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Biomedical subjects

S Feinstein

Publications and source records attributed to S Feinstein.

At least 19 recordsLinked to original sources
PubMed2006

Recurrent nephrotic syndrome in homozygous truncating NPHS2 mutation is not due to anti-podocin antibodies.

Mutations in NPHS2 are a common cause of focal segmental glomerulosclerosis (FSGS). It was initially assumed that FSGS caused by a genetically defective protein in the native kidney would not recur after transplantation; however, description of three patients with NPHS2 missense mutations challenged the validity of this assumption. A possible mechanism of recurrence in cases with stop-codon mutations is the formation of auto-antibodies against the truncated protein. In this case report, we describe a 9-year-old girl with the R138X NPHS2 mutation who presented with recurrent nephrotic syndrome 4 years after renal transplantation from a deceased donor, and was treated with plasmapheresis with a partial response. Renal histology did not demonstrate glomerular immunoglobulin deposition and an extensive search for anti-podocin antibodies based on indirect Western blot with recombinant podocin, was negative, as was the test for glomerular permeability factor (Palb). Taken together these findings confirm the possibility of post transplantation nephrotic syndrome in patients with NPHS2 mutations. Lack of immunoglobulin deposition, absence of circulating anti-podocin antibodies, and normal Palb suggest that other, unknown pathogenetic mechanisms are implicated.

Autoantibodies↗
PubMed2004

Clinical and biochemical manifestations and molecular characterization of the mutation HPRT Jerusalem.

A novel point mutation (I137T) was identified in the hypoxanthine-guanine phosphoribosyltransferase (HPRT) encoding gene, in a patient with partial deficiency of the enzyme. The mutation, ATT to ACT (substitution of isoleucine to threonine), occurred at codon 137, which is within the region encoding the binding site for 5-phosphoribosyl-1-pyrophosphate (PRPP). The mutation caused decreased affinity for PRPP, manifested clinically as a Lesch-Nyhan variant (excessive purine production and delayed acquisition of language skills). The partial HPRT deficiency could be detected only by measuring HPRT activity in intact fibroblasts (uptake of hypoxanthine into nucleotides).

Binding Sites↗
PubMed2001

Erythropoietin deficiency causes anemia in nephrotic children with normal kidney function.

Anemia in persistent nephrotic syndrome (NS) has been described in a few case reports but has not been studied systematically. We present a group of 19 children with NS who developed anemia before the deterioration of kidney function. The aim of our study is to determine whether erythropoietin (EPO) and/or iron deficiency are causative factors and to evaluate the effect of EPO replacement therapy. Serum EPO levels, iron status, and vitamin B(12) concentrations were measured in nephrotic patients with anemia (NS-A) and compared with those of nephrotic children with normal hemoglobin (Hb) levels (NS-NHb; n = 13). Two control groups consisted of age-matched patients without kidney disease or hypoxemia with either iron deficiency anemia (IDA; n = 19) or normal Hb concentrations (NHb; n = 16). Most NS-A patients experienced persistent steroid-resistant NS, whereas most NS-NHb children had steroid-responsive NS. Although serum iron, ferritin, and B(12) levels were significantly lower in NS-A children, appropriate replacement therapy that resulted in normalization of ferritin and/or cobalamin levels did not lead to correction of the anemia. NS-A patients had greater EPO levels than those without anemia (21.6 +/- 3.3 versus 5.5 +/- 0.8 IU/L; P: < 0.001), but their response to anemia was inappropriately low compared with IDA children (EPO, 94.6 +/- 15.1 IU/L) despite similar Hb concentrations. EPO therapy for 4 to 9 months in 6 NS-A children with Hb levels less than 9 g/dL led to resolution of the anemia. In conclusion, anemia is a common feature of persistent NS that develops before the deterioration of kidney function. Depletion of iron stores may contribute to the development of anemia, but iron replacement therapy is ineffective. Nephrotic patients have EPO deficiency with a blunted response to anemia. The EPO deficiency is amenable to EPO therapy, which is recommended for this group of patients.

Adolescent↗
PubMed2000

Kelley-Seegmiller syndrome due to a unique variant of hypoxanthine-guanine phosphoribosyltransferase: reduced affinity for 5-phosphoribosyl-1-pyrophosphate manifested only at low, physiological substrate concentrations.

A male child, who presented at the age of 3.5 years with acute renal failure, was diagnosed as having partial deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT; EC 2.4.2.8). The underlying HPRT mutation was unique in that the specific activity of HPRT in erythrocyte and in fibroblast lysates was normal, but the rate of uptake of hypoxanthine into nucleotides of intact cultured fibroblasts was markedly reduced (23% of normal). The low functioning of HPRT in the intact fibroblasts was associated with decreased utilization of endogenously generated hypoxanthine and with decreased utilization of the cosubstrate 5-phosphoribosyl-1-pyrophosphate (PRPP). The non-utilized hypoxanthine was excreted into the incubation medium. The accumulation of PRPP was indicated by the 2.3-fold increase in the rate of uptake of adenine into intact cell nucleotides and by the 7. 5-fold enhancement of the rate of de novo purine synthesis. Kinetic studies of HPRT activity in fibroblast lysates revealed reduced affinity of the enzyme for PRPP (apparent K(m) 500 microM in comparison to 25 microM in control lysates), manifested in low activity at low (physiological), but not at high PRPP concentrations. The apparent K(m) for hypoxanthine was normal (23 microM in comparison to 14.2 microM in control lysates). With allopurinol treatment, our patient has had no problems since presentation, and is developing normally at 5 years of age.

Acute Kidney Injury↗
PubMed2000

Hypothyroidism in primary hyperoxaluria type 1.

We describe 4 patients, aged 3 months to 23 years, with end-stage renal disease and severe, symptomatic hypothyroidism. All 4 had primary hyperoxaluria type 1 (PH1) with diffuse tissue (kidneys, skeleton, eyes, heart) calcium-oxalate deposition, a condition known as oxalosis. The hypothyroidism responded to thyroid hormone replacement therapy. Clinical hypothyroidism within the framework of PH1/oxalosis was probably caused by thyroid tissue damage from an abundance of calcium oxalate. We recommend that thyroid function be monitored in patients with PH1 and oxalosis.

Child, Preschool↗
PubMed1998

Use of an intravenous contrast agent (Optison) to enhance echocardiography: efficacy and cost implications. Optison Multicenter Study Group.

OBJECTIVE: To compare the overall diagnostic costs associated with non-contrast and contrast echocardiography. STUDY DESIGN: Phase III clinical trial. PATIENTS AND METHODS: In a secondary analysis of data from a phase III clinical trial of the intravenous contrast agent Optison, we compared the costs associated with obtaining a diagnosis in 203 patients who underwent non-contrast and contrast echocardiography. Costs for the initial test and any follow-up tests were derived from adjusted Medicare charges and a transition-1 microcost accounting system. RESULTS: Diagnostic yield from echocardiograms was 87% with the use of Optison (3 mL) and 49% when no contrast agent was used (P < 0.001). Because technically inadequate echocardiograms were more common in the non-contrast group, follow-up testing was recommended for 42% of patients in this group compared with 12% of those who had undergone a contrast-enhanced echocardiogram (P < 0.001). Although use of Optison increased the initial diagnostic cost by $125, overall costs were 17% lower when Optison was used (P < 0.0001). Use of Optison also resulted in a 17% to 70% decrease in confirmatory transesophageal echocardiography, catheterization, and nuclear studies. Optison improved diagnostic accuracy by 2.7-fold in patients with an initial non-diagnostic echocardiogram, resulting in a substantial cost savings of $269 per patient.

Cardiomyopathies↗
PubMed1998

Living unrelated (commercial) renal transplantation in children.

Long waiting times for cadaveric renal transplantation has led the frustrated parents of Arab children with end-stage renal disease treated in our center to seek commercial renal transplantation (CRT) outside Israel. During the past 3 yr, 18 children, aged 13 +/- 1 yr, underwent CRT in one center in Iraq. Post-CRT follow-up was 20.2 +/- 2.5 mo. Immediate complications (abroad) included: death on the day of surgery (n = 1) and vascular thrombotic events requiring removal of a previously functioning graft (n = 2). There was a high incidence of urologic problems, mainly as a result of inadequate uretero-vesical anastomosis. Calculated creatinine clearance at 6, 12, 18, 24, and 30 mo was 84.7 +/- 6.4, 91.0 +/- 6.8, 90.8 +/- 6.2, 82.5 +/- 9.5, and 77.7 +/- 8.2 ml/min per 1.73 m2 respectively, representing excellent graft function in 13 patients and slightly compromised function in two children. One- and two-year patient survival was 94.4%, with a graft survival of 83.3%. CRT in these Arab children had a favorable outcome despite severe early postoperative complications. Graft function at follow-up was comparable to cadaveric renal transplantation in Israel. This may reflect a propensity for healthy young adult donors. Despite these results, the authors oppose and discourage the practice of CRT on legal and ethical grounds. Not to provide follow-up care in this specific group of patients would not have been in their best interest.

Adolescent↗
PubMed1996

Loss of contrast intensity during systole in the left ventricular cavity with the use of the contrast agent Albunex. An analysis of its correlation with pressure and velocity.

RATIONALE AND OBJECTIVES: Several investigators have observed a decrease in video intensity in the left ventricular cavity during systole when using contrast echocardiography. It has been suggested that this phenomenon is related to microbubble instability. The authors propose that this phenomenon is, in part, related to the effects of pressure and velocity on the acoustic reflectance of ultrasound contrast agents. METHODS: Using an in vitro flow tube model and varying concentrations of Albunex contrast agent, the effects of pressure and velocity on microbubble video intensity were investigated. Velocity and pressure were varied independently and the imaging tube was scanned using three transducer frequencies at different concentrations of Albunex. Contrast video intensity was analyzed using high and low velocities (at constant pressure) and high and low pressures (at constant velocity). In addition, the fluid from the system was collected and imaged in a nonflowing reservoir tank to investigate the video intensity of the microbubbles when exposed to variable velocity and pressure. RESULTS: The video-intensity measurements were inversely and irreversibly related to ambient pressure changes (independent of velocity) in a tube model. However, video intensity varied inversely but reversibly with velocity (independent of pressure). This observation could not be explained simply by the "laminar flow" theory, by a change in transducer angulation, nor by a change in ultrasound imaging frame rate. This phenomenon was limited to Albunex microbubbles and was not observed with a contrast medium (corn starch) devoid of the acoustic properties of Albunex.

Albumins↗
PubMed1995

Retrograde cardioplegia does not adequately perfuse the right ventricle.

UNLABELLED: Surgeons often rely primarily on retrograde cardioplegia for myocardial protection, because it provides adequate left ventricular perfusion even in the presence of coronary artery disease. Clinically, however, adequate right ventricular perfusion by retrograde delivery has not been demonstrated. Using intraoperative transesophageal echocardiography, we examined retrograde delivery of cardioplegic solutions by contrast echocardiography, which directly assesses myocardial perfusion. In 15 patients (seven having coronary bypass and eight having valve operations), 4 ml of sonicated Isovue medium was injected retrograde via a coronary sinus catheter. Myocardial perfusion was assessed quantitatively by visual inspection and back-ground-subtracted videodensitometric analysis. In five patients undergoing aortic valve replacement, right and left coronary ostial drainage was estimated during retrograde infusion. Before the aortic crossclamp was removed, myocardial oxygen extraction was calculated in all 15 patients by first delivering warm blood cardioplegic solution for 2 minutes in a retrograde fashion and then taking samples from the cardioplegia line and aortic root. This determined the oxygen extraction ratio across the myocardium at the end of retrograde delivery. Warm blood cardioplegic solution was next given antegrade, and 15 seconds later samples were taken from the cardioplegia line and a right ventricular (acute marginal) vein to determine the oxygen extraction ratio across the right ventricle. As assessed by contrast echocardiography, retrograde infusion resulted in almost four times more perfusion to the left ventricular free wall and septum than to the right ventricular free wall (74 +/- 2 versus 69 +/- 2 versus 20 +/- 2, p < 0.05). In those five patients with an aortotomy the right ostial drainage was less than 5 ml/min whereas left ostial drainage was estimated at 80 ml/min during retrograde administration. Oxygen extraction across the myocardium supplied by retrograde infusion was low after 2 minutes. Conversely, when antegrade cardioplegia was started, right ventricular oxygen extraction rose fourfold (42% +/- 5% versus 11% +/- 1%, p < 0.05), demonstrating that retrograde cardioplegia had not adequately perfused the right ventricular myocardium. CONCLUSIONS: 1. Retrograde cardioplegia provides poor right ventricular myocardial perfusion as assessed by contrast echocardiography and coronary ostial drainage. (2) This poor perfusion is inadequate to meet myocardial demands as demonstrated by the high right ventricular oxygen extraction after a prolonged retrograde infusion. (3) Therefore surgeons must not rely solely on retrograde cardioplegia for right ventricular myocardial protection. This concept is especially important if continuous warm blood cardioplegia is used, because myocardial requirements are then higher.

Blood↗
PubMed1994

Oral pulse therapy with vitamin D3 for control of secondary hyperparathyroidism.

Twelve dialysis patients received oral pulse therapy with 1-alpha-hydroxyvitamin D3 in a dose of 0.1 microgram/kg body weight twice weekly and daily calcium carbonate (1.5-3.5 g) for a period of 8-12 months. This treatment was very effective in suppressing secondary hyperparathyroidism without causing hypercalcaemia and/or hyperphosphataemia.

Administration, Oral↗
PubMed1993

Myocardial distribution of cardioplegic solution after retrograde delivery in patients undergoing cardiac surgical procedures.

The myocardial distribution of both antegrade and retrograde cardioplegia for cardiac surgical intervention, after induction of cardioplegia via the aortic root, was directly assessed and compared in 19 patients by means of contrast echocardiography. Two-dimensional transesophageal echocardiographic images of the short axis of the left ventricle at the level of the papillary muscles were obtained after sonicated Renografin-76 microbubbles were injected into an aortic root and/or transatrial coronary sinus catheter during delivery of cardioplegic solution. Segmental distribution of cardioplegic solution was immediately noted in the myocardium at the time of contrast injections. In 11 of 18 patients (61%) cardioplegic solution was dispersed to all left ventricular myocardial segments after antegrade delivery. In 17 of 19 patients (90%) retrogradely delivered cardioplegic solution (after antegrade induction of cardioplegia in 18 of the 19 patients) was dispersed to all the left ventricular myocardial segments, including the septum. In 2 of the patients, initial lack of retrograde distribution of cardioplegic solution was remedied when the coronary sinus catheter was repositioned and contrast cardioplegic solution was reinjected. Imaging of the right ventricle was possible in only 4 of the 19 patients and revealed that after retrograde delivery, cardioplegic solution had been at least partially distributed to the right ventricle as well. We performed off-line videodensitometric analysis in 9 patients after retrograde delivery of cardioplegic solution. Mean peak pixel-intensity ratio of flow from the endocardium to the epicardium in the left ventricular free wall was 1.46 +/- 0.27, and mean peak pixel-intensity ratio of flow from the left to the right intraventricular septal endocardium was 1.39 +/- 0.33 (p < or = 0.05).

Aged↗
PubMed1990

Endocarditis associated with Comamonas acidovorans.

A case of endocarditis caused by Comamonas acidovorans (Pseudomonas acidovorans) in a 42-year-old intravenous-drug abuser is described. This article appears to be the first detailed report of the isolation of this organism from a systemic clinical infection and its identification as a pathogen.

Adult↗
PubMed1989

Cerebral vasculitis and hemorrhage in an adolescent taking diet pills containing phenylpropanolamine: case report and review of literature.

Phenylpropanolamine is consumed by millions of persons annually and is sold in varying dosages and combinations for different ailments. Adolescents are an especially susceptible group influenced by its action as an anorexiant. During the past 6 years, several cases have been reported of patients in whom intracerebral hemorrhage developed, with and without concomitant angiographic evidence of vasculitis, after taking phenylpropanolamine. In this report, the 11th documented case of phenylpropanolamine-associated intracerebral hemorrhage with vasculitis is described. This is the first case in an adolescent following the ingestion of an overdose of diet-aid pills. Cases of intracerebral hemorrhage with vasculitis have also been described in users and abusers of amphetamine, methamphetamine, and ephedrine, all sympathomimetics with chemical structures similar to that of phenylpropanolamine. This report should alert pediatricians to the potential use by their patients of nonprescription medications containing phenylpropanolamine whenever unexplained acute cerebral symptoms are present.

Adolescent↗
PubMed1988

A dominant trifluoperazine resistance gene from Saccharomyces cerevisiae has homology with F0F1 ATP synthase and confers calcium-sensitive growth.

The antipsychotic drug trifluoperazine has been long considered a calmodulin inhibitor from in vitro studies but may function in vivo as a more general inhibitor by disturbing ion fluxes and altering the membrane potential. Resistance to trifluoperazine can arise in Saccharomyces cerevisiae cells by alterations in at least three distinct genetic loci. One locus, defined by a spontaneous dominant trifluoperazine resistance mutation (TFP1-408), was isolated and sequenced. The sequence of the TFP1-408 gene revealed a large open reading frame coding for a large protein of 1,031 amino acids with predicted hydrophobic transmembrane domains. A search of existing amino acid sequences revealed a significant homology with F0F1 ATP synthase. Mutant TFP1-408 cells did not grow efficiently in the presence of 50 mM CaCl2, whereas wild-type cells did. Wild-type cells became resistant to trifluoperazine in the presence of 50 mM CaCl2 or 50 mM MgCl2. Mutant cells showed a higher rate of calcium transport relative to wild-type cells. These data suggest that the TFP1 gene product codes for a transmembrane ATPase-like enzyme possibly involved in Ca2+ transport or in generating a transmembrane ion gradient between two cellular compartments.

Amino Acid Sequence↗
PubMed1985

Determination of human IgG and IgM class antibodies to West Nile virus by enzyme linked immunosorbent assay (ELISA).

An enzyme-linked immunosorbent assay (ELISA) was developed and used for the detection of IgG and IgM antibodies to West Nile virus in human sera. Thirteen paired sera of clinical cases and 24 control sera taken randomly from a blood bank repository were tested. The sera were reacted in microtiter plates coated with PEG-treated WNV antigen. IgG or IgM antibodies were quantitated by the use of alkaline-phosphatase-conjugated anti-human IgG or IgM antibodies. Of the 24 randomly collected serum samples, 7 were positive in the IgG-ELISA test. One positive by the IgM-ELISA was found to contain rheumatoid factor. In 12 of 13 paired sera of clinical cases, IgM as well as IgG antibodies were detected in the second serum sample taken about 3 wk after the onset of clinical signs. The IgM positive sera were screened for rheumatoid factor (RF) on IgG-coated plates. None of them contained RF. Antibody titers obtained by ELISA showed a good correlation with titers obtained by hemagglutination inhibition, complement fixation, and neutralization tests. The ELISA tests for detection of IgM and IgG antibodies to WNV therefore can replace the other serological methods for epidemiological surveillance and diagnostic purposes.

Antibodies, Viral↗
PubMed1985

Studies on cell binding and internalization of human lymphoblastoid (Namalva) interferon.

The binding of iodinated human lymphoblastoid Namalva interferon to Namalva cells, to a human fibroblast cell strain (FS11), and to a bovine kidney cell line (MDBK) was characterized. Scatchard analysis of the binding data indicated the presence of about 1000-2000 receptors per cell and dissociation constants of the order of 0.1 to 0.01 nM. Two subspecies of Namalva interferon (16 K and 20 K), which differ in their antiviral activity toward bovine and human cells, were found to bind with the same affinity toward bovine MDBK cells but to differ in their affinity to human cells. Experimental results indicated that at 37 degrees C the bound interferon is internalized within 15 min after binding to Namalva cells, and then degraded in the lysosomes. Exposure of Namalva cells to interferon resulted in a 40% reduction of the number of cell surface receptors (down-regulation).

Animals↗