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Biomedical subjects

H Sacks

Publications and source records attributed to H Sacks.

At least 37 records · Page 2Linked to original sources
PubMed1982

Randomized versus historical controls for clinical trials.

To compare the use of randomized controls (RCTs) and historical controls (HCTs) for clinical trials, we searched the literature for therapies studied by both methods. We found six therapies for which 50 RCTs and 56 HCTs were reported. Forty-four of 56 HCTs (79 percent) found the therapy better than the control regimen, but only 10 of 50 RCTs (20 percent) agreed. For each therapy, the treated patients in RCTs and HCTs of the same therapy was largely due to differences in outcome for the control groups, with HCT control patients generally doing worse than the RCT control groups. Adjustment of the outcomes of the HCTs for prognostic factors, when possible, did not appreciably change the results. The data suggest that biases in patient selection may irretrievably weight the outcome of HCts in favor of new therapies. RCTs may miss clinically important benefits because of inadequate attention to sample size. The predictive value of each might be improved by reconsidering the use of p less than 0.05 as the significance level for all types of clinical trials, and by the use of confidence intervals around estimates of treatment effects.

Abortion, Habitual↗
PubMed1981

Reversible hyperinsulinuria in diabetic ketoacidosis in man.

Urinary clearance and fractional urinary clearance of immunoreactive insulin (IRI) and beta 2-microglobulin (I beta 2M) were studied in patients with diabetic ketoacidosis (DKA) before, during, and after treatment. Our results indicate that in DKA in man a) there is an approximate 250-fold increase in urinary and fractional urinary clearance of IRI and a 600-fold increase in urinary and fractional urinary I beta 2M clearance, which suggests that the hyperinsulinuria is secondary to a nonspecific defect in tubular luminal uptake of low-molecular-weight proteins, although decreased IRI degradation cannot be excluded; b) because increased IRI clearance is not changed by the pharmacologic plasma IRI levels achieved, the residual tubular absorptive capacity is not saturable; c) I beta 2M clearance but not IRI clearance is significantly improved by the time metabolic control is attained, suggesting separate tubular transport systems; d) a small, therapeutically insignificant fraction of the infused insulin is lost in the urine during therapy of DKA; and e) defective renal tubular luminal uptake (and possibly degradation) of IRI is reversible.

Adolescent↗
PubMed1981

Clearance of immunoreactive somatostatin by perfused rat liver.

Other investigators have demonstrated that concentrations of immunoreactive somatostatin (IRS) are higher in blood from the hepatic portal vein or its tributaries than in blood from the hepatic or peripheral systemic veins of man and animals. This suggests that there is hepatic extraction of IRS from the portal system in vivo. In the rat, portal vein plasma IRS is reported to be heterogeneous and to contain, in part, a 1,600 mol wt form of IRS which is immunochemically similar to synthetic somatostatin and not significantly bound to high molecular weight plasma protein. Our study was undertaken to determine directly whether unbound synthetic cyclic somatostatin was cleared by the rat liver perfused through the hepatic portal vein in vitro with a recirculating, plasma-free, erythrocyte-containing perfusate. At 37 degrees C and pH 7.40, perfusate IRS, at initial concentrations (1,728 pg/ml) within the range previously reported in rat portal venous blood, was removed by the liver at a rate commensurate with first-order kinetics. Hepatic clearance was 0.84+/-0.04 ml/min per g postperfusion wet weight (SE). Hepatic extraction was 36+/-2%, and t((1/2)) was 20.0+/-1.3 min. Recovery of IRS from the perfusate without the liver was >85%, excluding significant degradation by the medium. Clearance, extraction, and t((1/2)) of IRS were not changed by an unphysiologic IRS concentration (621,500 pg/ml), or by pharmacologic concentrations of insulin (8.2 muM) or glucagon (2.9 muM). The t((1/2)) was prolonged significantly to 28.2+/-1.9 and 45.6+/-4.7 min during perfusions at liver temperatures of 25 degrees and 16 degrees C, respectively. At 37 degrees C, the t((1/2)) was also significantly increased to 28.7+/-3.2 and 24.2+/-1.1 min at perfusate pH 7.06 and 6.78, respectively. These studies indicate that the rat liver clears unbound IRS from the perfusate by a first-order kinetic process that is (a) unsaturable at pharmacologic concentrations, (b) temperature-sensitive and, to a lesser extent, influenced by lowered pH, and (c) not affected by insulin and glucagon. The liver would appear to play an important role in the metabolism of the 1,600 mol wt form of somatostatin. Clearance of endogenous IRS by the liver should be considered in the interpretation of IRS concentrations in the peripheral systemic veins.

Animals↗
PubMed1979

Septicemia caused by Pseudomonas paucimobilis.

A case of septicemia caused by Pseudomonas paucimobilis is reported. This represents the first definitive case of disease produced by this yellow-pigmented, nonfermentative bacillus.

Aged↗
PubMed1978

Metabolism of synthetic human heptadecapeptide gastrin by the isolated perfused rat liver.

Synthetic human heptadecapeptide gastrin-1 (SHG-17-1) and rat insulin were perfused cyclically through the isolated rat liver in a plasma-free medium. Synthetic human gastrin did not disappear from the medium at either physiological or supraphysiological levels, whereas rat insulin was cleared rapidly. Chromatography of perfusion samples showed that the SHG-17-U was neither lysed to smaller peptides nor changed to the larger molecular weight species. The isolated rat liver apparently plays no role in the metabolism of synthetic human heptadecapeptide gastrin-I.

Animals↗