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Biomedical subjects

G Goldstein

Publications and source records attributed to G Goldstein.

At least 145 records · Page 8Linked to original sources

Treatment of hypertension in the elderly: II. Cognitive and behavioral function. Results of a Department of Veterans Affairs Cooperative Study.

This study was designed to determine whether blood pressure reduction, per se, causes adverse effects on cognitive and behavioral function in elderly hypertensive patients. Men with mild-to-moderate diastolic hypertension who had passed their 60th birthday were entered into the trial. After a placebo washout period, they were assigned in a randomized, double-blind manner to one of two groups receiving hydrochlorothiazide (either 25 mg once or twice daily or 50 mg once or twice daily). Responders entered a 1-year maintenance period. Nonresponders were randomly assigned to double-blind treatment with hydralazine, methyldopa, metoprolol, or reserpine added to the diuretic therapy. During the placebo and treatment periods, patients underwent a battery of psychometric tests designed to assess cognitive function, motor skills, memory, and affect. A separate questionnaire assessed the patient's ability to perform activities of daily living. A subset of patients blindly being treated with placebo received the same battery of tests as a control for practice effect. The results showed that there was similar improvement on the psychometric tests between those patients whose blood pressure was successfully reduced and the placebo-treated control group. Therefore, the practice effect did not obscure a true deterioration in function. There were no substantive differences between the lower and higher doses of diuretic or among the four drugs added to the diuretic, although there were qualitative differences in side effects. We conclude that blood pressure reduction, per se, does not adversely affect cognitive and behavioral function in elderly hypertensive patients and that antihypertensive treatment is safe and effective in these patients.

Activities of Daily Living↗

Neuropsychological heterogeneity in schizophrenia: a consideration of abstraction and problem-solving abilities.

The study examines heterogeneity in abstraction and problem-solving abilities among schizophrenic patients through a cluster analysis of scores from the Halstead Category Test, the Tactual Performance Test, Part B of the Trail Making Test and the Wisconsin Card Sorting Test obtained from 136 male schizophrenic inpatients. Extensive heterogeneity was noted among the five clusters extracted, marked by differences in both level and pattern of performance. Efforts were made to find associations between cluster membership and age, education, general intelligence, neurological comorbidity, and medication status. Such associations were noted in all cases, but the role of medication was viewed as equivocal. It was concluded that (i) there is extensive heterogeneity in both pattern and level of performance of schizophrenics on tests of abstraction and problem solving; and (ii) Some, but not all of this heterogeneity is associated with variations in age, education, general intelligence, and neurological comorbidity.

Journal Article↗

Interactions of the thymic polypeptide hormone thymopoietin with neuronal nicotinic alpha-bungarotoxin binding sites and with muscle-type, but not ganglia-type, nicotinic acetylcholine receptor ligand-gated ion channels.

Studies were conducted to assess the ability of the thymic polypeptide hormone thymopoietin (TPO) to interact with proto-typical ganglia-type or muscle-type nicotinic acetylcholine receptor ion channels (nAcChoR). Also investigated were interactions of TPO with neuronal nicotinic alpha-bungarotoxin binding sites (nBgtS), which share many features with nAcChoR and may belong to an extended nAcChoR family but do not appear to function as simple ligand-gated ion channels. TPO and alpha-bungarotoxin (Bgt) share the capacity for high affinity (IC50 values in the nanomolar range) interaction with nBgtS, which are expressed as high affinity radioiodinated Bgt binding sites by cells of the SH-SY5Y or IMR-32 human neuroblastomas. TPO and Bgt also share the capacity for high affinity interaction with muscle-type nAcChoR, which are expressed as high affinity binding sites for radioiodinated Bgt or tritium-labeled acetylcholine by cells of the TE671/RD human clone or the BC3H-1 mouse muscle cell line or on membrane preparations from Torpedo electroplax. TPO and Bgt act acutely as high affinity antagonists of muscle-type nAcChoR functional responses, which are measured using an isotopic rubidium ion efflux assay, on TE671/RD or BC3H-1 cells. In contrast, neither TPO nor Bgt are effective, at doses of up to 1 microM, as antagonists of ganglia-type nAcChoR function on SH-SY5Y or IMR-32 cells, nor are they potent as inhibitors of high affinity tritium-labeled acetylcholine binding to sites on putative ganglia-type nAcChoR expressed by SH-SY5Y or IMR-32 cells. These data indicate that some members of the extended nAcChoR family, including nBgtS and functional muscle-type nAcChoR but not ganglia-type nAcChoR, can interact with either Bgt or TPO. The results suggest that TPO may be an endogenous ligand active in both the nervous and immune systems and that some of its actions may be mediated via nBgtS or via functional blockade of muscle-type nAcChoR.

Acetylcholine↗

Thymopoietin inhibits function and ligand binding to nicotinic receptors at the neuromuscular junction.

Thymopoietin is a 48 to 49 amino acid polypeptide hormone of the thymus, which regulates immune function. The present experiments show that the polypeptide can cause a complete block of transmission of the phrenic nerve diaphragm junction of the rat in vitro; contractile responses evoked by phrenic nerve stimulation were blocked by concentrations of thymopoietin as low as 10(-8) M. The thymopoietin-induced inhibition of indirectly evoked muscle contractions was dose- and time-dependent, with the polypeptide being only slightly less potent than alpha-bungarotoxin (alpha-BGT). Twitch responses to direct electrical stimulation of the muscle were not affected by thymopoietin, indicating that it did not inhibit muscle tension by an action on the muscle contractile mechanism per se. Furthermore, thymopoietin did not alter resting or stimulated release of acetylcholine from the phrenic nerve, suggesting that it did not interact at a presynaptic level. On the other hand, thymopoietin inhibited the binding of [125I]alpha-BGT to the nicotinic receptor of rat hemidiaphragm. In intact muscle tissue, the IC50 value for inhibition of [125I]alpha-BGT binding by thymopoietin was 2.1 x 10(-7) M, a value similar to the concentration of polypeptide required to inhibit phrenic nerve-induced muscle contraction (IC50 value, 0.75-1.6 x 10(-7) M). In a muscle membrane preparation, the potency of thymopoietin to affect [125I]alpha-BGT binding was increased (IC50 value, 0.35 nM); thus thymopoietin has the potential to interact at the nicotinic receptor in the nM range. To conclude, the present results show that thymopoietin inhibits neuromuscular activity by an effect that appears to be a specific interaction at the nicotinic receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Thymopoietin, a thymic polypeptide, regulates nicotinic alpha-bungarotoxin sites in chromaffin cells in culture.

The identity of the neuronal nicotinic alpha-bungarotoxin (alpha-BGT) site, which appears to be distinct from the functional nicotinic receptor, is unclear. Recent work in our laboratory has shown that the thymus-derived polypeptide thymopoietin potently and specifically interacts at the nicotinic alpha-BGT site in brain. The present results show that thymopoietin also interferes with the binding of 125I-alpha-BGT to chromaffin cells in culture; a dose-dependent inhibition in binding was observed, with an IC50 of 10(-8) M. To assess the long term effect(s) of thymopoietin in nervous tissue, chromaffin cells were exposed to the polypeptide for varying periods of time. Incubation of the cells in culture with thymopoietin (10(-9) to 3 x 10(-7) M) for 2 to 7 days resulted in an approximate 3-fold increase in alpha-BGT binding. Saturation analysis indicated this was due to an increase in the Bmax. The thymopoietin-induced increase in binding could be reversed with nicotine: thus, the sites can be regulated by a nicotinic receptor ligand. Although thymopoietin potently interacted at the nicotinic alpha-BGT receptor, nicotinic receptor responsiveness was not affected after short or long term exposure to the peptide. Neither basal nor nicotinic receptor-stimulated tyrosine hydroxylase activity was altered by thymopoietin. As well, resting and acetylcholine-evoked noradrenaline release remained similar to control after exposure of the cells to the polypeptide. These results indicate that the thymic polypeptide thymopoietin specifically interacts with the nicotinic alpha-BGT receptor population and, furthermore, can regulate the toxin binding sites in chromaffin cells in culture.

Acetylcholine↗

Pharmacologic treatment of the adult respiratory distress syndrome.

Adult respiratory distress syndrome is an inflammatory disorder of the lung parenchyma that results in severe respiratory failure. It is associated with sepsis syndrome and multiple organ failure and may be mediated by a variety of substances, several of which have been discussed in this article. Because sepsis syndrome, ARDS, and multiple organ failure are associated with a high mortality rate that has not been reduced significantly by supportive treatment, a rationale exists for therapeutic intervention with agents that affect the inflammatory cascade. Several of these agents, notably corticosteroids and prostaglandin E1, have been shown to be of no benefit in humans despite laboratory and animal studies suggesting their utility. Other agents, including surfactant, antiendotoxin antibodies, and NSAIDs, are undergoing clinical trials and may prove to be effective. A third group, including anti-TNF antibodies and pentoxifylline, are of theoretical benefit but await clinical trials.

Adrenal Cortex Hormones↗

Family understanding of psychiatric illness.

Family members of patients with a diagnosis of schizophrenia were surveyed to ascertain their understanding of their relative's illness. This paper reports on deficits in knowledge of family members as they struggle to absorb the repercussions of chronic illness. It was useful for the development of a psycho-education treatment curriculum while dramatically demonstrating the need for it.

Adaptation, Psychological↗

A response to Mapou.

Mapou (1988) has suggested that detection of brain damage has become an irrelevant task for neuropsychology, and that neuropsychological assessment should be used to generate profiles of cognitive function useful for sophisticated diagnosis and rehabilitation. While agreeing the latter considerations are important and germane, we affirm that the detection of brain damage remains an important task for neuropsychology. This affirmation is based on considerations of the nature of brain damage, the development and validation of neuropsychological tests, the utilization of neuropsychological assessment in current practice and the appropriate professional practice of clinical neuropsychology.

Aged↗

A distinct pattern of personality disturbance following exposure to mixtures of organic solvents.

To assess systematically the pattern of psychologic distress in chemically exposed workers complaining of personality changes, we administered the Minnesota Multiphasic Personality Inventory to 22 men with a history of exposure to mixtures of organic solvents. Results indicated clinically significant profile elevations in more than 90% of the exposed workers. Moreover, a consistent response profile was noted, indicating a high rate of somatic disturbances, anxiety, depression, social isolation, and fear of losing control. In addition, those workers with the longest exposure duration had the highest elevations on the scale measuring disturbances of thinking, social alienation, poor concentration, and anxiety. Comparisons between these subjects and a group of former prisoners of war with posttraumatic stress disorder revealed strikingly similar clinical profiles. We present a case history that illustrates the nature of this psychologic disturbance.

Adult↗

Thymopoietin, a thymic polypeptide, specifically interacts at neuronal nicotinic alpha-bungarotoxin receptors.

alpha-Bungarotoxin (alpha-BGT), a snake venom polypeptide, interacts potently and specifically with a nicotinic receptor population in neuronal tissue. However, the identity of this site is unclear, because, unlike at the neuromuscular junction and in electroplax, in nervous tissue the toxin does not block nicotinic cholinergic responses. Therefore, we sought endogenous compounds other than acetylcholine that could interact with the neuronal alpha-BGT site. In the present experiments, thymopoietin, a polypeptide isolated from the thymus, is shown to inhibit potently alpha-BGT binding to brain membranes in a dose-dependent manner (IC50 = 3.1 nM). This effect was not shared by a wide variety of other peptides, including thysplenin, a closely related polypeptide. Thymopoietin did not inhibit the binding of other radioligands known to interact with different populations of cholinergic receptors, such as [3H]nicotine and [3H]methylcarbachol, which bind to nicotinic receptors, or [3H]quinuclidinylbenzilate, which binds to muscarinic receptors. These results show that thymopoietin potently and specifically affects 125I-alpha-BGT binding to brain membranes and suggest that thymopoietin might be an endogenous ligand for alpha-BGT receptors in neuronal tissue.

Animals↗

Immunohistochemical localization of bursin in epithelial cells of the avian bursa of Fabricius.

Antibodies to the avian B-cell-differentiating hormone bursin (lysyl-histidyl-glycine amide) were raised in mice and rabbits by immunizing with bursin conjugates in Freund's adjuvant. Immunohistochemical staining with these bursin-specific antibodies was restricted to follicular and dendritic reticular epithelial cells of the bursa of Fabricius, and was not found in control avian tissues.

Animals↗

Synthesis and secretion of an albumin-like protein by cultured bovine tracheal gland serous cells.

Bovine tracheal submucosal gland serous cells were incubated with (35S) methionine. The proteins synthesized and secreted into the culture medium during pulse and chase periods were analyzed. Three major protein bands with apparent molecular weight values of 67 kD, 47 kD and 32 kD were detected by fluorography following SDS-polyacrylamide gel electrophoresis. Based on the molecular weight, immuno-reactive cross reactivity and surface molecular change characteristics, the labeled Mr 67 kD protein was identified as an albumin-like protein. Our results suggest that albumin found in airway secretions can originate, at least in part, from tracheal gland serous cells.

Albumins↗

A controlled trial of prehospital advanced life support in trauma.

We compared the outcome of 472 trauma patients who required ambulance attention and who received prehospital advanced life support (ALS) with another similar 589 patients who received only basic life support (BLS). Nontrapped, critically injured ALS patients were treated for an average of 13 minutes at the scene of injury, compared with 17 minutes for BLS cases (P less than .05). Seventeen of 37 ALS deaths (36%) occurred within 24 hours of injury, compared with 24 of 33 BLS fatalities (73%) (P less than .05). However, the overall case fatality rate was similar in the two groups, and regression analyses did not demonstrate an impact of ALS care on mortality. ALS resuscitation did not reduce the duration of hospital or intensive care unit stay, or the incidence of disability after head injury. However, the incidence of respiratory failure in the critically injured patients was 5% (ALS) and 19% (BLS) (P less than .025). ALS care appeared to influence patient outcome during the first 24 hours after injury, but had little impact on the later clinical course. Our sample size was too small to rule out any effect of ALS on in-hospital mortality. However, the improved 24-hour survival associated with ALS care suggests some benefit of prehospital resuscitation in major trauma.

Adult↗

One-month prophylactic use of OKT3 in cadaver kidney transplant recipients.

Fifty-five recipients of first cadaveric renal allografts were randomly assigned to three treatment groups in order to compare the safety and efficacy of a mouse antihuman T cell monoclonal antibody (OKT3) given prophylactically for a one-month period. This long period of administration was made possible by concomitant administration of azathioprine. The immune response against the foreign immunoglobulin was thus delayed and decreased in both intensity and severity, and OKT3 treatment could be given during almost the entire month in the majority of patients. The 18 patients who were enrolled in this treatment group had significantly (P less than 0.01) fewer rejection episodes during the first month posttransplantation than the 19 patients allocated to the high-dose (HD) steroid control group or the 18 patients allocated to the low-dose (LD) control group. Actual 2-year as well as actuarial 4-year graft survival rates were 89% in the OKT3 group, whereas they were 70% and 67% respectively in the steroid control groups. Four-year serum creatinine levels were normal and doses of steroids and other immunosuppressive agents were lower in the OKT3 group as compared with the control groups. Tolerance to OKT3 was good, and while viral infections were more frequently observed in OKT3 treated patients, the total number and the severity of infectious episodes were similar in all groups. The combination of one-month OKT3 plus azathioprine prophylaxis followed by conventional azathioprine plus low-dose steroid maintenance produced very satisfactory long-term results comparable to the best results now being obtained with cyclosporine regimens.

Adult↗

Amino acid sequence of thymopoietin isolated from skin.

The isolation of thymopoietin-reactive material in fetal bovine skin was monitored by means of a radioimmunoassay to thymopoietin. The amino acid sequence of this material was determined to be identical with that of thymopoietin isolated from the thymus. Experimental evidence suggests that thymopoietin in the circulation derives from the thymus and not from the skin, suggesting that the thymopoietin in keratinocytes has a local function, either apocrine and/or immunoregulatory.

Amino Acid Sequence↗

Treatment of chronic refractory osteomyelitis with adjunctive hyperbaric oxygen.

Twenty-eight consecutive patients with chronic refractory osteomyelitis uncomplicated by persistent segmental bone defect, fracture nonunion, septic arthritis, total joint arthroplasty, or major systemic disease (immune deficiency, malignancy, diabetes mellitus, malnutrition, or renal or hepatic failure) were treated from January, 1980 through December, 1985 to evaluate the potential benefits of hyperbaric oxygen therapy. Patients were classified by a staging system that took into account the bone involved; subchondral, periarticular bone involvement; extent of bone involvement; quality of soft tissue envelope and vascular supply; and general health status of the patient. Using this staging system, patients were assigned to either hyperbaric oxygen therapy or control status after their initial debridement. A regimen of hyperbaric oxygen therapy consisting of 100% oxygen, two atmospheres pressure, two hour duration, one dive per day, six dives per week was used in 14 of the 28 patients. Hyperbaric oxygen had no effect on length of hospitalization, rapidity of wound repair, initial clinical outcome, or recurrence of infection noted to date in this patient population.

Adolescent↗