Submitted ACP Associates Meeting 2003
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, and from which myeloma may arise from malignant transformation.
Submitted ACP Associates Meeting 2003
Pulmonary blastomycosis may mimic pyogenic or fungal
infections, tuberculosis or malignancy. Cutaneous disease is the most common
hematogenous dissemination.
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.
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.
Submitted ACP Associates Meeting 2003
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.
Submitted ACP Associates Meeting 2003
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.
Submitted ACP Associates Meeting 2003
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 the treatment for this tumor type.
Submitted ACP Associates Meeting 2003
ABSTRACT INHIBITION
OF NUCLEAR FACTOR kB ACTIVATION IN BREAST CANCER BY GENISTEIN
Tannu Sahay, M.D., Associate,
Introduction- Genistein is an isoflavanoid present in soybean, which has been shown to inactivate Akt/NF-kB pathway ultimately leading to apoptotic cell death
Hypothesis- It has been shown that the activation of NF-kB leads to aggressive tumor growth and chemo-resistance. We therefore hypothesized that the cancer cells pre-treated with genistein would have greater cell killing compared to conventional chemotherapeutic agents.
Methods- We investigated the chemo-sensitizing effect of genistein for cisplatin in breast cancer MDA-MB-231 cells using the apoptosis assay and the gel electrophoresis mobility shift assay. Different drug concentration and combinations over different time intervals were tested.
Result- We found that apoptotic indices were greater in genistein pre-treated cells compared to either genistein or cisplatin alone. We were also able to demonstrate the down-regulation of NF-kB by genistein. Cisplatin-induced activation of NF-kB was abrogated in cells pre-treated with genistein
Discussion- Data from our laboratory showed that the transfection of cells by Akt cDNA leads to the activation of NF-kB directly, suggesting a molecular cross talk between Akt and NF-kB. The results supported our hypothesis of the chemosensitizing effects of genistein.
Conclusion- The inhibition of Akt/NF-kB pathway by genistein could be a novel approach for the treatment of breast cancer in the future.
Submitted ACP Associates Meeting 2003
IDIOPATHIC
HYPEREOSINOPHILIC SYNDROME OF THE HEART.
F Omar MD (Associate), D Obeid MD (Associate), G Krishnamorthy
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.
Submitted ACP Associates Meeting 2003
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.
Submitted ACP Associates Meeting 2003
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.
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.
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. This case
illustrates the difficulties and challenges seen in treating patients of
FSGS. We discuss the role of kidney
biopsy in diagnosis and management of FSGS and the difficulties of renal
transplant in patients with ESRD secondary to FSGS.
Concomitant
Lupus Nephritis and FSGS is uncommon.
When Lupus Nephritis is resistant to standard therapy, other diagnoses
should be considered.
Submitted ACP Associates Meeting 2003
THE ACTIVITY OF
CASPOFUNGIN ACETATE (CANCIDAS) AGAINST CANDIDA
GLABRATA: IN-VITRO ASSAYS. Vijayalakshmi Nagappan, MD, Associate, Dept.
of Internal Medicine, Sinai-Grace Hospital, Dina Boikov, MD, J.A..
Introduction: The medically important fungi are in a state of flux. Candida albicans is being replaced by many of the non-albicans Candida species, especially Candida glabrata, which is less susceptible to all antifungals. Caspofungin acetate (Cancidas) (Cfg) is the newest antifungal approved for the treatment of fungal infections. The objective was to evaluate the in-vitro activity of Cfg against C. glabrata.
Methods: 50 clinical isolates of C. glabrata were evaluated by MICs, MFCs and time kill assays. The assays were performed using NCCLS broth microdilution methodology and compared with amphotericin B (AB), fluconazole (FLZ) and voriconazole (VCZ). Additionally, synergy studies using checkerboard methodology were performed.
Results: Cfg showed excellent in-vitro activity against C. glabrata with MICs ranging from 0.125 to 1 mg/ml (MIC50 was 0.5 and MIC90 was 1mg/ml). Fungicidal activity was established at 0.5 to 4 mg/ml (MFC50 was 1 and MFC90 was 2 mg/ml). In comparison, MIC ranges for AB, FLZ and VCZ were 0.06 to 1, 0.03 to >16 and 2 to >64 mg/ml respectively. The MFC ranges for AB, FLZ and VCZ were 0.125 to 1, >32 and > 128 mg/ml respectively. Time kill assays evaluating 1FLZ-resistant and 1 FLZ-susceptible strain showed excellent fungicidal activity at 2 hours with Cfg kill rates of >99.99%. Synergy studies reveal excellent synergistic activity between Cfg + FLZ, an additive effect with Cfg + VCZ, indifference to additive effect with Cfg + AB.
Conclusions: In-vitro assays with Cfg demonstrated excellent fungicidal activity against C. glabrata, including FLZ- and VCZ- resistant strains. In addition, time kill assays also demonstrated excellent fungicidal activity against C. gabrata by 2 hours. Combination assays demonstrate excellent synergistic activity, especially with Cfg and either FLZ or VCZ, and indifference with AB. Cfg may be considered a possible alternative antifungal agent alone or in combination for difficult to treat C. glabrata infections.
Submitted ACP Associates Meeting 2003
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.
Submitted ACP Associates Meeting 2003
K Majekodunmi, MD (Associate), R M Ghurani, MD (Associate), W Hafeez, MD
(Member)
Sinai-Grace Hospital/Wayne State University, Detroit, Michigan.
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
Submitted ACP Associates Meeting 2003
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.
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.
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. He was a smoker and there was no significant
past or family medical history. 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.
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 includes class I antiarrhytmic drugs, beta blockers, amiodarone,
radiofrequency ablation and patients with high risk of sudden death should
receive an implantable cardioverter/defibrillator.
Submitted ACP Associates Meeting 2003
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 Essan, 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.
Submitted ACP Associates Meeting 2003
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.
Submitted ACP Associates Meeting 2003
Expression of B2 subunit mutants
alters localization of L-type calcium channels in rat adult 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.
Submitted ACP Associates Meeting 2003
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 thepancreas.
CASE:
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.
Submitted ACP Associates Meeting 2003
ASSOCIATION BETWEEN AGE, HEIGHT, WEIGHT AND BODY MASS INDEX WITH DISCORDANT CHANGES IN BONE MINERAL DENSITY ON SEQUENTIAL BONE DENSITOMETRY SCANS. Haleh Haerian, MD, Associate, Violeta Botea, MD, Associate, Gary W. Edelson, MD, Fellow and Rajika L. Munasinghe, MD, Member, Sinai-Grace Hospital/Wayne State University, Detroit, Michigan.
Introduction: Age and low body weight are two of the most important risk factors associated with accelerated bone loss leading to osteoporosis. Generally, osteoporosis is a systemic disease with generalized loss of BMD. However, in some patients, decline in bone mineral density (BMD) is discordant and more pronounced or limited to a single skeletal site. This study was done to compare the anthropometric characteristics of patients with concordant and discordant changes in BMD on sequential bone densitometry scans.
Methods. Data from 1180 patients serial scans were analyzed. Discordant and concordant changes in BMD were identified using one of two methods. In the first, change in BMD relative to the median rate of change for the entire cohort was used and in the second, absolute gain or loss of BMD from the first to the subsequent scan was used. The mean age, height, weight and body mass index (BMI) of patients with concordant and discordant changes in BMD were compared.
Results: Discordant detrimental change in BMD was most prevalent at the distal radius. When the group median was used for identifying patients with discordant BMD, patients with discordant detrimental change in BMD at the radius were significantly older (mean age 63.3 vs. 61.2, P<.05), heavier (mean weight 65.1 vs. 63.5 Kg, p<.05, BMI 26.2, vs. 25.0 Kg/m2, P < .001) than patients with concordant detrimental change in BMD. The results were similar when the absolute change in BMD was used to define discordancy.
Discussion: The differences in anthropometric characteristics between patients with concordant and discordant changes in BMD may be mediated by differential effects related to risk factors and treatment of osteoporosis, weight bearing and mechanical loading properties or composition of bone at the three principal skeletal sites.
Submitted ACP Associates Meeting 2003
MULTICENTRIC CASTLEMAN’S
DISEASE (MCCD) IN ASSOCIATION WITH EPSTEIN-BARR VIRUS (EBV).
Haleh Haerian, MD
(Associate),
Background: Castleman's
disease (CD), first described in 1956, is an uncommon lymphoproliferative
disorder associated with significant lymphadenopathy. HHV-8, interleukin (IL)-6
activity, HIV, and Kaposi’s sarcoma have been associated with MCCD and several
cases have been reported.
Case report: A 54
year-old native-American female presented with chest pain and difficulty in
breathing for one week, and was diagnosed with non ST-elevation myocardial
infarction. On examination patient was found to have significant pallor, and
splenomegaly. Initial laboratory results revealed pancytopenia with hemoglobin
of 5g/dl. During hospital course, pulmonary embolism was suspected and a spiral
CT of the chest was done. CT of chest revealed diffuse mediastinal and
bilateral axillary lymphadenopathy. CT of the abdomen revealed retroperitoneal
lymphadenopathy, and splenomegaly. Other laboratory findings were significant
for elevated sedimentation rate, polyclonal gammopathy with increased IgG and
IgM, presence of autoantibodies including ANA with a titer of 1: 2560, and anti
double and single stranded DNA. Her IL-6 activity, HHV-8, and HIV were
negative. Serologic tests for EBV revealed high titers of anti-viral capsid
antigen IgG (1:1280) and EBV anti-early antigen (>1:5120) that is strongly indicative of chronic active
EBV. A final diagnosis of MCCD was made based on lymph node biopsy revealing
mixed hyaline-vascular and plasma cell type CD.
Conclusion: CD is a rare lymphoid tumor of uncertain etiology. Of the cases reported in the literature, only four have been associated with EBV. We report the first case of MCCD with positive EBV and negative HHV-8, HIV, and (IL)-6 activity. This may indicate a pathogenetic link between the virus and MCCD.
Submitted ACP Associates Meeting 2003
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. Docetaxel is also a very potent inhibitor of our cell lines. The combination of Gossypol plus Docetaxel is more effective than Docetaxel alone.
Conclusion: The results suggest a potential role for these drugs in the treatment of patients with ACC could be considered.
Submitted ACP Associates Meeting 2003
CORONARY ARTERY DISEASE RISK FACTORS AMONG PATIENTS WITH UNRECOGNIZED DEPRESSION. Mehrdad Ghaffari, MD, Associate, Haleh Haerian, MD, Associate, Mohamed Karim, MD, Member, Rajika Munasinghe, MD, Member, Sinai-Grace Hospital, Wayne State University, Detroit, Michigan.
Introduction: Depression is associated with increased morbidity and mortality in patients with established coronary artery disease (CAD) but the association between depression and CAD risk factors has been found to be variable. The objective of this study was to determine the extent of unrecognized depression in an inner city, primary care internal medicine practice and to evaluate the CAD risk among patients with unrecognized depression.
Methods: Patients
without a prior diagnosis of depression were screened using the Prime MD
questionnaire, a validated screening tool developed to evaluate for depression.
Information on CAD risk factors was obtained from chart review. The prevalence
of individual CAD risk factors and the composite 10 year CAD risk based on the
Results: Out of a total of 215 patients evaluated, 53 (24.6%) screened positive for unrecognized depression. A total of 103 patients without depression and 39 patients with depression had complete information for a comprehensive assessment of 10 year risk of CAD. Patients with depression were younger (Mean age 51 vs 56 years P<.035) and had higher diastolic blood pressures (DBP 86 vs 76 mmHg, P<.01) compared to patients without depression. The 10 year CAD risk among patients with depression was 9% and comparable to patients without depression (11%, P=.15). Other CAD risk factors were similar between the two groups.
Discussion: Unrecognized depression among patients surveyed in our practice was comparable to previous estimates reported in the literature. We did not find unrecognized depression to be associated with a higher risk for CAD.
Submitted ACP Associates Meeting 2003
DO PATIENTS WITH UNRECOGNIZED DEPRESSION RESPOND DIFFERENTLY TO CAD RISK MODIFICATION IN THE PRIMARY CARE SETTING? Mehrdad Ghaffari, MD, Associate, Haleh Haerian, MD, Associate, Mohamed Karim, MD, Member, Rajika Munasinghe, MD, Member, Sinai-Grace Hospital, Wayne State University, Detroit, Michigan.
Introduction: Depression is known to adversely affect compliance with medical therapy and rehabilitation after myocardial infarction. The impact of unrecognized depression on the response of modifiable CAD risk factors to intervention in the primary care setting is less well known.
Methods:
Established patients in a primary care internal medicine practice were screened
for unrecognized depression using the Prime MD questionnaire, a validated tool
used to screen for depression. Information on the most recent CAD risk
assessment and the predicted 10 risk of CAD based on the
Results: The systolic and diastolic blood pressures, the LDL cholesterol level and the Hemoglobin A1c of diabetic patients decreased significantly with treatment. The mean 10 year risk of CAD declined from 13.7% to 11.9% (p<.001). There were no significant differences in the magnitude of change in CAD risk factors and the 10 year CAD risk between patients with unrecognized depression and controls. The power of this study to detect a 5% or greater difference in each of the CAD risk factors was greater than 80%.
Conclusion: Unrecognized depression does not appear to influence the treatment of CAD risk factors in the primary care setting. Independent of this finding both CAD prevention and screening and treatment of depression should be pursed aggressively to improve patient outcomes.
Submitted ACP Associates Meeting 2003
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.
Submitted ACP Associates Meeting 2003
COMPARISON OF ACUTE VENTRICULAR
DEFIBRILLATION THRESHOLDS UTILIZING BINARY SEARCH VS. SEQUENTIAL STEP-UP
PROTOCOL
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.
Submitted ACP Associates Meeting 2003
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.
Submitted ACP Associates Meeting 2003
TISSUE TRANSGLUTAMINASE EXPRESSION IN
MYOCARDIAL INFARCTION AND ITS INDUCTION BY CYTOKINES.
Muhammad Tariq Akbar, MD, Associate, (Dept of
Medicine,
Introduction
Myocardial infarction is associated with an
inflammatory response leading to extracellular matrix accumulation in the
injured area. Cross-linking of matrix proteins leads to maturation of the scar.
Extracellular matrix cross-linking enzymes (such as Tissue Transglutaminase)
may be induced in the infarcted heart for this purpose. Tissue transglutaminase
(TTG) catalyses the formation of lysine bonds (isopeptide bonds) between
peptide bound glutamine residues and the primary amine group of various
proteins. The covalent linking reaction increases the resistance of proteins to
chemical, enzymatic and physical disruption. TTG has been demonstrated to play
a role in the stabilization of the basement membrane and adhesion of cells,
which are important processes in wound healing and angiogenesis.
Methods
Healthy mongrel dogs were used for the study.
Coronary artery occlustion was achieved by a hydraulic occluder (previously
implanted). After one hour of occlusion the reperfusion intervals ranged from 1
hr to 28 days after which the dogs were sacrificed and heart tissue was removed
for immunohistochemical analysis and Northern Hybridization. The primary
antibodies used for immunohistochemistry included, anti-tissue transglutaminase
antibody, mouse anti-CD 31 antibody, anti-isopeptide antibody, anti Collagen
type III antibody and anti alpha smooth muscle antibody. RNA was isolated from
the myocardial tissue segments and Northern Hybridization was performed.
Endothelial cell isolation and stimulation was achieved using canine jugular
veins. These cells were stimulated with TNF-alpha, IL-1, TGF and PDGF. At the
end of the experiment the endothelial cells were used for RNA extraction and
Northern Hybridisation.
Results
TTG is expressed in ring structures at the
borders of healing infarcts. Theses structures also exhibit positivity for
mouse anti-CD-31 antibody (marker for endothelium) and anti alpha smooth muscle
antibody (marker for pericyte coated vessels). TTG mRNA is induced in healing
infarcts after 24h-28 days of reperfusion, with maximal expression around 7
days. TTG protein is localized in microvascular endothelial cells and the
connective tissue in the border zone of healing infarcts. During scar
maturation, many pericyte-coated neovessels show TTG and isopeptide expression.
TNF-alpha and PDGF induce TTG mRNA synthesis in canine endothelial cells.
Conclusion
TTG expression in healing infarcts is
consistent with a specialized role for this enzyme in regulating maturation of
the infarct neovasculature, through cross-linking of the endothelial basement
membrane. In addition, expression of TTG in the infarct border zone may
contribute to the formation of a "barrier" containing
proteolysis-resistant matrix, limiting expansion of the inflammatory process
into normal areas.
Submitted ACP Associates Meeting 2003
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.
Submitted ACP Associates Meeting 2003
DETERMINANTS
OF REACHING BLOOD PRESSURE GOAL IN DIABETICS WITH RENAL DISEASE
Bharathi Gavini, M.D., Associate,
Introduction: Diabetic Nephropathy is the number one
cause of end stage renal disease in the
Objective: We
sought to determine factors associated with reaching BP targets in diabetics.
Methods: The
charts of 146 diabetic patients seen in the WSU faculty
Nephrology clinic between
Results: The cohort was mostly African American (122), female (93), obese (mean BMI = 34.0), with moderate to severe renal insufficiency (mean serum creatinine = 2.42). The mean duration of diabetes was 15.7 years and over 90% of patients had hypertension (HTN) at presentation (duration = 13.7 yrs). The mean BP at presentations was 160/83.2 mm Hg. Fifteen patients were at BP goal at presentation. Of the 146 patients with follow-up 47 reached BP goal. The only factor that was significantly correlated with reaching BP goal was initial BP. The following factors did not predict who reached BP goal: BMI, age, gender, amount of proteinuria at initial visit, creatinine at initial visit, estimated GFR, duration of HTN, the number of BP meds at presentation or during follow-up, duration of diabetes, and duration of dyslipidemia. Compared to ACE inhibitors, the presence of a calcium channel blocker (CCB) in the regimen was associated with a longer time to reaching BP goal that appeared related to more advanced renal disease in those on CCB.
Conclusion: While
it is challenging, it is possible to achieve the aggressive BP goals set for
diabetics. Those with highest initial BP
are the most difficult to get to goal.
Submitted ACP
Associates Meeting 2003
MATURATION OF THE MICROVASCULATURE IN HEALING MYOCARDIAL
INFARCTS: A POTENTIAL ROLE FOR PDGF.
KAMAL
Department of
Internal Medicine, Sinai-Grace Hospital, Detroit Medical Center/Wayne State
University, Detroit MI, and 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: The infarct microvasculature undergoes dynamic changes leading to formation of mature pericyte-coated vessels. PDGF may play an important role in maturation of the infarct vasculature through regulation of vascular pericyte coating and by inducing endothelial expression of the cross-linking enzyme tTG, promoting endothelial basement membrane maturation. Further experiments using neutralizing antibodies in mice undergoing infarction protocols will determine the role of PDGF in healing infarcts.
Submitted ACP Associates Meeting 2003
ACUTE INTERSTITIAL NEPHRITIS SECONDARY TO OMEPRAZOLE.
Apurva Motivala MD, Associate,
Robert Mi