2004 ACP Associates Meeting Abstract Submissions
PROPOFOL ASSOCIATED
RHABDOMYOLYSIS WITH CARDIAC MUSCLE INVOLVEMENT IN AN ADULT PATIENT.
Haleh. Haerian, MD, (Associate) and Rajika L. Munasinghe, MD (Fellow), Sinai-Grace Hospital, Wayne State University, Detroit, Michigan.
Introduction: Propofol is a centrally acting agent used increasingly for sedation during mechanical ventilation. Rhabdomyolysis has been described as a dose dependant idiosyncratic reaction to propofol infusions in pediatric patients. Two adult cases (one fatal) of rhabdomyolysis have been reported when propofol was administered with steroids during mechanical ventilation for severe asthma and an interaction with steroids has been incriminated. Involvement of cardiac muscle in rhabdomyolysis is rare and has been usually reported in rhabdomyolysis due to drugs and toxins.
Case Report: A 29-year-old male with history of seizures, was intubated in the emergency room for airway protection following a breakthrough seizure and placed on mechanical ventilation. He received propofol infusion for sedation. After 38 hours, he developed acute renal failure with elevated CPK levels of 15,000 U/L. Approximately six hours later, he developed pulmonary edema from heart failure with an ejection fraction of 15% and elevated serum troponin-I of 25 µg/L. His condition gradually improved with management in the intensive care unit and he was weaned off the ventilator within a week. Cardiac catheterization performed after recovery from renal failure revealed no evidence of coronary artery disease and recovery of cardiac function with an ejection fraction of 50%.
Discussion: We report a unique case of rhabdomyolysis with reversible cardiac muscle involvement in an adult patient receiving propofol, without the concomitant use of steroids. Although seizures could have caused his rhabdomyolysis, the involvement of cardiac muscle supports a toxic etiology. It is important that this serious adverse reaction of propofol be recognized as discontinuation of the drug can lead to rapid recovery from cardiac and renal dysfunction.
PPAR-γ IS A
POTENT INHIBITOR OF NEUTROPHIL FUNCTION IN SEPSIS
Ghaffari M* (Associate), Reedy R, Smith I, Zeng X,
Newstead M, Rodriguez M, Standiford T, *Department of Internal Medicine,
Sinai-Grace Hospital, Wayne State University, Detroit, Michigan, Department of Internal Medicine,
Division of Pulmonary and Critical Care Medicine, University of
Introduction: Sepsis results in a profound state of immunosuppression, which occurs in association with a substantial impairment in leukocyte function. Peroxisome proliferator-activated receptor-gamma (PPAR-g) is a ligand-dependent transcription factor belonging to the nuclear hormone receptor superfamily. Importantly, activation of PPAR-g has been shown to negatively regulate the activation of monocyte/macrophage populations. However, the function of PPAR-g in regulating neutrophil function, and how PPAR-g expression in these cells may be altered in sepsis has not been defined.
Hypothesis: PPAR-g is an important negative regulator of neutrophil function, and activation of PPAR-g contributes to the dysfunction of the neutrophils observed during the septic response.
Methods: Neutrophils were isolated from healthy subjects and patients with sepsis. Expression of PPAR-γ mRNA was defined by RT-PCR. Neutrophils were treated with either endogenous (PGJ2) or exogenous (Troglitazone) PPAR-γ agonists, then effects on the neutrophil proinflammatory cytokine production, migration, and apoptosis determined by ELISA, chemotaxis bioassay and single strained DNA analysis, respectively.
Results: Neutrophils expressed minimal PPAR-γ mRNA at rest, but PPAR-γ message was induced by cytokines released in sepsis, including TNF and IL-4. Treatment of neutrophil with PPAR-γ agonists dose-dependently inhibited LPS induced cytokine production and FMLP-induced chemotaxis. Moreover, selected PPAR-γ agonists induced neutrophil apoptosis at 24 hours. Finally we observed constitutive expression of PPAR-γ mRNA in neutrophils isolated from sepsis patients, but not neutrophils from healthy control subjects.
Conclusion: PPAR-γ is a potent inhibitor of neutrophil function in vitro, and the expression and activation of PPAR-γ in sepsis may contribute to the suppression of neutrophil function observed in sepsis .Modulating the activity of PPAR-γ may serve as a potential therapeutic modality in the management of sepsis immunosuppression.
ADENOCARCINOMA OF THE
LUNG PRESENTING AS SYMPTOMATIC HYPERCALCEMIA
Tabarak Qureshi, MD (Associate), Shazia Essani, MD (Member),
Dr. O Al Zohaili, MD.
Objectives: Hypercalcemia with squamous cell cancer of the lung is a common metabolic problem. However hypercalcemia with Adenocarcinoma of the lung is a rare presentation.
Case History: A 51 year old African-American male with no significant past medical history was admitted for elevated calcium level of 18 mg/dl. He complained of right-sided lower rib and right upper quadrant pain with a six-month history of constipation & 40-pound weight loss. Physical exam was significant for tenderness over the lower right rib cage, with dullness to percussion and decreased breath sound over the right lower zone of the lungs. Laboratory analysis showed intact parathyroid hormone was <1.0, parathyroid related peptide was within normal limits. Work up for Multiple Myeloma was negative. A chest radiograph showed a right paratracheal suprahilar mass with a right-sided pleural effusion. CT showed a right-sided pleural effusion with a nodular surface and generalized mediastinal lymphadenopathy. Thoracentesis revealed an exudative picture and the cytology was significant for adenocarcinoma. A bone survey and bone scan did not show any evidence of metastases. Treatment of the hypercalcemia included intravenous fluids, pamidronate and lasix and mineral oil enema for constipation. Patient was discharged with a follow-up with oncology.
Conclusions: Adenocarcinoma of the lung presenting as symptomatic hypercalcemia is rare in the absence of a parathyroid dysfunction. Extensive search of the English literature did not report such a presentation.
PANCOAST SYNDROME AND METHICILLIN RESISTANT STAPHYLOCOCCUS PNEUMONIA: AN UNCOMMON PRESENTATION.
Anjali Gupta MD (Associate), Tabarak Qureshi MD
(Associate), Rose Andriacchi (Member),
Introduction: Staphylococcus aureus pneumonia is a common presentation. However, methicillin resistant staphylococcus aureus (MRSA) pneumonia presenting as Pancoast Syndrome is an uncommon presentation.
Case Report: A 47 year old African American female
with a history of T2 to T6 vertebral fusion after a MVA and an obsessive
compulsive disorder presented with severe back pain, Horner’s syndrome, and
numbness and tingling in her left arm. A
chest X-ray showed a left upper lobe mass. Laboratory analysis revealed a white
cell count of 14.7 K/CUMM. The patient was isolated and tuberculosis was ruled
out with three sputum samples negative for AFB, followed by a bronchoscopy and
BAL. Tissue samples from the bronchoscopy showed an organizing pneumonia.
Sputum and blood cultures were positive for MRSA. She was started on intravenous vancomycin and
a MRI was obtained. Results of the MRI showed a 3 cm x 4 cm mass in the left
upper lobe with encasement of the lower part of the brachial plexus.
Conclusion: Pancoast syndrome and methicillin resistant staphylococcus aureus pneumonia is a rare presentation. Extensive search of the English literature revealed one report similar to the case presented above. We report the second case.
SUCCESSFUL PREGNANCY
IN A PATIENT ON HEMODIALYSIS
Pregnancies and their successful completion in patients on hemodialysis is rare. Fetal survival rates on hemodialysis have been reported to be anywhere between 20% to 46%. The incidence of both maternal and fetal complications is high.
We present a 38-year old woman, G7 P4 A2, with chronic renal
insufficiency. At the time of
conception, her creatinine clearance was 12.
Patient was on hemodialysis when her pregnancy was diagnosed. Her hemodialysis regimen, which consisted of
three, three hour sessions a week was increased to six, three hour sessions a
week. The patient’s was allowed a weight
gain of 0.2 to 0.5 kg /week. Strict
blood pressure control was maintained.
Her target hemoglobin was
Improvement in dialysis techniques and growing knowledge of complications in a pregnant patient on hemodialysis has made successful completion of a full term pregnancy a viable option. We no longer feel that these women should be advised to terminate pregnancy as an only option. By increasing the frequency of dialysis regimen, maintaining strict control of clinical and laboratory parameters and coordinating between nephrology and obstetrics services, we can change the once perceived dismal outcomes of these pregnancies.
NEPHRIN REVERSE
TRANSCRIPTASE-QUANTITATIVE POLYMERASE CHAIN REACTION (RT-QPCR) OF URINARY
SEDIMENT IS A POTENTIAL EARLY MARKER FOR DIABETIC NEPHROPATHY.
Ahmed O. Kaseb,MD(1), David M. Kurnit,MD,PhD(2), Kun Yang,MD(2), Ayman Khafagi,MD(2), William H. Herman,MD(3). Sinai-Grace Hospital/Wayne State University(1), Departments of Pediatrics and Human Genetics(2) and Internal Medicine(3), University of Michigan Medical School.
Nephrin is a key component of the renal ultrafiltration barrier. In the urinary tract, it is expressed solely in glomerular podocytes. Loss of podocytes, and thus high urine nephrin levels is associated with the clinical and histologic features of diabetic nephropathy in animals and humans.
Methods: We have developed and validated a reverse transcriptase, quantitative polymerase chain reaction (RT-QPCR) assay that uses the gene product of NPHS1 (coding for nephrin) to detect abnormal excretion of podocyte cell products into the urine and have tested it in normal and diabetic volunteers.
Results: The assay was reproducible in diabetic subjects with and without renal disease over 1-2 years. A normal range of < 10 molecules (in an aliquot of urine sediment derived from 40 ml of urine) was established in non-diabetic volunteers with normal urinary sediments. In cross-sectional studies, 13/45 (29%) of type 1 diabetic patients with durations of diabetes < 10 years and without microalbuminuria had abnormal elevations of nephrin RT-QPCR. The majority (27/49 = 55%) of diabetic patients treated with ACE I or ARB had low nephrin RT-QPCR regardless of whether albuminuria was present.
Conclusions: The nephrin RT-QPCR assay is sensitive and reproducible. It may provide an early way to assess the status of glomerular podocytes in diabetics, especially in the pre-microalbuminuric state. Nephrin RT-QPCR may also be a useful non-invasive way to monitor response to anti-proteinuria therapy. Further prospective observational and treatment trials are indicated.
CD3+, CD4+, CD8+
LARGE GRANULAR LYMPHOCYTOSIS(LGL) FOLLOWING HODGLIN'S LYMPHOMA
Ahmed Kaseb, MD(1)(Associate), Brian Douglas Jenkins(2), Ayad Al-Katib,MD(2), Daniel Snower,MD(2), Anwar Mohamed,MD(3).
Sinai-Grace Hospital/Wayne State University(1), Van Elslander Cancer Center and Dept. of Pathology, St. John Hospital and Medical Center, Detroit, MI(2) and Cytogenetics laboratory, Dept. of Pathology/Wayne State University(3)
INTRODUCTION
Large Granular Lymphocytosis (LGL) has been reported in association with various diseases including Cytomegalovirus infection and autoimmune disorders. Only four cases of lymphocytosis of LGL following Hodgkin’s Lymphoma has ever been reported.
CASE REPORT
Our case is a 41-year-old female of Italian ancestry with a variant of LGL developed thirty months after her first complete remission following treatment with ABVD chemotherapy regimen for stage IIIA Hodgkin’s Lymphoma. The patient was found to have leukocytosis on a routine evaluation with WBC of 12,000/uL and an absolute lymphocyte count of 9,840/uL. She was asymptomatic and with normal physical examination. Immunophenotyping of the lymphocytes showed that 94% were CD2+, CD3+ and CD5+ T-cells. 80% of these cells were also CD4+ and CD8+. The patient remained asymptomatic as of the last follow up six months from the diagnosis of LGL.
DISCUSSION AND CONCLUSION
Only four cases of lymphocytosis of LGL following Hodgkin’s Lymphoma has ever been reported. Three cases were CD3- and one was CD3+. Our case is a variant of LGL that has more positive CD receptors. Our case is the fifth reported case of LGL following Hodgkin’s Lymphoma highlighting a possible association between the two entities.
GENETICS OF THE HUMAN URIC ACID TRANSPORTER (hUAT)
B.N. Nandish, M.D., Sinai Grace Hospital, Detroit Medical Center, Wayne State
University, Detroit, MI. Michael S. Lipkowitz, M.D., Associate Professor, Mount
Sinai School Of Medicine, New York, NY.
INTRODUCTION: Elevated levels of uric acid have been associated with an
increased risk for gout, hypertension, cardiovascular disease, and renal
failure. Recent studies suggest that hyperuricemia precedes and predicts the
development of hypertension in adults and adolescents. Molecular mechanisms for
diminished excretions of urate in theses disorders is not well understood.
HYPOTHESIS: Data suggests galectin 9 is a functional human homologue of the rat
UAT. It also contains the putative channel forming transmembrane domain of UAT.
Data clearly indicate that mutations in individual ion transport proteins in
renal tubule can result in significant renal disease.
METHODS: Patients are from the NIH funded ancillary study of African-American
study of kidney disease who are expected to have hyperuricemia due at least in
part to abnormal urate excretion. Genomic DNA are extracted from peripheral
blood leukocytes. Polymerase chain reaction (PCR) for exon 1are done using a
gradient cycler. PCR products are digested with restriction enzyme MSPA1
followed by gel electrophoresis using ethylene bromide dye.
RESULTS: Results of PCR gel electrophoresis were analyzed for genotype GG and
mutation genotype GA. The mean uric acid levels in studies done so far have
shown marginal elevation of uric acid in genotype GA.
DISCUSSION: Confirmed mutations will be generated in hUAT in expression vectors
and for normal expression in cells. Localization of hUAT as a membrane protein
will be done using the membrane biotinylation. Finally mutations detected are
being cloned into a bacterial expression vectors for generation of recombinant
protein to test for ion channel function in a lipid bilayer system.
CONCLUSION: There is good reason to believe that UAT ion channel may be
responsible for alterations in uric acid excretion by the kidneys, seen in
pathophysiologic states such as gout, hypertension and familial hyperuricemia
syndromes.
CASE REPORT OF ORAL AMIODARONE INDUCED FULMINANT HEPATIC FAILURE.
Tannu Sahay, MD, Associate, Samer El-Dirani, MD,
Associate, Jennifer Ui, MD, Arpita Patel, PharmD, Thomas Piskorowski, DO,
Department of Internal Medicine, Sinai-Grace Hospital/Wayne State University,
Detroit, Michigan..
CASE SUMMARY- Our patient is an 82-year-old male with no history of ethanol use
who came to the hospital with hypotension and a syncopal episode related to
hypovolemia that required intubation and mechanical ventilation. His past medical history was significant for
coronary artery disease with an EF of 20% and CABG performed approximately 9
years ago, tachy-brady syndrome for which he had a pacemaker-AICD placed and
end stage renal disease. Pacemaker interrogation did not reveal any arrhythmic
event. He had coagulopathy (INR-3) but no clinical evidence of any overt bleeding.
He had been on coumadin since the CABG.
Liver function tests were normal. The patient was successfully extubated
the next day and was sent to the general medical floor on hospital day number
3. His home medications, including
amiodarone 200 mg
DISCUSSION- Most cases of Amiodarone-induced hepatotoxicity are related to
parenteral administration, higher cumulative doses and prolonged duration of
therapy. Our patient is unique since he was on oral amiodarone for no longer
than 20 days. Amiodarone-induced hepatotoxicity is usually reversible with the
withdrawal of the medication.
CONCLUSION- Amiodarone-induced Hepatotoxicity is a rare complication. However,
it should be considered before addition of any other hepatotoxic agent. Also, liver function studies should be
followed on a regular basis.
PNEUMOCYSTOSIS OF THE BRAIN PRESENTING AS RING ENHANCING
LESIONS - A RARE CLINICAL MANIFESTATION.
A Reddy, MD (Associate), B Sudhir, MD (Associate), B Ismail, DPM, S.Marur,
MD (Member), L.Ganesan, MD; Department of Internal Medicine, Sinai Grace
Hospital/Wayne State University, Detroit, Michigan.
Introduction:
Pneumocystis carinii infection is predominantly localized to
the lungs. However, 0.5 to 2 % of persons with AIDS can present with extra
pulmonary Pneumocystitis. Among these, involvement of CNS is the most uncommon
presentation of Pneumocystis carinii infection.
Case Discussion:
A 42 Year old African American male with a past medical history of AIDS ,
Cryptococcal meningitis and seizure disorder, presented with focal seizures of
the right lower extremity followed by Todd’s paralysis. His medications
included fluconazole, bactrim, zithromax, neurontin and HAART therapy. At
presentation, he had an initial viral load of 10,000 and a CD4 count of 255. CT
Scan with contrast showed multiple ring enhancing lesions at vertex. MRI with
contrast showed irregular thickened meninges in the parietal region with
multiple ring enhancing lesions bilaterally in the parietal cortex. CSF was
positive for Cryptococcal antigen at a titer of 1:256. Serum titers were
negative for Toxoplasma. A stereotactic biopsy of the brain was performed with
a high clinical suspicion of cerebral lymphoma. The histo-pathology report of
the tissue was positive for Cryptococcus as well as Pneumocystis carinii. Chest
X ray was negative for Pneumocystis carinii pneumonia. Treatment was started
with amphoterecin-B along with flucytosine and bactrim. Patient developed
anaphylactic reaction both to regular as well as lipophilic amphotericin-B and
was treated with high dose fluconazole.
Conclusion:
This is the first time this condition presented with ring enhancing lesions
coexisting with Cryptococcus infection in a patient with AIDS. There have been
two previous reports of cerebral Pneumocystosis which were, however, diagnosed
on autopsy. Recognition of this coexistence can be a valuable consideration in
patients with AIDS who present with ring enhancing lesions on neuro-imaging.
Sterol and stanol ester based margarines have a
significant role in reducing plasma cholesterol levels.
Arvind Reddy, M.D, M.P.H .
Department of Medicine,
Research Question:
In normocholesterolemic and mildly
hypercholesterolemic individuals, do sterol and stanol ester based margarines
help in lowering cholesterol levels when used alone or in adjunct with other
cholesterol lowering agents?
Data Source:
Experimental studies from the MEDLINE database from
1998 – 2003 using Pubmed and Ovid.
Study Selection:
Randomized trials included in this review were
identified by a MEDLINE search term "plant sterols."
Studies focusing on normal to mildly hypercholesterolemic subjects who were not
on any cholesterol lowering therapy except the NCEP step 1 diet were selected.
A small group of studies involving subjects already on a single lipid lowering
drug were also selected.
Outcome Measures:
The data points chosen as outcome measures in these
studies were the plasma levels of total cholesterol, LDL cholesteorol and HDL
cholesterol.
Results:
The first randomized controlled study involving 224
subjects already on NCEP step 1 diet, showed that sterol based margarines
decreased total cholesterol by 7.1 % and LDL cholesterol by as much as 10% at
the end of the 5 week trial period with no significant impact on HDL levels. In
another study involving 100 subjects on three different doses of sterol based
margarines a dose dependent response was observed with a decrease in total
cholesterol by 4.9%, 5.9% and 6.8% and LDL cholesterol by 6.7%, 8.5% and 9.9%.
There was no significant change in HDL levels. In another study involving 141
subjects comparing sterol and stanol ester based margarines, stanols showed an
increase in HDL cholesterol levels by 1.4% apart from lowering LDL levels by
about 13% at the end of the 90 day period. In the last study involving 167
subjects, stanol ester based margarine showed a reduction in LDL cholesterol by
as much as 24% when used in adjunct to intermediate dose of statins at the end
of 8 weeks.
Conclusion:
Stanol and sterol ester based
margarines are very effective in reducing total and LDL cholesterol levels in
normocholesterolemic and mildly hypercholesterolemic individuals when used
alone or in adjunct to statin therapy. Stanol ester based margarines have an
additional benefit of raising HDL cholesterol levels when compared to sterol
ester based margarines.
ALTERNATIVE
METHODS OF BONE MINERAL DENSITY (BMD) ASSESSMENT.
Vibha Nayak, MD (Associate), Dept. Of Medicine,
Question:
A 50 year old woman with a family history of hip fracture is
seen by you for routine physical examination and preventive care. You are
contemplating the use of peripheral bone densitometry in favor of a complete
bone mineral density assessment.
- What
methods are available?
- Which
sites have been evaluated?
- How
effective are they as compared to standard BMD assessment of the hip,
spine, and forearm?
Data sources:
Studies were identified by searching MEDLINE (1998 to 2003),
journal reviews and the following sources
National Osteoporosis Foundation(NOF)
Ovid-Cochrane
Pubmed
American Journal of Densitometry
British Journal of Radiology
Study selection:
Mulitple studies were conducted for comparison of Pheripheral densitometry and central densitometry.
All were prospective studies conducted over a period of 2 – 10
months.
Data extraction:
One investigator independently extracted data on patients,
interventions, and outcomes.
Main results:
As compared to
- The
sensitivity (T-Score < -2.5) and specificity (T-score>-2.5) of heel ultrasound was 34 and 94 %
respectively. The figures were 23% and 92% for finger DXA. The sensitivity
of both methods went up as the cut-off values for diagnosis of
osteoporosis was increased, however the discordance rates increased
correspondingly.
- RA had
the highest specificity (67%) followed by quantitative ultrasound(64%)
at a sensitivity level of 90% for
both.
- Applying
a calcaneal ultrasound in the detection of osteoporosis but using a
T-score threshold of < -1, the overall sensitivity was 51% and
specificity was 93% in detecting low bone mass at the femoral neck .
Conclusion:
More studies are
needed to examine the efficacy and benefits of
peripheral densitometry methods over DXA. As seen previously
peripheral densitometry has a low sensitivity.
Hence, it does not have much of a role
in screening for low BMD. These devices are not an equitable replacement
for central DXA in screening for osteoporosis.
One strategy, however, might be to use DXA as a initial screener and once osteoporosis is detected and treatment initiated, subsequent follow up can be done by peripheral methods.
COPAXONE INDUCED PLEURAL EFFUSION AND HILAR
LYMPHADENOPATHY
V. Nayak, MD, Associate, D. Obeid, MD, Associate, L. MacDonald, MD,
Copaxone or Glatiramer Acetate is an
immunomodulatory agent used in the treatment of Multiple Sclerosis (MS). The drug has been shown in controlled
clinical trials to reduce the frequency of relapses in MRI-defined disease
activity and burden in relapsing –remitting MS. Most common side effects in
patients on copaxone include injection site reactions, vasodilatation,
depression, dizziness, dyspnea, and urticaria. This case report is to
demonstrate the manifestation of pleural effusion and hilar lymphadenopathy
secondary to copaxone.
We report a 28 year old African-american female who is a nursing home resident with history of MS maintained on copaxone 20 mg SC once daily since March 2003 who was admitted to the hospital in August 2003 with a one week history of progressively worsening shortness of breath. She was found to have a right pleural effusion as well as hilar lymphadenopathy. Additionally, soft tissue fullness was now evident in the subcarinal region that may have represented additional lymph nodes. The pleural effusion was found to be exudative with a predominance of macrophages. The possibilities of Tuberculosis, malignancy, granulomatous diseases and infections were considered. A thoracoscopic biopsy was done which showed focal perivascular chronic inflammation mainly composed of lymphocytes. No atypical cells or granulomata were identified. Therefore, we concluded that these findings are drug-induced secondary to Copaxone.
Copaxone has been shown to cause lymphadenopathy, mainly localized to draining lymph nodes. Biopsy findings on reported nodes in the literature were similar to that found in our patient. However, we present this case to demonstrate unilateral pleural effusion and hilar lymphadenopthy as a hitherto undocumented manifestation of copaxone.
DOES GENISTEIN HAVE A SYNERGISTIC THERAPEUTIC EFFECT WHEN
USED WITH CISPLATIN IN TREATING HEAD AND NECK CANCER CELL LINE?
Tawhida Khatoon, MD, Associate,
Fazlul Sarkar, PhD, Sinai-Grace Hospital and
Wayne State University, Detroit, Michigan.
Approximately
40,000 cases of Squamous Cell Carcinoma
of the head and neck are diagnosed every year in the
11,000
patients die of this disease every year. These patients are at increased risk
of developing second primaries involving their upper aerodigestive tracts.
Cisplatin is one of the main stay of treatment along with radiation.
We were looking for a new compound that is non-toxic that may be used as an effective chemotherapeutic agent for cancers of the head and neck in addition to Cisplatin. Genistein is a drug that is being used in phase I trial of breast cancer treatment.
Prior research by Alhasan,
Ensley and Sarkar has demonstrated strong molecular evidence of the antitumor
activity of Genistein in highly nondifferentiated squamous cell carcinoma
(HNSCC) cells by inducing cell cycle arrest and apoptosis in such cells. My
research hypothesis is that addition of Genistein to Cisplatin will
significantly enhance the therapeutic response of Cisplatin.
HN12 cells were cultured in
special media. Cells were treated with Genistein and Cisplatin separately and
in combination for various lengths of time, namely 24, 48 and 72 hours. Viable cell growth was
determined by the standard MTT reduction assay. Cell apoptosis
was determined by the cell death detection Elisa kit. The results revealed that either compound alone killed less than 50% of
the viable cells proving HN12 cell line to be a rather resistant cell line.
However, in combination using longer incubation periods, there was evidence of
minimal enhancement of the therapeutic effects Cisplatin. Therefore, the
combination of Cisplatin and Genistein did not prove to be synergistic in their
therapeutic benefits in the HNSCC cells. Nonetheless, there was some
cell-killing achieved by Genistein alone with longer incubation periods.
This may provide Genistein with a role in
chemoprevention of second primaries pending further research.
SYNDROME OF
INAPPROPRIATE SECRETION OF ANTI-DIURETIC HORMONE (SIADH) CAUSED BY
ADENOCARCINOMA OF THE
R Kotihal, MD, Associate,
M Ghaffari, MD, Associate, and O
SIADH has many etiologies including ectopic production of
anti-diuretic hormone (ADH) by lung cancer or other neoplasms, eutopic release
by various diseases or drugs, and exogenous administration of ADH or its
analogues. Among neoplastic producers of ectopic ADH, we know pulmonary tumors,
sarcomas, breast tumors and brain tumors are common.
We report a rare case of adenocarcinoma of the colon with
the classic features of SIADH. A 76-year-old-man who complained of abdominal
pain and constipation, had guaiac positive stools. At the time of admission, he
was found to be hyponatremic with a normal blood pressure and euvolemia. Laboratory
examination showed serum sodium of 124 mEq/L, plasma osmolality 257 mosm/kg,
urine sodium 83 mEq/L and urine osmolality of 268 mosm/kg. The liver function
tests, cortisol levels, TSH and imaging studies of the head and the lungs were
found to be normal. The hyponatremia was too early to be caused by the facial
trauma, which occurred one hour prior to the admission. Colonoscopy revealed a
mass at the rectosigmoid junction with more than 90% obstruction. Partial
colectomy was performed and pathologic analysis of the mass revealed a
moderately differentiated adenocarcinoma. Three days following the surgery, an
initially difficult to correct hyponatremia was found to be within the normal
range.
A review of literature revealed only two other cases of adenocarcinoma
of the colon presenting with SIADH. We report the third such case.
SIADH can be a paraneoplastic manifestation of colon carcinoma and this case underlines hyponatremia as one of the presenting symptoms of a colonic malignancy. After having ruled out the obvious causes of SIADH, a diagnostic colonoscopy could be included in the search for ectopic causes.
CASE REPORT OF
ISOLATED HYPOPARATHYROIDISM
Introduction: Hypoparathyroidism is a state of inadequate parathyroid hormone (PTH) secretion where ionized calcium in the extra cellular fluid decreases. The causes of primary hypoparathyroidism are diverse representing disruptions of one or more steps in development and maintenance of PTH secretion.
Case Report: We describe a case of 68 yr old middle-eastern female who came in with tingling of her fingers and toes, hand tremors, palpitations and muscle cramps of her legs for the past 3 years. Past medical history was strikingly negative for any neck surgery or irradiation of neck. Physical examination was significantly positive for chvostek’s and trousseau’s sign. Labs: Ca 4.5, P 6.5, Mg l.4. Albumin, activated vita D3, 24 hr urine Ca , TSH, prolactin and cortisol levels were all within normal limits but PTH was inappropriately low <5pg/ml (Normal PTH 11-65 pg/ml ). Patient was diagnosed with primary isolated hypoparathyroidism. Patient was started on calcium and vitamin D replacement therapy and was told to wear an alert bracelet. She follows up regularly and continues to do well.
Discussion: Primary hypoparathyroidism can be due to wide variety of causes. It is most commonly due to damage or removal of parathyroid glands during neck surgery like thyroidectomy or following removal of parathyroid adenoma for primary hyperparathyroidism or following neck irradiation. It can be seen as a part of autoimmune polyglandular syndrome, which is characterized by the presence of at least two of the following: candidiasis, hypoparathyroidism and Addison’s disease. Parathyroid deficiency can occur form developmental defects like DiGeorge syndrome or as a result of damage from heavy metals, granulomatous diseases. A very rare cause of hypoparathyroidism is primary isolated hypoparathyroidism where it is seen as isolated entity and not due to any of the causes as mentioned above the cause of which is exactly not known. Our patient was also thus diagnosed with isolated hypoparathyroidism.
Conclusion: The most common cause of
hypoparathyroidism is acquired like post surgical. Isolated hypoparathyroidism
is a diagnosis of exclusion and is a rare entity. It should be as a part of
differential diagnosis in a patient coming with hypocalcaemia secondary to
hypoparathyroidism. The index of suspicion should be high in patients who have
not had any neck surgery or irradiation. In our literary search we could not
find any case reports in
ATYPICAL CLINICAL COURSE OF SPLENIC LYMPHOID
HAMARTOMA: A CASE REPORT
Yadav,
Suresh MD (Associate); Tawde, Darshana MD (Associate); Eisenberg, Leopold
MD, FACP Sinai-Grace Hospital / Wayne State University,
Detroit, Michigan.
Introduction: splenic lymphoid hamartomas are rare lesions of the spleen, which
histologically show localized reactive lymphoid hyperplasia. The majority of
patients remain asymptomatic but in a small group of patients they present a
wide range of clinical manifestations.
Case report: a 24 years old caucasian male of italian descent with a history of
chronic anemia initially presented with fatigue and later, with syncope. His initial workup
revealed severe hypochromic microcytic anemia with thrombocytosis. Bone marrow
did not show iron depletion or any intrinsic marrow disease. His esr and
c-reactive protein levels were also highly elevated. Gastrointestinal studies
were normal. He was incidentally found to have iga deficiency. A detailed
assessment of his hemoglobin and that of his family members did not reveal any
hemoglobinopathy. Further work up with ct scan of the abdomen, unexpectedly,
revealed 3.6 x 3.8 cm solid mass in the spleen with
mild splenomegaly, which increased in size over a period of few months.
At this point,
an elective splenectomy was done. Histologically, the splenic mass revealed a
large distinct nodule and several satellite nodules. They were composed of
large follicles with large germinal centers and numerous plasma cells in the
interfollicular areas. In the normal part of spleen, there was an increase of
reactive follicles as well as large t zones but only a moderate number of
plasma cells. These were diagnosed as a localized reactive lymphoid hyperplasia
of the spleen or lymphoid hamartomas. Cytogenetic studies did not reveal any
abnormalities. Interestingly, after splenectomy, his hematological abnormalities normalized and the markers
of inflammation subsided to normal levels.
Conclusion: lymphoid hamartomas of the spleen are rarely reported entities and only
7 cases have been documented in the literature in adults. Seen mainly in
children, most patients are asymptomatic. A few present with hypersplenism and
are less commonly associated with acute infections such as measles and typhoid.
It can be differentiated from lymphoma, inflammatory psuedotumor of the spleen
and splenic hamartoma only by histopathology. This may be the first documented
case of a lymphoid hamartoma presenting with anemia of chronic disease.
NON-FUNCTIONING
ANAPLASTIC ADRENOCORTICAL CARCINOMA PRESENTING AS CARCINOMATOSIS.
Raghukumar D. Thirumala M.D, Associate; Apurva Motivala M.D, Associate;
and Manesh Kottapuram M.D, Member.
Adrenocortical carcinoma is a rare, aggressive tumor usually affecting young children and adults. Approximately 60% of tumors are hormone producing on presentation. Non-functioning anaplastic tumors are heralded by symptoms of local invasion by tumor or by metastasis. Most common sites of metastasis are peritoneum, lung, liver and bone.
We present a rare case of Non-functioning adrenocortical carcinoma presenting as carcinomatosis. The patient is a 34-year-old female, who presented with headache, neck pain, difficulty walking and tingling left arm of 2 days duration. No signs of neurological deficits or excessive steroid secretion were present. Medical history was significant for SLE, seizures secondary to lupus cerebritis, and asthma. Examination was significant for orthostasis, guaiac positive stools, and staggering gait. Labs were significant for a hemoglobin level of 2.5gm/ dl. Upper GI endoscopy revealed two bleeding gastric masses. A work up for ataxia with a non-contrast CT scan revealed a 2-3cm mass in the left occipital region. Subsequently, MRI brain revealed mass occupying lesions in both the cerebellar hemispheres with a 2cm lesion in the posterior left parietal area. CT thorax revealed a large mass in the right paratracheal region with mass effect on the airways and heart. CT abdomen revealed heterogeneous mass in right adrenal gland with lymphadenopathy in the porta and left paraaortic region. USG of pelvis demonstrated enlargement of the ovaries with cystic features. Autopsy revealed a large adrenal tumor with a large retroperitoneal hematoma and disseminated metastasis to the lungs, liver, pancreas, ileum, gastric wall, peritoneum, ovaries, and brain. Immunohistochemical stains were negative for vimentin, S100, synaptophysin, CK20 but positive for CK7, keratin, EMA and focally positive for HCG and PLAP, consistent with epithelial tumors.
At present, there is no pathognomic immunohistochemical profile for adrenocortical carcinoma. Negative neuroendocrine tumor markers may rule out the possibility of a malignant pheochromocytoma. This case highlights certain key features in the diagnosis of adrenocortical carcinoma. First, lack of specific immunohistochemical profile fails to localize the primary site of the tumor. Second, carcinomatosis secondary to adrenocortical carcinoma has rarely been reported.
SIGNET RING CELL CARCINOMA OF UNKNOWN PRIMARY WITH DIC: A CASE REVIEW
Amer Tfaili MD, Associate, Darshana Tawde MD, Associate, Geetha Krishnamoorthy MD, Member, Sinai-Grace Hospital, Wayne State University, Detroit, Michigan.
A 62-year-old African American female was hospitalized with a 1-month history of weight loss and a recent history of abdominal pain. Physical examination revealed a distended tender abdomen with ascites but without any jaundice. There was cyanosis of the 3rd and the 4th toes bilaterally. Laboratory evaluation revealed the presence of DIC. Alkaline phosphatase, CEA and CA 19-9 levels were significantly elevated.
Paracentesis revealed signet cell adenocarcinoma. CT of the abdomen and pelvis showed dilatation of the intra hepatic ducts, common bile duct and the pancreatic duct without any evidence of cholelithiasis. An ERCP done 1 year earlier for pancreatitis had shown the same dilatation, which was considered a normal variant then. MRI of the abdomen with MRCP failed to show any hepatobiliary or pancreatic mass. EGD and colonoscopy were negative for malignancy and a bone scan did not show bony metastasis.
The patient refused chemotherapy and died a month later after a cardiopulmonary arrest. The family refused an autopsy.
Our literature review revealed 2 cases of signet ring cell carcinoma of unknown primary, one of which was found to have a 0.8 cm carcinoma of the Ampulla of Vater on autopsy. Treatment with chemotherapy has been shown to improve DIC, decrease tumor burden and prolong survival in these patients. Hence chemotherapy should be offered to such patients. The diagnosis of signet ring cell carcinoma of the gastrointestinal tract by endoscopy remains a diagnostic challenge.
Our patient presented such a challenge. This is a rare case of signet ring cell carcinoma of unknown primary presenting with DIC and a greatly elevated alkaline phosphatase level with no evidence of obstructive hepatobiliary or pancreatic disease.
ROLE OF SURGERY IN REFRACTORY EPILEPSY.
Kavitha Potluri, MD, Associate, Department of Medicine, Sinai-Grace Hospital, Wayne State University, Detroit, Michigan.
Question: What surgical options including implantable devices have been evaluated for the treatment of refractory seizures? What are the known benefits and risks of such procedures?
Background:
The prevalence of epilepsy in
Data Sources: Medline and Cochrane databases were searched for all English language papers on treatment options available for drug resistant epilepsy.
Study Selection : Randomized double blind control trails with a P-value of <0.05 and those that are statistically significant have been selected. There is only one study conducted thus far on the role of surgery in epilepsy and two studies regarding vagal nerve stimulation.
Study Details: For the role of surgery in refractory epilepsy, 80 patients who had drug refractory epilepsy were randomly assigned to medical and surgical groups (original article in 2002 NEJM: Author: WEIBE at al ) and all the patients were followed for one year. The primary outcome was freedom from seizures that impair awareness and secondary outcome was reduction in severity of seizures and improvement in quality of life. For VNS, two active control trails of high versus low vagal nerve stimulation have been conducted (VNS Study in 1995 and Handsforth Study in 1998). The outcomes measured were 50% reduction in seizures and adverse effects of vagal nerve stimulation.
Main Results: In the study conducted by Weibe at al, the cumulative benefits from the various surgical options available for refractory epilepsy far exceeded than medical management. There was major reduction in all primary and secondary outcomes with a p-value of <0.001 in the surgical group with very few adverse effects. Similarly, in the VNS studies, > 50% reduction in seizure frequency was noted for partial onset seizures in the high stimulation group with few side-effects when compared to the control group.
Conclusion: In the treatment of drug resistant epilepsy, surgery and vagal nerve stimulation are effective alternative options available. Further studies comparing surgery and VNS , the optimal time to consider surgery in refractory seizures and the role of VNS in obesity, depression and pain need to be done.
NEUROSURGICAL TREATMENT OPTIONS IN PARKINSONISM.
Anjali Gupta, MD, Associate, Department of Medicine, Sinai-Grace Hospital, Wayne State University, Detroit, Michigan.
QUESTION
A 68 year old man has been
diagnosed with Parkinson’s disease for the last 5 years. His tremor and gait
problems have persisted despite medical therapy. What neurosurgical treatments
are available for this condition? How effective are they? What is the extent of
benefit compared to risk?
DATA SOURCE
Studies were selected from Pubmed,
Medline from 1960 to 2003 using the terminology “treatments in parkinsonism
disease.”
STUDY SELECTION
Almost
all the studies done are open, prospective trials for short duration of time
with small group of patients. There were few randomized comparison studies.
Tissue transplantation and administration of GDNF are experimental studies.
PROCEDURES
Deep brain stimulation of
Subthalamus, Globus pallidum and Thalamus Surgery was performed under local
anesthesia. Target was located by MRI, Contrast Ventriculography, and
Electrophysiological recording and stimulation. Electrodes were implanted
bilaterally or unilaterally in the nucleus.
Surgical ablation of
Thalamotomy, Subthalamotomy and Pallidotomy
Stereotactic pallidotomy,
thalamotomy and subthalamotomy were done either unilaterally or bilaterally.
Restorative procedures with
fetal nigral tissues or adrenal medula transplantation
Trophic factors (GDNF). These
tissues were implanted into deep tissues of brain to regain the dopaminergic
effects.
RESULTS
When we stimulate the brain tissues like Thalamus, Subthalamus, Globus pallidus either unilaterally or bilaterally, we found great improvement in motor symptoms such as akinesia, rigidity, and tremor of the upper and lower limbs, gait and postural stability in off meds state. It even reduces patients drug induced dyskinesias.
Surgical stereotactic ablation of thalamus, Subthalamus, Globus Pallidus improves all motor features of PD including bradykinesia, rigidity, gait, balance dyskinesia and tremor. In Gait, initiation of step quickened and balance was improved. The movement patterns often return to normal.
Dopamine replacement therapy provides dramatic clinical relief. Dopamine neurons subserve a modulatory function and provide tonic stimulation of striatal dopamine receptors.
CONCLUSION
In the patient having Parkinsonism disease, stimulation of brain tissues gave better long lasting responses and less side effects and more improvement in symptoms in both off and on medicine state.
RUPTURE OF ABDOMINAL
AORTA ANEURYSM IN A 24 YEAR OLD FEMALE WITH CYSTIC MEDIAL NECROSIS.
K Potluri, MD (Associate), S
Department of Medicine
and Department of Pathology*,
Abdominal Aortic Aneurysm is a disease that is rarely manifested before the age of fifty-five. The most common cause is atherosclerosis.
We present a 24 year old African American female, who came to the emergency room with sudden onset of abdominal pain, low back pain and vomiting. Physical examination revealed diffuse abdominal tenderness. CT Scan of the abdomen reported, a large infrarenal pseudoaneurysm and rupture of the abdominal aorta with extensive retroperitoneal hemorrhage. Patient was in shock and underwent an emergency resection of the abdominal aorta aneurysm with a bypass graft. Intra-operative findings revealed a nine centimeter infrarenal aortic “blow out” rupture. Although the post-operative period was complicated, the patient survived this event. The pathology of the aorta revealed extensive myxoid degeneration and cystic medial necrosis.
Aortic aneurysms in patients
younger than 40 years are most often associated with cystic medial necrosis.
The thoracic aorta is more commonly involved.
Very few cases of the abdominal
aorta aneurysm rupture secondary to cystic medial necrosis have been
reported. Cystic medial necrosis may
occur as an isolated abnormality or as part of a systemic connective tissue
disease such as Marfans
syndrome or Ehlers Danlos
syndrome. This patient had some features of Marfans but failed to
meet all the criteria of Marfans. There was no family history of aneurysms. Our
patient could have idiopathic cystic medial necrosis or a partial expression of
the Marfan syndrome with a possibility of a new missense mutation.
Regardless of the diagnosis,
prophylactic treatment and prevention of further complications associated with
cystic medial necrosis is important.
Awareness of the broad spectrum of manifestations in myxoid degeneration
disorders needs to be increased among practitioners, to lower the threshold of
suspicion necessary for referral to a specialist center.
MIXED SMALL /LARGE CELL CARCINOMAS OF THE LUNG, THERAPEUTIC AND PROGNOSTIC IMPLICATIONS. Bazzi,Kaled, MD. Associate, Marius Vidinas, MD, Associate and Lawrence Macdonald, MD, Fellow, Sinai-Grace Hospital/Wayne State University, Detroit, Michigan
Lung cancer is currently the most common cause of cancer mortality in the United States responsible for 157,200 deaths annually. Primary lung cancer can be generally categorized into four groups: these include squamous cell carcinoma (20-30%), adenocarcinoma (30-40%), large cell (10%) and small cell carcinoma (20%). Rarely, lung tumors may present with a mixed histological pattern.
We report the case of a 67 year-old Hispanic female with a 5 pack-year history of smoking who presented with a dry cough of 4 months that failed to respond to several courses of oral antibiotics. The patient also reported a weight loss of 15 pounds over the same time period associated with dysphagia to solid foods and a progressive weakness of the lower extremities. Three days prior to presentation the patient had developed urinary and fecal incontinence. Diagnostic evaluation showed a lung mass on chest X-ray and MRI of the spine demonstrated multiple metatstatic foci involving the vertebral bodies at various levels with signs of spinal cord compression. Bronchoscopy with biopsy of the lung revealed a mixed small/large cell lung cancer. Palliative treatment with radiation therapy was initiated but the patient deceased two weeks later from complications of her cancer and septic shock.
Mixed histology small cell/large cell carcinoma constitutes about 4-6% of all small cell cancers and is considered a distinct variant with clinical, therapeutic and prognostic implications. The distribution of the mixed elements can be heterogeneous and the definitive pathological features evident only after resection of the tumor or at autopsy. Although this case illustrates a small cell/large cell mixed cancer, mixed histology of small cell with squamous and/or adenocarcinoma have also been described. Interestingly, metastases from these tumors may consist of mixed elements or limited to the small cell or non-small cell component alone. When treated with aggressive chemotherapy protocols for small cell cancer, patients with mixed small cell/large cell cancer have lower partial or complete response rates (58% vs 91%), and shorter survival rates (median 6 vs. 10.5 months) than patients with pure small cell cancer.
Cryptococcal Pneumonia Mimicking as Pneumocystis Carnii Pneumonia in a patient with AIDS. Jayasree Grandhi, MD, Associate, Apuva Motivala, MD, Associate, Wasif Hafeez, MD, Fellow, Sinai-Grace Hospital, Wayne State University, Detroit, Michigan.
Introduction: The most common pulmonary complication of AIDS is pneumocystis carnii pneumonia (PCP). However, other opportunistic infections like cryptococcus neoformans and mycobacterium avium intracellulare (MAI) can present with diffuse pulmonary involvement and mimic PCP. We report a patient with disseminated cryptococcosis whose initial clinical presentation was indistinguishable from PCP.
Case Report: A 30 yr old homosexual male with AIDS and with multiple previous admissions for PCP came with difficulty in breathing, pleuritic chest pain and diarrhea of 1 week duration. He was on highly active antiretroviral therapy (HAART), azithromycin for MAI prophylaxis but was noncompliant with bactrim for PCP prophylaxis. He was slightly tachypneic with inspiratory rhonchi in bilateral lung fields with oxygen saturation of 92-95% on 2 liters of oxygen. Initial labs were WBC 21.9, CD4 count 0, HIV viral load 175,000 and chest X-ray showed bilateral perihilar interstitial infiltrates. He was treated for presumed PCP pneumonia. On day 2 patient became very tachypneic, desaturated and was intubated for impending respiratory failure. Cardiac arrest ensued and despite vigorous attempts at resuscitation, the patient died. Meanwhile, bronchoscopic alveolar lavage (BAL) was performed which showed budding yeasts with halos around them, suggestive of C. neoformans. Autopsy revealed disseminated cryptococcosis.
Conclusion: C. neoformans must be high in the differential diagnosis of diffuse interstitial pneumonia in patients with AIDS. Since cryptococcal infection is potentially treatable with antifungal agents, an early microbiological diagnosis is essential. Early aggressive investigations aimed at definitive diagnosis like serum cryptococcal antigen titer and identification of Cryptococcus in BAL washings will give strong support in planning therapy.
Neurologic symptoms as the initial manifestation of Legionella pneumonia, a case series. Irfan Hameed, MD, Associate, Wasif Hafeez, MD fellow, Sinai-Grace Hosptial, Wayne State University, Detroit, Michigan.
Infection with Legionella pneumophilia manifests as pneumonia in 90% of cases and can also manifest with neurologic findings ranging from headache to lethargy to frank encepholopathy. We describe a series of three cases of Legionella pneumonia that presented with prominent neurologic symptoms at our institution over a span of just five months. In all three patients, Legionella antigen was present in their urine.
Case 1: A 55 year-old man presented with a seizure, productive cough, RUL infiltrate, acute renal failure, temperature of 105o, WBC = 22,000 and CPK=32,000. Septic shock and respiratory failure ensued requiring ICU admission. He was treated with azithromycin and rifampin and eventually discharged to the rehabilitation service after a 42 day stay in the ICU.
Case 2: A 44 year-old man presented with delirium and had been having influenza-like symptoms for seven days. LUL infiltrate, acute renal failure, CPK = 15,000 and leukopenia were also present on admission. Septic shock with respiratory failure ensued. He was discharged to the rehabilitation service after a 57-day stay in the ICU.
Case 3:A 32 year-old man presented with obtundation progressing to coma. Bilateral infiltrates, WBC = 31,000 and coagulapathy were also present. Septic shock and respiratory failure ensued. Blood culture yielded pneumoccoccus. Despite aggressive antibiotic treatment the patient died on the 5th hospital day.
These three cases illustrate the propensity of Legionella infection to cause severe neurologic symptoms as compared to other causes of pneumonia. Patients who do present initially with predominantly CNS symptoms, in general, have more complications and are more likely to develop multiorgan involvement. The neurologic involvement may precede the pulmonary involvement and has been reported to develop in the absence of pulmonary disease. Encephalopathy, delirium, profound coma, hallucinations, cerebellar dysfunction, hemiparesis, quadraplegia, chorea, seizures and cranial nerve palsies have all been reported. Therefore, Legionella infection should be considered in all patients presenting with neurologic symptoms in the setting of pneumonia. Timely testing to confirm the diagnosis and appropriate treatment may be life saving.
EFFECTIVENESS OF AROMATASE INHIBITORS COMPARED TO TAMOXIFEN FOR THE SECONDARY CHEMO-PREVENTION OF BREAST CANCER. Wahed Ishaqsei, MD, Sinai Grace Hospital, Wayne State University, Detroit, Michigan
Introduction: Each year there are more than 200 000 new cases of breast cancer and more than 40,000 deaths due to breast cancer in the US. Tamoxifen has been studied and found to be effective for secondary prevention of breast cancer. The objective of this review was to compare the effectiveness and safety of the newer third generation aromatse inhibitors compared to tamoxifen for the secondary prevention of breast cancer.
Study design: Review of randomized double blind control trials and metaanalysis of randomized control trials completed by 2003, to study the use of tamoxifen and third generation aromatase inhibitors for the secondary prevention of breast cancer.
Results: The Early Breast Cancer Trialist’s Group in 1997 studied 37 000 women with early breast cancer from 55 randomized control trials comprising 87% of the worldwide evidence on the use of tamoxifen for secondary prevention of breast cancer. Tamoxifen therapy for1, 2 and 5 years was compared with placebo and the reduction of breast cancer recurrence at 10 year follow-up was 21%, 29% and 47% respectively (P<.001 for the 5 year group compared to placebo).
The ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial randomized, 9366 breast cancer patients in 21 countries from 1996-2000, comparing Arimidex, a third generation aromatase inhibitor to tamoxifen and the combination of tamoxifen and arimidex to tamoxifen alone (median follow-up, 47 months). Arimidex alone was confirmed to be more effective than tamoxifen alone and to the combination of arimidex and tamoxifen, for disease free survival with several important tolerability benefits, p<0.001. Based on the results of the ATAC trial, Arimidex was approved by the FDA for the secondary chemo-prevention of breast cancer in postmenopausal women. The Target and North American Trial, compared Arimidex 1mg versus Tamoxifen 20 mg, worldwide, involving 1021 subjects (median follow-up: 43.7 months). Arimidex was significantly superior to Tamoxifen in regard to time to tumor progression, 10.7 months versus 6.4 months, p=0.005, with fewer adverse effects from thromboembolic events and vaginal bleeding.
Conclusion: Based on the current trials, Arimidex is a valid alternative to tamoxifen for the secondary chemo-prevention of the early breast cancer in postmenopausal women with an overall favorable risk: benefit profile.
ANTIPLATELET THERAPY FOR SECONDARY PREVENTION OF CORONARY ARTERY DISEASE. Ramesh Kotihal, MD, MS, Associate, Sinai Grace Hospital, Wayne State University, Detroit, Michigan
Question: In patients undergoing thrombolysis for treatment of myocardial infarction, what is the optimal antiplatelet therapy regimen for secondary prevention of myocardial infarction (MI)?
Data sources: Studies were identified by searching MEDLINE (1966 to 2003), Cochrane Library, and Web of Science database.
Study Selection: Double-blinded randomized trials comparing an antiplatelet regimen with a control regimen or with another antiplatelet regimen, in patients with MI treated with pharmacological thrombolysis..
Data Extraction: Data was extracted from 12 trials comparing the efficacy of antiplatelet regimens in patients with history of MI and 15 trials comparing antiplatelet regimens in patients with acute MI. The occurrence of reinfarction (fatal and non-fatal) and the composite outcome of vascular death, MI and stroke were studied.
Results: In patients with ST-elevation MI, therapy with aspirin or clopidogrel was found to have equivalent effects on the prevention of reinfarction. In patients with a non ST-elevation MI receiving therapy with aspirin and clopidogrel, the relative risk of MI was 0.77 and the relative risk for the composite outcomes of MI, stroke or vascular death was 0.80 (p <0.001) as compared to those receiving aspirin only.
Conclusion: Optimal anitplatelet therapy for secondary prevention of coronary artery disease in patients with ST elevation MI consists of aspirin life long or clopidogrel life long in case of aspirin allergy, aspirin intolerance or aspirin resistance. In patients with non-ST elevation MI, therapy with aspirin life long combined with clopidogrel for the first 9 to 12 months provides maximum benefit. In non-ST elevation MI patients in whom aspirin cannot be used, therapy with clopidogrel life long should be used.
A RARE CASE OF POTT’S PUFFY TUMOR DUE TO GROUP C STREPTOCOCCAL INFECTION. Jayasree Grandhi, MD, Associate, Adeel Ijaz, MD, Associate, Sinai-Grace Hospital, Wayne State University, Detroit, Michigan.
Introduction: Pott’s puffy tumor is a subperiosteal abscess of the frontal bone associated with underlying frontal bone osteomyelitis, causing swelling and edema over the forehead. We describe a 38-year-old man with a Pott’s puffy tumor due to streptococcus C that was successfully treated with antibiotics and surgery.
Case Report: A 38-year-old male with HIV came with pain and swelling over the forehead and both eyes. Patient had similar complaints one month ago and was diagnosed with preseptal orbital cellulitis and treated with ampicillin-sulbactam. He gave a history of chronic sinusitis for 2 years without any regular treatment. On examination, there was an eythematous, tender, fluctuant swelling over the forehead and eyes. He had bilateral frontal, maxillary, ethmoid sinus tenderness, intact visual acuity and no evidence of opthalmoplegia. His CD4 count was 650 and CT and MRI imaging showed preseptal orbital cellulites, extensive pan sinusitis, frontal bone osteomyelitis, destruction of anterior wall of the right frontal sinus and a right frontal scalp abscess. Aspiration of the fluid grew streptococcus C. The patient was treated with ampicillin-sulbactam and underwent early surgical drainage with bilateral ethmoidectomy and revision of the frontal bone.
Discussion: Pott’s puffy tumor is usually a complication of chronic sinusitis rarely seen at present time due to the widespread availability of antibiotics. Suppurative complications such as epidural, subdural and intracerebral abscesses are common, therefore early recognition is very important. A review of 23 cases showed that it is mostly seen in children, with only 8 cases reported in adults, none of them were caused by streptococcus C.
Conclusion: Pott’s puffy tumor is most common in children; it should be included in the differential diagnosis of a swelling on the forehead in adults. Surgical drainage and antibiotic therapy remains standard of therapy.
ROLE OF SURGERY IN THE MANAGEMENT OF CHRONIC RHINOSINUSITIS. Jayasree Grandhi, MD, Associate, Sinai-Grace Hospital, Wayne State University, Detroit, Michigan.
Research Question: A 30 year old female has chronic sinusitis with recurrent episodes of acute exacerbations in spite of being treated with antihistamines, nasal steroid sprays, decongestants and antibiotics for acute exacerbations. What are the various surgical options available? What are the indications for surgery? How effective is surgery for the short and long term relief of symptoms in patients with chronic rhinosinusitis?
Background: Rhinosinusitis is a common medical complaint in primary care practice affecting approximately 33 million Americans annually. Patients continue to have symptoms of chronic sinusitis in spite of being on maximal medical therapy. Functional endoscopic sinus surgery (FESS) is the most commonly performed surgery now based on the theory that the manifestations of chronic sinusitis can be reversed if optimal conditions for ventilation and drainage are reestablished.
Data Source: Observational cohort studies from the MEDLINE database from 1994 to 2003 were identified using Pubmed and Ovid search engines.
Study Selection: Studies were identified from MEDLINE search using the term surgery in chronic sinusitis. Studies focusing on the subjective and objective assessment of symptoms pre and postoperatively were selected. Studies, which assessed both short and long term symptom relief, were also included.
Outcome Measures: The endpoints chosen as outcome measures were subjective assessment of symptoms using VAS (visual analog score), objective assessment of symptoms improvement using different methods and medication usage both short term and long term.
Results: We did not find any well-designed randomized trails on this subject although several observational cohort studies were identified. These observational cohort studies have shown a significant improvement in subjective symptoms (p value<0.05). There was an improvement in symptoms that were assessed objectively, but it was not statistically significant. The improvement in symptoms was maintained even 7 years after surgery. The degree of medication use has also been reduced significantly following surgery.
Conclusion: Medical management is still first line of therapy in patients with chronic rhinosinusitis. Based on observational cohort studies, improvement in symptoms, particularly subjective symptoms, can be expected from surgery in patients who fail to respond adequately to medical therapy.
ATYPICAL CLINICAL COURSE OF LOCALIZED REACTIVE LYMPHOID HYPERPLASIA OF THE SPLEEN (SPLENIC LYMPHOID HAMARTOMA): A CASE REPORT.
Yadav Suresh, MD, Associate, Tawde Darshana, MD, Associate, Eisenberg Leopold MD, FACP. Sinai-Grace Hospital, Wayne State University, Detroit, Michigan.
Introduction: Localized reactive lymphoid hyperplasia (lymphoid hamartoma) is a rare lesion of the spleen. Most of the patients are asymptomatic but a small group of patients present with a wide range of clinical manifestations.
Case report: A 24-year-old Caucasian male of Italian descent presented with severe microcytic anemia and thrombocytosis of a chronic nature with symptoms of tiredness, fatigue and syncope eventually requiring transfusions. The patient admitted to using anabolic steroids for body building. Diagnostic studies demonstrated a normal bone marrow with adequate iron stores, elevated ESR, fibrinogen, and CRP levels and an unexpected IgA deficiency. Familial hemoglobinopathy was excluded by hemoglobin electrophoresis of available family members. Panendoscopy of the gastrointestinal tract was negative for bleeding but revealed esophagitis due to C. Albicans and gastritis due to H pylori. CT scan demonstrated splenomegaly with a 3.6 x 3.8 cm mass that increased in size over a 2-month interval. Diagnostic and therapeutic splenectomy was performed revealing localized reactive lymphoid hyperplasia of the spleen consistent with a lymphoid hamartoma with negative cytogenetics and polyclonal flow cytometry. Follow up surprisingly demonstrated normalization of all hematological parameters with no additional therapy.
Conclusion: In our literature review of splenic lymphoid hamartoma, we did not find a previously described association with severe microcytic anemia. Additionally, no case reports of elevated ESR, fibrinogen or C-reactive protein were found except in association with Hodgkin’s disease. Lymphoid harmartomas are usually seen in children with most patients being asymptomatic although a few present with hypersplenism. Histopathology is important in differentiating splenic lymphoid hamartoma from lymphoma, inflammatory psuedotumor of the spleen and red-pulp hamartomas (splenic hamartoma due to malformed vascular elements). This case reports illustrates several important clinical features of lymphoid splenic harmatomas that have not been reported previously and the potential for a complete and sustained response to splenectomy.