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Diagnostic yield of renal biopsies: a retrospective single center review. - BMC nephrology
Previous studies have examined the spectrum of diseases identified with a kidney biopsy and the complications of the procedure. However, few studies have examined the utility of the test to clarify the diagnosis and guide treatment of pediatric patients. This retrospective, single-center chart review was performed to test the hypothesis that at least 80% of native kidney biopsies provide clinically valuable information that rationally guides diagnosis and patient management.200 biopsies performed between January 1, 2000 and June 30, 2008 were reviewed. A scheme composed of six categories was devised to classify the utility of each kidney biopsy.196 complete case files were available for review. Twenty-four (12.2%) biopsies did not shed light on the diagnosis and were unhelpful in patient management - 21 biopsies (10.7%) were non-diagnostic and 3 (1.5%) failed to yield enough tissue for examination. The number of unhelpful biopsies did not cluster in any specific disease entity.Our findings provide guidance to nephrologists about the total risk of a kidney biopsy, including uninformative results, when seeking informed consent for the procedure. The results suggest an appropriate balance has been reached which maximizes the use of kidney biopsies while minimizing the risk of this invasive procedure (word count: 202).
Vancomycin-induced acute granulomatous interstitial nephritis: therapeutic options. - The American journal of the medical sciences
Drug-induced acute renal failure is a commonly encountered mode of renal injury in the hospitalized patient. Vancomycin is a frequently used antibiotic in patients with Gram-positive bacterial infections. In the present study, we evaluated an index case of a patient who developed severe acute granulomatous interstitial nephritis and provided a review of the reported cases of vancomycin-induced acute renal failure in the literature. A Medline search revealed a total of 11 cases of vancomycin-induced interstitial nephritis. In 2 reported cases, interstitial nephritis has been reported with associated granuloma formation. However, the role of T cells in the formation of interstitial nephritis and in the choice of therapeutic modalities in this scenario has not been evaluated in the past. In the index case, we have evaluated the effect of treatment on the basis of the type of cellular infiltrates and provided a follow-up by carrying out the repeat biopsy.
Idiopathic membranous nephropathy in pediatric patients: presentation, response to therapy, and long-term outcome. - BMC nephrology
Idiopathic membranous nephropathy (IMN) is one of the most common causes of primary nephrotic syndrome in adults. However, it is a relatively rare entity in the pediatric population and there is a paucity of data about the incidence, prognosis, and optimal treatment of IMN in children and adolescents. We conducted this study to evaluate pediatric patients with IMN in order to clarify the presentation, response to therapy, and clinical outcome.A retrospective chart review was performed on patients identified with biopsy-proven IMN between 1988-2005. Patients with systemic lupus erythematosus or hepatitis-related lesions were excluded. The following data were tabulated: age, gender, ethnicity, presenting clinical and laboratory findings, proteinuria in a first morning urine specimen, estimated glomerular filtration rate (GFRe), histopathology, type and duration of treatment, and clinical status at final evaluation.13 cases of IMN were identified out of 460 renal biopsies performed for evaluation of primary kidney disease during the study interval. Mean age was 9.6 +/- 4.6, gender 6 M:7 F, ethnicity 8 W:2 B:3 H. At the initial visit hematuria was present in 9 patients, edema in 5, nephrotic-range proteinuria in 5, and hypertension in 3. Mean urinary protein:creatinine ratio 3.3 +/- 2.5 and all patients had a normal GFRe. Classic glomerular findings of IMN were seen in all renal specimens, with concomitant interstitial changes in 2 cases. Treatment included an angiotensin converting enzyme inhibitor or angiotensin receptor blocker in 11 cases. Most patients were also given immunosuppressive medications - prednisone in 10, a calcineurin inhibitor in 5, and mycophenolate mofetil or azathioprine in 3 patients. At the last follow-up, 42 +/- 35 months after the diagnostic biopsy, 7 children were hypertensive and the urine protein:creatinine ratio was 2.3 +/- 3.1. The mean GFRe was 127 +/- 57 mL/min/m2. Three patients had Chronic Kidney Disease Stage 3, all of whom were also hypertensive.IMN is a rare but serious glomerulopathy in pediatrics. We estimate that it accounts for approximately 3% of renal biopsies. Long-term prognosis is guarded because approximately 50% of patients may have evidence of progressive kidney disease.
Possible role of high density lipoprotein in the progression of glomerulosclerosis. - Journal of medicine
The collapsing variant of focal segmental glomerulosclerosis is a fulminant lesion characterized by rapid progression to end-stage renal disease. Substantial in vivo and in vitro evidence suggests that lipids, particularly low density lipoprotein (LDL), can contribute to the progression of glomerulosclerosis as they do in atherosclerosis. The nephrotic syndrome is typically associated with marked elevation of LDL and suppression of high density lipoprotein (HDL), abnormalities which may, accelerate both of these lesions. We report the case of a patient who presented with heavy proteinuria and hypertension and was found to have collapsing focal segmental glomerulosclerosis as well as, surprisingly, a markedly elevated HDL level. Despite the poor prognosis of this lesion, over a 3-year period the patient maintained normal renal function and has experienced a decline in her proteinuria to below-nephrotic levels while maintaining an elevated HDL level. Though this is only a single report, it may nevertheless be worthwhile to consider the possibility that HDL levels could potentially modulate the course of glomerular disease.
Monoclonal gammopathy presenting as recurrent nephrotic syndrome: therapeutic implications. - The American journal of the medical sciences
Most forms of renal disease associated with monoclonal gammopathy result from deposition of monoclonal immunoglobulins or their subunits in different compartments of the kidney. Renal monoclonal immunoglobulin deposition disease (MIDD) is defined by linear deposits of monoclonal light-chain components in renal basement membranes, often producing a nodular sclerosing glomerulopathy. Clinical features of renal MIDD include proteinuria, with or without renal failure, and an association with dysproteinemias. Three types of renal MIDD have been reported, namely, light-chain deposition disease (LCDD), light- and heavy-chain deposition disease (LHCDD), and heavy-chain deposition disease (HCDD). Reports on LHCDD are rare. At present, follow-up data are limited on the management of renal monoclonal protein deposition disease. We present a case of monoclonal protein deposition in the kidney containing both heavy and light chains with unique characteristics that did not conform to any of the above previous established classes. Its follow-up revealed an unusual relapsing and remitting course in response to treatment.
DEC-205-mediated internalization of HIV-1 results in the establishment of silent infection in renal tubular cells. - Journal of the American Society of Nephrology : JASN
HIV-1 infection of renal cells has been proposed to play a role in HIV-1-associated nephropathy. Renal biopsy data further suggest that renal tubular cells may serve as reservoir for HIV-1. The mechanism by which HIV-1 enters these cells has not been identified. Renal tubular cells do not express any of the known HIV-1 receptors, and our results confirmed lack of the expression of CD4, CCR5, CXCR4, DC-SIGN, or mannose receptors in tubular cells. The aim of this study, therefore, was to determine the mechanism that enables viral entry into renal tubular cells. An in vitro model was used to study the HIV-1 infection of human kidney tubular (HK2) cells and to identify the receptor that enables the virus to enter these cells. Results of these studies demonstrate that the C-type lectin DEC-205 acts as an HIV-1 receptor in HK2 cells. Interaction of HIV-1 with DEC-205 results in the internalization of the virus and establishment of a nonproductive infection. HIV-1-specific strong-stop DNA is detected in the infected HK2 cells for at least 7 d, and the virus can be transmitted in trans to sensitive target cells. HIV-1 entry is blocked by pretreatment with specific anti-DEC-205 antibody. Moreover, expression of DEC-205 in cells that lack the DEC-205 receptors renders them susceptible to HIV-1 infection. These findings suggest that DEC-205 acts as an HIV-1 receptor that mediates internalization of the virus into renal tubular cells, from which the virus can be rescued and disseminated by encountering immune cells.
Meprin-alpha in chronic diabetic nephropathy: interaction with the renin-angiotensin axis. - American journal of physiology. Renal physiology
Meprin (MEP) A is a metalloendopeptidase that is present in the renal proximal tubule brush-border membrane (BBM) and that colocalizes with angiotensin-converting enzyme (ACE). The MEP beta-chain gene locus on chromosome 18 has been linked to a heightened risk of diabetic nephropathy (DN) in patients with type 2 diabetes. This study evaluated 1) whether MEP-alpha and MEP-beta gene and protein expression are altered in db/db mice before the onset of DN and 2) the role of MEP-alpha in the pathogenesis of DN and the impact of the renin-angiotensin system on this interaction in two experimental models of diabetes. MEP-alpha and MEP-beta gene and protein expression were evaluated in db/db mice, 13-14 wk of age, compared with lean C57BLKS/J littermate animals. A treatment study was then performed in which db/db mice and controls were assigned to one of three groups: control (C) water, no therapy; ACE inhibitor therapy, enalapril (EN)-treated water, 50 mg/l; ANG II receptor type 1 blocker (ARB) therapy, losartan (LOS)-treated water, 500 mg/l. Treatment was started at 8 wk of age and continued for 52 wk. Male Sprague-Dawley rats with diabetes for 52 wk following a single dose of streptozocin (STZ; 60 mg/kg) were also studied. At 13.5 wk of age, MEP-alpha and MEP-beta kidney mRNA abundance and protein expression were significantly lower in db/db mice compared with lean controls, with greater changes in MEP-beta (P < 0.05). In the treatment study, EN ameliorated and LOS exacerbated DN in db/db mice. BBM MEP A enzymatic activity and MEP-alpha protein content were lower in db/db mice vs. control nonobese mice at 52 wk (P < 0.02). EN-treated db/db mice showed increased MEP A activity, MEP-alpha content in BBM, decreased urinary MEP-alpha excretion, and enhanced BBM staining for MEP-alpha protein vs. C and LOS-treated db/db mice. In nonobese mice, EN and LOS treatment had no effect on MEP-alpha expression. In rats with STZ-induced diabetes for 52 wk, urinary MEP-alpha excretion was increased and MEP A activity and MEP-alpha protein content per milligram of BBM protein were decreased compared with age-matched control animals (P < 0.05). These results indicate that db/db mice manifest decreased MEP-alpha and MEP-beta gene and protein expression, before the development of overt kidney disease. Moreover, in db/db mice with DN and rats with STZ-diabetes, there was an inverse relationship between renal MEP-alpha content and the severity of the renal injury. Treatment with an ACE inhibitor was more effective than ARB in ameliorating DN in db/db mice, a change that correlated with alterations in urinary excretion and BBM content of MEP-alpha. MEP-alpha may play a role in the pathogenesis of DN and the benefits of ACE inhibitor therapy on the progression of diabetic kidney disease may be related, in part, to its impact on renal MEP-alpha expression.
Prevention of renal fibrosis by spironolactone in mice with complete unilateral ureteral obstruction. - The Journal of urology
Recent data suggest that aldosterone directly mediates cardiac fibrosis and hypertensive nephrosclerosis. We conducted experiments to determine whether administration of spironolactone, a mineralocorticoid receptor antagonist, reduced renal fibrosis in an experimental model of obstructive uropathy.Complete unilateral ureteral obstruction (UUO) was created surgically in 8 to 10-week-old male C57BL/6 mice by placing sutures around the right ureter. Spironolactone (50 mg/kg/daily) or 1% dimethyl sulfoxide vehicle was administered by subcutaneous injection for 1 to 2 weeks, and renal fibrosis was assessed by measuring trichrome staining and type I collagen deposition in the kidney.UUO lasting 1 week was associated with minimal parenchymal damage and spironolactone had no demonstrable effect. In contrast, administration of the mineralocorticoid antagonist (8 mice) for a 2-week period significantly reduced renal fibrosis in the obstructed kidney, compared to mice given the dimethyl sulfoxide vehicle (9). The beneficial effect of spironolactone treatment was not associated with any changes in serum potassium or aldosterone concentration, or urinary concentrations of sodium or potassium.Administration of spironolactone reduced renal fibrosis in mice with UUO. These findings suggest that clinical trials are warranted to determine the efficacy of aldosterone antagonists in conjunction with angiotensin converting enzyme inhibitors and/or angiotensin receptor blockers as renoprotective agents in patients with obstructive uropathy.
Dermoid cysts of the tongue: report of five cases and review of the literature. - Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society
Dermoid cysts of the tongue are uncommon. To date, there have been nine reported cases in the English language literature. In this article, we describe five cases accessioned at our institution over a 12-year period, two of which have previously been reported. The prevalence of dermoid cysts at our institution over this period was quite low. Of 324,042 surgical cases, 0.24% (765 cases) were dermoid cysts. Of these, five were from the tongue, representing only 0.7% of the dermoid cysts accessioned and 0.0015% of the total surgical specimens. The literature is reviewed and the possible origin of these lesions is discussed.
Reliability of splenic index to assess splenic involvement in pediatric Hodgkin's disease. - Journal of pediatric hematology/oncology
The purpose of this study was to determine the reliability of the splenic index (SI) in children with Hodgkin's disease (HD). Seventeen patients who underwent staging laparotomy for HD were included in this study. Pretreatment computed tomography scans of these patients were reviewed retrospectively to determine the SI. The specificity, sensitivity, positive and negative predictive values, and accuracy of the SI were calculated. The sensitivity and specificity of the SI were 50% and 66%, respectively. The SI alone accurately identified or ruled out involvement with HD in 10 of 17 patients. Positive and negative predictive values of the SI were 57% and 60%, respectively. Even with the use of the SI, computed tomography alone remains unreliable to determine splenic involvement in children with HD. Additional imaging studies, especially fluorodeoxyglucose positron emission tomography, may improve the clinical staging of HD.
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