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S Goldfarb

Publications and source records attributed to S Goldfarb.

At least 37 records · Page 2Linked to original sources
PubMed1995

Nephrotoxicity of ionic and nonionic contrast media in 1196 patients: a randomized trial. The Iohexol Cooperative Study.

The incidence of nephrotoxicity occurring with the nonionic contrast agent, iohexol, and the ionic contrast agent, meglumine/sodium diatrizoate, was compared in 1196 patients undergoing cardiac angiography in a prospective, randomized, double-blind multicenter trial. Patients were stratified into four groups: renal insufficiency (RI), diabetes mellitus (DM) both absent (N = 364); RI absent, DM present (N = 318); RI present, DM absent (N = 298); and RI and DM both present (N = 216). Serum creatinine levels were measured at -18 to 24, 0, and 24, 48, and 72 hours following contrast administration. Prophylactic hydration was administered pre- and post-angiography. Acute nephrotoxicity (increase in serum creatinine of > or = 1 mg/dl 48 to 72 hours post-contrast) was observed in 42 (7%) patients receiving diatrizoate compared to 19 (3%) patients receiving iohexol, P < 0.002. Differences in nephrotoxicity between the two contrast groups were confined to patients with RI alone or combined with DM. In a multivariate analysis, baseline serum creatinine, male gender, DM, volume of contrast agent, and RI were independently related to the risk of nephrotoxicity. Patients with RI receiving diatrizoate were 3.3 times as likely to develop acute nephrotoxicity compared to those receiving iohexol. Clinically severe adverse renal events were uncommon (N = 15) and did not differ in incidence between contrast groups (iohexol N = 6; diatrizoate N = 9). In conclusion, in patients undergoing cardiac angiography, only those with pre-existing RI alone or combined with DM are at higher risk for acute contrast nephrotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1995

Are cytotoxic agents beneficial in idiopathic membranous nephropathy? A meta-analysis of the controlled trials.

The use of cytotoxic agents for the treatment of idiopathic membranous nephropathy is controversial. Although several controlled trials have been published, both the comparison groups and the study findings have varied, resulting in clinical uncertainty. To explore this uncertainty, a meta-analysis of controlled trials of treatment with cyclophosphamide or chlorambucil was performed in patients with idiopathic membranous nephropathy and nephrotic-range proteinuria. Patients in the control groups received only symptomatic treatment or corticosteroids. Descriptive and quantitative data from each trial were abstracted independently. Outcomes included effects of treatment on renal function and proteinuria, with a complete remission (CR) or partial remission (PR) defined as the complete or partial resolution of proteinuria without deterioration of renal function. For patients having either any response (CR or PR) or only a CR, both the relative risk (RR) and the number needed to be treated were calculated. The five trials that satisfied criteria for inclusion in the analysis were clinically and statistically homogeneous. There were no placebo-controlled trials that met the criteria for inclusion. Among the 228 patients in these studies, the RR of achieving any response with cytotoxic agents was 2.3 (95% confidence interval, 1.7 to 3.2) and the RR for a CR was 4.6 (95% confidence interval, 2.2 to 9.3), with respective numbers needed to be treated of 2.9 and 4.7, meaning that between three and five patients would need to be treated with cytotoxic agents to achieve one response. Exclusion of the only nonrandomized trial had no significant effect on the results. Both chlorambucil and cyclophosphamide showed similar beneficial effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Chlorambucil↗
PubMed1995

Proving the link between outcomes and resource utilization.

Medical practice profiling is a popular way of helping to reduce variation in resource utilization among providers in managed care organizations. Usually, these programs take into account severity of illness, patient demographics, and so forth, but rarely are clinical practice patterns linked with outcome. The authors offer information about an information system-based program that attempts to do just that.

Critical Pathways↗
PubMed1994

Nephrotoxic risks of renal angiography: contrast media-associated nephrotoxicity and atheroembolism--a critical review.

Renal angiography remains the "gold standard" procedure for the detection of renal artery stenosis. However, clinicians often avoid renal angiography because of fears of contrast media-associated nephrotoxicity (CM-AN) and atheroembolism. This review focuses on these potential angiographic complications, with particular emphasis, in the case of CM-AN, on clinical features, incidence, risk factors with an emphasis on pre-existing renal insufficiency and diabetes mellitus, volume of contrast media, low osmolar versus high osmolar contrast media, and prophylaxis. For atheroembolism, areas emphasized are pathology, clinical features, precipitating features, and incidence in various settings. Although the literature contains an abundance of information about CM-AN and atheroembolism, this review identified multiple areas of uncertainty regarding features of both of these complications. For example, additional studies are needed to determine the incidence of CM-AN, both asymptomatic and clinically severe, in patients with a wide range of pre-existing renal insufficiency with and without diabetes mellitus, following low volume digital subtraction renal angiography with low osmolar contrast media. In a similar manner, studies are needed with adequate postcontrast observation periods to determine the true incidence of clinically significant atheroembolism following diagnostic renal angiography and angioplasty and techniques that may modify this complication. Until further knowledge in both of these areas is available, it is difficult to precisely determine the risks of renal angiography and/or angioplasty in the azotemic patient suspected of or having renal ischemic disease using modern radiologic techniques.

Acute Kidney Injury↗
PubMed1994

Polyol pathway mediates high glucose-induced collagen synthesis in proximal tubule.

The polyol pathway in diabetes is activated in tissues that are not dependent on insulin for glucose uptake. To examine the role of the polyol pathway in renal extracellular matrix accumulation, we incubated murine proximal tubule cells in either normal or high glucose concentration in the presence or absence of the aldose reductase inhibitor sorbinil. Rising medium glucose from 100 to 450 mg/dl for 72 hours increased cell sorbitol levels sevenfold. Addition of 0.4 mM sorbinil reduced sorbitol content to virtually undetectable levels as measured by gas chromatography. Sorbinil (0.1 to 0.2 mM) also reduced the secretion of collagens types IV and I in the high glucose concentration after 48 to 72 hours but had no appreciable effect in the normal glucose concentration. Concordantly, 0.1 mM sorbinil inhibited the high glucose-induced stimulation of alpha 1(IV) and alpha 2(I) mRNA levels without affecting levels in normal glucose concentration. To study the role of transcriptional activation of collagen genes, we transfected proximal tubule cells with a chloramphenicol acetyltransferase (CAT) reporter gene linked to the promoter and regulatory elements of alpha 1(IV) gene. CAT activity increased several-fold in the cells grown in the high versus normal glucose concentration; this transcriptional activation in culture media containing high glucose concentration was reduced by treatment of the cells with 0.1 mM sorbinil. Thus, high ambient glucose activates the polyol pathway in proximal tubule cells, and may mediate the high glucose-induced stimulation of gene expression for collagens types IV and I.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldehyde Reductase↗
PubMed1994

Cholestatic hepatitis after ingestion of chaparral leaf: confirmation by endoscopic retrograde cholangiopancreatography and liver biopsy.

The use of herbal and other "natural" health products by healthy and ill people is more common than is appreciated by many health care providers. Since most of these substances are not categorized as medicines, they are exempt from U.S. Government approval processes, and are essentially uncontrolled. In this article we describe a patient who developed painless jaundice, fatigue, and pruritus after taking chaparral tablets, 160 mg/day, for approximately 2 months. Serial liver biopsies and serum chemistries documented severe cholestasis and hepatocellular injury, i.e., a severe cholangiolitic hepatitis. Serum enzyme levels were markedly elevated: alk. phos. to four-fold, alanine aminotransferase and aspartate aminotransferase to 25-fold, total bilirubin to 30-fold, and gamma-glutamyl transpeptidase to 35-fold. Endoscopic retrograde cholangiopancreatography showed smooth, but severely narrowed biliary ducts without sclerosing cholangitis, distal obstruction, tumor, or stenosis. The diagnosis remained in doubt until the publication of two cases of chaparral hepatotoxicity. Because of the similarity of our patient's illness to those cases we concluded that chaparral was almost certainly the cause. Chaparral, also known as creosote or greasewood, is used by some practitioners to treat a diverse group of ailments including ethanol withdrawal. This report should heighten the awareness by primary care physicians and gastroenterologists that any chaparral herbal preparation is a potential hepatotoxin that can lead to serious illness.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcoholism↗
PubMed1994

Diet and nephrolithiasis.

Pharmacologic therapy of recurrent nephrolithiasis continues to be the mainstay of the strategy to prevent recurrence. This approach persists even in the face of increasing evidence of a marked benefit of mere entry into a nonpharmacologic diet and fluid modification protocol at a clinic specializing in the evaluation and therapy of recurrent nephrolithiasis (the "Stone Clinic effect"). This review examines the role of diet in the pathogenesis of various forms of nephrolithiasis and the effectiveness of dietary therapy in preventing new stone formation. Recent and older evidence support a primary role for modification of diet, particularly diet protein and sodium intake, in the prevention of recurrent nephrolithiasis.

Calcium↗
PubMed1994

Proinflammatory cytokines and hemofiltration membranes.

To determine whether the clinical improvement noted in some septic patients undergoing hemofiltration is in part due to the removal of proinflammatory mediators, in vitro hemofiltration of a 1% albumin solution containing recombinant human tumor necrosis factor alpha and interleukin-1 was performed through a variety of hemofilters. Observed sieving coefficients of these cytokines was much higher (up to 0.35) than expected, considering their molecular weights of 17 kd. In addition, binding of up to 32% of the total mass to selected membranes (polyamide and AN69) was noted. These data are consistent with the concept that either the convective or adsorptive removal of proinflammatory cytokines may play role in the clinical efficacy of hemofiltration in sepsis.

Cytokines↗
PubMed1993

Multicenter trial of ionic versus nonionic contrast media for cardiac angiography. The Iohexol Cooperative Study.

Contrast agents used for cardiac angiography are different in regard to ionicity, osmolality and physiologic effects. The nonionic contrast media have been shown to have less toxic effects and a better safety profile than do higher osmolar agents. To better assess this risk, clinically stable patients undergoing cardiac angiography were stratified according to the presence of diabetes mellitus, and level of serum creatinine, and then randomized to receive either iohexol (Omnipaque 350) or sodium meglumine diatrizoate (Renografin 76). All adverse events that occurred during and immediately after angiography were tabulated. A multivariate model was used to identify patients at increased risk for adverse outcome. The 1,390 patients were randomized to iohexol (n = 696) or diatrizoate (n = 694). Significant differences were found in the number of patients with contrast media-related adverse (iohexol vs diatrizoate: 10.2 vs 31.6%; p < 0.001) and cardiac adverse (7.2 vs 24.5%; p < 0.001) events. Severe reactions and the need for treatment were more frequent with diatrizoate than with iohexol, but there was no difference in the incidence of death. The presence of New York Heart Association classification 3 or 4 and serum creatinine > or = 1.5 mg/dl predicted a higher incidence of adverse events as a result of contrast media alone. Use of iohexol is associated with a lower incidence of all types of adverse events during cardiac angiography than is diatrizoate.

Adult↗
PubMed1993

Low-osmolality contrast media and the risk of contrast-associated nephrotoxicity.

OBJECTIVES: The authors review clinical data, including those from the recent Iohexol Cooperative Group trial, regarding the nephrotoxic potential of low-osmolar versus high-osmolar contrast media. The clinical characteristics and postulated mechanisms of contrast-associated nephrotoxicity are also considered. METHODS: The principal strategy for identifying relevant articles was to search the MEDLINE database using the MeSH heading "contrast media nephrotoxicity." Articles from 1966 through 1992 that were considered included original research papers as well as reviews. Those articles selected for detailed review documented original research pertaining to use of low-osmolar or high-osmolar agents. Selected abstracts for pertinent society meetings were also used. No attempt was made to be complete in describing the field. Rather, specific articles that selectively address the question of nephrotoxicity related to the osmolar content of contrast media were used for discussion. RESULTS AND CONCLUSIONS: In-vitro and animal studies indicate that renal changes possibly involved in the pathogenesis of contrast-associated nephrotoxicity seem to be ameliorated with low-osmolar contrast media, compared with high-osmolar agents. Several recent clinical trials, as well as a meta-analysis combining 24 randomized studies, suggest that the risk of contrast-associated nephrotoxicity is similarly low with high-osmolar and low-osmolar agents among otherwise stable patients with normal renal function, but that low-osmolar contrast is less nephrotoxic than media with high osmolality in patients with pre-existing renal insufficiency.

Animals↗
PubMed1992

Growth kinetics of microscopic hepatocellular neoplasms in carcinogen-resistant and carcinogen-responsive strains of mice.

The initiation and growth of microscopic hepatocellular neoplasms in C57BL/6 mice, considered relatively resistant to hepatocarcinogenesis, was compared with that of the more responsive C3H and B6C3F1 (C57BL/6 x C3H) strains. Tumors were induced by giving male mice injections of diethylnitrosamine when they were 15 days old. During the first 18 weeks postinjection, the growth rates of neoplasms in the three strains were almost identical (doubling time of 2.1 to 2.5 weeks). However, after that time, only the growth rates of the C57BL/6 neoplasms slowed; between 30 and 42 weeks the doubling time had increased to 13 weeks. In addition, at all sacrifice times the number of neoplasms in the C3H strain was at least 2.5 times higher than in the C57BL/6 and B6C3F1 strains. These results suggest that the genetic determinant(s) for inhibited tumor growth (expressed only in C57BL/6 mice) are recessive to those for unimpeded tumor growth (expressed in C3H and B6C3F1 mice), while the determinant(s) for large numbers of tumors (expressed only in C3H mice) are recessive to those for small numbers of tumors (expressed in C57BL/6 and B6C3F1 mice). In addition to the interstrain differences in tumor growth, two other types of tumor growth heterogeneity were identified. First, in each of the three strains, the largest tumors were found to grow faster than the smaller tumors. This suggests that the very broad range in tumor size that is seen in this model results from the long-term differences in the growth rates of individual neoplasms. Second, we found that in microscopic hepatic neoplasms in B6C3F1 mice, the thymidine labeling indices were 2.3 times greater in the outer 50-microns shell (2 cells thick) than in the next deeper 50-micron layer cells. This suggests that even in these minute neoplasms, gradients in blood-borne oxygen, nutrients, or growth factors are responsible for heterogeneous growth.

Animals↗
PubMed1992

Elevated glucose stimulates TGF-beta gene expression and bioactivity in proximal tubule.

Our previous studies have demonstrated that raising ambient glucose from 100 to 450 mg/dl significantly inhibited the proliferation of mouse renal proximal tubule cells in culture. This effect was demonstrated after a latent period of 24 to 48 hours. Because transforming growth factor-beta (TGF-beta) inhibits cell proliferation in most epithelial cell lines, we hypothesized that the inhibitory effect of high glucose levels on cell proliferation may be mediated by TGF-beta. The present studies were performed to test the hypothesis that TGF-beta is an autocrine cytokine whose activity can be modulated by ambient glucose. Exogenous TGF-beta inhibited [3H]-thymidine incorporation in a dose-dependent fashion and with high affinity (picomolar range), but with slightly lower potency in high versus normal glucose media. Northern analysis of mRNA demonstrated that proximal tubule cells constitutively express TGF-beta 1 transcripts, and that the steady state level of TGF-beta 1 mRNA was, on average, 63% higher in the cells grown for 48 hours in high versus normal glucose media. Furthermore, the conditioned media of cells exposed to 450 mg/dl glucose exhibited endogenous TGF-beta bioactivity as measured by inhibition of cell proliferation. The addition of a rabbit antiporcine TGF-beta neutralizing antibody significantly increased basal thymidine incorporation in high glucose media to levels approaching those of cells grown in normal glucose media. In contrast, the anti-TGF-beta antibody did not have a significant effect on the growth of cells in the normal glucose media.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Nephrotoxicity of contrast media following cardiac angiography: pathogenesis, clinical course, and preventive measures, including the role of low-osmolality contrast media.

OBJECTIVE: To review the incidence, definition, clinical course, risk factors, pathogenesis and prevention of contrast-associated nephropathy (CAN) following cardiac angiography with emphasis on differences between high-osmolality contrast media (HOCM) and low-osmolality contrast media (LOCM). DATA SOURCES: Investigations in animal models and in patients following cardiac angiography. DATA EXTRACTION: Animal models of the pathogenesis of CAN are presented. Human studies describing the incidence, clinical course, risk factors, and prevention of CAN are reviewed. Comparative clinical trials of HOCM (diatrizoate, metrizoate) and LOCM (iohexol, iopamidol, ioxaglate) nephrotoxicity following cardiac angiography are critically evaluated. DATA SYNTHESIS: All clinical studies comparing CAN of HOCM versus LOCM following cardiac angiography have some methodologic limitations (e.g., small sample size, lack of control for other factors) that may affect renal function, lack of stratification for other reported risk factors, and variable or short follow-up periods. CONCLUSIONS: Whether the incidence of CAN following cardiac angiography is reduced with LOCM remains controversial. The incidence of CAN in patients with normal renal function does not appear to differ in patients treated with LOCM versus HOCM because few patients in each group develop renal failure. Additional controlled clinical trials comparing CAN of LOCM and HOCM in patients with renal dysfunction are needed. Because of greater product cost and scarcity of documented benefit compared with HOCM, selection of LOCM based on the presence of renal dysfunction cannot be recommended at this time.

Animals↗
PubMed1991

The influence of glucose concentration on angiotensin II-induced hypertrophy of proximal tubular cells in culture.

Incubation of cultured murine proximal tubular cells in serum-free media containing 450 mg/dl of glucose resulted in cellular hypertrophy as defined by an increase in cell size, total protein content, and synthesis after 72 h. 10 nM angiotensin II further increased this hypertrophy, but failed to have any effect on cells grown in 100 mg/dl glucose. This enhancement by angiotensin II was blocked by treatment with 1 microM of the angiotensin-receptor antagonist DuP 753. Although cells incubated in either glucose media exhibited similar high-affinity angiotensin II-receptors, the receptor density was elevated only in cells grown in the presence of high glucose. Stimulation of cells in high glucose for 60 min with 10 nM angiotensin II also reduced significantly intracellular cAMP concentrations. This was not the case for proximal tubular cells cultured in normal glucose. Our results indicate that high glucose and angiotensin II have additive effects on the induction of hypertrophy in renal tubular cells.

Angiotensin II↗
PubMed1991

Susceptibility and resistance to poliovirus-induced paralysis of inbred mouse strains.

Susceptibility to human poliovirus-induced disease in different inbred mouse strains was analyzed after intracerebral inoculation of two mouse-adapted type 2 polioviruses, the attenuated W-2 strain and the virulent Lansing strain. In contrast to inoculation with the Lansing strain, which was invariably lethal, inoculation with the W-2 strain defined three groups of mice with high, intermediate, or low disease incidence. Those in the high-disease-incidence group, the DBA/1J and DBA/2J mice, exhibited a high level of virus replication in the spinal cord by day 2 postinfection, with no detectable neutralizing-antibody response. Mice in the intermediate- and low-incidence groups had lower levels of virus replication in the spinal cord and/or produced neutralizing antibodies. No correlation was observed between H-2 haplotype and the extent of virus replication, production of neutralizing or enzyme-linked immunosorbent assay-detectable antibodies, or T-cell-proliferative response. However, mice of the H-2k haplotype manifested a low incidence of disease.

Animals↗
PubMed1991

Effect of myo-inositol on cell proliferation and collagen transcription and secretion in proximal tubule cells cultured in elevated glucose.

Tubulointerstitial lesions often develop in the kidneys of patients and experimental animals with diabetes mellitus. In an in vitro model of diabetic renal disease, it has been previously demonstrated in this laboratory that elevated glucose levels stimulate procollagen transcription and secretion in proximal tubule cells in culture while inducing cellular hypertrophy and reducing cellular proliferation. Previous experiments in other tissues have suggested that myo-inositol supplementation, probably by reversing a disturbance in cell myo-inositol metabolism related to increased activity of the polyol pathway, reverses the effects of glucose on cell function. We tested the effect of myo-inositol supplementation on proximal tubule cells in culture in the presence of elevated medium glucose level. Incubation in 450 mg/dL of glucose media reduced cell proliferation; 450 mg/dL of glucose plus myo-inositol (800 microM) increased proliferation, returning the value to that seen in cells incubated in 100 mg/dL of glucose. Incubation in 450 mg/dL of glucose media increased type IV and type I procollagen mRNA levels and peptide secretion rates compared with those seen in cells incubated in medium containing 100 mg/dL of glucose. This glucose-induced stimulation of procollagen mRNA levels and procollagen secretion was not observed when the elevated glucose medium was supplemented with 800 microM myo-inositol. On the other hand, myo-inositol supplementation did not prevent the glucose-induced cellular hypertrophy: there was no reduction in the increased leucine incorporation and cellular protein content. Cell incubation in 450 mg/dL of glucose media did not lead to a measurable decrease in total cellular myo-inositol.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Effects of polyol-pathway inhibition and dietary myo-inositol on glomerular hemodynamic function in experimental diabetes mellitus in rats.

Early functional disturbances in nerve, retina, and lens in diabetes mellitus appear to result from a common mechanism involving increased polyol-pathway activity with an associated effect on tissue myo-inositol metabolism. We tested the role of increased polyol-pathway activity in the early glomerular hemodynamic abnormalities in experimental diabetes in rats with dietary myo-inositol supplementation or the administration of sorbinil, an aldose reductase inhibitor. Each maneuver prevented the glomerular hyperfiltration of early streptozocin-induced diabetes and reversed the hyperfiltration of established diabetes of 10 days' duration. We also found that the abnormal response to captopril in diabetic rats was improved by dietary myo-inositol supplementation or sorbinil administration. Although nonhypotensive doses of captopril lowered glomerular filtration rate (GFR) in diabetic rats on a 0.01% myo-inositol diet, GFR increased substantially after captopril infusion in diabetic rats treated with sorbinil or myo-inositol supplementation. These data suggest that normalization of tissue myo-inositol metabolism restores normal responsiveness to angiotensin II; this may contribute to the reduction in GFR with the two experimental maneuvers. We also tested the interaction between polyol-pathway activation and high dietary protein intake. Aldose reductase inhibition and dietary myo-inositol supplementation had no effect on the component of increased GFR due to 50% dietary protein intake but specifically inhibited the hyperfiltration attributable to diabetes. These results suggest that hyperglycemia acts through increased polyol-pathway activity and its effects on tissue myo-inositol metabolism to play a fundamental role in the pathogenesis of the glomerular hyperfiltration characteristic of early diabetes.

Animals↗