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Biomedical subjects

J Goldman

Publications and source records attributed to J Goldman.

At least 217 records · Page 12Linked to original sources

Absorbance nephelometry of C1q-precipitable immune complexes: method comparisons and clinical correlations.

Using a double-beam spectrophotometer, we investigated the clinical utility of a nephelometric method for assaying immune complexes. The complexes were concentrated from serum by precipitation with polyethylene glycol (PEG) and assayed by reaction with C1q. Testing of more than 100 sera showed a Spearman's rank correlation (p) between the present assay and the C1q-binding assay of 0.57, and 0.39 between the Raji cell assay and the present assay. Clinical sensitivity of the methods was not statistically different (p less than or equal to 0.5). Twenty-four of 30 patients with symptoms of disease showed increased concentrations of immune complexes by the present assay; only one of 38 normal individuals showed an increase. In a longitudinal study, we found that the concentrations of immune complexes paralleled clinical changes, indicating good clinical utility. The use of this assay with single-beam analyzers is limited because of the poor aqueous solubility of the PEG precipitate. Ongoing investigations designed to circumvent this problem are described.

Antigen-Antibody Complex↗

Inconsistency and institutional review boards.

To assess the adequacy of peer review for research on human subjects, identical research protocols in oncology and anesthesiology were submitted to 32 institutional review boards (IRBs) at major universities with medical colleges. Each of the protocols posed serious ethical issues, contained flaws in scientific design, and provided an incomplete consent form. Twenty-two IRBs participated in the investigation, which revealed (1) consistency in the nonapproval of the three protocols, (2) substantial inconsistency among IRBs in the reasons offered in support of similar decisions, and (3) substantial inconsistency in the application of ethical, methodological, and informed-consent standards for individual review boards. This evidence suggests that revision of the protocols to satisfy particular objections would result in approval of flawed investigations.

Clinical Trials as Topic↗

Acanthosis nigricans, hirsutism, insulin resistance and insulin receptor defect.

A 24-year-old negress with the triad of acanthosis nigricans, hirsutism associated with polycystic ovaries and insulin resistance is reported. Metabolic studies were done 3 years after a bilateral ovarian wedge resection. Partial remission of the hirsutism and return of menstrual cycles occurred after surgery. Extreme resistance to endogenous and exogenous insulin was observed. Three studies of insulin receptors on circulating red blood cells (RBC) showed abnormal inhibition-competition curves, characterized by increased percentage insulin binding at higher unlabelled insulin levels. Scatchard plots suggested an apparent increase in the number of low affinity receptors. Despite the changes in receptor-insulin interaction, the defect does not seem to explain the insulin resistance since binding of insulin to a target tissue (RBC) appeared to be quantitatively normal at physiological insulin levels, suggesting a simultaneous post receptor defect.

Acanthosis Nigricans↗

Evaluation of rapid colonoscopy preparation using a new gut lavage solution.

The traditional colonoscopy preparation of laxatives and enemas requires 2 days to complete and is occasionally unsatisfactory. The alternative method, gut lavage with saline-based solutions, is hazardous in elderly or compromised patients because of overhydration. We studied a new, orally ingested electrolyte solution containing sodium sulfate and polyethylene glycol as preparation for elective colonoscopy in a consecutive series of 43 patients. Almost all patients achieved a good to excellent preparation. There were no changes in fluid or electrolyte balance and no complications of the procedure. Colonoscopy preparation with this technique is rapid, effective, and well tolerated and is a safe alternative to the standard approach.

Administration, Oral↗

Preparation and in vitro evaluation of a new extracorporeal dialyzer with immobilized insulin.

A specific extracorporeal immunoadsorbent system has been developed that has potential application for the treatment of complications related to the presence of plasma insulin antibodies, namely severe insulin resistance and autoimmune hypoglycemia. The immunoadsorbent system described here makes use of a commercially available cellulose-based, hollow-fiber hemodialyzer. Optimal conditions for the coupling of insulin to cellulose matrices were found to involve activation with 1,4-butanediol diglycidyl ether and reaction with insulin at pH 7.4. The insulin-dialyzer prepared under these conditions contained 35.5 mg to 37.9 mg of insulin which correspond to a theoretical binding capacity of 887.5 to 947.5 units of insulin. Recirculation of human plasma with high insulin antibody titers through the insulin-dialyzer resulted in the clearance of 82-99% and 50-83% of high affinity and total insulin antibodies, respectively. The clearance of insulin antibodies approached a steady state after 15 minutes of recirculation at a flow rate of 50 ml/min. Regeneration of used insulin-dialyzers was accomplished by treatment with 0.02 M citrate buffer pH 3.2, which restored their ability to clear 90% and 40% of high affinity and total insulin antibodies, respectively. The principle of the insulin-dialyzer may find application in other disease states where removal of specific antibodies or other high molecular weight species may be of therapeutic value.

Animals↗

Alloreactive cloned T cell lines. VI. Multiple lymphokine activities secreted by helper and cytolytic cloned T lymphocytes.

Culture supernatants generated by alloantigenic or lectin stimulation of a cloned helper T lymphocyte, designated L2, contain interleukin 2 (IL 2), granulocyte/macrophage colony-stimulating factor (CSF), B cell stimulating factor (BCSF), macrophage (Ia+)-recruiting factor (MIRF), (Ia+)-inducing activity, gamma-interferon, Fc receptor-enhancing activity, macrophage migration inhibitory factor (MIF), macrophage activation factor (MAF), interleukin 3 (IL 3), and a factor responsible for prolonging the synthesis and secretion of the fourth and second components of complement by guinea pig peritoneal macrophages. Erythropoietin was not detected. A spontaneously arising variant of L2, designated L2V, produces much lower quantities of macrophage-stimulating activities, IL 2, and interferon. However, when compared to L2, L2V produces much higher levels of BCSF, equivalent amounts of IL 3, and slightly smaller amounts of CSF. Unlike L2V, a cytolytic clone, designated L3, secretes lymphokines that primarily affect macrophage function. The time course of lymphokine production by L2 cells indicates that for the six lymphokine activities studied there are three different times at which maximal or near maximal levels are reached, as follows: 1) IL 2, 12 to 24 hr; 2) IL 3 and CSF, 24 to 48 hr; and 3) (Ia+)-inducing activity, MAF, and interferon, 48 hr or later. Only IL 2 activity disappears during the 8-day culture cycle. The time course data and the differential production of activities by the three types of lymphocyte clones suggest that at least four terminal effector lymphokine molecules account for the ten biologic activities tested.

Animals↗

Measuring hemoglobin in plasma by reaction with tetramethylbenzidine.

The reaction of hemoglobin with tetramethylbenzidine was studied with a centrifugal analyzer. We found that the hemochromogen reaction was significantly influenced by albumin. Increasing amounts of albumin apparently stimulate the hemochromogen reaction during the earlier part of an incubation and inhibit it later in the incubation. However, during an intermediate period, when the crossover from stimulation to inhibition occurs, the assay is independent of albumin and bilirubin concentrations. Increasing the temperature of incubation or the hydrogen peroxide concentration, or decreasing the tetramethylbenzidine concentration, shortens the crossover time. By adjusting these variables the method can be used with most instrumentation. We developed procedures for use on a centrifugal analyzer or for manual assay (reaction times, 4 and 20 min, respectively). Accuracy, as indicated by a comparison with a direct hemoglobin method (r = 0.990) and by recovery experiments, was excellent. The CV for the automated assay was less than 3%. Plasma collected in citrate and heparin showed good recovery of hemoglobin; recovery in EDTA was poorer.

Benzidines↗

Islet cell autotransplantation after pancreatectomy for chronic pancreatitis. Its limitations.

Of 12 patients operated on for intractable pain from chronic pancreatitis, only the three with adequate preoperative insulin reserve were selected to undergo islet-cell replantation after subtotal pancreatectomy. Fourteen, nine, and four months postoperatively, they require no therapy with insulin. Since most techniques for obtaining islet cells have been performed with normal pancreata, chronic pancreatitis was produced in ten dogs by ligating the main and accessory pancreatic ducts. These dogs 162.6 +/- 15.8 days later underwent total pancreatectomy. The scarred pancreatic fragments were dissociated with collagenase for 20 minutes in five dogs or subjected to two intermittent digestions of ten minutes in the other five dogs and were autotransplanted to the liver. One dog from each group became normoglycemic within one week of replantation, and their percent per minute decreases of serum glucose level were 2.72 and 3.46, respectively. Our experimental and clinical data suggest that (1) present techniques for dissociating fibrotic tissue are unsatisfactory and lead to a very low yield of islet cells; (2) postoperative assessment of islet-cell function involves complicated invasive procedures (portal and hepatic vein cannulation) to determine accurately the source of insulin; and (3) careful preoperative evaluation of beta-cell function is needed.

Adult↗

Evaluation of the gonadotropic responsiveness of the pituitary to acute and prolonged administration of LH/FSH-releasing hormone (lhrh) in untreated patients with congenital adrenal hyperplasia.

The pituitary gonadotropic responsiveness to acute and prolonged administration of LH/FSH-releasing hormone (LHRH) were assessed in 6 patients with untreated congenital virilizing adrenal hyperplasia (partial 21-hydroxylase deficiency). The oldest subjects had normal response in comparison to females at the midfollicular phase, to the acute infusion of 25 ug LHRH regarding both gonadotropins whereas LH secretory area was decreased during the prolonged (100 ug LHRH in 8 hours) infusion with normal FSH secretion. The two youngest subjects, with higher steroid levels in our series, were either unresponsive on both ways of testing or presented pre-pubertal response.

Adolescent↗

The Neugebauer-Le Fort operation: a review of 118 partial colpocleises.

The Neugebauer-Le Fort operation or partial colpocleisis is a safe, simple and rapid procedure for the repair of uterine prolapse in elderly women who are poor surgical risks. The operation was performed in 188 women with total procidentia. Good anatomic results were obtained in 90.7% of the women. Late complications were rare, including recurrence of prolapse (3 patients), and urinary incontinence (12 patients). Immediate postoperative complications were not common. The main disadvantage is the inaccessibility of the uterus in case of postmenopausal bleeding (2 patients). Partial colpocleisis has a place in the armamentarium of the gynecologist treating isolated cases of prolapse of the uterus, and may be indicated in the elderly women with total procidentia who is a poor surgical risk an in whom general anesthesia is contraindicated, and who is certain she wants to forego sexual intercourse.

Aged↗

Alterations in glomerular RNA in diabetic rats: roles of glucagon and insulin.

Incorporation in vivo of labeled orotate into RNA and total nucleotides was measured in isolated glomeruli and whole renal cortex. In 2-day diabetic animals, glomerular RNA was increased, and there was greater incorporation of orotate into total nucleotides and RNA as compared with controls. Insulin reversed the exaggerated incorporation at infusion rates that corrected hyperglucagonemia without reducing plasma glucose and with only minimal changes in insulin concentrations. The addition of glucagon to insulin infusions reproduced the increased incorporation observed in untreated diabetics. Similar changes occurred in renal cortex, where differences in orotate incorporation into nucleotide precursors seemed to be the main cause for alterations in RNA labeling. Isotope incorporation in glomeruli correlated positively with plasma glucagon, but not with insulin or glucose concentrations. Although in 7-month diabetic animals orotate incorporation into RNA was less than in controls, probably as a consequence of renal disease, 24-hour insulin infusion decreased it further. Our results confirm that in the diabetic kidney, abnormal uracil nucleotide metabolism and increased cellular content of RNA are demonstrable in glomeruli as in the renal cortex. These changes appear to be related directly to hyperglucagonemia.

Adenine↗

Platelet functions before, during and after labor.

Platelet functions were evaluated in 20 healthy pregnant women in the last months of pregnancy, during labor, and 5-12 weeks after labor. The results showed an increased platelet count, bleeding time and nitroblue tetrazolium (NBT) test, as well as an increased plasma calcium level postlabor. ADP- and epinephrine-induced aggregation during labor was markedly decreased, followed by a statistically significant increase postlabor. These findings are in correlation with the high incidence of thromboembolic phenomena occurring postlabor.

Adolescent↗

Oestrogen dynamics in adrenal venous effluents in congenital virilizing adrenal hyperplasia.

Four patients with untreated congenital virilizing adrenal hyperplasia (partial 21-hydroxylase deficiency) were studied by bilateral adrenal vein catheterization. Simultaneous right and left adrenal and peripheral blood samples were collected for determination of oestrone (E1) and oestradiol (E2). The concentrations of both were higher in the adrenal effluents than in the peripheral blood samples, indicating their secretion by the adrenals. All patients were also studied during a sequential test of suppression (0.5 h after i.v. administration of 4 mg dexamethasone) and stimulation (5 min after i.v. administration of 250 microgram ACTH 1-24; Synacthen). Mean peripheral E2 concentrations did not change significantly whereas E1 increased above control levels after stimulation. In contrast, suppression of adrenal venous blood concentrations with dexamethasone, and stimulation with ACTH, was demonstrated for every patient. The results indicate that in congenital adrenal hyperplasia the adrenal glands secrete significant amounts of E1 and E2.

Adolescent↗