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 National OCT 2002
IDIOPATHIC LEFT
VENTRICULAR OUTFLOW TRACT TRACHYCARDIA: A RARE ARRHYTHMIA IN A FEMALE PATIENT. Muhammad
Akbar, MD, Associate and
Idiopathic
ventricular tachycardia (IVT) is an unusual form of ventricular tachycardia
mainly seen in young individuals with no structural heart disease. In 80% of
patients it originates in the right ventricle. An uncommon form of IVT is the
left ventricular outflow tract tachycardia which is associated with RBBB
configuration, left axis deviation, verapamil sensitivity and also rarely with
sudden death; hence the importance of recognizing this entity. This arrhythmia
has been mainly described in males, rarely reported in females.
A 26 years old female presented with multiple daily episodes of palpitations since two years. Her 24 hour Holter revealed 174 runs of rapid ventricular tachycardia (unifocal with RBBB configuration) with a rate of 170-210 lasting up to 7 minutes. Echocardiography and exercise stress test showed no significant abnormalities. Pace mapping identified earliest ventricular activation originating from the left ventricular outflow tract. Radiofrequency ablation was performed at the anterio-superior medial region of the mitral valve. There was immediate cessation of the tachycardia and no induction with isoproterenol infusion upto a heart rate of 130. The patient has remained symptom free for ten months of follow up.
Although
radiofrequency ablation has been shown to be of benefit in idiopathic left
ventricular tachycardia in reported cases, the exact nature of the reentry
circuit and the optimal site of ablation is still a matter of debate. This case
demonstrates success of radiofrequency ablation at a site in the left
ventricular outflow tract determined by pace mapping, with no recurrence on
follow up.
Submitted ACP National OCT 2002
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ALEUKEMIC PRESENTATION OF ACUTE PROMYELOCYTIC LEUKEMIA.
Bakhtiar Ali, MD, Associate,
Danny Obeid, MD, Associate, Atul Singh, MD, Associate Rajika Munasinghe, MD,
Member, and Leopoldo Eisenberg, MD,
Member.
Acute Promyelocytic Leukemia (APL-M3) accounts for 10% of all acute myeloid leukemias. The median age of presentation is 37 years. DIC is present in approximately 80% of patients at the time of diagnosis. We describe an atypical case of APL, presenting with aleukemia (absence of blast cells in the peripheral smear) in a 75-year-old female patient.
The patient was admitted for elective surgery for a large 7 cm, abdominal aortic aneurysm. Routine blood counts showed pancytopenia (WBC 700/mm3, Hemoglobin 6.7 g/dL and platelet of 18,000/mm3). No blast cells were detected on peripheral smear. Bone marrow biopsy showed 100% cellularity with 28.6% blasts. The diagnosis of AML-M3 (APL) was confirmed by flow cytometery and cytogenetic studies that revealed the (t 15;17) translocation. The patient was treated with all-trans-retinoic acid (ATRA) therapy. Clinical remission was confirmed after one month of treatment by repeat bone marrow studies that showed a marrow cellularity of 80% with 2.9% blasts. The peripheral smear showed improvement in the pancytopenia (WBC 2900/mm3, Hb 8.4 g/dL and Platelets of 361,000/mm3). Cytogenentic studies revealed a normal karyotype.
ATRA therapy has revolutionized the treatment of APL, which was highly fatal previously. This case report demonstrates that ATRA is effective in elderly patients with atypical presentations of APL. The absence of the (t 15;17) translocation after therapy is associated better long term remission. Aleukemic presentation occurs in only 10% of all myeloid luekemias. We failed to find any previous case reports of APL presenting as aleukemia in the medical literature.
Submitted ACP National OCT 2002
TREATMENT OF CENTRAL PONTINE MYELINOLYSIS WITH
IMMUNOGLOBULIN. Atul Singh, MD, Associate, Nandita Keole, MD, Associate and
Mohamed Karim, MD, Member.
Central pontine myelinolysis (CPM), a neurological disorder usually associated with rapid correction of hyponatremia. It has also been reported with chronic alcoholism, liver transplantation, adrenal insufficiency and sepsis. The disease has a universally dismal outcome and no effective treatment is established. 75 % of the surviving patients are left with persistent neurological deficit.
We present a case of CPM that survived without any residual neurological deficit. Our patient is a 34-year-old woman, a chronic alcoholic, who initially presented with a sodium of 119 mmol/L. She was discharged after appropriate correction of hyponatremia, using normal saline. She was readmitted 3 weeks later with new onset seizures. Initial neurological examination was normal. On day 4 of hospitalization, the patient was noted to have nystagmus, slurred speech, hyporeflexic tertraplegia, progressive psuedobulbar palsy and finally locked-in-syndrome. MRI of the brain showed changes in the pons consistent with CPM. She was intubated for airway protection and treated with intravenous immunoglobulin (IVIG) 0.4 gm/kg body weight per day for 5 days. On day 13, she began to show signs of neurological recovery with eventual ability to ambulate by day 25. After intensive physical therapy she was functionally independent by day 51.
Finsterer et al. have reported using IVIG for the treatment of CPM in a young male alcoholic patient with good clinical response. Ours is the second such case report that supports IVIG as a promising treatment modality for CPM.
Submitted ACP National OCT 2002
HEMODIALYSIS RELATED PSEUDOMONAS PAUCIMOBILIS SEPTICEMIA
TREATED WITHOUT GRAFT REMOVAL. Parminder
Chahal, MD, Associate, Viji Nagappan, MD, Associate and Wasif Hafeez, MD,
Member.
Widely distributed in soil and water, Pseudomonas paucimobilis is a non-fermenting, strict aerobe, oxidase and catalase positive, gram-negative bacillus. Rarely implicated in community acquired and nosocomial infections of chronically sick humans, including bacteremia associated with hemodialysis, chemotherapy, peritonitis in continuous ambulatory peritoneal dialysis, empyema, visceral organ abscess, meningitis and wound infection. No fatalities reported. At least one case of catheter related septicemia successfully treated without catheter removal is reported.
We present a case of Pseudomonas paucimobilis septicemia in a 54 year old female with end stage renal disease on outpatient hemodialysis via gortex arteriovenous shunt that developed fever immediately after dialysis. She had received a dose of empiric antibiotics after blood cultures were drawn. Blood cultures grew Pseudomonas paucimobilis in 48 hours and the patient was admitted to the hospital only after it was known that she had a bacteremia. At admission her blood cultures had become negative, but because she continued to be febrile she was treated with 14 days of intravenous antibiotics. The patient never had a clinically identifiable source and her AV graft site looked intact so it was decided to only medically manage this infection. An epidemiologic investigation of the outpatient dialysis center showed no other cases and no positive surveillance cultures.
Pseudomonas paucimobilis is rarely found in the hospital water supply, hemodialysis fluids and respirators. In most cases, the source of infection is endogenous as in this case and it represents a case of successful treatment without removal of the graft.
Submitted ACP National OCT 2002
A CASE REPORT OF SEVERE GROUP B STREPTOCOCCAL (GBS)
INFECTION AND A REVIEW OF GBS BACTEREMIA.
GBS in
humans can be an asymptomatic colonizer of the genital and lower GI tract or a
pathogen causing an invasive infection with substantial morbidity and
mortality. We present a case of an
unusually severe GBS infection, which prompted a review of all cases of GBS bacteremia
at our hospital.
Our
patient is a 48 years old woman who presented with high fevers, headache, neck
and back pain, right shoulder pain and confusion progressing over a 2 day
period. Diagnostic evaluation resulted
in GBS being isolated from blood culture, CSF culture and right shoulder
aspirate. MRI of the spine revealed
L5-S1 vertebral osteomyelitis with discitis with epidural and paraspinal
abscess.
The
patient was treated with ampicillin and underwent surgical drainage of her
right shoulder and L5-S1 laminectomy and debridement. Her response to treatment was slow but
complete. Her primary source of
infection remained unclear.
At
Of the 16
cases, identifiable clinical entities included nine primary bacteremia, two
pneumonia, one genital tract infection, one pharyngeal abscess, one penile
gangrene, and one line sepsis.
Severe
GBS infection in adults usually presents as one of several clinical expressions
of infection such as primary bacteremia, female genital tract infection,
pneumonia, endocarditis, arthritis, osteomyelitis, abscesses or meningitis. Our patient presented with several of these
clinical entities, others at our hospital have had more focal manifestations of
the infection.
Submitted ACP National OCT 2002
HOW DOES MUPIROCIN RESISTANCE AMONG STAPHYLOCOCCUS AUREUS ISOLATES EMERGE IN LONG-TERM CARE FACILITIES (LTCF)?
Rasha M.Ghurani, MD1, Associate, Lona Mody, MD2, and Susan F. Bradley, MD2.
Introduction: Eradication of persistent Staphylococcus aureus (SA) colonization with mupirocin (MUP) may reduce the spread of infection and thus mortality in LTCF. The effect of MUP on persistence of decolonization, reduction in infection and the increased risk for emergence of resistance (MUP-R) has not been prospectively studied in LTCF in a randomized, double-blinded, placebo controlled fashion.
Methods: Residents from a community LTCF and a VA LTCF with persistent colonization in nares or wounds were enrolled. Colonized sites were treated with MUP or placebo for 14 days. Cultures for SA and coagulase negative Staphylococci (CNS) were performed on a regular basis over 6 months. SA and CNS isolates were screened for the presence of MUP-R before and after treatment.
Results: 128 of 150 eligible patients were enrolled and 108 completed 14 days of MUP (n=65) or placebo (n=63) treatment. Of 65 patients randomized to MUP, 87% cleared their SA versus 17% in the placebo group, P<0.0001. All patients who failed MUP treatment at 14 days harbored MUP-R SA either before (n=4) or during (n=3) MUP treatment. All patients with MUP-R SA harbored high level (>500mg/ml) MUP-R CNS. MUP-R SA strains post-treatment had similar genotypes by CHEF typing when compared with pre-treatment susceptible strains.
Conclusion: MUP was effective in clearing SA carriage long-term, however, a significant proportion of residents became recolonized. Whether recolonization is due to relapse or new acquisition of SA strains is being assessed. CHEF typing results are highly suggestive that resistance emerged with treatment in the original strains (i.e…relapse of the same strain).
Submitted ACP National OCT 2002
SYMPTOMATIC LACTIC ACIDOSIS SECONDARY TO NUCLEOSIDE ANALOGUE
REVERSE TRANSCRIPTORS INHIBITORS (NRTI). Haleh Haerian, MD, Associate,
Manesh Kottapuram, MD, Associate and Geetha
Krishnamoorthy, MD, Member. Department of Medicine,
Introduction: Type “B” lactic acidosis is a rare but potentially life-threatening complication of NRTI therapy and is often accompanied by other serious clinical manifestations of mitochondrial toxicity, such as hepatic steatosis, pancreatitis, myopathy, and peripheral neuropathy.
Objective: To describe the development of symptomatic lactic acidosis in four patients treated with NRTIs and to emphasize on the importance of early recognition since a fatal course will follow shortly.
Cases: Our four patients were 30 to 61 years of age and diagnosed with HIV infection. Their CD4+ counts were in the range of 7 to 920 and the viral loads ranged from undetectable to 400,000 copies/ml. They presented with symptoms of exertional dyspnea, sever fatigue, leg pain, nausea, and pedal edema. Arterial lactate ranged from 4.3 to 14.9 mmol/L. The NRTIs that these patients were on were AZT, Stavudine, and Lamivudine. All the four patients responded to discontinuation of NRTI, administration of CoQ, Riboflavin, Thiamine, Levocarnitine and supportive therapy.
Discussion: An often-fatal syndrome of lactic acidosis and hepatic steatosis is a recognized but rare complication of NRTI therapy for HIV infection. Nucleoside analogues can inhibit Gamma-DNA polymerase, the enzyme responsible for mitochondrial DNA synthesis, which is the underlying mechanism of lactic acidosis. The first case was reported in 1991 and was linked to monotherapy with Zidovudine. Since then, other NRTI drugs have been linked to the condition, particularly Stavudine, Didanosine and Lamivudine.
Submitted ACP National OCT 2002
EPIDEMIOLOGY
OF HEPATOCELLULAR CARCINOMA IN HEPATITS C VIRUS INFECTED PATIENTS.
Recent studies have shown an increase in incidence of Hepatocellular carcinoma (HCC) in the United States, from 1.4 to 2.4 per 100,000 patients. We analyzed the epidemiology of patients with hepatitis C virus associated HCC treated at an inner city hospital.
Epidemiological and histological parameters for 94 patients were collected retrospectively using diagnostic code for primary liver cancer (ICD-9-CM 155.0) and presence of HCV antibodies. All patients (except for one patient, who had MRI Abdomen documented HCC) had histologically proven HCC.
There was male predominance in our patients as a group (male: female ratio of 67:33 %) and also when divided into sub groups by age and race. 60% of patients were African American, 26% Caucasians and the remainder were Hispanic, and Arab Americans. 21 % of patients had concomitant exposure to HBV. 82% of the patients were more than 50 years old (mean age 61 years). AFP was elevated in 90 % of the patients, with very high levesl (>1000μg/l) in one third of the patients. Histologically, most of the tumors were moderately differentiated (47 %). It is noteworthy that 51 % of our patients did not have any known risk factors for HCV infection.
The age specific trends for HCC have been towards younger people; we found that our patients had lower mean age than national averages. Predominance of HCC in males and African American was seen, but with higher female percentages. Study further supports the use of AFP levels in screening for HCC in patients with HCV infection.
Submitted ACP National OCT 2002
Introduction: Thyroglossal Duct Cysts are the most common mid line neck swellings and carcinoma is found in approximately 1 percent of the lesions. In the literature, less than 200 cases are reported. The cysts are usually asymptomatic and distinction from carcinoma is seldom possible clinically. Papillary carcinoma comprises 80 percent of the thyroglossal cyst carcinomas.
Case Report: A 35-year-old male presented with a lump in his neck that was increasing in size. On physical exam, a 3 cm mobile, cystic, nontender, midline neck mass was present at the level of the hyoid bone. The mass moved up with protrusion of the tongue. Ultrasound was consistent with the diagnosis of a thyroglossal cyst. Sistrunk procedure was done and the histopathology revealed papillary carcinoma. The lymph nodes were negative for neoplasm. Thyroid scan and thyroid function tests were normal and thyroxin was started.
Discussion: Controversy exists over the origin of thyroglossal duct carcinoma, whether it is a primary tumor or a metastasis from the thyroid gland. The question arises as to what to do with the thyroid gland, and whether prophylactic thyroidectomy is advised. Given the excellent prognosis and low risk of recurrence, the optimal surgical procedure for the thyroglossal duct carcinoma is the same as for a benign cyst. Thyroid suppression is recommended for all patients with papillary carcinoma of the thyroglossal duct.
Conclusion: Surgery provides the best prognosis for thyroglossal duct carcinoma. Thyroid suppression is recommended for all patients with papillary carcinoma of the thyroglossal duct.
Submitted ACP National OCT 2002
ISOLATED FAMILIAL HYPERPARATHYROIDISM - A CASE REPORT.
Tawhida Khatoon, MD, Associate, Savitha Balaraman, MD,
Associate and Geetha Krishnamoorthy, MD, Member.
Although primary hyperparathyroidism is a relatively common condition, the subset of isolated familial hyperparathyroidism is quite rare. We report a case of isolated familial hyperparathyroidism.
A twenty nine year old African American female presented to the hospital with severe abdominal pain, nausea, constipation and bone pain. Her past medical history included right ankle fracture following minor trauma and major depression. Her family history was significant for hyperparathyroidism in her maternal grandmother, father, two maternal aunts and her twin sister requiring surgery. Laboratory studies revealed a serum calcium of 13.7 mg/dL, parathormone level of 605 pg/ml and a creatinine of 0.8 mg/dL. Urine analysis showed 5-10, white cells, 5-10 red cells and calcium oxalate stones. Abdominal X-ray revealed bilateral renal calcifications. A diagnosis of primary hyperparathyroidism was entertained. No other endocrinopathies were reported in her family members. A neck exploration revealed a 2x3 cm adenoma in her right inferior parathyroid gland which was excised. Postoperative course was complicated by hungry bones syndrome that was managed medically.
Primary Hyperparathyroidism is a relatively common condition with an annual incidence of 1 in 1000 men and 2-3 in 1000 women beyond the age of 50. A small subset of primary hyperparathyroidsm may occur as a part of Multiple Endocrine Neoplasia I or IIA or as Isolated Familial Hyperparathyroidism. Isolated Familial Hyperparathyroidism has been reported only in 70 families in the literature. Its inheritance is autosomal dominant, presenting at the mean age of 22 with hypercalcemia, early nephrolithiasis and aggressive bone disease. The pathology usually reveals parathyroid hyperplasia though chief cell adenomas have been reported rarely.
The significant features of this case report including a literature review of this rare clinical entity is presented.
Submitted ACP National OCT 2002
PROTECTION OF CARDIOMYOCYTES AGAINST METABOLIC STRESS BY 17b-ESTROGEN IN CULTURE. Manesh T. Kottapuram, MD, Associate and Tuan H. Kuo, MD. Dept. of Internal Medicine and Dept. of Cell Pathology, Sinai-Grace Hospital, Detroit Medical Center/Wayne State University - Detroit, Michigan.
Objective: To understand the mechanism in which
estrogen protects cardiomyocytes in culture against metabolic stress
injury.
Background: The beneficial effects of estrogen on the
cardiovascular system have been traditionally ascribed to decrease in
peripheral vascular resistance and antiatherogenic action. However, the molecular mechanism for this
protection is still poorly understood.
Hypothesis: Estrogen protects cardiomyocytes by
upregulating the Akt kinase signal transduction pathway and by accomplishing Ca2+
homeostasis at cellular level.
Methods:
Ventricular cardiomyocytes isolated from female Sprague- Dawley rats were
incubated in serum free culture medium with and without 17 b- estradiol.
Then cells were either lysed to isolate proteins for detection of Akt
signal transduction pathway activation or treated with various agents (2-3 DNP,
Thapsigargin, and Ionomycin) to induce chemical hypoxia and Ca2+
loading in cardiomyocytes. Activation of
Akt kinase was determined by western blot assay using specific anti-phospho-Akt
antibody. Ca2+ loading and
its subsequent homeostasis assessed by Fura-2 dye and dual excitation
fluorometer.
Results:
Estrogen may upregulate Akt signal transduction pathway in
cardiomyocytes. Pre-treatment with
estrogen significantly affects Ca2+ loading in cardiomyocytes either
by decreased rate of loading or by facilitating efflux of cytoplasmic Ca2+.
Conclusion: The preliminary reports may support the
hypothesis that the protective effect of estrogen on cardiovascular system can
be attributed either to the upregulation of Akt kinase signal, which is a
well-known ‘antiapoptotic’ cell survival signal or to the efficient cytoplasmic
Ca2+ homeostasis in cardiomyocytes.
Submitted ACP National OCT 2002
AORTIC DISSECTION PRESENTING AS UNSTABLE ANGINA COMPLICATED
BY FEVER AND ATELECTASIS.
We describe a
42-year-old African-American male with hypertension, tobacco and cocaine use
who presented with severe sharp substernal pain strongly suggestive of
angina. Physical examination was
unremarkable except for an elevated blood pressure of 160/90 mmHg. Peripheral pulses and blood pressure in the
upper extremities were equal. The ECG showed left ventricular hypertrophy. The chest radiograph revealed cardiomegaly
and serial troponin levels were normal.
Echocardiogram revealed a dilated left ventricle with severe
hypokinesis. Patient was admitted and
treated for unstable angina. The next
day he developed a temperature of 100 F, with leukocytosis. Repeat chest radiograph showed the
development of plate-like atelectasis of both lung bases. He was started on antibiotics for pneumonia
but chest pain, fever and leucocytosis persisted. A chest CT was done to
ascertain the cause of atelectasis revealed Stanford type B aortic
dissection. The patient was managed
conservatively and discharged shortly afterwards.
The diagnosis of
thoracic aortic dissection may be missed when patients present with atypical
symptoms instead of the characteristic severe tearing chest pain associated
with hypertension. Previous case reports
have described fever in patients with aortic dissection thought to result from
injury to the vessel wall, hematoma formation and tissue ischemia. Atelectasis in our patient was most likely
due to diminished respiratory effort from chest pain, which also could have
contributed, to his fever.
Clinicians should be
aware that fever, chest pain and atelectasis are clinical findings that can be
associated with aortic dissection and pursue this diagnosis when clinically
indicated.
Submitted ACP National OCT 2002
A RARE CASE OF ADULT MEDULLOBLASTOMA.
Medulloblastoma is the most common type of
primary solid malignant brain tumor in children, accounting for 30% of
childhood brain tumors. In contrast, medulloblastoma represents only 0.2% of
all brain tumors found in adults older than forty years of age.
We describe a case of a 48 year-old
African-American male who presented to our clinic with a two-month history of
headache and clumsiness when walking. The patient’s medical history was
significant for injection drug use, Hepatitis B, and Hepatitis C infection. On physical examination the patient had
difficulty with tandem walking. MRI
showed a mass involving the vermis of the cerebellum. A stereotactic resection
of the brain tumor was performed. The pathology revealed the mass to be a
primitive neuroectodermal tumor with glial differentiation. Chromosomal
analysis was performed on 20 cells with 4/20 cells showing a deletion in
chromosome 22. This is an uncharacteristic finding in medulloblastoma.
Postoperatively, he was scheduled to have radiation and chemotherapy.
In this case report, we describe a patient
with a midline adult medulloblastoma. We will discuss the clinical
characteristics of this case and compare it to other cases of adult
medulloblastoma that have been reported in the literature.
Submitted ACP National OCT 2002
MEDICAL IMPROTANCE
OF APERT'S SYNDROME.
Apurva Motivala, MD, Associate, Atul Singh, MD,
Associate, Mamatha Reddy, MD, Associate, and Geetha Krishnamoorthy, MD, Member.
We describe a 51 year old Caucasian male brought to our hospital after he was found unresponsive in his driveway. The patient was cyanotic at presentation. We noted exophthalmos, large ears, hypertelorism, syndactyly, evidence of skin infection and ecchymosis secondary to leg trauma. In the emergency department, the patient had improvement after supplemental oxygen and was fully awake with reversal of cyanosis. He admitted to alcohol intake prior to this episode. Based on his clinical features, we diagnosed the patient with Apert's syndrome.
Apert's Syndrome was first described in a newborn in 1906. It's inheritance is autosomal dominant. However, more commonly it is caused by a sporadic mutation of Fibroblast Growth-factor receptor-2 located on chromosome 10. It is a form of acrocephalosyndactyly which involves developmental defects of the skull and digital fusion. Associated congenital defects include hydrocephalus, sleep apnea, tracheo-esophageal fistula, anomalous tracheal cartilage, pulmonary aplasia, pyloric stenosis, biliary atresia, ventricular septal defect, polycystic kidneys, hydronephrosis, severe acne, ear infections, absent right middle lobe of the lungs and mental retardation.
These patients, due to improved modalities of corrective surgery in childhood, now have a better median survival. Recognition of this syndrome is important to the internist as the presenting medical conditions may have an underlying congenital pathology that should be recognized and treated appropriately. Our patient is one of the oldest surviving patients diagnosed with Apert's syndrome reported.
Submitted ACP National OCT 2002
COMPLEMENT DEPENDANT CYTOTOXICITY (CDC) IS A MAJOR MECHANISM OF ACTION OF RITUXIMAB. Nagaprasad Nagajothi, MD1, Associate, William Matsui, MD2; Galina Mukina, MD2; Robert A. Brodsky, MD2.. 1Department of Medicine, Sinai-Grace Hospital, Detroit Medical Center/Wayne State University - Detroit and 2 The Johns Hopkins Oncology Center - Baltimore.
Rituximab is an anti-CD20 monoclonal antibody used to treat B cell lymphoproliferative disorders. Rituximab is believed to kill cells through (CDC), antibody-dependent cellular toxicity and apoptosis. Recent data demonstrate that a major cause of resistance to rituximab is upregulation of the complement regulatory proteins, CD59 and CD55. Paroxysmal nocturnal hemoglobinuria (PNH) is a hematopoietic disorder which results in loss of all glycosylphospatidylinositol (GPI)-anchored proteins from the cell surface including, CD55 and CD59. PNH is caused by somatic mutations in the PIGA gene, the product of which is required for the biosynthesis of GPI-anchors.
The purpose of this study is to examine the impact of disrupting cell surface GPI-anchor proteins in order to augment rituximab-mediated CDC.
Here, we used the PNH cell line LD- which is a CD20+ve B cell line that is devoid of GPI-anchor proteins; the isogenic cell line LD-PIGA+ was established by stably transfecting an expression vector containing the full-length PIGA gene to restore GPI-anchor protein expression. Both cell lines were cultured in media containing rituximab (10g/ml), complement (25% human serum), or rituximab and complement. Viability at one hour was measured using propidium iodide and annexin V staining.
The combination of rituximab and complement resulted in greater than 65% killing of the LD- line and less than 20 killing in the LD-PIGA+ line. Complement alone or rituxan alone resulted in less than 10 killing of both cell lines.
To confirm that disruption of GPI-anchor proteins augments rituximab mediated CDC we treated the LD-PIGA+ line with PIPLC, a phospholipase that selectively cleaves GPI-anchored proteins. Following PIPLC treatment, the LD-PIGA+ line became as sensitive to the combination of rituximab and complement as the LD- cells.
Thus, CDC is a major mechanism for action of rituximab. Disrupting cell surface GPI-anchor proteins may improve the efficacy of ritiximab for treating lymphoproliferative disorders and B cell-mediated autoimmune disorders.
Submitted ACP National OCT 2002
AUREOBASIDIUM PULLULANS INFECTION OF THE KNEE JOINT IN A PATIENT WITH HISTORY OF SPOROTRICHOSIS OF THE SAME JOINT.
Danny Obeid, MD, Associate, Bakhtiar Ali, MD,
Associate, Viji Nagappan, MD, Associate, and Wasif Hafeez, MD, Member.
Aureobasidium Pullulans is a fungus that is widely found as a saprophyte. It is rarely associated with human infections; usually it causes fungal keratitis and peritonitis in patients on continuous ambulatory peritoneal dialysis (CAPD).
Here we report a case of Aureobasidium Pullulans infection of the right knee in a 47 year old male with a history of alcohol abuse and a history of sporotrichosis of the same knee diagnosed 2.5 years ago and treated with Itraconazole for 1.5 years. He used to be a gardener and his job makes him deal with dead decaying wood. Six months after he finished the antifungal course, he presented with swelling, pain, and limitation of movement of his right knee. The joint was tapped and synovial fluid grew Aureobasidium Pullulans. The patient was treated with Itraconazole and he reported improvement of his symptoms in a few weeks although not completely resolved.
The importance of this case comes from the fact that
Aureobasidium Pullulans knee infection has not been reported before. We don’t
know yet whether the history of sporotrichosis predisposed him for this infection
or it is a completely independent one.
Submitted ACP National OCT 2002
NON-OBSTRUCTIVE TRIPLE VESSEL CORONARY ARTERY
ANEURYSMS CAUSING ST ELEVATION
MYOCARDIAL INFARCTION: A CASE REPORT.
Fadi A.
Saab, MD, Associate,
Multiple Coronary Artery Aneurysms are rarely seen in adults. In association with Myocardial Infarction, there are less than ten cases reported since 1967.
A 55 year-old African- American male presented to the emergency department with classical features of myocardial infaction. Risk factors for coronary artery disease included cigarette smoking and strong family history. EKG displayed ST-elevations in the inferolateral leads. He was treated with Reteplase, intravenous heparin, intravenous nitroglycerin, beta-blocker, and aspirin. He continued to have angina and underwent emergency cardiac catheterization which revealed diffuse aneurysmal dilatation of the Right Coronary, Left Anterior Descending and Left Circumflex Arteries with slow flow. Dilatations ranged from 6 to 8 millimeters. No occlusions were seen. Our patient was discharged two days later with standard medical management and Cardiac Rehabilitation Phase II.
In adults, in addition to congenital aneurysms the etiology of Multiple Coronary Aneurysms includes Systemic Lupus Erythematosis, Neurofibromatosis, Atherosclerosis and Chest Trauma. Treatment options include lifelong anticoagulation, stenting, and surgery although not all authors agree that any treatment is required. Our patient had no evidence of any of the above etiologies for Coronary Aneurysm outside of possibly a Congenital cause.
Coronary Aneurysms are rare in adults and even more rarely lead to ST-Elevation Myocardial Infarction. A consensus on any treatment in addition to the standard Myocardial Infarction medical management has yet to be reached.
Submitted ACP National OCT 2002
(313) 336-4604
ACP #01209023
CARDIAC AMYLOIDOSIS:
A RARE PRESENTATION OF WALDENSTROM’S MACROGLOBULINEMIA.
Waldenstrom’s Macroglobulinemia (WM) is a rare lymphoplasmacytoid cell disorder with an overall annual incidence of 2.5/million/year. Of these, less than 5% develop amyloidosis. From 1978 to 1998, only five cases of WM. were reported in African-American women.
We describe a case of 54-year old African-American female with Waldenstrom’s Macroglobulinemia presenting with worsening shortness of breath, orthopnea, and paroxysmal nocturnal dyspnea of 3 weeks duration. Physical examination revealed an elevated JVD, a displaced point of maximal impulse and a S4 gallop. The EKG and 2-D Echocardiogram suggested an old inferior wall infarction and dilated cardiomyopathy respectively. Cardiac catheterization revealed normal coronary arteries. Endomyocardial biopsy was done to search for the cause of cardiomyopathy, which stained positive with Congo red indicating amyloid deposits within the cardiac tissue.
From 1969 to 1990 only 11 cases of systemic amyloidosis with WM. have been reported, thus emphasizing the rarity of the disorder. The clinical course of amyloidosis associated with monoclonal IgM appears to be different from that of other patients with primary amyloidosis. The most striking difference being a higher incidence (44% versus 27%) of cardiac involvement with IgM than with IgG amyloidosis.
In conclusion, when patients with WM. develop symptoms of heart failure, amyloidosis should be suspected and confirmed as amyloidosis complicating WM. is associated with a much shorter survival than in patients with WM. alone.
Submitted ACP National OCT 2002
BRONCHOCUTANEOUS FISTULA: A RARE COMPLICATION OF TUBE
THORACOSTOMY. Sinoj K. John MD, Associate and Thomas Piskorowski, DO,
Bronchocutaneous fistula is a very rare complication of chest-tube placement. It can also happen as complication of positive pressure ventilation and pneumonectomy. Although usually benign, bronchocutaneous fistula can be annoying to the patient.
Our
patient is a 53-year-old female with history of carcinoma of the soft palate,
who presented with rll pneumonia and effusion. Thoracocentesis drained fluid
with ph 7.1, glucose <20 mg/dl,
and LDH of 2500 mg/dl, but no organisms. Thoracic surgery was consulted
for a complicated parapneumonic effusion. After a difficult chest-tube
placement, CXR and CT-Scan revealed persistent loculated hydropneumothorax.
The original chest-tube was removed, and a second tube was placed in a lower intercostal space. On expiration, a loud gurgling gush of air could be heard over the original chest-tube site. CT-Scan revealed a fistulous tract from the bronchus to the skin at the site of the original chest-tube and CXR revealed a subcutaneous fistulous air tract in the lateral chest. Thoracotomy was required with fibrin-glue placement to close the fistula.
Krumpe et.al described a unique physical sign in patients with bronchocutaneous fistula - a high-pitched squeak over the affected chest area during sustained valsalva maneuver. CXR may show air in the subcutaneous space and CT-Scan may reveal the fistula. Treatment options include endoscopic repair, parietal pleurectomy or chemical pleurodesis.
Our case is the only case of bronchocutaneous fistula reported after chest-tube placement. In addition, the unique ct findings presented in this case helped to confirm the diagnosis of bronchocutaneous fistula in the setting of subtle CXR findings, which may be easily overlooked.
Submitted ACP National OCT 2002
ARDS WITH BRONCHO-PLEURAL FISTULA TREATED WITH
ULTRA-HIGH FREQUENCY JET VENTILATION (UHFJV). Sinoj K.
John, MD, Associate and Thomas Piskorowski, DO, FACP.
We report a case of ARDS complicated with Broncho-Pleural fistula successfully treated with UHFJV.
A 24-year-old male presented with multiple rib fractures, pulmonary contusions and hemothorax after a Pedestrian-Motor Vehicle accident. He was intubated, had bilateral chest-tubes placed and was mechanically ventilated. With worsening of his respiratory status and increasing levels of PEEP, he developed worsening bilateral pneumothoraces. Despite nine chest-tubes, he had bilateral pneumothoraces with inability to oxygenate or ventilate. At that point he was placed on UHFJV. Over the next two weeks, his condition improved to where conventional ventilation could be re-initiated with minimal levels of PEEP. While on UHFJV, there were several episodes of sudden O2-desaturation requiring urgent fiber-optic bronchoscopy to clear large mucus-plugs obstructing the airway. One week later he was extubated and all chest-tubes were removed.
Conventional ventilation may cause additional lung injury in ARDS from overdistention during inspiration, repeated opening and closing of small bronchioles and alveoli, or from excessive stress at margins between aerated and atelectatic regions. Smaller tidal volumes and higher end-expiratory lung volumes may be protective. UHFJV is a extreme mode of low tidal volume ventilation. High respiratory rates allow near-normal PaCO2 levels. High inspiratory airway pressures with conventional ventilation can generate and/or increase leak through Broncho-Pleural fistulas. UHFJV can decrease the airway pressures during ventilation.
Our case represents a dramatic example of benefit from UHFJV in a unique patient population, but also demonstrates the hazards described with UHFJV, with several life-threatening episodes of airway-obstruction by jet-induced tracheal mucous-plugs.
Submitted ACP National OCT 2002
VALPROIC ACID (VA) OVERDOSE - SUCCESSFULLY TREATED WITH
HIGH-FLUX HEMODIALYSIS WITHOUT CHARCOAL HEMOPERFUSION.
Objective: To report a case of valproic acid overdose successfully treated with high-flux hemodialysis without charcoal hemoperfusion.
Case Summary: A 24-year-old male was brought to the emergency room several hours after ingesting an unknown amount of valproic acid (VA). The patient was found to be comatose, hemodynamically unstable, with an anion gap metabolic acidosis, and a valproic acid level of 789 mcg/ml (therapeutic range of VA is 50-100 mcg/ml and half-life is 15 to 30 hours in cases of toxicity). High-flux hemodialysis was performed for four hours with an F80A dialyzer. Pre- and post-procedure total drug levels were 596mcg/ml and 260 mcg/ml respectively. The calculated half-life of VA pre-, during and post-procedure was 20 hours, 3.3 hours and 23.9 hours respectively. This suggests high-flux hemodialysis effectively reduce the half-life of VA. The patient’s anion gap metabolic acidosis resolved, and the hemodynamic status and mental condition improved with the acute reduction in the VA levels.
Discussion: In the setting of VA overdose, respiratory depression, coma and even death has been reported. 80 to 95 % of VA is protein bound at therapeutic concentrations and is considered undialyzable. At levels greater than 150 mcg/ml, the fraction of unbound VA increases. There is limited information about the use of high-flux hemodialysis without charcoal hemoperfusion for VA overdose. On performing an extensive medline search, only one case report was found. We report the second case.
Conclusion: High-flux hemodialysis without charcoal hemoperfusion is an effective therapeutic modality for rapidly reducing toxic concentration and serious adverse effects of VA along with other standard measures of treatment.
Submitted ACP National OCT 2002
METASTATIC MALIGNANT LYMPHOMA PRESENTING AS SUPRAVENTRICULAR TACHYCARDIA.
A 38 year old man presented to the hospital with Intermittent palpitations and was found to have supraventricular tachycardia that spontaneously resolved. On physical examination, the patient was noted to have an enlarged, hard right testis measuring about 8 x 5 cms. Ultrasound of the testis revealed a heterogenous, diffuse enlargement of the right testis with increased vascularity. Beta-HCG and alphafetoprotein were within normal limits. Echocardiography performed to evaluate for structural heart disease revealed a 4cm mass effluxing in and out of the tricuspid valve with significant infiltration into the interatrial septum, peri-tricuspid and peri-aortic area with septal thickening. Further staging with CT scan revealed bilateral hilar and retroperitoneal adenopathy with pleural and pericardial effusions and ascites. High inguinal orchiectomy of the right testis revealed a high grade, aggressive, Non-Hodgkin's lymphoma with significant vascular and spermatic cord invasion. HIV serology turned out to be positive. The patient was discharged home uneventfully, but unfortunately died of unknown cause after the first cycle of chemotherapy.
Malignant lymphoma in HIV-positive individuals is an AIDS-defining illness that carries a poor prognosis. Cardiac metastases in the form of endocardial, myocardial and pericardial invasion occur in about 8% of patients with lymphoma and carry a very high mortality. A literature review revealed that it is more common in Non Hodgkins lymphoma than in Hodgkin's lymphoma and can frequently be the cause of death in this population.
We would therefore like to review the incidence, clinical presentation, course, and prognosis of lymphoma with significant cardiac invasion in HIV-positive individuals.
Submitted ACP National OCT 2002
The patient is a 68-year-old African-American male who presented with hemoptysis of one weeks duration. He denied other symptoms. He had never smoked during his lifetime. He did have colon cancer in 1997 for which he underwent surgery and chemotherapy. He had apparent lung metastases by chest X-ray in June 2000. Chest films during this admission revealed multiple nodules, which had increased in number and size, compared to prior films. Bronchoscopy revealed a mass arising from the right upper lobe. Pathology revealed poorly differentiated adenocarcinoma. Immunostaining confirmed metastatic colon cancer with strong positivity for CK20. Immunostains were negative for CK7 and TTF.
Endobronchial metastases from nonpulmonary tumors are uncommon, with estimated incidence of 2%. Breast, colon, and renal carcinomas have been found to predominate. Bronchoscopy is usually diagnostic; the yield is optimized with both biopsy and bronchial brushings. Treatment is usually palliative. Endobronchial metastases occur by direct spread to the bronchus, invasion by a parenchymal lesion or mediastinal or hilar lymph nodes, or peripheral lesions extending along proximal bronchi. In our patient, we believe metastases developed via extension of peripheral lesions. This is supported by bronchoscopic findings and the location of the pulmonary nodules with interval increase in size.
This is one of the few documented cases in the literature of endobronchial spread from a nonpulmonary tumor.
Submitted ACP National OCT 2002
LONG
TERM SURVIVAL IN SMALL CELL CARCINOMA WITH NO EVIDENCE OF REMISSION. Tannu Sahay MD, Associate,
We report a patient surviving more than four years with small-cell carcinoma without evidence of remission.
Our patient is a 55-year-old African-American female who was diagnosed with small-cell carcinoma metastatic to the liver (Biopsy diagnosis) in October 1997. The primary could not be identified. Her symptoms have included abdominal pain, nausea, vomiting, seizures, and obstructive symptoms. CT of the abdomen showed multiple metastases to the liver. No brain metastases were demonstrable. The patient has so far received 6 cycles of etoposide and a palliative dose of external beam radiation. She continues to have massive hepatomegaly with CT scan evidence of metastasis.
Small cell carcinoma is an aggressive tumor with a median survival of 14 to 18 months with limited disease and 8 months with extensive disease. Location of the primary tumor plays an important role in survival. Other factors that have been associated with survival benefit are Diploidy, monoclonality and cells in synthetic phase of DNA replication.
This patient has survived greater than 4 years and has never
shown any radiographic evidence of remission. What needs to be looked into is
whether factors relating to survival can be translated into better treatment of
this disease.
Submitted ACP National OCT 2002
UNUSUAL
PRESENTATION OF WEGENER’S GRANULOMATOSIS. Darshana Tawde, MD, Associate and
Rajika Munasinghe, Member, MD, Sinai-Grace Hospital, Wayne State University,
Detroit, Michigan.
Wegener’s Granulomatosis in a rare vasculatides that presents with involvement of the lungs, kidneys and upper respiratory tract. The majority of patients are C-ANCA positive. A rare pathergic, micronecrotic variant of this disease may present in the pre-granulomatous phase with limited organ involvement. We present such a case and discuss its important clinical and histopathological findings.
A 49 years old male, known smoker presented with productive cough and progressive shortness of breath of 3 months duration. He had a 15-pound weight loss with night sweats, but no fever or haemoptysis. He had been treated for pulmonary tuberculosis on two previous occasions based on abnormal chest radiograph findings. On examination he had an emphysematous chest with decreased breath sounds in the left apex.
Chest x-ray showed a calcified nodule in the left upper lobe and diffuse interstitial infiltrates. Urinanalysis was normal. CT scan of the chest revealed tiny nodules in the left upper and lower lobes. Sputum AFB was negative.
The initial result of an open lung biopsy supported a diagnosis of low grade B cell MALT lymphoma as flow cytometry showed CD19 positivity. Further interpretation by a pulmonary histopathologist lead to a diagnosis of pathergic variant of Wegener’s granulomatosis. The patient responded well to treatment with predinsone and cyclophosphamide.
The prevalence of Wegener’s granulomatosis in the
Submitted ACP National OCT 2002
PULMONARY
VENO-OCCLUSIVE DISEASE (PVOD) in A colon cancer patient treated with
mitomycin-c Ahmed Kaseb, MD, Associate, Dhaval
Shah, MD, Associate, Raj Popat, MD, Lawrence MacDonald, MD, Fellow.
Pulmonary veno-occlusive disease (PVOD) is a very rare cause of pulmonary hypertension characterized by intimal fibrosis of medium sized and small pulmonary veins. Although its etiology remains unclear, on rare occasions it has been associated with several different chemotherapeutic agents.
A 66 year old female with adenocarcinoma of the colon treated with surgery and chemotherapy (mitomycin-c, fluorouracil, and irinotecan) presented to our hospital with increasing dyspnea. Physical examination revealed jugular venous distension, lower extremity edema, a right ventricular heave and bilateral pulmonary rales. Chest radiograph showed bilateral alveolar infiltrates, pulmonary artery enlargement and cardiomegaly. Pulmonary artery catheter recorded a normal pulmonary capillary wedge pressure (12mmHg) and increased pulmonary artery pressure (65mmHg/31 mmHg). There was no evidence of deep vein thrombosis or pulmonary embolism. Echocardiogram showed normal left ventricular function and confirmed severe pulmonary hypertension with right atrial and ventricular dilatation and severe tricuspid regurgitation. PVOD was suspected based on severe pulmonary hypertension and pulmonary edema in absence of left ventricular dysfunction. An open lung biopsy confirmed the diagnosis by presence of thickening of small to medium-sized veins with intimal proliferation and narrowing of the lumina. The patient experienced rapid hemodynamic collapse and expired after bleeding from an unknown source.
PVOD should be suspected in patients treated with chemotherapeutic agents (bleomycin, vincristine, cisplatin, carmustine and mitomycin-c) when they present with pulmonary hypertension and pulmonary edema without left ventricular dysfunction. PVOD can be confused with several more common entities if clinician is unaware of it. Making a positive diagnosis can help avoid otherwise unnecessary diagnostic workup and treatment.
Submitted ACP National OCT 2002
INFECTED VENTRICULOPERITONEAL (VP) SHUNT PRESENTING AS
PERITONITIS.
Bacterial peritonitis is an uncommon presentation of Ventriculoperitoneal
(VP) shunt infection.
We are presenting a
case of a 26-year-old lady with a VP shunt for more than 20 years. She presented with abdominal pain, nausea,
vomiting and fever for 4 days. She had
three shunt revisions in the past, and the most recent one was 3 weeks
ago. On examination she had diffuse
abdominal tenderness and rebound with decreased bowel sounds. She had no
meningeal signs and VP shunt path showed no signs of infection. White cell count was 15900/cumm. CSF exam
showed RBC 34/cumm ,WBC 5/cumm , glucose 102 mg/dl and protein 18 mg/dl.
Peritoneal fluid was hazy straw colored with RBC 3370/cumm WBC 6540/cumm with
91 % neutrophils. Abdominal X- ray
showed ileus pattern and CT abdomen showed evidence of peritonitis.
Exploratory laparotomy
was performed with externalization of the shunt. CSF and peritoneal fluid culture grew Gram
Positive Cocci, later identified as Staph aureus (MRSA). Vancomycin and
Rifampin were started. Once CSF became
negative and she became afebrile shunt revision was done.
Bacterial peritonitis is an uncommon complication of VP shunts. Index of suspicion should be high when abdominal findings of peritonitis are seen in a patient with a VP shunt. Infection has been reported to develop in 5%-27% of VP shunts. The risk factors include cause of hydrocephalus, the variability of surgical experience, operating time, type of procedure, age less than 4 months, early postoperative period and skin contamination at time of operation. There is a 13% mortality rate associated with VP shunt infection. Treatment requires immediate Externalization plus antibiotics and revision once the infection is controlled.
Submitted ACP National OCT 2002
NEOSTIGMINE
AND GHRH EFFECTS ON GH RELEASE IN SHEEP.
Sinai-Grace
Hospital, Detroit Medical Center/Wayne State University – Detroit, Michigan and
Department of Endocrinology, The University of Michigan - Ann Arbor, Michigan.
The responses of growth hormone
(GH) to several pharmacological stimuli are additive or synergistic with a
maximum dose of GH-releasing hormone (GHRH). This suggests that these agents
have GH releasing mechanisms that are, at least in part, independent of GHRH
secretion. It was previously reported that neostigmine is synergistic with
GHRH, stimulates hypothalamic GHRH secretion but does not decrease somatostatin
release and has no direct pituitary effect on GH. Ghrelin, a novel acylated
peptide that was recently identified as the endogenous ligand for the growth
hormone secretagogue (GHS) receptor. We hypothesized that ghrelin might be
involved in mediating the GH response to neostigmine.
Eight castrated male
lambs were studied after an overnight fast on 4 separate days. Treatments
included saline control, GHRH, neostigmine or GHRH + neostigmine I.V. Studies
were performed in random order. Jugular blood was collected every 20 min from
an indwelling catheter. GH and ghrelin levels were measured by ELISA using
assays developed in our laboratory.
No correlation could be made between ghrelin and GH release
after pharmacological stimulation, as neostigmine administration was not
followed by any increase in GH release, as previously reported in a French
experiment. However, GHRH administration
induced a significant increase in GH release that was sustained during the two
hours of measurements, also a discordant result from the French data. Ghrelin
levels remained in the same range throughout the experiment. Could sex hormones
play a role in this mechanism, or neostigmine doesn’t release GH in sheep?
Possibilities are discussed.
Submitted ACP National OCT 2002
SICKLE CELL PAIN
CRISIS GONE AWRY: ACUTE MULTIORGAN FAILURE SYNDROME (MOSF) COMPLICATING SICKLE
CELL PAIN CRISIS Dhaval Shah, MD, Associate, Barry Lesser, MD, Member.
Acute MOFS is a rare, life threatening complication of the pain crisis in sickle cell disease. It is characterized by development of severe dysfunction of at least two out of three major organs (lung, liver, kidney) during a sickle cell pain episode.
A 28-year-old African American female with
Acute MOFS complicating sickle cell pain episode is more common in patients with otherwise mild sickle cell disease (with less frequent and less severe pain crises) who have high baseline hemoglobin levels. It is important to recognize this entity because early recognition and aggressive transfusion therapy may promptly reverse the disease process. All clinicians who manage patients with sickle cell disease should be aware of this life threatening complication.
Submitted ACP National OCT 2002
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.
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 National OCT 2002
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.
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 National OCT 2002
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.
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