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Biomedical subjects

D Shine

Publications and source records attributed to D Shine.

13 recordsLinked to original sources
PubMed2004

Nerve growth factor, brain-derived neurotrophic factor, and neurotrophin-3 are sorted to dense-core vesicles and released via the regulated pathway in primary rat cortical neurons.

Neurotrophins (NTs) play an important role in the modulation of synaptic transmission and in morphological changes in synaptic structures. Although there is agreement that brain-derived neurotrophic factor (BDNF) is sorted to large dense-core vesicles (LDCVs) and released via the regulated secretory pathway, there has been some dispute regarding the mode of secretion of nerve growth factor (NGF) and neurotrophin-3 (NT-3), two structurally related members of the NT family. In this study, we examined the subcellular localization and release characteristics of NGF, BDNF, and NT-3 in adenovirus-infected primary cortical neurons. We found that all members of the NT family colocalized with markers for the endoplasmic reticulum and Golgi within cell bodies and in a punctate manner with a marker for LDCVs within processes. Moreover, their release was triggered by depolarization, indicating that NGF, BDNF, and NT-3 are released via the regulated secretory pathway. When neurons were coinfected with two separate adenoviruses coding for NGF or BDNF, both NTs showed almost complete vesicular colocalization within single cells, suggesting that different NTs might be packaged into shared vesicles. We also examined whether the two splice variants of NGF, the short and long precursors, differ in their release characteristics. We found that neurons infected with viruses coding for either splice variant released NGF in a regulated way. Overall, our study supports the notion that all members of the NT family undergo activity-dependent regulated release from neurons, enabling them to act as "synaptotrophins" on electrically active neurons.

Animals↗
PubMed2001

Association of resident coverage with cost, length of stay, and profitability at a community hospital.

OBJECTIVE: The effect of care by medical residents on hospital length of stay (LOS), indirect costs, and reimbursement was last examined across a range of illnesses in 1981; the issue has never been examined at a community hospital. We studied resource utilization and reimbursement at a community hospital in relation to the involvement of medical residents. DESIGN: This nonrandomized observational study compared patients discharged from a general medicine teaching unit with those discharged from nonteaching general medical/surgical units. SETTING: A 620-bed community teaching hospital with a general medicine teaching unit (resident care) and several general medicine nonteaching units (no resident care). PATIENTS: All medical discharges between July 1998 and February 1999, excluding those from designated subspecialty and critical care units. MEASUREMENTS AND MAIN RESULTS: Endpoints included mean LOS in excess of expected LOS, mean cost in excess of expected mean payments, and mean profitability (payments minus total costs). Observed values were obtained from the hospital's database and expected values from a proprietary risk-cost adjustment program. No significant difference in LOS between 917 teaching-unit patients and 697 nonteaching patients was demonstrated. Costs averaged $3,178 (95% confidence interval (CI) +/- $489) less than expected among teaching-unit patients and $4,153 (95% CI +/- $422) less than expected among nonteaching-unit patients. Payments were significantly higher per patient on the teaching unit than on the nonteaching units, and as a result mean, profitability was higher: $848 (95% CI +/- $307) per hospitalization for teaching-unit patients and $451 (95% CI +/- $327) for patients on the nonteaching units. Teaching-unit patients of attendings who rarely admitted to the teaching unit (nonteaching attendings) generated an average profit of $1,299 (95% CI +/- $613), while nonteaching patients of nonteaching attendings generated an average profit of $208 (95% CI +/- $437). CONCLUSIONS: Resident care at our community teaching hospital was associated with significantly higher costs but also with higher payments and greater profitability.

Hospital Charges↗
PubMed1999

Limits of confidence in tracer compounds as a means of measuring patient compliance with medication.

Chemical tracers are thought to be a desirable means of measuring patient compliance with medication. However, no compound has emerged as a standard. To explain this observation, the authors explored the mathematics of simulated tracers with half-lives 5 to 140 days over a month of daily dosing. To model assay variability, they added random "noise" to calculated tracer serum levels. They then fitted those altered levels to the dosing pattern most likely to have produced them, given known kinetics of the tracers. The large number of possible dosing patterns over a month (268,435,456) magnified uncertainty in interpreting noise-altered levels. At best, with an assay variability of 5%, compliance could be estimated only within 4 to 8 doses per month. The tracer with a half-life of 30 days performed best. Pairing tracers did not improve uncertainty. The authors found that even a model neglecting many real-world variables suggests a limited role for tracers in measuring compliance.

Clinical Trials as Topic↗
PubMed1997

A computer model for the measurement of compliance using a dual tracer technique.

AIMS: We aimed to determine whether simultaneous use of two tracer compounds with long and differing elimination half-lives may permit more precise recognition of percent compliance and discrimination among remote, intermediate, and recent patterns of daily dosing. METHODS: We have derived, through computer modelling, the potential utility of digitoxin and phenobarbitone as simultaneous tracers. From kinetic data on these reliably measured compounds with long half-lives we defined the percentage error below which this pair of tracers can be expected to discern the precise, and the approximate, pattern and number of daily doses taken over a mouth. RESULTS: The longer the half-lives of the tracers the greater the sensitivity of our model to percentage compliance. At extremely long half-lives, relative to the period of dosing being monitored, sensitivity approaches 100% if measurement error is in the 1-2% range. The ratio of the half-lives between the two tracers that is optimal for detection of percentage compliance is 0.2 to 0.8. The detection of pattern does not depend importantly either on the tracer half-lives or on their ratio to each other. The greater the percentage compliance, the more accurately our two-tracer model determines the pattern of dosing. CONCLUSIONS: Precise characterization of compliance using tracers must probably await the development of compounds with half-lives measured in weeks or months. The probability of compliance of a given degree can be derived from our two-tracer technique with best-fit analysis such as we describe.

Anti-Arrhythmia Agents↗
PubMed1987

Serologic, immunologic, and clinical features of parenteral drug users from contrasting populations.

We screened inpatient and outpatient parenteral drug users with no clinical evidence of AIDS for immunodeficiency and antibodies to HTLV-III by ELISA. Among 20 outpatient drug users, 5 (25%) were seropositive. Three of these (and 2 who were seronegative) had low T-cell ratios. Over 6 months, 1 seropositive patient with a low ratio developed oral thrush and weight loss. We also studied 13 parenteral drug users hospitalized for conditions other than AIDS. Eight had low T-cell ratios, and at least 6 of these developed AIDS or ARC within 4 months. Serum from 8 of 13 inpatients was available for HTLV-III testing: 6/8 were seropositive and 3 of these 6 were among those developing AIDS or ARC. Abnormal T-cell ratios among all patients were associated with abnormal HTLV-III serology (p = .02). Of the 7 patients who developed AIDS or ARC, 4 were tested for both antibodies and T-cell ratios: all 4 were seropositive and had low ratios. A low ratio (p = .0004), a positive ELISA (p = .014), and abnormalities of both tests (p = .001) were associated with the development of AIDS or ARC. Of the 26 patients without AIDS or ARC, 3 were lost to follow-up and 23 did not develop AIDS or ARC. Six of these 26 had abnormal ratios. Of the 21 patients who did not develop AIDS or ARC and who were tested for HTLV antibodies, 2 were lost to follow-up. Seven of 21 were seropositive and 2/21 were both seropositive and had a low ratio. One of these 2 seropositive patients with low ratios also had lymphadenopathy, but he was lost to follow-up. The other had no adenopathy and remained well until her death from trauma a year later. This study found two populations with very different risks. Six of 13 hospitalized parenteral drug users and only 1 of 20 healthy outpatients developed AIDS or ARC.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Intravenous drug abusers and the acquired immunodeficiency syndrome (AIDS). Demographic, drug use, and needle-sharing patterns.

We studied the demographic characteristics, drug use patterns, and sexual habits of intravenous (IV) drug abusers to further define this population at risk for acquired immunodeficiency syndrome (AIDS). Sixteen IV drug abuser patients with AIDS, 24 IV drug abuser patients with AIDS-related complex (ARC), and 14 IV drug abuser controls without evidence of AIDS or ARC were evaluated. The subjects in each group were similar demographically, in drug use practice, and in sexual orientation and experience. Of the AIDS and ARC patients, 34 (88%) of 40, including all seven homosexual men, shared needles, as did all drug abusers without AIDS or ARC. Seventy-four percent of patients, including all homosexual men, attended "shooting galleries," where anonymous multiple-partner needle sharing took place. Needle sharing supports the hypothesis of AIDS transmission by a blood-borne route, can explain the spread of AIDS and the high rate of seropositivity to the putative AIDS agent among IV drug abusers, and is a logical link between IV drug abusers and male homosexuals, the two largest groups with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Knowledge of medical students, residents, and attending physicians about opiate abuse.

A questionnaire concerning knowledge of opiate abuse and attitudes about abusers was administered to 94 randomly selected physicians and medical students at a large urban teaching hospital. Physicians from four clinical departments and at each level of residency training and medical students in the final year were represented. The mean knowledge score was 3.3 out of a possible 12. Neither the level of training nor specialty was related to test score for the group as a whole. However, family practitioners gained knowledge with increasing experience, while medical and surgical specialists scored lower as they advanced in training. On the attitude section, physicians had strong but individualistic views about drug abuse. Level of training, specialty, and knowledge test score were on the whole unrelated to attitude. The results indicated that physicians at every level of training might benefit from improved teaching in the area of opiate abuse.

Analysis of Variance↗
PubMed1981

Reliability of the toxic screen in drug overdose.

To determine the reliability of the laboratory in detecting drugs taken by overdosed patients, we evaluated laboratory performance on an unbiased sample of actual clinical specimens. Replicate serum and urine samples from a series of 20 consecutive clinically overdosed patients were sent to three commercial laboratories and one academic research laboratory for identification and quantification of intoxicating agents. All laboratories used the advance analytical techniques of gas chromatography-mass spectrometry. The results suggest that laboratories do not reliably identify drugs in the serum of overdosed patients, partly because of technical limitation, partly because of laboratory error, and possibly because of inadequate specimens. Drugs judged responsible for the overdose were identified in only 50% to 70% of the cases, depending on the laboratory. Reported concentrations sometimes varied over a 10-fold range.

Evaluation Studies as Topic↗
PubMedDate not supplied

The diagnosis of drug dependence by primary care providers.

HIV infection cannot be treated nor can its spread among those who use drugs be contained unless physicians diagnose and treat drug dependence. Recent changes in the DSM-III definitions simplify diagnosis. It is primarily by the presence and extent of the dependence syndrome that decisions are made regarding early HIV counseling and testing, medical management, referral for drug dependence treatment, and the approach to minimizing disease spread by the patient.

HIV Seropositivity↗
PubMedDate not supplied

Diagnosis and management of acquired immune deficiency syndrome in intravenous drug users.

Acquired Immune Deficiency Syndrome (AIDS) is a clinical entity that is part of a spectrum of immune dysfunction found in specific high risk groups, among them intravenous drug users. In drug users AIDS almost always presents as an opportunistic infection, usually Pneumocystis carinii. The leading etiologic hypothesis is of a viral agent acting, it is possible, on a previously immunocompromised host. Recent research at hospitals affiliated with The Albert Einstein College of Medicine, where an unusually large proportion of AIDS patients are drug users, is described. Suggestions are advanced for the management of IV drug users with immune dysfunction.

Acquired Immunodeficiency Syndrome↗