2004 ACP National Meeting Abstracts Submissions
MATURATION OF THE
MICROVASCULATURE IN HEALING MYOCARDIAL INFARCTS: A POTENTIAL ROLE FOR PDGF.
(1)KAMAL NASSER, MD, (2)GUOFENG REN, PhD AND (2)NIKOLAOS FRANGOGIANNIS, MD, 1-Department of Internal Medicine, Sinai-Grace Hospital, Detroit Medical Center/Wayne State University, Detroit MI, and 2-Section of Cardiovascular Sciences, DeBakey Heart Center, Baylor College of Medicine, Houston TX.
BACKGROUND: The microvasculature in healing wounds undergoes dynamic changes leading to formation of mature pericyte-coated vessels. Platelet Derived Growth Factor (PDGF) is crucial for the formation of a pericyte coat in the developing embryonic vasculature. We hypothesize an important role for PDGF in vascular maturation of infarct neovessels, critically regulating healing. AIMS: To investigate the dynamic changes in the infarct microvasculature and the phenotypic characteristics of smooth muscle cells and fibroblasts in canine and murine models of experimental myocardial infarction, and to study the role of PDGF in maturation of the infarct neovasculature. METHODOLOGY: We used established canine and murine models of experimental myocardial infarction. Hearts were processed and used for histological studies. Isolated canine jugular vein endothelial cells were used for in vitro experiments. RESULTS: The proliferative stage of infarct healing is characterized by myofibroblast accumulation and a high number of capillaries critical for sustaining metabolism. In both canine and murine models, infarct maturation is associated with a decreasing capillary density and an increasing number of pericyte coated vessels (p<0.01, 7d reperfusion vs 28 days reperfusion). The muscular coat of infarct vessels stains for a-Smooth Muscle Actin (a-SMAc) and calponin. Only a subset of the vessels exhibits expression of desmin and smoothelin, markers of mature contractile smooth muscle cells. PDGF is highly expressed in infarct neovessels. In addition, PDGF Receptor b is markedly upregulated in pericyte-like cells infiltrating the infarcted myocardium. PDGF receptor a synthesis is found in a subset of myofibroblasts and endothelial cells. Purified PDGF and recombinant PDGF-AA and –BB significantly induce mRNA expression of the matrix cross-linking enzyme tissue transglutaminase (tTG) in canine endothelial cells. CONCLUSION: PDGF may play an important role in maturation of the infarct vasculature.
RENAL FAILURE AND
MONOCLONAL GAMMAPATHY OF UNKNOWN SIGNIFICANCE.
O White, MD (Associate), S Marur, MD (Member), R Hillyer, MD,
INTRODUCTION: MGUS is present in 1% of all adults and 3% of adults over age 70. Myeloma is distinguished from MGUS by findings of replacement of the bone marrow, bone destruction, and progression of renal failure and hypercalcemia. MGUS does not present with renal failure.
CASE REPORT: We present a case of a 73 year old African American man who presented to our emergency department with chest pain and shortness of breath. He was found to have pneumonia, but during work-up was also ruled out for myocardial infarction and pulmonary embolism (PE). He subsequently developed acute renal failure secondary to CT contrast when ruled out for PE, despite prophylactic measures, and his renal failure was refractory to subsequent management as well. Creatinine rose rapidly from baseline of 1.5 to 10.3 in 4 days, and he required hemodialysis for his acute renal failure (ARF) and intubation for respiratory failure. Once extubated, the patient underwent left renal biopsy which yielded results consistent with a myeloma kidney. Shortly thereafter, serum protein electrophoresis revealed a monoclonal gamma globulin band at a concentration of 1.13 g/dL. However, bone marrow biopsy was not consistent with a diagnosis of multiple myeloma.
DISCUSSION: The patient met criteria for a diagnosis of monoclonal gammopathy of undetermined significance (MGUS). MGUS is generally thought of as a benign condition with a benign course, but it is very noteworthy that the patient developed an unusual, refractory, irreversible, and rapidly progressive onset of ARF superimposed on CRF when given contrast for CT scan. MGUS supposedly has a benign clinical course, but it has not been precisely defined what MGUS truly is. It is considered by some to be a premyeloma state, in which the complications of myeloma are encountered after transformation into true myeloma has occurred. However, this patient was already having renal complications when he didn’t meet criteria for myeloma, and was even histologically diagnosed as having a myeloma kidney.
CONCLUSION: This case seems to lend further credibility to the hypothesis that MGUS is a premyeloma state, in which some of the complications of myeloma may be encountered including malignant transformation.
ATYPICAL CLINICAL
COURSE OF PULMONARY BLASTOMYCOSIS.
Marius Vidinas, MD (Associate), Violeta Botea, MD (Associate), Hassan Makki, MD (Member), Sinai-Grace Hospital / Detroit Medical Center – Detroit, Michigan.
Introduction
Pulmonary blastomycosis may mimic pyogenic or fungal infections, tuberculosis or malignancy. Cutaneous disease is the most common hematogenous dissemination.
Case Report
A 27 year old immigrant Lebanese female, smoker, was referred to the Pulmonary Clinic with complains of fever, night sweats, weight loss, cough and shortness of breath for one month. Initial chest X-ray and CT of the chest revealed a large left apical alveolar infiltrate. PPD was negative. Sputum gram stain and culture for AFB (acid fast bacilli) were negative. Fiberoptic bronchoscopy with transbronchial biopsy and BAL (bronchoalveolar lavage) was non-diagnostic. Fluoroscopic guided transthoracic fine needle aspiration revealed necrotizing granulomatous inflammation. No malignant cells or organisms (aerobic, anaerobic, AFB or fungal) were noted on the BAL specimen or the biopsy specimens. The patient completed a six months course of antituberculous treatment. The repeated X-ray during treatment showed complete resolution of the left apical infiltrate within two months. The patient developed a skin lesion on the left cheek during treatment. The skin biopsy revealed noncaseating granulomas. Fungal cultures from the skin lesion grew Blastomyces dermatitidis. Patient was started on Itraconazole.
Conclusion
Spontaneous resolution of symptomatic acute pneumonia caused by Blastomyces dermatitidis has been recognized in the literature. Our case is one of the few reports of spontaneously resolved Blastomyces pneumonia followed by secondary skin dissemination. Whether or not the lung lesion resolves spontaneously, the infection commonly spreads hematogenously to other body sites, and should be treated with Itraconazole, Fluconazole or Amphotericin B.
MILLER-FISHER
SYNDROME: AN ACUTE NEUROPATHY.
Tabarak A. Qureshi, MD (Associate),
Objectives: The classical triad of ophthalmoplegia, ataxia and areflexia presenting as Miller Fisher Syndrome.
Case History: A 28-year-old Caucasian female with a preceding diarrheal illness presented to the emergency center with a chief complaint of diplopia. Initial physical examination revealed bilateral abducens nerve palsies. The patient progressed to complete ophthalmoplegia. Muscle strength testing revealed global weakness graded at 3/5. Muscle stretch reflexes were absent. The patient demonstrated appendicular and gait ataxia. Brain imaging with MRI was normal. Initial spinal fluid analysis revealed normal protein and glucose without significant pleocytosis. Further analysis of CSF demyelinating markers including myelin basic protein, IgG synthesis rate, and oligoclonal bands proved unremarkable. Tensilon test and Acetylcholine receptor antibodies were negative. Campylobacter jejuni titer was normal. Antibody to GQ1b ganglioside was positive. The patient was diagnosed with the Miller Fisher variant of Guillain-Barre syndrome and was started on IVIG. Lack of improvement prompted the transfer to a monitored ICU bed and the patient underwent five plasmapheresis exchange transfusions. Her neurological status stabilized and upon discharge from the hospital, the patient had minimal residual eye weakness.
Discussion: In patients with the triad of gait ataxia, ophthalmoplegia and areflexia, Miller Fisher syndrome should be suspected. The presence of antibodies to the GQ1b ganglioside favors this diagnosis.
PRIMARY MALIGNANT
LYMPHOMA IN EXTRAAXIAL FASHION
Prathyusha Savarapu, M.D., Associate, Fadi Saab, M.D., Associate,
Eisenberg Leopoldo, M.D., F.A.C.P.
Introduction
Extraaxial primary malignant lymphoma is an extremely rare disorder. To our knowledge, this the first case report of lymphoma that is extradural in location.
Case Report
A sixty-one year old male presented with dizziness and increasing headaches. Part of the work up included MRI scan of brain which demonstrated a fairly large homogeneous enhancing extraaxial mass seen in the posterior interhemispheric fissure with extension into the bilateral parietal regions.
Symptoms persisted and the lesion clinically progressed which was confirmed by follow up MRI scan. Therefore, resection was performed and a gross tumor was removed noted to be in the extradural space. The histological and immuno-histo-chemical analysis revealed this to be a high grade non-hodgkin’s lymphoma of B-cell origin with positive CD20.
Completion of the work up for lymphoma included a PET scan of the whole body which showed two small foci in right and left axilla with abnormal FDG (Fluorodeoxyglucose) uptake. SUV (Standard Uptake Value) was between 2.3 to 2.6 suspicious for malignancy. Therapy was instituted with CHOP Rituxan followed by radiation to the primary site.
Discussion
Primary malignant lymphoma is usually a B-cell lymphoma that arises within and is limited to CNS. Primary CNS lymphoma is mostly seen in immunodeficient patients particularly AIDS. Despite its three fold increased incidence in immunocompetent host, it remains a rare tumor. This particular case is unique as it is the first reported case of extraaxial lymphoma located extradurally.
CASE REPORT OF ADENOCARCINOMA OF THE RETE TESTIS
Tannu Sahay, M.D., Associate,
Adenocarcinoma of the rete testis is extremely rare with only a few sporadic cases being reported since it was first described in 1945. It is a highly malignant tumor mainly presenting as a scrotal mass with diffuse enlargement of the testes.
Tumors are diagnosed based on their distinctive histology. Recent reports have implicated HBME1 and thrombomodulin as positive markers.
We report a 53 year old Asian male diagnosed with adenocarcinoma of the rete testis. The patient had wide spread metastasis to the liver, lung, retroperitoneal and mediastinal lymph nodes. A radical orchiectomy was performed with retroperitoneal lymph node dissection. The patient received multiple chemotherapeutic agents with no evidence of disease regression. These included cisplatin, carboplatin, gemcitabine, capecitabine, etoposide, and paclitaxel. He is currently on phase 1 trial with DX-8951F, a camptothecan analog.
Only limited data is currently available on the appropriate treatment for this tumor type.
IDIOPATHIC
HYPEREOSINOPHILIC SYNDROME OF THE HEART.
F Omar MD (Associate), D Obeid MD (Associate), G Krishnamoorthy MD (Member).
Idiopathic Hypereosinophilic Syndrome (Loeffler’s syndrome) is a rare disease characterized by eosinophilia associated with signs and symptoms of end organ dysfunction. Most commonly it affects the heart, skin, nervous system, lung and spleen.
Here we present a case of Loeffler’s syndrome with a cardiac presentation.
The patient is a 30 year old male presented with atypical chest pain. He had normal physical exam but stress test showed a partially reversible apical defect. He had high eosinophil count unexplained by any other etiologies. Cardiac catheterization showed normal coronaries; 2-D echo showed increased endomyocardial echodensity at the apex which suggested Loffler’s syndrome. Biopsy of the Myocardium revealed eosinophilic infiltrates thus confirming the diagnosis of Loeffler’s syndrome of the heart. The patient was started on steroids and experienced significant clinical improvement.
It is very important to diagnose Loeffler’s syndrome as early as possible because starting treatment early will decrease mortality and morbidity especially in younger male patients.
IMPACT OF
INTERMITTENT HYPOXIA ON CENTRAL AND PERIPHERAL CHEMOREFLEX COMPONENTS. J.H.
Mateika MD, C. Mendello MD, D.A. Obeid MD (Associate), M.S. Badr MD.
Introduction: We examined whether facilitation of ventilation after intermittent hypoxia (IH) was due to adaptations in one or more of the central and/or peripheral chemoreflex components {i.e. basal ventilation (ventilation below the chemoreflex threshold), central and peripheral chemoreflex threshold and sensitivity}.
Methods: Six healthy subjects completed 4 modified hypercapnic rebreathing trials under iso-oxic conditions before and 20 minutes after exposure to IH. Two rebreathing trials were completed while the partial pressure of oxygen (PETO2) was maintained at 50 mmHg (H50 - central + peripheral chemoreflex response combined) and 2 were completed with the PETO2 maintained at 140 mmHg (H140 - central chemoreflex alone). The IH protocol consisted of 8-4 minute trials of isocapnic hypoxia (8 % oxygen) separated by 5 minute recovery periods.
Results: Ventilation at a PETCO2 of 45 mmHg was significantly greater during the H50 rebreathing trials after IH. This occurred because basal ventilation was significantly greater (p<0.05) for the H50 (11.51 ± 1.19 vs. 16.66 ± 2.32) but not the H140 (11.81 ± 1.7 vs. 13.49 ± 2.53) trials after IH. Moreover, the central + peripheral chemoreflex sensitivity (H50) (8.51 ± 0.79 vs. 11.60 ± 1.80) was enhanced after IH but not central chemoreflex sensitivity (H140) (6.31 ± 0.75 vs. 7.14 ± 1.14) alone. No change in central and peripheral chemoreflex thresholds occurred after IH.
Conclusions: Ventilation is facilitated both below and above the peripheral chemoreflex threshold after exposure to IH. This enhancement might be due to an increase in peripheral chemoreflex sensitivity.
FOCAL SEGMENTAL
GLOMERULOSCLEROSIS A CASE REPORT OF (P) FOCAL SEGMENTAL GLOMERULOSCLEROSIS
COMPLICATING IN A PATIENT WITH LUPUS NEPHRITIS.
B.N. Nandish, M.D. (Associate), S Marur, M.D. (Member), and I Omar, M.D.
BACKGROUND: Lupus Nephritis is a well-known complication of SLE. We are reporting a case of focal segmental glomerulosclerosis (FSGS) in lupus nephritis. FSGS is a difficult category of glomerular disease to diagnose pathologically and to treat. Many patients with FSGS progress into end stage renal disease. FSGS accounts for about one third of cases of nephrotic syndrome in adults. Occurrence of FSGS in the setting of SLE with lupus nephritis is not common.
CASE REPORT: This is a 20-year-old African American woman, with a diagnosis of SLE. She has a history of nephrotic syndrome, presumed to be secondary to lupus nephritis. The patient also has arthritis, erythematous rash with photosensitivity, and acute psychosis. Patient denied any IV drug abuse. Her medications included prednisone and plaquenil. The patient presented with a fever, headache, abdominal pain, and a skin rash. Her physical exam revealed a macular rash on her face, patchy alopecia, cervical lymphadenopathy, and right upper quadrant abdominal tenderness. On investigation, a 24-hour urine for protein revealed nephrotic range proteinuria. Her other lab results included BUN 11, Serum Creatinine 1. Anticardiolipin screen was positive (IgG and IgM). ANA, Anti-dsDNA and Anti-ssDNA were also positive. Complements CH50, C3, and C4 were elevated. Kidney biopsy was suggestive of FSGS immune complex mediated, and mesangial proliferative glomerulonephritis with rare subepithelial and subendothelial deposits consistent with lupus nephritis, WHO class IIb.
DISCUSSION: FSGS is difficult to treat and progresses to ESRD rapidly. Even cyclophospamide and cyclosporine have no role in management of steroid resistant FSGS. Renal transplantation is also complicated by recurrence of FSGS in the allograft. In most cases of SLE, renal dysfunction is mostly secondary to lupus nephritis. If clinical and pathological evidence appear to be discordant, an alternative or contributing renal process should be entertained.
CLINICAL PRESENTATION OF MYOSITIS OSSIFICANS. Kalyani Mehta, MD, Associate, Violeta Botea, MD, Associate, Gary W. Edelson, MD, Fellow, Sinai-Grace Hospital, Wayne State University-Detroit, Michigan.
Introduction: Myositis Ossificans is a disorder defined by ectopic bone formation in soft tissues mostly following trauma, neurologic injury, surgery, or burns.
Case report: A 55-year-old white male presented with left
shoulder pain. At the age of 39, he had developed multiple painful
calcifications bilaterally in the hips and knees as well as in an abdominal
surgical scar during a 140-day hospitalization following an appendectomy
complicated by sepsis, ARDS and cardiopulmonary arrest. He was diagnosed with myositis ossificans in hips, knees and
abdominal surgical scar and most of these lesions have been surgically
removed. He denies any other trauma or
extra calcium intake. Physical
examination revealed a well-nourished male with no thyromegaly or thyroid
nodularity. He had a 3 cm tender hard
mass in the left supraclavicular area. Laboratory studies revealed total serum
calcium of 9.0 mg/dl (8.5-10.5), and alkaline phosphatase was 30.5 (
Discussion: Myositis Ossificans has been reported mainly in children, following trauma or burns and was associated with pain only early in the course. Our patient developed the condition in his adulthood, without a clear trigger and developed painful lesions throughout the course. The molecular basis as well as specific treatment of this disorder remains to be explored.
K Majekodunmi, MD (Associate), R M Ghurani, MD (Associate),
W
West Nile Virus (WNV) is a mosquito-borne Flavivirus that
primarily affects birds with humans and horses being incidental hosts. The
virus is indigenous to
We present our case series of all
Our results reflect a total of 14 confirmed cases of West
Nile Virus encephalitis. The patients’ mean age was 59years. 57% of the cases
were females with an average length of stay of 8.8 days in the hospital. All
were
WNV is expanding its geographical range into the western
parts of the
ARRHYTHMOGENIC RIGHT
VENTRICULAR CARDIOMYOPATHY/ DYSPLASIA: PRESENTING AS SHOCK, ACUTE RENAL FAILURE
AND TRANSIENT MESENTERIC ISCHEMIA.
Manesh Kottapuram, M.D. (Associate), Barry Lesser, M.D., F.C.C.P. (Member), Department of Medicine, Sinai-Grace Hospital, Wayne State University, Detroit, Michigan.
INTRODUCTION: Arrhythmogenic right ventricular (RV) Cardiomyopathy/Dysplasia (ARVC/D) is a rare myocardial disease affecting primarily the RV and characterized histologically by the gradual replacement of cardiomyocytes by fibro-fatty tissue. It can diffusely involve the whole myocardium and culminate in biventricular heart failure, arrhythmias and sudden death in young patients.
CASE REPORT: We
present a forty-five year old African-American man brought to the emergency
room (ER) with complaints of fever, abdominal pain, vomiting and bloody
diarrhea of four days duration. At
admission, he was hypothermic (93oF), tachycardic (130/minute), tachypneic
(40/minute) and hypotensive (50/palpable).
He appeared drowsy, dehydrated and had diffusely tender abdomen with
decreased bowel sounds. His stool was
positive for occult blood. Initial labs
were significant for Na+ 127, Cl- 82, HCO3- 12 (mmol/L); BUN 70, Creatinine 8.7
(mg/dL); WBC 10.6 (bands 3.8) K/mm3; ALT 162, AST 257 (U/L), and lactic acid
4.9 mmol/L. Electrocardiogram was
significant for sinus tachycardia and abdominal x-ray showed small bowel wall
edema with ileus. He remained
hypotensive despite intravenous fluids, vasopressors and broad spectrum
antibiotics.
CONCLUSION: ARVC/D is typically seen in young men as an autosomal dominant trait with multiple factors facilitating gene expression. Physicians should consider this condition in young subjects with cardiac arrhythmias or unexplained cardiomyopathy. Treatment options are discussed.
NEISSERIA
MENINGITIDES PNEUMONIA DIAGNOSED BY CT-GUIDED THORACOCENTESIS OF ASSOCIATED
EMPYEMA
Manish Kesliker, MD MS (Associate), Kashif Qureshi, MD
(Associate), Atul Singh, MD (Member), Shazia Essani, MD (Member), Latha
Ganesan, MD (Member).
Background: Neisseria meningitides infection in humans is usually associated with meningitis and septicemia with skin manifestations. While infections of the lower respiratory tract with N meningitidis have been documented in the past, they remain exceedingly rare, but may be due to the fact that isolation is difficult. Despite presence of bacteremia, many patients do not develop meningitis and its associated complications.
Case Report: A 62 year old African American female developed fever and chills, shortness of breath and tachypnea. CT-thorax revealed right middle and lower lobe infiltrate with loculated effusions of right hemithorax. Patient was treated for presumed community acquired pneumonia with IV Ceftriaxone. Loculated pleural fluid was aspirated by CT-guided thoracocentesis confirmed empyema which grew gram-negative diplococci, later identified as Neisseria meningitidis. Subsequent blood cultures collected on admission later revealed the same. Patient was treated with Penicillin G 4 million units IV every four hours and prophylactic antibiotics were provided to immediate family contacts. Patient continued to experience respiratory distress and was transferred to MICU for impending respiratory failure. Pigtail catheters were placed for drainage of empyema and patient responded well over three weeks. Patient was later discharged home with few lasting complications.
Discussion: Pneumonia caused by Nessieria meningitides is rare, with 58 cases described from 1974 to 2000. The difficulty of diagnosis and recognition of rare manifestations of meningococcal infection because of risk of spread to contacts including health care professionals and other patients is discussed.
HPV-16 AND
SCHISTOSOMIASIS-CAUSED BLADDER CANCER.
Ahmed Kaseb, MD 1, Associate, David Kurnit, MD,PhD 2 and Kun
Yong, MD 2. Sinai-
INTRODUCTION: Schistosomiasis afflicts over 200 million people in the world. Using quantitative PCR (QPCR) system we were able to detect HPV-16 in tumor, serum and some urine specimens from patients with this disorder. In distinction, only 1/29 french bladder cancers not caused by schistosomiasis were associated with HPV-16 infection.
MATERIALS and METHODS:
We collaborated with the National Cancer Institute in
RESULTS: With this
more sensitive anlysis, we found that more than two thirds of the tumor
specimens (17/22) were positive for HPV-16 as identified by sequencing later
on. Especially usefully, we found that
serum was often more positive than tumor (20/22). Urine sediments were positive in only 9
cases. We found five cases where the
tumor was negative or very weakly positive and the serum was positive. In three of these cases, the urine sediment
was positive meaning that the bladder tumor is actually present as micro
satellites or that a more sensitive technique is needed to detect the
virus. Compared with our previous
analysis of non-schistosomiasis bladder cancers from
CONCLUSION: HPV-16 infection is one of the predisopsing factors for schistosmiasis-caused bladder cancer. This is the first time to apply the QPCR technique to detect the virus in specimens from patients with this disorder with the serum ones identified as the most sensitive among them. This now establishes the potential of screening serum for HPV-16 as a rapid and sensitive means of searching for a predisposing factor for bladder cancer in these patients.
EXPRESSION OF BETA-2 SUBUNIT
MUTANTS ALTERS LOCALIZATION OF L-TYPE CALCIUM CHANNELS IN ADULT RAT
CARDIOMYOCYTES
Sinoj K John MD (Associate) Sabine Telemaque-Potts MD, Terrie Grain MD, Jeffrey T Potts MD, James D Marsh MD. Sinai-Grace Hospital, Wayne-State University, Detroit, Michigan, Internal Medicine - Cardiology, Wayne-State University, Detroit, Michigan.
Introduction: The a1C subunit of the L-type calcium channel is the pore-forming subunit of the channel, allowing calcium entry into cardiomyocytes and other cells. The intracellular b2a subunit acts as a chaperone and interacts with the intracellular loop of the a1C subunit. We tested the hypothesis that overexpession of mutated b subunits could alter membrane localization and ultimately channel function.
Methods: Isolated rat adult cardiomyocytes were infected with adenovirus constructs. The GFP-fusion constructs encoded either the full-length b2a subunit (GFP-Full) or putative dominant-negative mutants of the beta interaction domain (BID) portion of the subunit (GFP-BID: BID only; GFP-N-BID: N-terminal + BID), under CMV promoter control. After 24 hr, cells were fixed and visualized by epifluorescence microscopy using standard methods.
Results: Analysis of 5 independent cell isolations showed that GFP or GFP-BID are localized to the cytosol of the myocyte. In GFP-N-BID-infected myocytes, a distinct punctate pattern of protein expression was observed in all infected cells, without cell membrane localization. In cells infected with the full-length b2a subunit adenovirus (GFP-Full), the fluorescence was exclusively visible at the cell membrane.
Conclusion: These results suggest that beta subunit decoys can alter localization of the L-type calcium channel to the sarcolemma, which could result in reduced contractile performance.
ACUTE PANCREATITIS
SECONDARY TO ACUTE AORTIC DISSECTION
A Ijaz MD (Associate),
Sinai-Grace Hospital/Wayne State University-Detroit,
INTRODUCTION: Acute pancreatitis is an intense inflammation of the pancreas with variable involvement of the regional tissues or remote organ systems. Etiology in around 85% of the cases is gall stones or alcoholism. A rare but documented cause of acute pancreatitis is hypoperfusion of the pancreas.
CASE REPORT: We describe a 50 year old male with a history of hypertension, end stage renal disease on hemodialysis and no alcohol consumption, who presented with abdominal pain and vomiting. At the time of his presentation, his blood pressure was 180/118, with labs revealing an amylase of 1109 and lipase of 5599. A diagnosis of acute pancreatitis and hypertensive urgency was made and patient was admitted to general medical floor. His acute pancreatitis started resolving and an abdominal ultrasound was subsequently done which was suggestive of an acute aortic dissection showing an intimal flap with flow in both lumens and no gall stones. Patient was transferred to MICU and a CT scan of the thorax and abdomen with IV contrast was performed revealing an acute aortic dissection from the arch of the aorta to the abdominal aorta just inferior to superior mesenteric artery origin. The patient was managed medically.
DISCUSSION: Regional and systemic hypoperfusion is an important factor in acute pancreatitis which in this case was brought on by the acute dissecting aneurysm of the aorta. The cause of pancreatitis in such a case is a result of pancreatic ischemia which leads to the release of oxygen free radicals, activation of polymorphonuclear lymphocytes, failure of micro vascular perfusion, cellular acidosis and disturbance of intracellular homeostasis causing ischemia induced acute pancreatitis. The management of ischemic pancreatitis is similar to that of acute pancreatitis of any etiology.
IN VITRO STUDY OF THE
EFFECT OF GOSSYPOL IN COMBINATION WITH DOCETAXEL ON TWO DIFFERENT HUMAN
ADRENOCORTICAL CARCINOMA CELL LINES.
Haleh Haerian, MD, Associate, Sinai-Grace Hospital, Detroit Medical Center/Wayne State University-Detroit; Recardo Benitez, MD; David E. Schteingart, MD,The University of Michigan-Ann Arbor.
INTRODUCTION: Adrenocortical carcinomas, ACC, are rare but highly malignant tumors with poor prognosis. Several treatment strategies have resulted in temporarily and partial tumor regression but very few cases have attained long survival. The absence of an effective therapeutic regimen for ACC, suffices the need for more studies with new drugs. Gossypol is a lipid soluble polyphenolic compound isolated from cottonseed oil, which has been extensively tested in clinical trials as a male contraceptive agent and found to be well tolerated. One proposed mechanism of action for gossypol is stimulation of apoptosis in human tumor cells by inhibition of the anti-apoptotic activity of certain proteins (e.g., Bcl-XL). Docetaxel is an effective chemotherapeutic agent used in breast and non-small cell lung cancers. It inhibits mitosis and induces apoptosis in cancer cells. In view of a potential clinical use, we assessed the antiproliferative and possible synergistic effect of these drugs in ACC cell lines. METHODS: We used two different cell lines: RL-251 with high expression of Bcl-XL, and H295R without Bcl-XL expression. We tested eight different concentrations of each drugs separately and their combination. We used Sulforhodamine B assay (SRB) to measure the inhibition of cell proliferation. RESULTS: Gossypol induced a dose-dependent inhibition of cell proliferation in both H295R (IC50=0.71mM), and RL-251 (IC50=1.5mM) cell lines. Docetaxel also induced a dose-dependent inhibition of cell proliferation in both H295R (IC50=0.015mM), and RL-251 (IC50=0.0003mM) cell lines. Addition of 1mM of Gossypol to Docetaxel decreases the IC50 value for both cell lines to less than 0.0001mM. DISCUSSION: Gossypol has a potent, dose dependant inhibitory effect on both H295R and RL251 cell lines. The greater effect of Gossypol on H295R in comparison to RL-251 is against the proposed mechanism of action of Gossypol through Bcl-XL. The combination of Gossypol plus Docetaxel is more effective than Docetaxel alone.
PROPOFOL ASSOCIATED
RHABDOMYOLYSIS WITH CARDIAC MUSCLE INVOLVEMENT IN AN ADULT PATIENT.
Haleh. Haerian, MD, (Associate) and Rajika L. Munasinghe, MD (Fellow), Sinai-Grace Hospital, Wayne State University, Detroit, Michigan.
Introduction: Propofol is a centrally acting agent used increasingly for sedation during mechanical ventilation. Rhabdomyolysis has been described as a dose dependant idiosyncratic reaction to propofol infusions in pediatric patients. Two adult cases (one fatal) of rhabdomyolysis have been reported when propofol was administered with steroids during mechanical ventilation for severe asthma and an interaction with steroids has been incriminated. Involvement of cardiac muscle in rhabdomyolysis is rare and has been usually reported in rhabdomyolysis due to drugs and toxins.
Case Report: A 29-year-old male with history of seizures, was intubated in the emergency room for airway protection following a breakthrough seizure and placed on mechanical ventilation. He received propofol infusion for sedation. After 38 hours, he developed acute renal failure with elevated CPK levels of 15,000 U/L. Approximately six hours later, he developed pulmonary edema from heart failure with an ejection fraction of 15% and elevated serum troponin-I of 25 µg/L. His condition gradually improved with management in the intensive care unit and he was weaned off the ventilator within a week. Cardiac catheterization performed after recovery from renal failure revealed no evidence of coronary artery disease and recovery of cardiac function with an ejection fraction of 50%.
Discussion: We report a unique case of rhabdomyolysis with reversible cardiac muscle involvement in an adult patient receiving propofol, without the concomitant use of steroids. Although seizures could have caused his rhabdomyolysis, the involvement of cardiac muscle supports a toxic etiology. It is important that this serious adverse reaction of propofol be recognized as discontinuation of the drug can lead to rapid recovery from cardiac and renal dysfunction.
FIRST CASE REPORT OF
EOSINOPHILIC PERITONITIS IN A PATIENT WITH INTRAPERITONEAL CATHETER PRIOR TO
THE INITIATION OF PERITONEAL DIALYSIS.
Mehrdad Ghaffari, MD (Associate); Haleh Haerian, MD (Associate); Latha Ganesan, MD (Member), Sinai-Grace Hospital / Wayne State Universiy – Detroit, Michigan.
Background: Eosinophilic Peritonitis, EP, is a rare but benign complication of continuous ambulatory peritoneal dialysis, CAPD, that tends to resolve spontaneously. EP is defined by presence of more than100 eosinophil per milliliter of peritoneal fluid in patients with clinical symptoms of peritonitis.
Case Report: A 55-year-old African American woman developed end-stage renal disease secondary to diabetes mellitus in 1995. She had been on hemodialysis since then. In Aug 2002, a Tenckhoff peritoneal catheter was placed. In Sept 2002, while she was still on hemodialysis, she presented to our emergency room complaining of severe abdominal pain, nausea, and vomiting. On physical examination, she was found to have moderate abdominal tenderness without rebound or rigidity. Her catheter site appeared clean without any signs of infection. Peritoneal fluid aspirated from her catheter was cloudy and had 3650/CUMM nucleated cell with 76% eosinophil and with a normal serum eosinophil count. Fluid gram stain and cultures including fungal and mycobacterial were negative. Based on the above-mentioned results, a diagnosis of EP was made and she was treated with oral prednisone. She responded well within a week. Her peritoneal dialysis was started subsequently without any complication thus far.
Discussion: EP is a rare complication of CAPD. Among the cases reported in the literature, all of them occurred after the initiation of peritoneal dialysis. Here we report the first case of EP developed prior to the initiation of CAPD. The development of EP prior to CAPD may indicate the pathogenesis linked to the catheter itself and not the CAPD.
COMPARISON OF ACUTE VENTRICULAR DEFIBRILLATION THRESHOLDS UTILIZING BINARY SEARCH VS. SEQUENTIAL STEP-UP PROTOCOL Siddhartha Annamraju, M.D. (Associate), Randy Lieberman, M.D., Marc Meissner, M.D., Venkata Sagi, M.D., Detroit Medical Center/ Wayne State University Paul DeGroot, Sr. Staff Scientist / Fellow, Tachyarrythmia Research Medtronic, Inc
INTRODUCTION: Determination of defibrillation threshold (DFT) at the time of ICD (Implantable Cardioverter-Defibrillator) implant enables programming the ICD to an energy less than full output. This decreases capacitor charge time and episode duration and conserves battery energy. However, accepted DFT protocols such as Binary Search (BS) or Step-Down methods require multiple VF (ventricular defibrillation) inductions. Fewer VF inductions and an appropriate determination of DFT are clinically desirable. We hypothesized that the DFT can be determined by a single VF induction utilizing a Step-Up (SU) protocol.
METHODS: After informed consent was obtained, paired DFTs were determined in patients undergoing initial ICD implant for approved indications using an active Can + transvenous RV lead system. In the SU protocol, energies of 3-6-10-12-15-18 joules were delivered sequentially after a single VF induction until VF was terminated. SU DFT was defined as the energy that terminated VF. DFT was also measured using BS protocol starting at 12 J with 6 J and then 3 J steps. VF not terminated by highest protocol energy was shocked externally and a DFT of 24 J assigned.
RESULTS: 25 patients were enrolled. Age – 54 ± 15 years, EF 25 ± 9 % and CAD 65%. SU DFT and BS DFT were identical in 15/25 patients. In 5 patients, SU DFT was 3 J < BS DFT. In 5 patients, SU DFT was 3 J > BS DFT. On a second repeated VF episode, SU DFT was identical to the first in 21/25 patients.
CONCLUSIONS: SU DFT highly correlates with BS DFT and is highly reproducible. SU protocol reduces the number of VF inductions needed to determine DFT. SU protocol reduces total time in VF compared to the BS protocol. Further clinical research is required to verify the suitability of determining DFT and programming ICDs based on a single VF induction via SU protocol.
CASE REPORT OF ATYPICAL PRESENTATION OF SEVERE LEGIONNAIRE’S DISEASE. A Abdussalam, MD (Associate); D Obeid, MD (Associate); Wasif Hafeez, MD (Member) – Department of Medicine, Sinai-Grace Hospital, Wayne State University – Detroit, Michigan.
INTRODUCTION: Legionella infection ranks among the three or four most common causes of community-acquired pneumonia. The diagnosis must be considered whenever the etiology of a pneumonia is in question. Rarely, Legionnaire’s disease is complicated by rhabdomyolysis and subsequent acute renal failure.
CASE REPORT: 54 year old African-american female with history of hypertension, tobacco/ethanol/cocaine use was admitted with 3 days history of mental status changes. She had no respiratory symptoms upon admission. Temperature 104, pulse 100/min., RR 30 /min., no focal neurological signs, CT head with and without contrast showed suspicious low density areas adjacent to the right sylvian fissure, basil ganglia, and right thalamic region, EEG did not show any focal activity. CXR showed right lung infiltrate, Na=128, Creatinine=0.9, WBC=15000, platelet=155000. CSF showed 6 nucleated cells, protein 62mg/100ml and glucose 91mg/100ml. Patient received ceftriaxone and azithromycin for CAP. Two days later creatinine went up to 3.5. BUN to 49, Calcium dropped to 5.8, Phosphorus=5.5, CPK = 128,858 and AST=1348. Urine myoglobin=200. Multiple cultures of blood urine and cerebrospinal fluid for bacteria, fungi and viruses were negative. Urinary assay for L.pneumophilia antigen serogroup 1 was positive.
Patient went into respiratory failure soon after admission and was ventilated for 4 days, she had full recovery of her renal, respiratory and neurological function, and was sent home 3 weeks after admission.
DISCUSSION: Legionnaire‘s disease is a multisystem disease; it ranks forth among the organisms causing CAP. It typically presents with cough, chills, fever, dyspnea, headache, myalgia/arthralgia, diarrhea, nausea/vomiting, neurological abnormalities and chest pain. Rarely, Legionnaire’s disease is complicated by rhabdomyolysis with subsequent acute renal failure. Pathogenesis of rhabdomyolysis and encephalitis in Legionnaire’s disease remains speculative. We recommend that a routine determination of creatine phosphokinase be preformed in the evaluation of all Legionnaire disease patients.
IMPLANTABLE-DEFIBRILLATOR
THERAPY IN COXSACKIE VIRUS-INDUCED CARDIOMYOPATHY
Lourin Chahin, MD, Associate, Apurva Motivala, MD, Associate, Atul Singh, MD, Member, Marc Meissner, MD FACC, Dept. of Medicine, Sinai-Grace Hospital, Wayne State University - Detroit, Michigan.
CASE REPORT
We describe a 20-year-old African-American male presenting with severe symptoms of congestive heart failure (CHF) following an upper respiratory infection. Physical examination revealed respiratory distress, bilateral rales, summation gallop and mitral regurgitation murmer. 2D-echocardiography revealed left ventricular ejection fraction of 20%, global hypokinesis, mitral and tricuspid regurgitation. He was discharged after good response to pharmacologic therapy.
Hypertension, alcohol, toxins, illicit drugs were excluded as etiologies. His presentation was felt to be due to post-viral myocarditis/cardiomyopathy. Thus, we requested Coxsackie blood titers. B5 titers returned as 1:320.
The patient returned 2 weeks later with CHF exacerbation. Telemetry tracings variously revealed unsustained atrial tachycardia, AV- block (Wenckebach, high-grade, 4-second ventricular asystole), and rapid unsustained ventricular tachycardia (VT).
A dual-chamber implantable defibrillator (ICD) system was placed, to allow safe optimization of medical therapy (eg. use of beta blockers in face of above-noted AV-block), and to protect against sudden death, to which such patients are very vulnerable. Subsequent ICD testing revealed elevated defibrillation thresholds (DFTs), and the system was modified: generator change and addition of defibrillation-pacing lead placed in a posterolateral coronary vein via the coronary sinus. This resulted in successful biventricular pacing and good DFTs.
CONCLUSION
This case highlights several interesting points: wide range of brady- and tachy-arrhythmias in a young man with Coxsackie cardiomyopathy; technical feasibility and potential therapeutic value of biventricular 3-lead ICD system capable of improving CHF symptoms and protecting against sudden death.
ACUTE INTERSTITIAL
NEPHRITIS SECONDARY TO OMEPRAZOLE.
Apurva Motivala
MD, Associate, Robert Michaels MD, Irfan Omar MD
Dept. of Internal Medicine,
We describe a 75 year old male who presented with acute on chronic renal insufficiency (creatinine increased from 1.5 to 3.7 over six months) . He had a history of hypertension, gout, chronic hypertensive nephropathy, benign prostatic hypertrophy and gastro-esophageal reflux disease (GERD). The patient was on amlodipine, colchicine and sucralfate and omeprazole (recently initiated). His blood pressure was well controlled and no abdominal was auscultated. The leukocyte count was 11,000/mm3 without eosinophilia Urinalysis showed 10-20 leukocytes per high powered field but no proteinuria or nitrates, The patient was subsequently worked up for his acute renal failure : renal ultrasound, C3, C4 , ANCA , ANA, serum protein and immunoelectrophoresis, sedimentation rate, rheumatoid factor, recent captopril renogram and 24 hour urine protein were normal. A renal biopsy confirmed acute interstitial nephritis (AIN) and background gouty nephropathy. Omeprazole was discontinued and oral steroids initiated followed by a resolution of the acute renal failure. A diagnosis of omeprazole induced AIN was made because of the temporal relation between its initiation and development of AIN confirmed by biopsy.
Acute interstitial nephritis accounts for 15 % of all lesions in renal biopsies performed for evaluation of acute renal failure. The most common drugs associated with AIN are penicillins, cephalosporins, sulfonamides and non steriodal anti-inflammatory agents. We hereby report the 22nd case of omeprazole induced AIN in the literature. Acute interstitial nephritis is an increasingly recognized side effect of the commonly used proton pump inhibitor, omeprazole, of which the internist needs to be aware.
THE ROLE OF FINE PARTICULATE AIR POLLUTION AND ELEVATION OF CIRCULATING ASYMMETRIC DIMETHYLARGININE (ADMA) LEVELS. Apurva Motivala, MD (Associate)(1) and Jack R. Harkema, DVM PhD(2) –(1)Sinai-Grace Hospital/Wayne State University, Detroit, (2)Michigan State University, East Lansing.
Background and Aim: The health effects of fine ambient particulate matter (PM2.5) and its potential impact on vascular endothelial function have not been thoroughly investigated. As endothelial dysfunction plays an important role in atherosclerosis and cardiovascular disease, we examined the effects of concentrated fine ambient particles (CAPs) on the plasma levels of asymmetric dimethylarginine (ADMA) in a pilot study. ADMA is an endogenous inhibitor of nitric oxide synthase that is associated with impaired vascular function and an increased risk of cardiovascular events.
Methods: A mobile air research laboratory (AirCARE 1),
equipped with whole body inhalation chambers and a Harvard type ambient fine
particle concentrator, was used in the study. AirCARE 1 was designed and
constructed collaboratively by
Results: Plasma concentrations of ADMA were significantly elevated in the rats exposed to CAPs versus those exposed to FA (1.49 ± 0.18 vs 1.29 ± 0.26 *M, p*0.05 by 1 tailed t-test).
Conclusion: Fine particulate air pollution exposure at high concentrations triggers an acute increase in circulating ADMA level. This could potentially cause impaired vascular endothelial function and enhance the risk for cardiovascular disease.
CRYPTOCOCCAL
MENINGITIS IN A NON-HIV PATIENT
Mohamed Iqbal P. Rouf, MD, Associate, Latha Ganesan, MD, Member,
Department of Internal Medicine, Sinai-Grace Hospital, Detroit Medical Center/Wayne State University, Detroit, Michigan.
INTRODUCTION: Cryptococcal meningitis is one of the most common fungal meningitis in both immunocompromised hosts and non-immunocompromised hosts.
CASE REPORT: Here, we present a case of a 47-year-old male with known end-stage renal failure, diabetes mellitus and hepatitis C, admitted with a history of change in mental status in the form of drowsiness, decreased appetite, weight loss and progressive deconditioning over a period of 4 months. On the day of admission, the patient was found to be unresponsive at home. On examination patient was comatose, pulse-67beats/min, blood pressure-100/68mmHg, respiratory rate-12breaths/min. Neurological exam revealed unequal, unreactive pupil and absent corneal and gag reflexes. Examination of other systems were normal. His laboratory data revealed normal CBC, sodium, potassium, chloride and bicarbonate. He had BUN of 59mg/dl, creatnine of 7.7mg/dl, phosphorus of 6.2mg/dl, blood glucose19mg/dl. His liver enzymes, bilirubin, lactic acid, serum acetone levels were all normal.. Urine analysis showed proteinuria, positive leukocyte esterase, RBCs and more than 100 WBCs. Chest x-ray was normal and computed tomography scan of the head showed hydrocephalus. Urine drug screen was negative. Based on the above, the patient was treated initially as hypoglycemic encephalopathy. Since there was no significant improvement in the patient’s mental status, and urine culture was growing cryptococcus, lumbar puncture was done. CSF study showed WBC- 145, neutrophil 88%, cryptococcal antigen was 1:128. His HIV serology was negative. He was initially treated with amphotericin B and 5 flucytosine but ultimately treated with supportive measures as per his family’s wish. He died two weeks later.
CONCLUSION: This case illustrates the importance of recognizing cryptococcal meningitis in non-HIV patients with chronic meningitis. In this patient, Diabetes mellitus and renal failure could be the risk factors for impaired immunity.
CHOLECYSTITIS AND PANCREATITIS ASSOCIATED WITH EDWARDSIELLA TARDA SEPSIS IN AN IMMUNOCOMPROMISED HOST.
Aamir A. Memon M.D, Associate, Nagaprasad Nagajoythi M.D, Associate, Shazia Essani M.D, Member, Department of Internal Medicine, Sinai-Grace Hospital/Wayne State University, Detroit, Michigan.
Edwardsiella tarda is a gram-negative bacteria that causes zoonotic infections but rarely causes human disease. There are approximately 300 reported cases of Edwardsiella tarda sepsis in the literature. We report the first case of Edwardsiella tarda sepsis associated with acute myelocytic leukemia.
A 50-year-old African American male with acute myelocytic leukemia, who presented with abdominal pain, chills and fever for two weeks. He was febrile with epigastric and right hypochondrial tenderness. Laboratory studies showed neutropenia with excess blasts, elevated amylase, lipase, alkaline phosphatase and bilirubin. Hence, patient was admitted for relapse of acute myelocytic leukemia with febrile neutropenia, acute pancreatitis and acute cholecystitis. Imaging studies did not reveal any gallstones. Blood cultures were positive for Edwardsiella tarda. Patient responded well to antibiotics with resolution of his symptoms.
Edwardsiella tarda is a zoonotic bacteria that infrequently causes gastroenteritis in humans. Extra-intestinal manifestations are rare and include septicemia, wound infection myonecrois, cholecystitis and pancreatitis. Human disease is more common in the immunocompromised. Human infection is acquired through contact with or ingestion of infected fish. Our patient had a significant history of recreational fishing and had eaten his catch a few days prior to the onset of his symptoms. He was also at a higher risk for infection because of immunosuppression from acute leukemia.
MASSIVE RIGHT
VENTRICULAR THROMBUS PRESENTING AS ACUTE ABDOMEN
Manesh Kottapuram, MD (Associate); Shazia Essani, MD (Member) Department of Internal Medicine, Sinai-Grace Hospital, Wayne State University, Detroit, Michigan.
Acute cor pulmonale due to massive right ventricular thrombus presenting as acute abdomen is a rare event.
We present a 21 year old caucasian woman who presented to the emergency room with sudden onset of abdominal pain and shortness of breath. Pain was continuous and generalized but mainly in the left upper and lower quadrant. She had three episodes of vomiting. Past medical history was significant for asthma. She was actively using cocaine and heroin at the time of hospital admission. Her initial blood pressure was 100/60 mm of Hg, pulse rate of 112/minute, respiration of 36/minute and was afebrile. Her oxygen saturation was 92% on 50% oxygen. She had diffusely tender abdomen with rebound and guarding but no rigidity. Bowel sounds were sluggish. She had 2 cm jugular venous distention and a 2/6 pansystolic murmur in left lower sternal border. Her labs were significant for ALT 143, AST 214 (U/L), and PT 13.6. Electrocardiogram was significant for sinus tachycardia, right atrial enlargement and incomplete right bundle branch block. Her CT scan of abdomen and pelvis showed hepatomegaly, large ascites, and cardiomegaly with dense opacification of cardiac chambers suggestive of delayed circulation. 2D echo showed dilated right atrium and 80% of right ventricle cavity occupied by a heterogeneous echoic mass suggestive of tumor. She also developed DVT involving left brachial, axillary, internal jugular and subclavian vein during hospitalization. She underwent open heart surgery and the mass was removed. Histology of the lesion demonstrated a chronic organized thrombus. Culture of the thrombus was negative. Her initial hypercoagulable workup (including antiphospholipid antibody syndrome) was negative.
Right ventricular thrombus has been described in literature, as they were associated with antiphospholipid antibody syndrome and Behcet’s disease. In our patient none of these were found. Also in our patient right ventricular thrombus simulated a cardiac tumor, which is a rare presentation.
ADENOCARCINOMA OF THE
LUNG PRESENTING AS SYMPTOMATIC HYPERCALCEMIA
Tabarak Qureshi, MD (Associate), Shazia Essani, MD (Member),
Dr. O Al Zohaili, MD.
Objectives: Hypercalcemia with squamous cell cancer of the lung is a common metabolic problem. However hypercalcemia with Adenocarcinoma of the lung is a rare presentation.
Case History: A 51 year old African-American male with no significant past medical history was admitted for elevated calcium level of 18 mg/dl. He complained of right-sided lower rib and right upper quadrant pain with a six-month history of constipation & 40-pound weight loss. Physical exam was significant for tenderness over the lower right rib cage, with dullness to percussion and decreased breath sound over the right lower zone of the lungs. Laboratory analysis showed intact parathyroid hormone was <1.0, parathyroid related peptide was within normal limits. Work up for Multiple Myeloma was negative. A chest radiograph showed a right paratracheal suprahilar mass with a right-sided pleural effusion. CT showed a right-sided pleural effusion with a nodular surface and generalized mediastinal lymphadenopathy. Thoracentesis revealed an exudative picture and the cytology was significant for adenocarcinoma. A bone survey and bone scan did not show any evidence of metastases. Treatment of the hypercalcemia included intravenous fluids, pamidronate and lasix and mineral oil enema for constipation. Patient was discharged with a follow-up with oncology.
Conclusions: Adenocarcinoma of the lung presenting as symptomatic hypercalcemia is rare in the absence of a parathyroid dysfunction. Extensive search of the English literature did not report such a presentation.
SUCCESSFUL PREGNANCY
IN A PATIENT ON HEMODIALYSIS
Pregnancies and their successful completion in patients on hemodialysis is rare. Fetal survival rates on hemodialysis have been reported to be anywhere between 20% to 46%. The incidence of both maternal and fetal complications is high.
We present a 38-year old woman, G7 P4 A2, with chronic renal
insufficiency. At the time of
conception, her creatinine clearance was 12.
Patient was on hemodialysis when her pregnancy was diagnosed. Her hemodialysis regimen, which consisted of
three, three hour sessions a week was increased to six, three hour sessions a
week. The patient’s was allowed a weight
gain of 0.2 to 0.5 kg /week. Strict
blood pressure control was maintained.
Her target hemoglobin was
Improvement in dialysis techniques and growing knowledge of complications in a pregnant patient on hemodialysis has made successful completion of a full term pregnancy a viable option. We no longer feel that these women should be advised to terminate pregnancy as an only option. By increasing the frequency of dialysis regimen, maintaining strict control of clinical and laboratory parameters and coordinating between nephrology and obstetrics services, we can change the once perceived dismal outcomes of these pregnancies.
NEPHRIN REVERSE
TRANSCRIPTASE-QUANTITATIVE POLYMERASE CHAIN REACTION (RT-QPCR) OF URINARY
SEDIMENT IS A POTENTIAL EARLY MARKER FOR DIABETIC NEPHROPATHY.
Ahmed O. Kaseb,MD(1), David M. Kurnit,MD,PhD(2), Kun Yang,MD(2), Ayman Khafagi,MD(2), William H. Herman,MD(3). Sinai-Grace Hospital/Wayne State University(1), Departments of Pediatrics and Human Genetics(2) and Internal Medicine(3), University of Michigan Medical School.
Nephrin is a key component of the renal ultrafiltration barrier. In the urinary tract, it is expressed solely in glomerular podocytes. Loss of podocytes, and thus high urine nephrin levels is associated with the clinical and histologic features of diabetic nephropathy in animals and humans.
Methods: We have developed and validated a reverse transcriptase, quantitative polymerase chain reaction (RT-QPCR) assay that uses the gene product of NPHS1 (coding for nephrin) to detect abnormal excretion of podocyte cell products into the urine and have tested it in normal and diabetic volunteers.
Results: The assay was reproducible in diabetic subjects with and without renal disease over 1-2 years. A normal range of < 10 molecules (in an aliquot of urine sediment derived from 40 ml of urine) was established in non-diabetic volunteers with normal urinary sediments. In cross-sectional studies, 13/45 (29%) of type 1 diabetic patients with durations of diabetes < 10 years and without microalbuminuria had abnormal elevations of nephrin RT-QPCR. The majority (27/49 = 55%) of diabetic patients treated with ACE I or ARB had low nephrin RT-QPCR regardless of whether albuminuria was present.
Conclusions: The nephrin RT-QPCR assay is sensitive and reproducible. It may provide an early way to assess the status of glomerular podocytes in diabetics, especially in the pre-microalbuminuric state. Nephrin RT-QPCR may also be a useful non-invasive way to monitor response to anti-proteinuria therapy. Further prospective observational and treatment trials are indicated.
CD3+, CD4+, CD8+
LARGE GRANULAR LYMPHOCYTOSIS(LGL) FOLLOWING HODGLIN'S LYMPHOMA
Ahmed Kaseb, MD(1)(Associate), Brian Douglas Jenkins(2), Ayad Al-Katib,MD(2), Daniel Snower,MD(2), Anwar Mohamed,MD(3).
Sinai-Grace Hospital/Wayne State University(1), Van Elslander Cancer Center and Dept. of Pathology, St. John Hospital and Medical Center, Detroit, MI(2) and Cytogenetics laboratory, Dept. of Pathology/Wayne State University(3)
INTRODUCTION
Large Granular Lymphocytosis (LGL) has been reported in association with various diseases including Cytomegalovirus infection and autoimmune disorders. Only four cases of lymphocytosis of LGL following Hodgkin’s Lymphoma has ever been reported.
CASE REPORT
Our case is a 41-year-old female of Italian ancestry with a variant of LGL developed thirty months after her first complete remission following treatment with ABVD chemotherapy regimen for stage IIIA Hodgkin’s Lymphoma. The patient was found to have leukocytosis on a routine evaluation with WBC of 12,000/uL and an absolute lymphocyte count of 9,840/uL. She was asymptomatic and with normal physical examination. Immunophenotyping of the lymphocytes showed that 94% were CD2+, CD3+ and CD5+ T-cells. 80% of these cells were also CD4+ and CD8+. The patient remained asymptomatic as of the last follow up six months from the diagnosis of LGL.
DISCUSSION AND CONCLUSION
Only four cases of lymphocytosis of LGL following Hodgkin’s Lymphoma has ever been reported. Three cases were CD3- and one was CD3+. Our case is a variant of LGL that has more positive CD receptors. Our case is the fifth reported case of LGL following Hodgkin’s Lymphoma highlighting a possible association between the two entities.
PPAR-GAMMA IS A POTENT INHIBITOR OF NEUTROPHIL FUNCTION
IN SEPSIS
Ghaffari M, Reedy R, Smith I, Zeng X, Newstead M, Rodriguez M, Standiford T.
Department of Internal Medicine, Sinai-Grace Hospital, Wayne State University,
Detroit., Michigan and Department of Internal Medicine, Division of Pulmonary
and Critical Care Medicine, University of Michigan Medical Center, Ann Arbor,
Michigan
INTRODUCTION: Sepsis results in a profound state of immunosuppression, which
occurs in association with a substantial impairment in leukocyte function.
Peroxisome proliferator-activated receptor-gamma (PPAR-•) is a ligand-dependent
transcription factor belonging to the nuclear hormone receptor superfamily.
Importantly, activation of PPAR-• has been shown to negatively regulate the
activation of monocyte/macrophage populations. However, the function of PPAR-•
in regulating neutrophil function, and how PPAR-• _expression in these cells
may be altered in sepsis has not been defined.
HYPOTHESIS: PPAR-• is an important negative regulator of neutrophil function,
and activation of PPAR-• contributes to the dysfunction of the neutrophils
observed during the septic response. Method: Neutrophils were isolated from
healthy subjects and patients with sepsis. _Expression of PPAR-gamma mRNA was
defined by RT-PCR. Neutrophils were treated with either endogenous (PGJ2) or
exogenous PPAR-gamma agonists (Troglitazone) and the effects on the neutrophil
proinflammatory cytokine production, migration, and apoptosis determined by
ELISA, chemotaxis bioassay and single strained DNA analysis, respectively.
RESULTS: Neutrophils expressed minimal PPAR-gamma mRNA at rest, but PPAR-gamma
message was induced by cytokines released in sepsis, including TNF and IL-4.
Treatment of neutrophil with PPAR-gamma agonists dose-dependently inhibited LPS
induced cytokine production and FMLP-induced chemotaxis. Moreover, selected
PPAR-gamma agonists induced neutrophil apoptosis at 24 hours. Finally we
observed constitutive expression of PPAR-gamma mRNA in neutrophils isolated
from sepsis patients, but not in neutrophils from healthy control subjects.
CONCLUSION: PPAR-gamma is a potent inhibitor of neutrophil function in vitro.
GENETICS OF THE HUMAN URIC ACID TRANSPORTER (hUAT)
B.N. Nandish, M.D., Sinai Grace Hospital, Detroit Medical Center, Wayne State
University, Detroit, MI. Michael S. Lipkowitz, M.D., Associate Professor, Mount
Sinai School Of Medicine, New York, NY.
INTRODUCTION: Elevated levels of uric acid have been associated with an
increased risk for gout, hypertension, cardiovascular disease, and renal
failure. Recent studies suggest that hyperuricemia precedes and predicts the
development of hypertension in adults and adolescents. Molecular mechanisms for
diminished excretions of urate in theses disorders is not well understood.
HYPOTHESIS: Data suggests galectin 9 is a functional human homologue of the rat
UAT. It also contains the putative channel forming transmembrane domain of UAT.
Data clearly indicate that mutations in individual ion transport proteins in
renal tubule can result in significant renal disease.
METHODS: Patients are from the NIH funded ancillary study of African-American
study of kidney disease who are expected to have hyperuricemia due at least in
part to abnormal urate excretion. Genomic DNA are extracted from peripheral
blood leukocytes. Polymerase chain reaction (PCR) for exon 1are done using a
gradient cycler. PCR products are digested with restriction enzyme MSPA1
followed by gel electrophoresis using ethylene bromide dye.
RESULTS: Results of PCR gel electrophoresis were analyzed for genotype GG and
mutation genotype GA. The mean uric acid levels in studies done so far have
shown marginal elevation of uric acid in genotype GA.
DISCUSSION: Confirmed mutations will be generated in hUAT in expression vectors
and for normal expression in cells. Localization of hUAT as a membrane protein
will be done using the membrane biotinylation. Finally mutations detected are
being cloned into a bacterial expression vectors for generation of recombinant
protein to test for ion channel function in a lipid bilayer system.
CONCLUSION: There is good reason to believe that UAT ion channel may be
responsible for alterations in uric acid excretion by the kidneys, seen in
pathophysiologic states such as gout, hypertension and familial hyperuricemia
syndromes.
CASE REPORT OF ORAL AMIODARONE INDUCED FULMINANT HEPATIC FAILURE.
Tannu Sahay, M.D. (Associate), Jennifer Ui, M.D., Arpita
Patel, Pharm. D., Thomas Piskorowski, D.O., Department of Internal Medicine,
Sinai-Grace Hospital/Wayne State University, Detroit, Michigan..
CASE SUMMARY- Our patient is an 82-year-old elderly non-alcoholic male who came
to the hospital with hypotension and a syncopal episode related to hypovolumia
that required intubation and mechanical ventilation. His past medical history
was significant for coronary artery disease with an EF of 20% and CABG done
approximately 9 years ago, tachy-brady syndrome for which he had a
pacemaker-AICD placed and end stage renal disease. Pacemaker interrogation did
not reveal any arrhythmic event. He had coagulopathy (INR-3) but no clinical
evidence of any overt bleeding. He had been on coumadin since the CABG and
coumadin was discontinued. Liver function tests were normal. Patient was
successfully extubated the next day and was sent to the general medical floor
after 3 days of stabilization. His home medications including, amiodarone 200
mg PO t.i.d was restarted once on floor. The next day patient was found
confused and having melanotic stools and epistaxis. Liver panel showed markedly
elevated AST, ALT, indirect hyperbilirubinemia, LDH and results consistent with
DIC. Clinical laboratory studies (absence of other markers of liver disease
including viral serologies) seem to rule out common causes of liver failure.
Patient was not hypotensive at any point while on general medical floor.
Therefore, the cause of his hepatic failure was thought to be Amiodarone.
DISCUSSION- Most cases of Amiodarone-induced hepatotoxicity are related to
parenteral administration, higher cumulative doses and prolonged duration of
therapy. Our patient is unique since he was on oral amiodarone for no longer
than 20 days. Amiodarone-induced hepatotoxicity is usually reversible with the
withdrawal of the medication.
CONCLUSION- Amiodarone-induced Hepatotoxicity is a rare complication. However,
it should be considered before addition of any other hepatotoxic agent. Also
liver function studies should be followed on a regular basis.
PNEUMOCYSTOSIS OF THE BRAIN – PRESENTING AS RING
ENHANCING LESIONS - A RARE CLINICAL MANIFESTATION.
A Reddy, MD Associate, B Sudhir, MD Associate, B Ismail, DPM, S.Marur, MD
Member, L.Ganesan, MD; Department of Internal Medicine, Sinai Grace
Hospital/Wayne State University, Detroit, Michigan.
Pneumocystis carinii infection is predominantly localized to the lungs.
However, 0.5 to 2 % of persons with AIDS can present with extra pulmonary
Pneumocystitis. Among these, involvement of CNS is the most uncommon
presentation of Pneumocystis carinii infection.
A 42 Year old African American male with a past medical history of AIDS ,
Cryptococcal meningitis and seizure disorder, presented with focal seizures of
the right lower extremity followed by Todd’s paralysis. His medications
included fluconazole, bactrim, zithromax, neurontin and HAART therapy. At
presentation, he had an initial viral load of 10,000 and a CD4 count of 255. CT
Scan with contrast showed multiple ring enhancing lesions at vertex. MRI with
contrast showed irregular thickened meninges in the parietal region with
multiple ring enhancing lesions bilaterally in the parietal cortex. CSF was
positive for Cryptococcal antigen at a titer of 1:256. Serum titers were
negative for Toxoplasma. A stereotactic biopsy of the brain was performed with
a high clinical suspicion of cerebral lymphoma. The histo-pathology report of
the tissue was positive for Cryptococcus as well as Pneumocystis carinii. Chest
X ray was negative for Pneumocystis carinii pneumonia. Treatment was started
with amphoterecin-B along with flucytosine and bactrim. Patient developed
anaphylactic reaction both to regular as well as lipophilic amphotericin-B and
was treated with high dose fluconazole.
This is the first time this condition presented with ring enhancing lesions
coexisting with Cryptococcus infection in a patient with AIDS. There have been
two previous reports of cerebral Pneumocystosis which were, however, diagnosed
on autopsy. Recognition of this coexistence can be a valuable consideration in
patients with AIDS who present with ring enhancing lesions on neuro-imaging.
PANCOAST SYNDROME AND METHICILLIN RESISTANT
STAPHYLOCOCCUS PNEUMONIA; AN UNCOMMON PRESENTATION
Tabarak Qureshi, MD (Associate), Rajiv Pai, MD, Rose Andriacchi, MD (Member).
Sinai Grace Hospital, Wayne State University/ Detroit Medical Center, Detroit,
MI.
OBJECTIVES: Staphylococcus aureus pneumonia is a common occurrence. However,
methicillin resistant staphylococcus aureus (MRSA) pneumonia presenting as
Pancoast Syndrome is an uncommon presentation.
CASE HISTORY: A 47 year old African American female with a history of T2 to T6
vertebral fusion after a MVA and an obsessive compulsive disorder presented
with severe back pain, Horner’s syndrome, numbness and tingling in her left
arm. A CXR performed in the emergency department showed a left upper lobe mass.
Laboratory analysis showed a white count of 14.7 K/CUMM. The patient was
isolated and tuberculosis was ruled out with three sputum samples negative for
AFB, followed by a bronchoscopy and BAL. Tissue samples from the bronchoscopy
showed an organizing pneumonia. Sputum and blood cultures were positive for
MRSA. She was started on intravenous vancomycin and a MRI was obtained. Results
of the MRI showed a 3 cm x 4 cm mass in the left upper lobe with encasement of
the lower part of the brachial plexus. A CT guided biopsy of the mass showed
inflammatory changes. The source of the MRSA was probably her obsessive-compulsive
disorder of skin picking as she had multiple wounds on her face and hands in
different stages of healing. A trans-esophageal echocardiogram and white cell
tagged scan was negative for any other source of infection. The patient
improved dramatically after six weeks of intravenous antibiotics with
resolution of the mass on CT scan and of her symptoms.
CONCLUSION: Pancoast syndrome and methicillin resistant staphylococcus aureus
pneumonia is a rare presentation. Extensive search of the English literature
revealed one report similar to the case presented above.