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Biomedical subjects

D Rabinowitz

Publications and source records attributed to D Rabinowitz.

At least 37 records · Page 2Linked to original sources

Components of variability in the systolic blood pressures of preschool children.

The term "horse-racing effect" refers to a positive correlation between the slope at which blood pressure increases with age and blood pressure level at a baseline. Previous studies have reported such an effect in adults, while studies in children have found a negative correlation (termed "the Jenss effect"). These studies used analytic methods in which it was assumed that the blood pressure slopes were constant or the blood pressure profiles were linear. In this study, the authors used a components-of-variance approach that did not require this assumption in order to model serial blood pressure measurements made in 216 US preschool children (mean age at first analyzable blood pressure observation, 58.9 months) at 6-13 visits over a 3-year period (1986-1989). Measurements were made using an automated blood pressure monitor. Values from the second and third measures at each visit were averaged to obtain each observation. Data from 2,203 blood pressure observations were available for analysis. For the full group, over the mean period of observation of 21.1 months, the mean rate of increase was 3.45 mmHg/year for systolic blood pressure and 0.06 mmHg/year for diastolic blood pressure. In the authors' model, 33 percent of the total marginal variability in systolic blood pressure was attributed to random error (visit-to-visit variability); average (constant) subject-specific difference from the population slope accounted for 42 percent, and a nonlinear component of variability around the subject-specific average accounted for the remaining 25 percent. All three components were statistically significant. Models which assumed that the slopes were constant did not fit these data, and fitting these models to the data led to an artifactual negative correlation between subject-specific slopes and intercepts. An implication of this is that the concepts of "horse-racing" and "the Jenss phenomenon," which have been operationalized by testing the covariance of the subject-specific slopes and intercepts using models which assume that the blood pressure slopes are constant over time, should not be applied to data that contain this nonlinear component of variance.

Adult↗

Networks of coactive neurons in developing layer 1.

Spontaneous neuronal activity plays an important role in the development of cortical circuitry, yet its spatio-temporal dynamics are poorly understood. Cajal-Retzius (CR) neurons in developing layer 1 are necessary for correct cortical lamination and are strategically located to coordinate early circuit activity. To characterize the spontaneous activity of CR and other layer 1 neurons during cortical development, we imaged calcium transients in populations of layer 1 neurons in hemispheres and slices from postnatal rat somato-sensory neocortex. The spontaneous activity in layer 1 had complex spatio-temporal patterns. Groups of non-CR cells showed synchronous activations and formed networks of correlated neurons superimposed in the same territory. Correlated activity among non-CR cells was mediated by a depolarizing effect of GABA and was modulated by glutamate, probably released by CR cells. Our findings demonstrate that developing layer 1 can sustain complex patterns of correlated activity and reveal a circuit mechanism that can mediate this patterned activity.

Acetylcholine↗

Intraarterial vs intravenous administration of antivenin for the treatment of Crotalidae atrox envenomation: a pilot study.

OBJECTIVE: Standard therapy for significant snake envenomation includes antivenin. i.v. administration is currently the only recommended route. Intraarterial (i.a.) administration has potential advantages over i.v. that could improve outcome. To study this, the authors compared i.v. and i.a. antivenin administrations for the treatment of experimental snake envenomations. METHODS: 14 adult female swine were anesthetized and prepared with femoral artery and ear vein catheters, and baseline hoof, forearm, and thigh circumference and volume displacement measurements were taken. Crotalidae atrox venom was injected into the subcutaneous tissue of the hoof. The doses of venom were 4.75, 9.50, 19.00, 37.90, 47.30, 56.90, and 66.40 mg. Immediately following injection of venom, polyvalent antivenin (Crotalidae) (0.285 mg/10 mL saline) was infused over 30 minutes into the femoral artery (i.a. group) or ear vein (i.v. group). As a control, 10 mL of saline was infused into the ear vein (i.a. group) or femoral artery (i.v. group). Measurements were recorded up to 48 hours. Linear mixed-effect regression models were used for each measurement and to compare the i.a. and i.v. groups. RESULTS: Venom dose and time after administrations were associated with increased circumferences and increased volumes (p < 0.05). i.v. administration was associated with larger hoof (1.26 cm) and forearm (0.42 cm) sizes and volume displacement (21.71 mL) when compared with i.a. administration ( p < 0.05). CONCLUSION: i.a. antivenin results in a modest but significant decrease in tissue edema when compared with i.v..

Animals↗

Hypertensive vascular disease as a cause of death in blacks versus whites: autopsy findings in 587 adults.

Cardiovascular disease is the major cause of excess mortality among urban US blacks, but autopsy data comparing black-white differences in underlying pathological causes of cardiovascular death are lacking. We reviewed all 720 adult cases autopsied in 1991 in the New York City Medical Examiner's Office in which the coded cause of death was cardiovascular disease (International Classification of Diseases, 9th Revision, codes 391, 393 to 398, 401 to 404, 410, 411, 414 to 417, 420 to 438, and 440 to 444). After exclusion of 133 cases because race was missing or coded as other than black or white, gender was not coded, or there was an unusual circumstances of death or extreme obesity, 587 cases were available for analysis. There were 314 black and 273 white subjects. Black women were younger than white women at time of death (mean age, 54.7 versus 61.5 years; P<.001), whereas black and white men did not differ in mean age at death. Hypertensive vascular disease was the autopsy cause of death in 42% of blacks compared with 23% of whites (P<.001). Conversely, atherosclerotic heart disease was the autopsy cause of death in 64% of white subjects but only 38% of blacks. These patterns were consistent in both sexes and after adjustment for age. Hypertensive vascular disease was far more common than atherosclerotic heart disease as the cause of death at autopsy among blacks compared with whites in New York City, whereas atherosclerotic heart disease was more common in whites. These findings suggest that ineffective control of hypertension is a major factor contributing to excess cardiovascular mortality among urban blacks.

Adult↗

Femorocaval bypass with femoral crossover bypass for iliofemoral and caval occlusion.

Progress in the management of major venous obstruction has lagged far behind advances in arterial reconstruction. As a result, literature reports consist of small numbers of patients, and most vascular surgeons have little or no experience in performing bypass procedures for major venous obstruction. In this setting, individual reports add to our cumulative knowledge in treating this disease. We therefore present our experience in the management of a patient with extensive bilateral femoropopliteal, iliac, and vena caval occlusion.

Constriction, Pathologic↗

The effect of marker heterozygosity on the power to detect linkage disequilibrium.

The relationship between marker heterozygosity and the power to detect linkage disequilibrium is examined through the analysis of an example and through a simulation study. The analysis suggests that, despite the penalties for multiple testing incurred with multiple alleles, greater heterozygosity results in greater power. The results of the simulation study are in accord with those of the analysis.

Genetic Markers↗

Compensation to a department of medicine and its faculty members for the teaching of medical students and house staff.

BACKGROUND: Changes in the organization and financing of health care threaten to alter the prevailing system of financing the teaching of medical students and residents. Little information is available from private medical schools and teaching hospitals about the extent of teaching by faculty members or the mechanisms and levels of reimbursement for teaching. METHODS: We surveyed faculty members in the Department of Medicine at Columbia-Presbyterian Medical Center to ascertain the extent of their teaching activities. A standard number of hours was assigned to each activity, and the total number of teaching hours was calculated for each faculty member. Teaching of fellows and in continuing medical education programs was excluded. We also determined how much money the Department of Medicine received in payment for faculty members' teaching activities, and the sources of this compensation. RESULTS: In the 1992-1993 academic year, the 188 full-time faculty members spent a total of 46,086 hours teaching (mean [+/- SD], 245 +/- 178 hours per faculty member); 10,780 hours (23.4 percent) were spent teaching medical students, and 35,306 hours (76.6 percent) teaching house staff. Eighty percent of faculty members taught for 137 or more hours each. In a multivariate analysis including faculty rank, subspecialty division, years since graduation from medical school, sex, and tenure or clinical track, senior faculty members (P = 0.02), members of certain subspecialty divisions (P < 0.001), and women (P = 0.05) contributed more than the average number of teaching hours. An additional 56 non-full-time faculty members contributed a total of 5684 hours. The net reimbursement to the department for teaching totaled $965,808, or about $16 per hour of teaching by full-time faculty members, after the cost of fringe benefits was excluded. CONCLUSIONS: Faculty members of the department of medicine at a major medical center contribute a large number of hours teaching medical students and house staff. This effort is poorly compensated. Cost-containment efforts have the potential to jeopardize fragile social contracts at academic health centers whereby the faculty participates in teaching by contributing unreimbursed or underreimbursed time.

Academic Medical Centers↗

A pseudolikelihood approach to correcting for ascertainment bias in family studies.

The Cannings and Thompson approach to correcting for ascertainment bias in family studies is extended to settings with multiple ascertainment. The extension is based on maximizing a pseudolikelihood. Two approaches to computing standard errors for the maximum pseudolikelihood estimate are described. One is especially simple to compute, while the other is more generally applicable. Simulation experiments suggest that the standard-error computations can be quite accurate.

Computer Simulation↗

Weight-reducing effects of the plasma protein encoded by the obese gene.

The gene product of the ob locus is important in the regulation of body weight. The ob product was shown to be present as a 16-kilodalton protein in mouse and human plasma but was undetectable in plasma from C57BL/6J ob/ob mice. Plasma levels of this protein were increased in diabetic (db) mice, a mutant thought to be resistant to the effects of ob. Daily intraperitoneal injections of either mouse or human recombinant OB protein reduced the body weight of ob/ob mice by 30 percent after 2 weeks of treatment with no apparent toxicity but had no effect on db/db mice. The protein reduced food intake and increased energy expenditure in ob/ob mice. Injections of wild-type mice twice daily with the mouse protein resulted in a sustained 12 percent weight loss, decreased food intake, and a reduction of body fat from 12.2 to 0.7 percent. These data suggest that the OB protein serves an endocrine function to regulate body fat stores.

Adipose Tissue↗

Fc gamma RII/III and CD2 expression mark distinct subpopulations of immature CD4-CD8- murine thymocytes: in vivo developmental kinetics and T cell receptor beta chain rearrangement status.

We have recently identified a dominant wave of CD4-CD8- (double-negative [DN]) thymocytes in early murine fetal development that express low affinity Fc gamma receptors (Fc gamma RII/III) and contain precursors for Ti alpha/beta lineage T cells. Here we show that Fc gamma RII/III is expressed in very immature CD4low single-positive (SP) thymocytes and that Fc gamma RII/III expression is downregulated within the DN subpopulation and before the CD3-CD8low SP stage in T cell receptor (TCR)-alpha/beta lineage-committed thymocytes. DN Fc gamma RII/III+ thymocytes also contain a small fraction of TCR-gamma/delta lineage cells in addition to TCR-alpha/beta progenitors. Fetal day 15.5 DN TCR-alpha/beta lineage progenitors can be subdivided into three major subpopulations as characterized by cell surface expression of Fc gamma RII/III vs. CD2 (Fc gamma RII/III+CD2-, Fc gamma RII/III+CD2+, Fc gamma RII/III-CD2+). Phenotypic analysis during fetal development as well as adoptive transfer of isolated fetal thymocyte subpopulations derived from C57B1/6 (Ly5.1) mice into normal, nonirradiated Ly5.2 congenic recipient mice identifies one early differentiation sequence (Fc gamma RII/III+CD2(-)-->Fc gamma RII/III+CD2(+)-->Fc gamma RII/III-CD2+) that precedes the entry of DN thymocytes into the CD4+CD8+ double-positive (DP) TCRlow/- stage. Unseparated day 15.5 fetal thymocytes develop into DP thymocytes within 2.5 d and remain at the DP stage for > 48 h before being selected into either CD4+ or CD8+ SP thymocytes. In contrast, Fc gamma RII/III+CD2- DN thymocytes follow this same developmental pathway but are delayed by approximately 24 h before entering the DP compartment, while Fc gamma RII/III-CD2+ display accelerated development by approximately 24 h compared with total day 15.5 thymocytes. Fc gamma RII/III-CD2+ are also more developmentally advanced than Fc gamma RII/III+CD2- fetal thymocytes with respect to their TCR beta chain V(D)J rearrangement. At day 15.5 in gestation, beta chain V(D)J rearrangement is mostly, if not entirely, restricted to the Fc gamma RII/III-CD2+ subset of DN fetal thymocytes. Consistent with this analysis in fetal thymocytes, > 90% of adult thymocytes derived from mice carrying a disrupting mutation at the recombination-activating gene 2 locus (RAG-2-/-) on both alleles are developmentally arrested at the DN CD2- stage. In addition, there is a fivefold increase in the relative percentage of thymocytes expressing Fc gamma RII/III in TCR and immunoglobulin gene rearrangement-incompetent homozygous RAG-2-/- mice (15% Fc gamma RII/III+) versus rearrangement-competent heterozygous RAG-2+/- mice (< 3% Fc gamma RII/III+). Thus, Fc gamma RII/III expression defines an early DN stage preceding V beta(D beta)I beta rearrangement, which in turn is followed by surface expression of CD2. Loss of Fc gamma RII/III and acquisition of CD2 expression characterize a late DN stage immediately before the conversion into DP thymocytes.

Aging↗

Fluphenazine.

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Fluphenazine↗

Reduction of serum cholesterol in two patients with homozygous familial hypercholesterolemia by dichloroacetate.

Dichloroacetate is known to reduce plasma cholesterol and triglyceride in patients with Fredrickson Types IIb or IV hyperlipoproteinemia. We now report the effects of chronic, oral dichloroacetate administration (as the sodium salt) in two patients with severe homozygous familial hypercholesterolemia. Dichloroacetate markedly reduced serum total and low density lipoprotein cholesterol levels and lowered the low density lipoprotein to high density lipoprotein cholesterol ratio. One patient developed a polyneuropathy while receiving dichloroacetate which resolved following discontinuation of the drug. Because of its apparent toxicity, dichloroacetate cannot be recommended for chronic oral use. Investigation of the mechanism of its lipid-lowering effect, however, may provide insight into the pathogenesis and treatment of hypercholesterolemic disorders.

Acetates↗

The carbohydrate moiety of human chorionic gonadotropin: lack of competition with HCG for testicular receptors and anti-HCG-serum.

A glycopeptide fraction has been prepared from human chorionic gonadotropin (HCG) by digesting the reduced, S-carboxymethylated hormone with pronase and fractionating the digest by gel exclusion chromatography. The glycopeptide fraction was estimated to contain (w/w) 29% sialic acid, 31% hexose, 23% hexosamine, and 17% amino acids and/or peptides; thus, the glycopeptide mixture is 83% carbohydrate compared to intact HCG which is about 30% carbohdyrate. There was no cross-reactivity of the glycopeptide fraction with an antiserum directed against HCG. Also, when corrected for minimal non-specific effects, the fraction failed to displace 125I-HCG from a rat testicular preparation even when tested at a 10,000-fold (w/w) excess. Thus, any model involving carbohydrate effects in gonadotropin action must include the protein moiety as a necessary component.

Binding, Competitive↗

Hyperglycemia per se (insulin and glucagon withdrawn) can inhibit hepatic glucose production in man.

We examined the effect of hyperglycemia per se on net splanchnic glucose balance. In 2 groups of normal postabsorptive men who had undergone hepatic vein catheterization, somatostatin was administered to block endogenous insulin and glucagon secretion. Exogenous glucose was infused in both groups to maintain euglycemia for 2 h in one group (n = 7) and to induce hyperglycemia of 220-240 mg/dl after 30 minutes of euglycemia in the second group (n = 4). In both groups the induction of insulinopenia and glucagonopenia with euglycemia maintained resulted in an initial 75% fall in net splanchnic glucose production (NSGP). In the group in which euglycemia was maintained NSGP returned to basal rates (157 +/- 31 mg/min) within 2 h. However, in the group in which hyperglycemia was induced, NSGP did not return to basal rates but remained suppressed (28 +/- 4 mg/min) for the duration of the study. These data in normal man indicate that hyperglycemia per se with insulin and glucagon acutely withdrawn can suppress splanchnic glucose production but does not induce net splanchnic glucose storage.

Blood Glucose↗

Heterogeneity of the human chorionic gonadotropin alpha-subunit secreted by cultured choriocarcinoma (JEG) cells.

The cultured human choriocarcinoma cell line, JEG-clone 3, secretes substantial quantities of both biologically active hCG and an immunoreactive alpha-subunit (JEG-alpha). This study is concerned with a comparative characterization, using RIA, of the chromatographic properties (via gel exclusion and isoelectric focusing) of JEG-alpha and standard urinary hCG-alpha. Most of the molecules comprising the JEG-alpha fraction have an apparent molecular weight greater than that of hCG-alpha. Both hCG-alpha and JEG-alpha exhibit heterogeneity on electrofocusing. However, JEG-alpha contains a major component with an isoelectric pH (pI) of 4.8; this is a minor component, if present at all, in hCG-alpha. The JEG-alpha pI 4.8 component chromatographs with an apparent molecular weight greater than hCG-alpha, while a minor JEG-alpha pI 7.0 component chromatographs with an apparent molecular weight similar to that of the standard. Heterogeneity is expected in the carbohydrate moieties of the glycoprotein hormone subunits. Results of studies on the incorporation of 14C- and 3H labeled amino acids into JEG-alpha suggest that heterogeneity also exists in the protein moiety of JEG-alpha. An interesting possibility is that the form(s) of JEG-alpha with larger apparent molecular weight represents a precursor of the alpha-subunit used to form hCG.

Biological Assay↗

Circulating big human prolactin: conversion to small human prolactin by reduction of disulfide bonds.

The heterogeneity of circulating human PRL (hPRL) in sera of patients with hyperprolactinemia was studied by exclusion chromatography on Sephadex G-100. Big hPRL, which elutes between the void volume and the elution position of monomeric small hPRL, is stable upon rechromatography but is almost entirely converted into small hPRL after reduction with 0.5% mercaptoethanol. These results suggest that the existence of circulating big hPRL is dependent upon the formation of interpolypeptide disulfide bonds and does not represent a classical biosynthetic precursor of hPRL.

Adolescent↗