Search PubMed⌕ Search

Biomedical subjects

G Gold

Publications and source records attributed to G Gold.

At least 55 records · Page 3Linked to original sources

Sensitivity and specificity of newly proposed clinical criteria for possible vascular dementia.

The objective of this study was to determine the sensitivity and specificity of clinical criteria for possible vascular dementia (VaD) recently developed independently by two groups: the State of California Alzheimer's Disease Diagnostic and Treatment Centers (ADDTC) and the National Institute for Neurological Disorders and Stroke with the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN). We also wished to compare the performance of the new criteria to that of the Hachinski Ischemic Score (HIS). The study was comprised of a retrospective chart review and clinicopathologic correlation, and took place in 304-bed acute-care geriatric hospital. The subjects were 113 autopsied elderly patients with dementia, who were assessed to determine sensitivity and specificity of the ADDTC and NINDS-AIREN criteria for possible VaD. Sensitivity and specificity were calculated using the neuropathologic diagnosis as a gold standard. Sensitivity was 0.63, and specificity was 0.64 for the ADDTC, 0.58 sensitivity and 0.80 specificity for the NINDS, and 0.43 sensitivity and 0.88 specificity for the HIS. Test combinations did not lead to substantial gains in sensitivity or specificity. The majority of patients with Alzheimer's disease were successfully excluded by the ADDTC (87%), the NINDS-AIREN (91%), and the HIS (97%). The proportion of mixed dementia cases clinically misclassified as VaD was 54% for the ADDTC, 29% for the NINDS-AIREN, and 18% for the HIS. Low sensitivity is the main weakness of the above clinical criteria for possible VaD. Mixed dementia is better excluded by the NINDS-AIREN than the ADDTC. Data from this validation study should provide valuable information to clinicians and researchers who wish to apply these criteria to the diagnosis of VaD.

Aged↗

Enhancement of proxy appointment for older persons: physician counselling in the ambulatory setting.

OBJECTIVE: To determine the effectiveness of physician-initiated counselling on the rate of health care proxy appointment. DESIGN: Observational study of an intervention in a convenience sample. SETTING: A geriatric outpatient clinic in a tertiary care teaching hospital, New York, New York. PARTICIPANTS: A total of 687 patients enrolled in the geriatric clinic during the study period March 1991 through June 1993. INTERVENTION: Physician counselling about the New York State Health Care Proxy Law, distribution of educational materials and healthcare proxy forms, and reminders in 331 of 466 eligible patients. MEASUREMENTS: Rate of healthcare proxy appointment in eligible and counselled groups; predictors of appointment and non-appointment; time elapsed from counselling to appointment; reasons for non-appointment; characteristics of the proxy appointment process. RESULTS: A healthcare proxy was appointed for 31.5% of patients eligible for counselling and for 44% of patients who actually received the intervention, compared with a 2.3% proxy appointment rate at baseline. Eighty-one percent of the patients completing the proxy appointment process did so at or before their third clinic return visit after the counselling intervention. Of the counselled patients who did not appoint a proxy, 25% explicitly declined, and 75% had not come to a decision by the end of the study period. Proxy completion was associated with ethnicity, education, and more frequent clinic visits. Of those who appointed a proxy, 97% had good or fair comprehension of the procedure, 92% discussed the appointment with their designees, 63% appointed a daughter or son, and 80% discussed their wishes for care at the end of life with their proxy. CONCLUSIONS: Physician counselling of older outpatients is an effective means of increasing healthcare proxy appointments.

Advance Care Planning↗

Imidazoline compounds stimulate insulin release by inhibition of K(ATP) channels and interaction with the exocytotic machinery.

A novel imidazoline compound, RX871024, was used to investigate the mechanisms by which imidazoline derivatives promote insulin secretion in rat pancreatic beta-cells and HIT T15 cells. RX871024 stimulated insulin release from rat pancreatic beta-cells and HIT T15 cells in a glucose-dependent way. This effect was not related to alpha2-adrenergic, I1-, and I2-imidazoline receptors. RX871024 promoted insulin release by at least two modes of action. One included an increase in cytoplasmic free Ca2+ concentration ([Ca2+]i), subsequent to blocking of ATP-dependent K+ channels, membrane depolarization, and activation of voltage-dependent Ca2+ channels. The other, a more distal effect of imidazoline, affected the exocytotic machinery and was unrelated to changes in membrane potential and [Ca2+]i. The mechanism of RX871024-induced insulin release was dependent on protein kinases A and C. The sensitizing effect of a low dose of RX871024 on glucose-induced insulin secretion suggests that imidazoline compounds of this kind may constitute the basis for development of a new class of oral hypoglycemic agents.

Animals↗

A standardized patient program in a mandatory geriatrics clerkship for medical students.

This article describes the development and implementation of a new standardized patient program in a required geriatrics clinical clerkship for fourth-year medical students. A student survey was also conducted to provide evaluations of the program and to determine the frequency with which students' clinical skills are directly evaluated by faculty. Thirty-six percent reported never having been observed while obtaining a history and 24% having been observed only once; 26% had never been observed while completing a physical examination and 39% had been observed only once. The implementation of a standardized patient program provided students with direct feedback on their clinical skills and was rated positively, (good, very good, or outstanding) by 76% of the students.

Clinical Clerkship↗

Hypertension: special concerns in managing the older patient.

In most populations, average diastolic BP increases with age until the sixth decade and then remains constant, whereas average systolic BP continues to rise. Many studies have shown an increase in cardiac and stroke risk with increasing BP, even in elderly populations. Antihypertensive therapy in the elderly has been shown to reduce the risk of nonfatal and fatal stroke, nonfatal and fatal coronary heart disease, and all-cause mortality. The right combination of diet and lifestyle changes can help to control hypertension and reduce cardiovascular risk. For optimal results, give the patient as much informed choice as possible in the selection of therapies and setting of goals. Proceed cautiously when it is necessary to add pharmacologic therapy, whatever agent is chosen.

Aged↗

Guaranteeing real-time response with limited resources.

Unanticipated problems detected by patient-monitoring systems may sometimes require real-time response in order to provide high-quality care and avoid catastrophic outcomes. In this paper, we present an approach for guaranteeing a response to such events by a monitoring agent even in situations where we have limited problem-solving resources. We show that an action-based hierarchy can accomplish this goal. We also analyze the performance of this hierarchy under varying resource availability and discuss decision-theoretic approaches to enable us to best structure such a hierarchy. We also describe an implementation of these ideas, called ReAct, in the BB1 architecture. All the ideas are illustrated with examples from the surgical intensive care unit (SICU).

Algorithms↗

Education in geriatrics: a required curriculum for medical students.

The mandatory geriatrics and gerontology curriculum at The Mount Sinai School of Medicine in New York includes two modules for first- and second-year students and a four-week block experience for fourth-year students. The first-year curriculum emphasizes socioeconomic, psychosocial, biomedical, and attitudinal issues. The second-year experience serves as an introduction to clinical geriatrics. The fourth-year clerkship allows students to further develop their fund of geriatric knowledge, learn specific geriatric skills, and build on their internal medicine foundation, integrating new knowledge and skills and developing into comprehensive practitioners who can apply the team approach to address all the medical, functional, psychosocial, and ethical aspects of caring for the elderly.

Curriculum↗

Health care for the homebound older adult: a medical model.

The medical home-care program is a logical and indispensable addition to the comprehensive, multilevel geriatric care offered by the Department of Geriatrics. The home-care program enables the frail and homebound elderly to remain in their home environment and continue to receive comprehensive primary medical care and supportive services. It also serves as a valuable teaching site for medical trainees. Program evaluation through assessment of patient and caregiver satisfaction, estimates of costs of care, and frequency of hospitalization and emergency room visits are ongoing.

Aged↗

Human and rat amylin have no effects on insulin secretion in isolated rat pancreatic islets.

Amylin, an islet amyloid peptide secreted by the pancreatic beta cell, has been proposed as a humoral regulator of islet insulin secretion. Four separate preparations of amylin were tested for effects on hormone secretion in both freshly isolated and cultured rat islets and in HIT-T15, hamster insulinoma cells. With all three experimental models, exposure to human amylin acid and human and rat amylin at concentrations as high as 100 nM had no significant effect on rates of insulin or glucagon secretion. These observations suggest that amylin, even at concentrations appreciably higher than those measured in peripheral plasma, is not a significant humoral regulator of islet hormone secretion.

Amyloid↗

Unregulated secretion of an exogenous glycotripeptide by rat islets and HIT cells.

Freshly isolated rat islets and cultured hamster insulinoma cells (HIT T15) were incubated with a membrane-permeable octanoyl tripeptide (N-octanoyl-ASN-TYR-THR-NH2), which contains an acceptor sequence for ASN-linked glycosylation. Labeled octanoyltripeptide (125[I]TYR) was glycosylated by both islets and HIT cells. The carbohydrate moiety of this glycotripeptide was removed by N-glycanase indicating that glycotripeptide was formed in the lumen of endoplasmic reticulum and, subsequently was secreted via the route for secretory protein. Secretion of glycotripeptide began more rapidly than that of insulin newly synthesized from 3[H]leucine. At 30 min glycotripeptide secretion was already significant but, over a 3-h period, it never represented more than 21% of glycotripeptide produced. Glycotripeptide secretion was not affected by compounds shown to regulate insulin secretion (glucose, forskolin, EGTA and streptozotocin). Thus in beta cells, it appears that glycotripeptide secretion is unregulated and that its cellular secretory pathway is different from that for insulin.

Adenoma, Islet Cell↗

Biosynthetic regulation of endogenous hamster insulin and exogenous rat insulin II in transfected HIT cells.

To investigate mechanisms underlying biosynthetic regulation of an insulin gene, the rat insulin II gene was introduced into hamster beta-cells (HIT) by cotransfection with the neomycin phosphotransferase-selectable marker. The insulin gene fragment was 2.2 kilobases (kb) in length and contained all exons, introns, and approximately 700 base pairs (bp) of 5'-flanking DNA and 300 bp of 3'-flanking DNA. The HIT cell was known to have endogenous hamster insulin production under regulation by glucose and dexamethasone. In a pool of stably transfected cells (HIT M62pR2), rat insulin II and hamster insulin were produced at comparable rates. Glucose (20 mM) stimulated cellular [3H]leucine labeling of both hamster insulin and rat insulin II by approximately twofold. Addition of 10(-6) M dexamethasone to media containing 11.1 mM glucose inhibited biosynthesis of both hamster insulin and rat insulin II by greater than 90%. Thus, with both positive and negative biosynthetic regulation, changes in the cellular labeling of exogenous rat insulin II were qualitatively and quantitatively similar to those of the endogenous hamster insulin. These data suggest that the 2.2-kb rat insulin II gene fragment contained sufficient information for both expression and apparently "normal" biosynthetic regulation of exogenous rat insulin II (when compared with endogenous hamster insulin) in response to glucose and dexamethasone.

Animals↗

Insulin biosynthesis in HIT cells. Effects of glucose, forskolin, IBMX, and dexamethasone.

Glucose, forskolin, 3-isobutyl-1-methylxanthine (IBMX), and dexamethasone were tested as regulators of proinsulin biosynthesis in HIT T-15 cells, which are glucose-responsive simian virus 40-transformed hamster beta-cells. Rate of [3H]leucine incorporation into proinsulin was increased as glucose concentrations were raised from 0 to 20 mM. Biosynthetic rate increases were significant after 48 but not at 4 or 24 h of glucose and were greater for proinsulin than for total extractable proteins. After 48 h, glucose-stimulated proinsulin biosynthesis was unaffected by 10(-6) M forskolin and/or 3 x 10(-5) M IBMX but was specifically and significantly inhibited by 10(-6) M dexamethasone. Four hours of exposure to dexamethasone had no effect. When cells were incubated for 24 h and then continuously labeled for an additional 24 h, cellular conversion of labeled proinsulin to insulin was increased by glucose, and this increase was reversed or inhibited by 10(-6) M dexamethasone. Therefore, proinsulin biosynthesis in transformed HIT T-15 cells is regulated in several ways by metabolites and hormones in a manner that compares with biosynthetic regulation in normal beta-cells.

1-Methyl-3-isobutylxanthine↗

Effects of tolbutamide pretreatment on the rate of conversion of newly synthesized proinsulin to insulin and the compartmental characteristics of insulin storage in isolated rat islets.

Tolbutamide (1 g/kg body wt) was administered to male rats for 3 days to determine the effects of this pretreatment on subsequent insulin biosynthesis and compartmental storage characteristics of freshly isolated islets. Islets were isolated 16 h after the last tolbutamide administration, at a time when fed plasma glucose concentrations were normal. Islet glucagon was unchanged but insulin content was significantly reduced (38 +/- 1.2 ng IRI/islet from seven untreated rats versus 7.9 +/- 1.2 ng IRI/islet from eight treated rats). After tolbutamide pretreatment, the rate of incorporation of 3H-leucine into islet proinsulin was unchanged, but the t1/2 of labeled proinsulin-to-insulin conversion was significantly (P less than 0.001) decreased from 36 to 20 min. After treatment, actual rates of glucose-stimulated insulin secretion were 50% lower, however, because due to the proportionately greater depletion of islet insulin content, the fractional rate of secretion was increased two-fold. After treatment, there was evidence of compartmental, heterogeneous insulin storage, and glucose still marked newly synthesized insulin for preferential release; however, the differential release of new and old insulin converged rapidly with time. Mathematical integration of the data suggested dilution of the newly synthesized insulin compartment with unlabeled insulin during the chase period, but additionally indicated more rapid mixing of newly synthesized with previously stored, unlabeled insulin. Thus, tolbutamide-treated rats partially compensated for acute insulin depletion by increasing the rate of proinsulin-to-insulin conversion, but not increasing the rate of proinsulin biosynthesis; doubling the glucose-stimulated fractional secretory rate of the depleted cellular insulin storage compartment; and retaining compartmental storage characteristics but mixing newly synthesized insulin more rapidly with the compartment of previously stored, unlabeled insulin.

Animals↗