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Biomedical subjects

D Roth

Publications and source records attributed to D Roth.

At least 91 records · Page 5Linked to original sources
PubMed1996

Recipient body size and cadaveric renal allograft survival.

Transplantation of renal allografts inadequate to meet recipient metabolic demands has been hypothesized to be one cause of chronic allograft failure. This cohort study examined the relationship of each of three measures of recipient body size and one measure of recipient metabolic rate to the rate of allograft failure among 239 recipients of cadaveric renal allografts between 1985 and 1990. All subjects were followed until allograft failure, death, or December 31, 1992, whichever occurred first. Using multivariate Cox proportional hazards analysis, all measures of recipient size and metabolic rate were found to be strong and statistically significant predictors of allograft survival adjusted for other predictors of allograft survival including allograft rejection, delayed allograft function, recipient race, prior renal transplantation, and donor age. The adjusted relative risk (RR) of allograft failure for a 15-kg increase in recipient body weight was 1.47, P < 0.0001 (95% confidence interval (CI), 1.21-1.78); adjusted RR for a 10-U increase in recipient body mass index was 2.34, P < 0.0001 (95% CI, 1.53-3.58); adjusted RR for a 0.5 m2 increase in recipient body surface area was 2.34, P < 0.001 (95% CI, 1.40-3.91); and adjusted RR for a 250 Kcal increase in metabolic rate was 1.49, P < 0.01 (95% CI, 1.17-1.89). These results are consistent with prior research indicating that a renal tissue supply-demand mismatch may accelerate failure of renal allografts. Alternative explanations of this relationship between recipient body size and allograft survival include inadequate immunosuppressive medication administration among recipients with a larger body size. Additional research is warranted to examine more fully the relationship between recipient body size and allograft survival.

Adolescent↗
PubMed1995

[Initial results of the HOT-study in Switzerland (hypertension optimal treatment)].

The HOT study (hypertension-optimal treatment) is an international clinical study on primary prevention of cardiovascular events in 19,193 hypertensive patients worldwide. It aims at the recognition of the optimal diastolic blood pressure value (< 90, < 85 or < 80 mmHg?) in order to maximize the possible benefit of an antihypertensive therapy. In addition, the HOT study investigates whether low doses of aspirin (75 mg/day) are able to reduce the occurrence of severe cardiovascular events. In Switzerland a total of 797 patients have been enrolled in the study. Antihypertensive therapy was initiated with felodipine = Plendil (5 mg/day). This vasoelective calcium antagonist could reduce diastolic blood pressure values to < 90 or < 80 mg/Hg, respectively, in one of two or one of three patients within the first three months. In nine or six patients, respectively out of ten a reduction of diastolic blood pressure values to < 90 or < 80 mmHg was reached within one year by combination of felodipine with other antihypertensive drugs (ACE inhibitors, beta blockers and diuretics).

Adrenergic beta-Antagonists↗
PubMed1995

Stimulation of catecholamine secretion from adrenal chromaffin cells by 14-3-3 proteins is due to reorganisation of the cortical actin network.

Catecholamine release from digitonin-permeabilized adrenal chromaffin cells is increased by exogenous 14-3-3 proteins. In order to determine how 14-3-3 proteins stimulate exocytosis their effect on the cortical actin network was examined. Increased amounts of beta and gamma isoforms of 14-3-3 proteins were associated with the Triton-insoluble cytoskeleton of chromaffin cells following incubation with exogenous 14-3-3 proteins. The stimulation of catecholamine release by 14-3-3 proteins was abolished by prior incubation with the actin filament stabilising drug phalloidin. Rhodamine phalloidin staining showed that the cortical actin network was disassembled and actin reorganised into intracellular foci following treatment with 14-3-3 proteins. These data suggest that 14-3-3 proteins enhance catecholamine release in permeabilized chromaffin cells by reorganisation of the cortical actin barrier to allow increased availability of secretory vesicles for exocytosis.

14-3-3 Proteins↗
PubMed1995

A preliminary report of the safety and efficacy of fluvastatin for hypercholesterolemia in renal transplant patients receiving cyclosporine.

Hypercholesterolemia is common following renal transplantation and undoubtedly contributes to morbidity and mortality due to occlusive atherosclerosis in these patients. Although 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are more tolerable as low density lipoprotein cholesterol (LDL-C)-lowering agents than other classes of drugs, their use in transplant patients has been limited due to potentially serious interactions with cyclosporine. Fluvastatin is the first wholly synthetic HMG-CoA reductase inhibitor. Because it has a shorter half-life and greater protein-binding capacity than other drugs of this class and has no active circulating metabolites, fluvastatin may be safer than other HMG-CoA reductase inhibitors in this group of patients. To study this question, 19 renal transplant recipients (age, 21-70 years) with hypercholesterolemia (LDL-C > 180 mg/dL; triglycerides < 400 mg/liter) were entered into a 14-week active-treatment period with fluvastatin at 20 mg/day following dietary stabilization and a 3-week placebo washout period. Changes in LDL-C levels were compared with those obtained in control hypercholesterolemic subjects treated in the same way. The lipid-lowering ability of fluvastatin was not imparied in these patients, indicating a lack of interaction with cyclosporine. Mean liver enzyme levels, creatine phosphokinase (CPK), and creatine did not change significantly from baseline. Two subjects experienced myalgias without CPK elevations, and another subject experienced an asymptomatic increase in CPK to > 10 times the upper limit of normal, related to exercise. In conclusion, fluvastatin safely and effectively lowers elevated LDL-C levels in renal transplant recipients.

Adult↗
PubMed1995

De novo membranoproliferative glomerulonephritis in hepatitis C virus-infected renal allograft recipients.

Hepatitis C virus (HCV) is the leading cause of non-A, non-B hepatitis among renal allograft recipients. We sought to identify and describe a proteinuric renal disease occurring in our HCV-infected renal transplant patients. Patients with proteinuria exceeding 1 g/day were identified from a cohort of 98 HCV-infected kidney recipients. Qualitative and quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and restriction fragment-length polymorphism of the amplified RT-PCR product was performed to detect circulating HCV RNA, viral titer, and strain type, respectively. An immune complex nephritis (ICN) of the membranoproliferative pattern (MPGN) was found on five of eight biopsies. Two patients infected with the Hutch strain-type developed nephrotic-range proteinuria within three months posttransplant while the remaining three MPGN patients had been transplanted greater than 5 years prior to the onset of proteinuria. Testing for rheumatoid factors, cryoglobulins, hypocomplementemia, and circulating immune complexes failed to show a consistent pattern. Sucrose density gradient (SDG) equilibrium centrifugation was used to determine the buoyant-density of HCV virions from control (HCV-infected nonproteinuric recipients; n = 5) and nephrotic patients (n = 5). Whereas HCV virions from the control patients had a low buoyant density on sucrose gradients, a substantial percentage of the circulating HCV RNA from the MPGN patients was present in the high-density fractions in association with IgM and IgG. Treatment of the pooled high-density layers with NP40 followed by recentrifugation resulted in a shift of the HCV RNA to the medium-density layers. In conclusion, MPGN developed in five HCV-infected kidney recipients despite pharmacologic immunosuppression. Both the physicochemical properties of the HCV virions on SDG and their association with IgG and IgM in the high-density layers provide indirect evidence for the presence of circulating complexes of anti-HCV antibody and HCV antigen(s).

Adult↗
PubMed1995

Acute graft loss secondary to necrotizing vasculitis. Evidence for cytokine-mediated Shwartzman reaction in clinical kidney transplantation.

A small number of kidney transplant recipients abruptly lose function secondary to acute renal artery or vein thrombosis or more rarely a form of necrotizing vasculitis. We report a group of four kidney transplant recipients who lost renal function and share the following features: (1) diabetes (type I, insulin-dependent diabetes mellitus, type II or steroid-induced); (2) abrupt change/loss of renal function; (3) a concomitant clinical event (fever, viral symptoms, menometrorrhagia, viremia, bacteremia); (4) severe necrotizing vasculitis with hemorrhagic necrosis on histopathology; (5) patent renal artery and vein at time of transplant nephrectomy (i.e., no vascular thrombosis); and (6) high levels of peripheral serum gamma-IFN 1-5 days before transplant nephrectomy (467 +/- 175 pg/ml) compared with that of patients experiencing severe rejection (8.4 +/- 3.7 pg/ml) (P < 0.002). These data support the concept of a cytokine (IFN-gamma)-mediated accelerated inflammatory response resulting in graft loss from necrotizing vasculitis--the clinical equivalent of an organ-specific Shwartzman reaction.

Adult↗
PubMed1995

Three-month efficacy and safety of once-daily diltiazem in chronic stable angina pectoris.

The 3-month efficacy and safety of a once-daily controlled formulation of diltiazem (180 to 360 mg/day) were assessed in a study of 54 patients with angina pectoris. This multicenter study was a nonrandomized, placebo run-in, open-label, 3-month trial followed by a 1-week, double-blind, randomized period during which most patients (89%) received placebo. There were only minimal changes in the time to termination (mean change +/- SEM -5.8 +/- 9.6 seconds), time to onset of angina (10.5 +/- 12.2 seconds), and the time to 1 mm ST-segment depression (2.9 +/- 12.5 seconds) from the end of the titration phase to the end of the open-label study. There were, however, statistically significant differences between the end of the 3-month treatment phase and the end of the 1-week randomized placebo phase for those 3 efficacy parameters (-37.3 +/- 11.2, -58.6 +/- 13.6, and -45.6 +/- 16.4 seconds, respectively). Diltiazem significantly decreased the frequency of anginal attacks and nitroglycerin use at the end of the 3-month treatment phase compared with results at the end of the randomized double-blind placebo phase. No new or unusual adverse events were reported during treatment. The present results suggest that there is no loss of efficacy of once-a-day diltiazem when administered for a long period to patients with chronic stable angina pectoris.

Aged↗
PubMed1995

Dieting behavior and eating attitudes in Israeli children.

Using an Israeli school-age group, this study replicates and extends the age group of Maloney et al.'s (Pediatrics, 84, 482-489, 1989) study of American schoolchildren's abnormal eating attitudes and behaviors. Maloney's Children's Eating Attitudes Test (ChEAT) and a Demographic and Dieting Questionnaire (DDQ) were given to 186 students from Grades 3 to 6 and to 290 students from Grades 7 to 11. In Grades 3-11, 54% of students expressed a desire to lose weight and 41.6% showed behaviors aimed toward losing weight. These attitudes and behaviors were already evident in Grades 3-6. Of this group, 8.8% had ChEAT scores > or = 20 (a possible at-risk indicator of anorexia), similar to the findings of Maloney et al. Marked gender differences in the at-risk index emerged in Grades 7-11: girls, 16.3%; boys, 1.5%. Starting at Grade 8, an exacerbation was noted in girls', in contrast to boys', preoccupation with thinness and weight-losing behaviors. DDQ items were found to identify at-risk groups in Grades 5-7 and 8-11. Issues were raised concerning cross-cultural studies and strategies for timing preventative interventions.

Child↗
PubMed1995

Transmission of hepatitis C virus by kidney transplantation: impact of perfusion techniques and course of viremia post transplant.

Hepatitis C virus (HCV) infection is the leading cause of post-transplant non-A, non-B hepatitis. Although many end-stage renal disease patients present for transplantation already infected with HCV, some recipients acquire the infection by transmission from the donor organ. We have detected serological evidence for HCV infection in 6.8% of our organ donors using second-generation anti-HCV assays. Approximately one-third of the patients who received an organ from a HCV carrier donor developed chronic transaminasemia and 8 of 14 (56%) patients converted from HCV RNA negative to positive in the posttransplant period. Demonstration of the course of viremia and transaminasemia is presented for 2 patients in whom transmission of HCV occurred. Using pulsatile machine perfusion, we were able to demonstrate that a standard perfusion of 20 h reduced the viral load in the kidney by 75%, additional flushes and a subsequent perfusion reduced the total viral titer by more than 99%. Thus, although transmission of HCV does occur with solid-organ transplantation, differences in the incidence of transmission between centers may be related to techniques of organ preservation.

Hepacivirus↗
PubMed1995

Hepatitis C virus: the nephrologist's view.

The last 4 years have been a period of rapid expansion in our understanding of both the molecular biology and clinical significance of hepatitis C virus (HCV) infection. Initial studies using first-generation enzyme-linked immunosorbent assays suggested that the end-stage renal disease population had an exceptionally high prevalence of anti-HCV compared with asymptomatic healthy blood donors. Subsequent analyses with second-generation assays and polymerase chain reaction techniques to detect viremia confirmed these earlier studies. Considering the prevalence of HCV within the dialysis population, it comes as no surprise that several studies confirmed HCV as the leading cause of non-A, non-B hepatitis among renal allograft recipients. Furthermore, transmission of HCV by transplantation of a kidney from an HCV-infected organ donor has been unequivocally demonstrated. The natural history of HCV infection in the immunosuppressed allograft recipient and its impact on long-term patient outcome are still being analyzed. Finally, HCV has been associated with essential mixed cryoglobulinemia and several histologic patterns of immune complex glomerulonephritis, including membranous and membrano-proliferative glomerulonephritis. Although HCV antigen-antibody complexes have not been demonstrated in the kidney, the marked decrease in proteinuria following clearance of HCV RNA with interferon alpha-2b therapy suggests an etiologic role for HCV in these glomerular diseases. Furthermore, the demonstration of HCV RNA in the cryoprecipitate of patients with essential mixed cryoglobulinemia and a beneficial response to treatment with interferon alpha-2b also suggest a role for HCV in the pathogenesis of these clinical syndromes.

Cryoglobulinemia↗
PubMed1995

Distinct effects of alpha-SNAP, 14-3-3 proteins, and calmodulin on priming and triggering of regulated exocytosis.

We have used stage-specific assays for MgATP-dependent priming and for Ca(2+)-activated triggering in the absence of free MgATP to examine the effects of alpha-SNAP, 14-3-3 proteins and calmodulin on regulated exocytosis in permeabilized adrenal chromaffin cells. All three proteins lead to a Ca(2+)-dependent increase in catecholamine secretion. Both alpha-SNAP and 14-3-3 proteins stimulated in a priming but not in a triggering assay. In contrast, calmodulin was stimulatory in triggering but not priming. The effects of alpha-SNAP and 14-3-3 proteins were likely to be due to distinct mechanisms of action since they differed in Ca(2+)-dependency, time course and extent of stimulation and their effects were additive. alpha-SNAP and 14-3-3 proteins did not appear to exert their priming action through changes in synthesis of phosphatidylinositol (4,5) bisphosphate. The data show that these three proteins have distinct stage-specific actions on exocytosis and indicate that alpha-SNAP acts in an early MgATP-requiring stage and not in the late Ca(2+)-triggered steps immediately prior to membrane fusion as previously suggested.

14-3-3 Proteins↗
PubMed1995

Analgesic effect in humans of subanaesthetic isoflurane concentrations evaluated by experimentally induced pain.

The analgesic effect of subanaesthetic concentrations of ether, trichloroethylene, methoxyflurane and halothane has been investigated previously using either clinical assessment or pain threshold measurements, but with conflicting results. The purpose of the present study was to evaluate the analgesic effect of isoflurane using experimental pain models. We studied 12 healthy volunteers at three randomly chosen subanaesthetic isoflurane concentrations: low (0.10-0.14 vol%), middle (0.16-0.20 vol%) and high (0.22-0.26 vol%). We used thermal pain detection and pain tolerance thresholds to argon laser stimulation, pressure pain detection and pain tolerance thresholds, immersion of the hand in ice water, and the nociceptive reflex to single and repeated (temporal summation) electrical stimulations, as experimental models to assess analgesia. There were no significant changes in the response to heat, cold or mechanical pressure at any of the subanaesthetic concentrations of isoflurane used. The nociceptive reflex thresholds to single stimulations, but not the thresholds for repeated stimulations, were significantly increased in all three isoflurane groups compared with baseline values. The difference between the different isoflurane concentrations was not statistically significant. In experimental pain models, subanaesthetic isoflurane concentrations have little or no analgesic potency.

Adult↗
PubMed1995

Effect of demographic and behavioral variables on burden of caregivers of chronic mentally ill persons.

OBJECTIVE: Persons who provide care for individuals with chronic mental illness experience both objective burden (observable, tangible cost) and subjective (perceived) burden. This study sought to determine the relative power of behaviors of chronic mentally ill clients, behaviors required of caregivers, and demographic characteristics of both groups in predicting burden. METHODS: A total of 189 caregiver-client dyads were studied using a cross-sectional, correlational design. Caregivers were interviewed by phone about clients' needs for help in nine areas and about seven potentially troublesome client behaviors. Correlation and regression analyses were used to determine relationships among variables. RESULTS: Caregivers reported much less subjective than objective burden, although the relationship between the two types of burden was not consistent across the various areas in which clients needed help. Overall, more of the reported burden was related to caregivers' behaviors (their day-to-day tasks) than to clients' behaviors. Burden was greatly increased for caregivers who lived with the client. Caregivers most at risk for burden were those who lived with male clients who threatened suicide. CONCLUSIONS: Caregivers become accustomed to the stabilized behavioral profile of the client. Mental health professionals should be sensitive to profiles and situations that may produce increased objective and subjective caregiver burden.

Adult↗
PubMed1995

Dietary protein restriction, blood pressure control, and the progression of polycystic kidney disease. Modification of Diet in Renal Disease Study Group.

In the Modification of Diet in Renal Disease Study, a follow-up (mean, 2.2 yr) of 200 study participants with autosomal dominant polycystic kidney disease (ADPKD) was conducted to determine the effect of lowering protein intake and blood pressure on the rate of decline in GFR. The rate of decline was faster in participants with ADPKD than in persons with other diagnoses, reflecting, in part, faster disease progression in the ADPKD group. Baseline characteristics that predicted a faster rate of decline in GFR in persons with ADPKD were greater serum creatinine (independent of GFR), greater urinary protein excretion, higher mean arterial pressure (MAP), and younger age. In patients with initial GFR values between 25 and 55 mL/min per 1.73 m2, neither assignment to a low-protein diet group nor assignment to a low blood pressure group significantly reduced the rate of decline of GFR in ADPKD participants. Similarly, the decline in GFR was not related to achieved protein intake or MAP. In participants with GFR values between 13 and 24 mL/min per 1.73 m2, assignment to the low MAP group led to a somewhat more rapid decline in GFR. However, the more rapid decline in GFR did not appear to be due to a detrimental effect of low blood pressure or the antihypertensive agents used to reach the low blood pressure goal. Lower protein intake, but not prescription of the keto acid-amino acid supplement, was marginally associated with a slower progression of renal disease.

Adult↗