Search PubMed⌕ Search

Biomedical subjects

M Gold

Publications and source records attributed to M Gold.

At least 73 records · Page 4Linked to original sources

Current issues in depression in Parkinson's disease.

Depression affects 40%-50% of Parkinson's disease (PD) patients. The authors, by use of a Mednet and manual search of pertinent literature, summarize current issues in the treatment of depression in PD. Open-label studies suggest that antidepressants may be effective for treating depression in PD. Although case reports indicate that selective serotonin reuptake inhibitors (SSRIs) can potentially worsen the motor symptoms of PD, this effect has not been confirmed in the small number of open-label studies that have been performed to date. The occurrence of the serotonin syndrome resulting from a combination of selegiline and an SSRI appears to be rare. Double-blind prospective studies are needed to evaluate the safety and efficacy of antidepressants in PD and their effect on motor function.

Aged↗

The health effects of swimming in ocean water contaminated by storm drain runoff.

Waters adjacent to the County of Los Angeles (CA) receive untreated runoff from a series of storm drains year round. Many other coastal areas face a similar situation. To our knowledge, there has not been a large-scale epidemiologic study of persons who swim in marine waters subject to such runoff. We report here results of a cohort study conducted to investigate this issue. Measures of exposure included distance from the storm drain, selected bacterial indicators (total and fecal coliforms, enterococci, and Escherichia coli), and a direct measure of enteric viruses. We found higher risks of a broad range of symptoms, including both upper respiratory and gastrointestinal, for subjects swimming (a) closer to storm drains, (b) in water with high levels of single bacterial indicators and a low ratio of total to fecal coliforms, and (c) in water where enteric viruses were detected. The strength and consistency of the associations we observed across various measures of exposure imply that there may be an increased risk of adverse health outcomes associated with swimming in ocean water that is contaminated with untreated urban runoff.

California↗

Medicaid managed care: interpreting survey data within and across states.

This paper uses household survey data from four states to examine whether perceptions are sensitive to differences in state implementation and unique to Medicaid managed care. The study finds survey data provide valuable insight into system performance, but are less likely to provide targeted measures of programs' specific features. Also, the perception of Medicaid managed care relative to other insurance differs among states. Thus, survey data and case study information from interviews, documents, and administrative data provide complementary insights. Effective oversight of Medicaid managed care can benefit by using both kinds of information together.

Health Services Accessibility↗

The -491A/T apolipoprotein E promoter polymorphism association with Alzheimer's disease: independent risk and linkage disequilibrium with the known APOE polymorphism.

The epsilon4 allele of the apolipoprotein E gene (APOE) has repeatedly been associated with increased risk for Alzheimer's disease (AD). Bullido and colleagues recently identified a polymorphism in the promoter region of the APOE gene (-491A/T) and found that -491A homozygosity predicted AD independently of APOE epsilon4. Since the -491A/T polymorphism and the known APOE polymorphism must be in tight linkage disequilibrium, and the later polymorphism is know to be associated with the disease, we wished to determine to what extent this linkage disequilibrium explained the -491A/T polymorphism association with Alzheimer's disease. We genotyped a community-based control sample (n = 132) and a clinic-based Alzheimer's disease sample (n = 190) for the known APOE and -491A/T polymorphisms, and find that, while the -491A/T polymorphism confers some independent risk for AD, linkage disequilibrium between the known APOE and -491A/T polymorphic sites explains most of the -491A association. Furthermore, when considering the known APOE and -491A/T polymorphisms alone, APOE epsilon4 status is the best predictor of the disease.

Aged↗

ATP-reactive sites in the bacteriophage lambda packaging protein terminase lie in the N-termini of its subunits, gpA and gpNu1.

ATP-reactive sites in terminase and its subunits have been successfully identified using three different affinity analogs of ATP (2-and 8-azidoATP and FITC) GpA, the larger subunit of terminase, was shown to have a higher affinity for these analogs than gpNu1, the smaller subunit. The suitability of these reagents as affinity analogs of ATP was demonstrated by ATP protection experiments and in vitro assays done with the modified proteins. These analogs were thus shown to modify the ATP-reactive sites. The results obtained from these experiments also indicate the importance of subunit-subunit interactions in the holoenzyme. Terminase, gpA, and gpNu1 were modified with these analogs and the ATP-reactive sites were identified by isolating the modified peptide by reverse-phase chromatography. The sequence analysis of the modified peptides indicates a region including amino acids 18-35 in the N-terminus of gpNu1 and a region including amino acids 59-85 in the N-terminus of gpA as being the ATP-reactive sites.

Adenosine Triphosphatases↗

The butyrylcholinesterase gene is neither independently nor synergistically associated with late-onset AD in clinic- and community-based populations.

The K variant of the butyrylcholinesterase gene (BChE) was recently found to occur at an increased frequency in a late onset Alzheimer's disease (AD) population, specifically in individuals carrying the epsilon4 allele of the apolipoprotein E (APOE) gene. This suggested synergy between these two genes resulting in an increased risk of late-onset AD. We have genotyped 62 community-based and 329 clinic-based AD cases, and 201 community-based controls at BChE and APOE and find no independent association between BChE and AD nor interaction with APOE in risk for AD in either our clinic or community-based samples.

Aged↗

Site-directed mutagenesis combined with chemical modification as a strategy for altering the specificity of the S1 and S1' pockets of subtilisin Bacillus lentus.

By combining site-directed mutagenesis with chemical modification, we have altered the S1 and S1' pocket specificity of subtilisin Bacillus lentus (SBL) through the incorporation of unnatural amino acid moieties, in the following manner: WT --> Cysmutant + H3CSO2SR --> Cys-SR, where R may be infinitely variable. A paradigm between extent of activity changes and surface exposure of the modified residue has emerged. Modification of M222C, a buried residue in the S1' pocket of SBL, caused dramatic changes in kcat/KM, of an up to 122-fold decrease, while modification of S166C, which is located at the bottom of the S1 pocket and is partially surface exposed, effected more modest activity changes. Introduction of a positive charge at S166C does not alter kcat/KM, whereas the introduction of a negative charge results in lowered activity, possibly due to electrostatic interference with oxyanion stabilization. Activity is virtually unaltered upon modification of S156C, which is located toward the bottom of the S1 pocket and surface exposed and whose side chain is solvated. An unexpected structure-activity relationship was revealed for S166C-SR enzymes in that the pattern of activity changes observed with increasing steric size of R was not monotonic. Molecular modeling analysis was used to analyze this unprecedented structure-activity relationship and revealed that the position of the beta-carbon of Cys166 modulates binding of the P1 residue of the AAPF product inhibitor.

Amino Acid Substitution↗

Plasma thiamine deficiency associated with Alzheimer's disease but not Parkinson's disease.

In this study we compared plasma and erythrocyte thiamine levels in a group of patients with idiopathic Parkinson's Disease (iPD) to a group of patients with probable Alzheimer's Disease (pAD). pAD patients had significantly lower plasma thiamine levels (raw and z-score) than iPD patients. A significantly higher number of pAD patients had plasma thiamine deficiencies than iPD patients. The demographics of our patient groups were similar to those reported by other investigators, making age, sex and nutritional status unlikely explanations for our findings. These results suggest that plasma thiamine deficiency is associated with pAD but not with iPD.

Adult↗

Refusal of out-of-hospital medical care: effect of medical-control physician assertiveness on transport rate.

OBJECTIVE: Previous studies have shown that contacting an on-line medical-control physician increases the transport rate of patients who attempt to refuse medical assistance. The authors studied the physician-patient interaction to determine the type of interaction that was more likely to result in patient transport. METHODS: A prospective, observational study of patient-initiated refusals of medical assistance (RMAs) was performed in a suburban volunteer emergency medical services (EMS) system, with 12 receiving hospitals county-wide. Medical-control contact was required for all patient-initiated RMAs. Consecutive patients who attempted out-of-hospital RMA over a 3-month period were monitored. Structured data instruments were completed by the medical-control operator and medical-control physician for all patients who attempted RMA. Data collected included patient demographics and contact information, scene characteristics, history and physical examination data, length of time of interaction, and the physician's assessment of the need for transport and the patient's capacity to refuse transport. The operator and physician independently graded the physician's assertiveness in talking to the patient on a continuous 10-point scale. RESULTS: There were 130 patients who attempted RMA; 69 (53%) refused transport even after discussion with the medical-control physician, while 61 (47%) were transported to a hospital. The patients who were transported did not differ from those not transported with respect to age, chief complaint, vital signs, or presence of police on scene. Using the operators' independent assessments, the physicians were more assertive when they graded the patient as being more ill (needs transport, 8.8; may need transport, 7.7; doesn't need transport, 4.1; p < 0.01). When the physicians were more assertive, the patients were more likely to agree to transport (assertiveness > 8, 81% transport; assertiveness < 8, 19% transport; p < 0.01). CONCLUSIONS: Contact with a medical-control physician appears to markedly improve the transport rate for patients who initially attempt to refuse out-of-hospital medical care. This is especially so when physicians are more assertive in recommending transport.

Chi-Square Distribution↗

A 67-year-old woman with polymyalgia rheumatica and left hemispatial neglect.

A 67-year-old woman with a diagnosis of polymyalgia rheumatica presented initially with periods of confusion and incontinence. A CT scan of the brain was normal and she was treated with tapering doses of corticosteroids and clinical improvement. After a brief period off steroids, the patient presented with a progressive dementia, left-sided clumsiness, gait disturbances and left hemispatial neglect. An MRI at this time demonstrated a large area of edema over the right parietal lobe and intense cortical enhancement. A chest CT demonstrated multiple nodules. Biopsies of the lung and brain failed to identify any infectious organisms or malignant tissue. The leptomeningeal biopsy revealed multiple granulomatous areas with central necrosis and hystiocytic cells consistent with idiopathic hypertrophic pachy-meningitis.

Aged↗

Beyond coverage and supply: measuring access to healthcare in today's market.

OBJECTIVE/PURPOSE: To stimulate discussion within the research and policy community about the value of and issues surrounding different ways to describe access to care in a health system reconfigured by the growth of managed care, competition, and other marketplace changes. PRINCIPLE FINDINGS: The concept of access has evolved over time to address shifting health policy concerns like the growing interest in looking beyond utilization as a measure of access to a better consideration, too, of the effectiveness of services used as judged by costs and outcomes. Yet current frameworks used to look at access are person-based and do not capture the complexity of the healthcare system and the complex structures involved in managed care organizations that combine delivery and financing and vary substantially within and across markets. In addition, many at times competing or conflicting policy goals on access exist. There also is an increasingly diverse and widening set of uses that include benchmarking against national goals, measuring performance of accountable entities, and providing consumer information. CONCLUSIONS AND RECOMMENDATIONS: Traditional access frameworks are invaluable in encouraging focus on historical measures of access, like insurance coverage and other barriers to system entry. But much greater attention needs to be paid to adapting current access frameworks so that they also better support the ability to understand how processes inherent in diverse health delivery and financing arrangements influence access to services within a system and what this means for how well individuals negotiate healthcare systems and the effects on care outcomes. The increasing demands on access measures and the growing diversity of users also point to a need for collaboration to better pool insights, share experiences, and honestly confront trade-offs or disagreements to progress in addressing these issues.

Delivery of Health Care↗

Needle exchange programs: an economic evaluation of a local experience.

OBJECTIVE: To determine whether providing a needle exchange program to prevent HIV transmission among injection drug users would cost less than the health care consequences of not having such a program. DESIGN: Incidence outcome model to estimate the number of cases of HIV infection that this program would prevent over 5 years, assuming that the HIV incidence rate would be 2% with the program and 4% without it, and that an estimated 275 injection drug users would use the service over this time. SETTING: Hamilton, Ont. OUTCOME MEASURES: Estimated number of cases of HIV infection expected to be prevented with and without the program over 5 years; estimated lifetime health care costs of treating an AIDS patient. The indirect costs of AIDS to society (e.g., lost productivity and informal caregiving) were not included. Projected costs were adjusted (discounted) to reflect their present value. In a sensitivity analysis, 3 parameters were varied: the estimate of the HIV transmission rate if no needle exchange program were provided, the number of injection drug users participating in the program, and the discount rate. RESULTS: With very conservative estimates, it was predicted that the Hamilton needle exchange program will prevent 24 cases of HIV infection over 5 years, thereby providing cost savings of $1.3 million after the program costs are taken into account. This translates into a ratio of cost savings to costs of 4:1. The sensitivity analysis confirmed that these findings are robust. CONCLUSION: Needle exchange programs are an efficient use of financial resources.

Canada↗

No interaction between the APOE and the alpha-1-antichymotrypsin genes on risk for Alzheimer's disease.

It is now known that possession of one of the three common forms of the apolipoprotein E gene (allele epsilon 4) confers an increased risk for Alzheimer's disease (AD), both familial and sporadic, and that this risk is dose-dependent. Other genes that may play a role in AD, either through independent association with the disease or through modification of, or interaction with, the existing apolipoprotein E (APOE) risk, are now under investigation including the alpha-1-antichymotrypsin (ACT) gene, the very low density lipoprotein receptor (VLDL-R) gene, and the presenilin-1 (PS-1) gene. Kamboh et al. [1995] reported that a polymorphism in the alpha-1-antichymotrypsin gene could modify the risk for AD conferred by the APOE locus, specifically by increasing the risk for AD among epsilon 4 homozygotes. The ACT gene, which is found on chromosome 14, has previously been proposed as a candidate for AD due to the presence of the ACT protein in senile plaques and the reported elevation of the protein in the cerebro-spinal fluid (CSF) and serum of AD cases. We have investigated this reported association within our familial and sporadic AD dataset, where we find no independent association between ACT and the occurrence of AD. Logistic regression analysis excludes ACT or the interaction between ACT and APOE as significant contributors in the prediction of disease status. By this analysis, ACT genotyping does not provide additional information about an individual's risk of Alzheimer's disease beyond the risk information conferred by APOE genotype alone.

Aged↗

No association between the intronic presenilin-1 polymorphism and Alzheimer's disease in clinic and population-based samples.

Mutations in the Presenilin 1 (PS1) gene on chromosome 14 cause most early-onset familial Alzheimer's disease (AD). An intronic polymorphism in the PS1 gene was recently identified and reported to be associated with late-onset AD [Wragg et al., Lancet 347: 509-512, 1996]. The authors found an excess of homozygotes for the more common allele (allele 1) in AD cases, associated with an approximate doubling of risk. In the present study, we report the PS1 polymorphism distributions in clinic and population-based samples. We were not able to replicate the findings of Wragg et al. [1996]. Our results are consistent with those of other researchers and do not support the conclusion that the PS1 polymorphism is associated with late-onset AD.

Alleles↗