and Pertussis (IgA). Azithromycin was started with an improvement in symptoms and a decrease in FiO2 requirement down to 40% for two days and ready to be extubated. Unfortunately, the patient developed a high-grade fever and ventilator associated pneumonia with Acinetobacter baumannii, treated with Unasyn and was extubated. After 4 weeks of illness the repeat serology for Chlamydia pneumoniae (IgG) remained unchanged while the Pertussis (IgA) titer was negative. In retrospect we concluded that this was a diagnosis of Pertussis induced ARDS.

Discussion: There is increasing evidence that pertussis occurs frequently in adults, but information is limited on the clinical course of this disease beyond childhood. It is of note that Pertussis has been added this year to the Adult Immunization Schedule as single dose of Tdap , booster immunization against tetanus, diphtheria, and pertussis every 10 years. We report this case to emphasize the significance of this rare infectious cause of ARDS in adults. To our knowledge, one case report in the pediatric population and no similar presentation in adults have been reported in the literature. We therefore suggest that Pertussis should be thought of as a potential etiologic agent of adult ARDS.

 

 

 

Allergic bronchopulonary asperigillois: An unusual cause of resistant bronchial asthma

Malini Venkatram M.D.,  Asadulla S Mohammed M.D. Department of Internal Medicine, Wayne state University/ Detroit Medical Ceneter (Sinai- Grace Hospital), Detroit, Michigan

Introduction: Allergic Bronchopulmonary Aspergillosis (ABPA) is an underdiagnosed pulmonary disorder in patients with bronchial asthma and cystic fibrosis. We present an unusual case of ABPA in a 58 year male presenting as resistant bronchial asthma. He had recurrent exacerbations of asthma which was difficult to control. CT Scan chest revealed infiltrates & central bronchiectasis. His serology showed elevated total IgE levels & IgE antibodies to Aspergillus fumigatus. His symptoms responded fully to prednisone & Itraconozole.

Discussion: ABPA is due to allergic response to antigens expressed by fungi, most commonly Aspergillus fumigatus. ABPA is present in 2-28% of asthmatics.The natual history and prognosis of ABPA are not well characterized but may be complicated by progression to bronchiectasis and pulmonary fibrosis. If ABPA is diagnosed and treated before the development of bronchiectasis and fibrosis, these complications may be prevented. The clinical course is characterized by chest infiltrates associated with cough, wheeze and sputum production that usually respond to oral steroids. Specific immunologic and radiologic markers include elevation of the total serum IgE levels, presence of aspergillus IgE antibodies and central bronchiectasis. Long term treatment with steroids is often required for effective management. The adverse effects of chronic steroid use have led to attempts at treatment with antifungal agents such as itracanazole.

Summary: ABPA should be considered in patients with difficult to treat asthma with radiographic infiltrates, central bronchiectasis, supported by elevated serum IgE levels and increased IgE to A. fumigatus. It responds well to long term steroids. Itraconozole may be effective as a steroid-sparing agent & in some cases as a sole therapy.

 

 

Do Brain Natriuretic Peptide (BNP) levels correspond to the response of congestive heart failure (CHF) to medical therapy?

George Nassif, M. D. (Associate), Sinai-Grace Hospital/Wayne State University, Detroit Medical Center, Michigan

Introduction

BNP is secreted from the ventricles of healthy individuals and patients with CHF.  Females have higher plasma concentrations than males while BNP levels increase in both sexes with advancing age.

Plasma BNP concentration correlates with pulmonary capillary wedge pressure and left ventricular pressure.

   BNP levels can be measured using Radioimmunoassay, Immunoradiometric assay and Immunofluorometry.

Clinical Question

     A 70 year old man has been diagnosed with CHF, with a BNP of 4000, and ejection    fraction of 24%. He is started on diuretics, ACE-Inhibitors, beta blockers and digoxin.

     How useful are the changes in BNP level to assess the response of his CHF to medical therapy?      

Search Methods & Results

     PubMed keywords: Brain Natriuretic peptide & treatment of heart failure, 19 review studies, Brain Natriuretic peptide & follow up of heart failure(limit to clinical trial) 28 studies.

    Ovid keywords: Brain Natriuretic peptide (full text) 94 studies, heart failure (full text) 455 studies, Brain Natriuretic peptide & heart failure 15 studies .    

Criteria for selection

      Randomized clinical trials, multi-centered, placebo-controlled, double-blinded, large number of the patients.      

 Discussion and conclusion

We identified four studies including Val-HeFT, and they suggest that physicians can  rule out decompensated heart failure with low BNP concentrations (i.e., < 80 to 100 pg/mL), whereas high BNP values (>400) are more specific but less sensitive to confirm a diagnosis of CHF.  Intermediate values (100 to 400 pg/mL) may not be accurate to confirm a diagnosis of CHF.  BNP falls after effective pharmacologic treatment of CHF. Persistent elevation of BNP level, despite optimal medical therapy, has also prognostic significance (death and readmission). BNP levels can help monitor patients with an established diagnosis of CHF and appears more specific for high LV filling pressure and NYHA class. However, BNP is of limited value in follow-up of some patients with severe chronic CHF, in whom BNP may remain elevated regardless of treatment. Also, BNP cannot be used for clinical assessment in patients being treated with Nesiritide (recombinant human BNP).

 

 

 

NON HORMONAL THERAPIES FOR THE TREATMENT OF HOT FLASHES

Raylene Platel, MD, Associate. Sinai-Grace Hospital, Wayne State University, Detroit, Michigan.

Clinical Question: 55-year-old Caucasian female is experiencing severe hot-flashes and requesting non-hormonal therapy for her hot-flashes. Her mother used HRT and this patient is aware of the WHI outcome, what can she be prescribed?

Data Sources: Medline database from 1985-2005 using PubMed and Ovid.

Search Terms: Non-hormonal-therapy for hot-flashes, hot-flashes, non-hormonal therapy.

Results: Ovid Medline: 7

                   Pubmed: 78

Search limited to: RCT, human studies.

Studies reviewed: SSRIs-Paroxetine andVenlafaxine.

                                       Gabapentin.Clonidine.ICE.

Paroxetine: RCT (Stearns et al.) Intervention: 1 wk. Placebo run in phase.

     Placebo/12.5 mg per day/25 mg per day in a 1:1:1 ratio for 6 wks. N=165

Venlafaxine: RCT (Evans et al.)  Intervention: 1 tab daily, 1 week followed by 2 tabs daily, 11 wks. N=80

Gabapentin: RCT (Guttuso et al.) Intervention: 900 mg/day of gabapentin, 12 weeks followed by 5 week open-label-treatment-phase with option to increase dose to 2700 mg/day.2 week screening baseline assessment. N=59

Transdermal-Clonidine:  RCT (Manubai et al.) Intervention:  Arm Patch changed every week delivers 0.1mg/day of clonidine, 2 weeks. Baseline and 8 weeks treatment. N=30

ICE: Isoflavone-Clover-Extract-Study, RCT (Tice et al.) Intervention: 2 week Placebo run in. Random assignment to Promensil (82 mg), Rimostil (57 mg), placebo with f/u for 12 weeks. N=252

 

Outcome Measure: Hot-flash score recorded as frequency of hot-flashes by participants in the Clonidine study, severity was also measured.

Results: Paroxetine:  62.2%, 64%and 37.8% score reduction for 12.5 mg, 25 mg and placebo groups respectively.

 Venlafaxine: Average score reduction was 2 points (p=0.25).

Gabapentin: 54% and 31% reduction in score with gabapentin and placebo respectively (p=. 01)

Clonidine: 80% and 36% score reduction in treatment and placebo groups respectively.73% and 29% decrease in severity in treatment and placebo groups.

ICE: Decrease in daily score was 5.1,5.4 and 5.0 respectively for promensil, rimostil and placebo groups respectively.

Conclusion: FDA approval of a medication for hot-flashes mandates study periods of at least 12 weeks. ICE, Gabapentin and Venlafaxine were the three studies that qualified of which only Gabapentin showed significant reduction in hot-flash frequency. Paroxetine and transdermal clonidine were found to be effective but inadequate study periods of only 6 weeks/ 8 weeks respectively.

 

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Upregulation of calcium-sensing receptor and mitogen-activated protein kinase signalling in the regulation of growth and differentiation in colon carcinoma.

 

Bhagavathula N, Kelley EA, Reddy M, Nerusu KC, Leonard C, Fay K, Chakrabarty S, Varani J.

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

In the present study, we demonstrate that Ca2+-induced growth inhibition and induction of differentiation in a line of human colon carcinoma cells (CBS) is dependent on mitogen-activated protein (MAP) kinase signaling and is associated with upregulation of extracellular calcium-sensing receptor (CaSR) expression. When CBS cells were grown in Ca2+-free medium and then switched to medium supplemented with 1.4 mM Ca2+, proliferation was reduced and morphologic features of differentiation were expressed. E-cadherin, which was minimally expressed in nonsupplemented medium, was rapidly induced in response to Ca2+ stimulation. Sustained activation of the extracellular signal-regulated kinase (ERK) occurred in Ca2+-supplemented medium. When an inhibitor of ERK activation (10 microM U0126) was included in the Ca2+-supplemented culture medium, ERK-activation did not occur. Concomitantly, E-cadherin was not induced, cell proliferation remained high and differentiation was not observed. The same level of Ca2+ supplementation that induced MAP kinase activation also stimulated CaSR upregulation in CBS cells. A clonal isolate of the CBS line that did not upregulate CaSR expression in response to extracellular Ca2+ was isolated from the parent cells. This isolate failed to produce E-cadherin or undergo growth inhibition/induction of differentiation when exposed to Ca2+ in the culture medium. However, ERK-activation occurred as efficiently in this isolate as in parent CBS cells or in a cloned isolate that underwent growth reduction and differentiation in response to Ca2+ stimulation. Together, these data indicate that CaSR upregulation and MAP kinase signalling are both intermediates in the control of colon carcinoma cell growth and differentiation. They appear to function, at least in part, independently of one another.

 

 

 

CHALLENGING MANAGEMENT OF BREAST CANCER ‘is it inflammatory or not’

Sabeeh Siddiqui M.D( ACP Associate),.Padmaja Naidu M.D(ACP Associate)

Leopoldo Eisenberg M.D (FACP)

SINAI GRACE HOSPITAL DETROIT MEDICAL CENTER

WAYNE STATE UNIVERSITY SCHOOL Of MEDICINE

 

CASE REPORT:A 72-year old African American Female presented with c/o pain on L-breast which was diagnosed as Invasive Ductal Carcinoma by needle biopsy. Past medical history included perforated diverticulosis requiring colostomy, and antibiotic therapy for MRSA bacteremia. In preparation for neoadjuvant chemotherapy, a  chemoport was placed and 24 hours later, infection developed at site.Treatment included levofloxacin for fourteen days.

Patient was seen by oncologist 3 weeks after initial evaluation, redness, swelling and pain of the involved breast was noted along with fever. Extensive erythema of chest wall and breast was noted . Patient looked septic and was thus admitted. Cultures were obtained and antibiotic stated.

U/S and CT of breast revealed doubling of massin size,no abscess and central necrosis.

Inspite of  antibiotics patient remained febrile with cultures being negative and therefore chemotherapy was administered as Infectious Disease questioned tumor fever.

CT of Breast showed probable central necrosis but no evidence of Abscess. Surgery was consulted for biopsy or mastectomy about nine days into chemotherapy and felt breast was improving as consulting surgeon had seen patient just prior to admission. By day nine patient became afebrile ,local symptoms improved substantially and patient was discharged home.

DISCUSSION: Inflammatory Breast Cancer is usually diagnosed when patient presents with peau-d-orange, redness and pain. In this case, none of these were present initially. We question whether delay in treatment because of patient being staged could generate picture of ‘inflammatory cancer’.

CONCLUSION: Inflammatory breast cancer has not been noted to cause fever, even when locally advanced therefore, are we dealing with a late manifestation of inflammatory cancer or a superimposed infection ? Our conclusion is that in cases like this all suspected entities should be treated

 

 

 

A Case Report of Asymptomatic Hashimoto,s Thyroiditis

Author: Dr.Mohammad Kang,M.D,pgy1,WSU,Detroit,MI.

Dr.Bhawankumar,Dalal,M.D,PGY 111,WSU,Detroit,MI.

dR.Feldman,Marc,M.D,Associate Program Director,WSU,Sinai Grace,Detroit,MI.

 

Introduction: Hashimoto’s Thyroiditis is most common cause of hypothyroidism in iodine sufficient areas of the world. Characterized clinically by goiter and thyroid failure, this disease is caused by immune mediated destruction of thyroid gland. Hashimoto’s thyroiditis is more prevalent in women with a Male:Female ratio of approximately 7:1. We present an unusual case of an asymptomatic male healthcare worker diagnosed as Hashimoto’s thyroiditis.

Case Report: 34 years old thin, active male health care worker decided to order lipid profile and TSH level. A TSH level  of  120 microU/ ml  was called as a panic value.

History was not significant for any depression, weight gain, skin changes, slowed mentation , decreased libido, constipation or fertility problems. On repeat questioning he admitted to have tiredness after long working hours (12-16 hours). Paradoxically, he was  active and had good appetite. Physical examination reveals thin male, a normal thyroid exam and pulse rate of  75-85. The rest of physical examination was normal.

Further Lab evaluations revealed total T4 and free T4 were low(2.5mcg/dl and 0.6ng/dl respectively). Thyroglobulin was increased .T3 was normal.

Antithyroglobulin and anti TPO (Antimicrosomal antibodies) were increased . Lipid profile was normal. A thyroid Scan showed lower normal limit of Iodine uptake.

 Patient was diagnosed as Hashimoto’s thyroiditis and was started on Synthroid 100 mcg daily . Repeat TSH after 6 weeks of treatment was 3.5microU/ml and free T4 was  (2.9ng/dl).Thyroxin dose was decreased to 75mcg daily. Later, patient’s Family was screened for thyroid disease and all results were normal.

Discussion and Conclusion: Hashimoto’s  Thyroiditis is  well recognized as a disease with female predominance and is rarely asymptomatic. Our literature search did not find any case which was asymptomatic . Our case is unique in that our patient is a active male who presented  as  symptomfree and his TSH was level was markedly elevated. We can conclude from this case that Hashimoto’s disease can present  asymptomatically even  when  the TSH is extremely high.