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Biomedical subjects

M McManus

Publications and source records attributed to M McManus.

At least 37 records · Page 2Linked to original sources
PubMed1994

Ketoconazole blocks organic osmolyte efflux independently of its effect on arachidonic acid conversion.

Ketoconazole, cinnamyl-3,4-dihydroxy-alpha-cyanocinnamate, and gossypol are reported inhibitors of the lipoxygenase (LO) and cytochrome P-450 enzyme systems and are potent blockers of swelling-activated efflux of organic osmolytes and volume-sensitive anion channels in C6 glioma cells. To directly test the hypothesis that LO- or cytochrome P-450-derived products of arachidonic acid (AA) participate in the regulation of these volume-sensitive transport pathways, we incubated C6 cells with [1-14C]AA and observed the extent and profile of its conversion under basal conditions and after acute swelling. High-performance liquid chromatographic analysis revealed that most (70-80%) of the labeled AA remained unchanged with only 6-8% and 10-20% of label converted to LO- [12(S)- and 15(S)-hydroxyeicosatetraenoic acid (12- and 15-HETE)] and cyclooxygenase- [prostaglandin (PG) E2 and PGF2a] derived products, respectively. Leukotrienes and epoxyeicosatrienoic acid compounds were not produced. The conversion profile of [1-14C]AA was not altered substantially by cell swelling. Treatment of cells with the LO-derived products 5-, 12-, and 15-HETE or their immediate metabolic precursors, 5(S)-, 12(S)-, and 15(S)-hydroxyperoxyeicosatetraenoic acid, at 5 microM concentrations did not stimulate efflux of [3H]inositol. In addition, treatment with HETEs did not override the inhibition of efflux observed with the LO-cytochrome P-450 blocker ketoconazole. Whole cell patch-clamp experiments demonstrated that volume-sensitive anion channels, the postulated pathway for organic osmolyte efflux in C6 cells, are rapidly and reversibly blocked by ketoconazole in a fashion suggestive of direct inhibition rather than via interruption of a second messenger pathway.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Laser light-scattering system for studying cell volume regulation and membrane transport processes.

A simple and relatively inexpensive device utilizing laser light scattering for the study of volume regulatory behavior and membrane transport phenomena in cells cultured on or affixed to a rigid substrate is described in detail. Validation of the method is provided by study of cell types with known volume regulatory responses. The method we describe has numerous advantages over currently available techniques used to monitor cell volume changes. These advantages include 1) the ability to rapidly detect and quantify small cell volume changes on-line, 2) the ability to maintain natural cell morphology, cell surface contacts, and cell-to-cell interactions, 3) the ability to easily control solution temperature and gas and solute composition, and 4) the ability to perform multiple perturbations in a single experiment. The light-scattering system we describe can be modified to allow for simultaneous measurement of light-scattering signals and fluorescence emission from intracellular ion-sensitive probes and membrane potential dyes. In addition, our method may be useful for the study of apical and basolateral membrane transport processes in epithelial monolayer cell cultures.

Animals↗
PubMed1992

Osmoregulation of Na(+)-inositol cotransporter activity and mRNA levels in brain glial cells.

During plasma hypertonicity brain volume is regulated acutely by electrolyte uptake and chronically by accumulation of organic solutes such as inositol. Cultured rat C6 glioma cells, an astrocyte-like cell line, show a similar pattern of volume control. Volume regulatory accumulation of inositol requires external inositol, indicating that membrane transport plays a central role in this process. The inositol uptake pathway is Na+ dependent and exhibits Michaelis-Menten kinetics. Chronic hypertonic acclimation results in a twofold increase in the maximum velocity of the transporter without changing the Km. Hypertonic stress also results in a 17-fold increase in transporter mRNA. Elevation of mRNA levels precedes activation of the transporter by 4-6 h, suggesting that increased inositol uptake is mediated by synthesis and membrane insertion of new transport proteins. Reacclimation of hypertonic cells to isotonicity causes a rapid reduction of transporter mRNA levels to control levels within 4 h. In contrast, downregulation of transport activity does not begin until between 10 and 24 h after reexposure to isotonicity.

Animals↗
PubMed1992

Continuing your education ... with CATS.

MIKE McMANUS and ANNE DEAN discuss the credit accumulation and transfer scheme (CATS) and consider many of the common questions regarding the system: how to accredit current professional qualifications; use of credited learning, and potential continuing education pathways open to health visitors. Finally, the authors discuss the validity of such awards.

Education, Nursing, Baccalaureate↗
PubMed1991

Hospital use by adolescents and young adults.

This article provides a descriptive profile of hospital use by adolescents (10-14 and 15-18 years of age) and young adults (19-24 years) based on the 1987 National Hospital Discharge Survey. During 1987, nearly 5 million adolescents and young adult patients were discharged from short-stay hospitals. The discharge rate for adolescents was 56.5 per 1000 compared to 127.0 per 1000 for young adults. Two diagnostic categories--complications of pregnancy, childbirth, and the puerperium; and injury and poisoning--together accounted for 24% of discharges for patients aged 10-14 years, 51% for patients aged 15-18 years, and 65% for patients aged 19-24 years. Average length of stay varied substantially by age and diagnosis; that for adolescents averaged 1.1 days longer than that for young adults and for other age groups and was longest for mental disorders. Between 1980-1981 and 1986-1987, the rates of hospitalization for mental disorders increased markedly, particularly among adolescents aged 15-18 years with the diagnoses of adjustment reaction and disturbance of conduct, and psychosis, neurosis, and personality disorders. Hospitalizations for substance abuse increased most among young adults during this time period. Most adolescents and young adults relied on private health insurance as their primary payment source, followed by Medicaid. Still, there was no insurance coverage to pay for hospital bills for 729,000 discharges in 1987. Implications of these findings are discussed. Briefly, examining hospitalization patterns by narrower age intervals elucidates important differences by age, sex, diagnostic category, and expected source of payment.

Adolescent↗
PubMed1991

The adequacy of college health insurance coverage.

This analysis of private health insurance plans offered in 100 four-year colleges and universities in 1988 indicates a tremendous diversity in plan options, benefits covered, cost-sharing requirements, and catastrophic protections. Consistent with relatively low premium prices, most student health insurance plans offer limited benefits and expose students to significant out-of-pocket medical cost liabilities. Only a minority of schools use financial incentives, such as preferred provider arrangements, to integrate their health insurance plans with their university health service system. We conclude that universities should carefully reexamine the adequacy of their health insurance plans and their relationship to student health centers. As more students rely on student health insurance as their only source of coverage, the quality of these plans assumes an even greater importance.

Adolescent↗
PubMed1991

The adequacy of physician reimbursement for pediatric care under Medicaid.

This article examines 1989 Medicaid physician reimbursement for pediatric care in 47 states and the District of Columbia. To assess the adequacy of payment, several state reimbursement policies were analyzed, including physician payment methods, frequency of payment updates, and fee data for five common evaluation and management codes and two Early and Periodic Screening, Diagnosis, and Treatment visit categories. Physician payment rates were evaluated to determine overall state and regional patterns of Medicaid reimbursement. They were also compared with regional private market fee data and average national Medicare fees to assess their adequacy. The majority of state Medicaid programs used fixed fee schedules as their physician reimbursement method. Nearly one fourth of states that update their fees overall by physician specialty have not adjusted their rates since 1985 or before. Medicaid reimbursement rates for five commonly used evaluation and management Physicians' Current Procedural Terminology (4th ed) office visit codes and Early and Periodic Screening, Diagnosis, and Treatment screening and follow-up examinations varied substantially across states and among regions. States in the West paid the highest rates for most office visits, while Northeastern states generally paid the least. A comparison of Medicaid payment rates with private market fee data revealed that Medicaid payments for established patients averaged less than two thirds of market rates for pediatricians, family physicians, and general practitioners. New patient care is reimbursed somewhat better. Regional variations are substantial. In addition, a comparison of Medicaid payment rates with 1988 Medicare fee data showed that average Medicaid reimbursement rates were less than four fifths of average allowed Medicare charges. Policy implications include the need to increase Medicaid rates so that they are much closer to private insurance and Medicare rates, particularly in the Northeast and in selected states, in order to increase participation by pediatric providers in Medicaid. In addition, efforts to re-evaluate reimbursement relative to level of service, as used in Medicare's resource-based relative value scales, deserve further research. Finally, comparable access to comprehensive pediatric care especially in underserved urban areas will require not only improvements in physician reimbursement but also more deliberate efforts to affect the maldistribution of mainstream medical care. Approaches to measure the impact of enhanced reimbursement on access to care by Medicaid-eligible children are discussed.

Delivery of Health Care↗
PubMed1990

Effects of age and gender on in vitro properties of human liver microsomal monooxygenases.

Aging in humans is associated with marked declines in the disposition of numerous drugs and other xenobiotics that require hepatic biotransformation before elimination. Considerable pharmacokinetic evidence in humans, coupled with data on in vitro liver microsomal monooxygenase functions generated in inbred male rodent models, has implicated impaired liver phase I drug metabolism (i.e., diminished efficacy of microsomal monooxygenases) in reduced drug clearance in the elderly. This study (1) assessed the in vitro activities and amounts of liver microsomal monooxygenases as a function of donor age and gender in healthy humans and (2) provides the most extensive and comprehensive data to date demonstrating the absence of significant age- and gender-dependent differences in the activities and contents of human liver monooxygenases.

Adolescent↗
PubMed1989

Hodgkin's cell lectin, a lymphocyte adhesion molecule and mitogen.

We have previously shown a novel galactose/N-acetylgalactosamine specific lectin activity (Hodgkin's disease (HD) lectin) on the surface of cultured HD cells (lines L428, its variants, and line L540) to mediate lymphocyte adhesion. We here demonstrate that both surface membrane-bound and secreted HD lectin activities participate in the activation of agglutinated lymphocytes. Among known adhesion molecules expressed by the HD cells, only the intercellular adhesion molecule-1 (ICAM-1) contributed to this activation as an alternative PBL binding site. As yet we have not identified the cellular ligand(s) for the HD lectin on the lymphocyte surface. Pretreatment of lymphocytes with mAb to the accessory molecules CD2, CD3, CD4, CD8, CD11b, or CD11c did not interfere with their response to HD cells. mAb to CD11a (LFA-1), the alleged ligand of ICAM-1, inhibited the ICAM-1 but not the HD lectin-mediated lymphocyte stimulation. Although lymphocyte binding could proceed via either pathway, lymphocyte activation always depended upon factors secreted by the HD cells, one of which we identified as a soluble form of the HD lectin based on its shared properties with the membrane-bound form including immunologic cross-recognition and carbohydrate-binding specificity. Although HD cell-conditioned medium alone stimulated lymphocytes, HD cell plasma membranes could compensate for low concentrations of this medium. In addition, resting lymphocytes, normally unresponsive, were triggered into DNA synthesis by growth medium when cocultured with HD cell membranes. The unique functions of the surface-expressed HD lectin and its soluble counterpart as lymphocyte adhesion molecule and mitogen might be physiologically relevant to the severe immunodeficiencies occurring in patients with HD.

Antigens, CD↗
PubMed1989

Alprazolam, propranolol, and placebo in the treatment of panic disorder and agoraphobia with panic attacks.

Fifty-five patients completed a 5-week double-blind study comparing alprazolam, propranolol, and placebo in the treatment of panic disorder and agoraphobia with panic attacks. There was no concomitant behavioral treatment. Patient and therapist rating scales included Sheehan's Panic and Anxiety Attack Scales, the Marks-Sheehan Phobia Scale, the Hamilton Anxiety Scale, the Hamilton Depression Scale, and the Side Effects Checklist. The results generally support the efficacy of alprazolam, but not propranolol, in the treatment of panic disorder and agoraphobia with panic attacks. The significance of the results are discussed, as well as a number of the unique aspects of our procedures and patient population.

Adolescent↗
PubMed1987

Hospital use patterns for children in the United States, 1983 and 1984.

The hospital discharge rate of children less than 15 years of age in the United States declined 12% from 1983 to 1984. This was the first time in the 20-year history of the National Hospital Discharge Survey that there was a statistically significant decrease in children's hospital discharge rates in a 1-year period. The change occurred during a period when prospective hospital payment systems were introduced and when prepaid group health plans and alternative systems of providing health care were expanding. The unprecedented decrease in children's hospital use was evaluated using data from the National Hospital Discharge Survey. This is a continuous survey in which data from a national sample of medical records of discharged patients are collected. Children's hospital use rates were reviewed by age, sex, region, and expected principal source of payment. Significant decreases in discharge rates were found for the age group 1 to 4 years and for all children with private insurance. The patterns and changes in hospital use by diagnostic category were also investigated. The major finding was a 19% decrease in children's discharge rate for diseases of the respiratory system. Mortality statistics and data from the National Health Interview Survey were evaluated for indications of changes in children's health status or use of physician services accompanying the decline in hospital use. Although there were fewer deaths due to respiratory diseases for children less than 5 years of age in 1984 than in 1983, most measures of health status were unchanged. The only significant change in physician use was a decrease in the percentage of acute conditions that were medically attended, also among children less than 5 years of age. It is important to continue monitoring children's hospital use patterns, as well as their health status and use of alternative health services, to further assess the impact of changes in the organization and financing of health services.

Adolescent↗
PubMed1985

Applications of cost-effectiveness analysis for evaluation of health care programs.

Increasing pressures to justify health services on the basis of cost-effectiveness have resulted in a flurry of economic analyses by providers, policymakers and researchers. In what follows we attempt to briefly describe the rationale for performing cost-effectiveness analysis, summarize the basic analytical steps involved in performing a cost-effectiveness analysis, and describe some of the common pitfalls encountered when conducting cost-effectiveness analyses. An annotated list of references is included for further reading.

Cost-Benefit Analysis↗
PubMed1984

The characterization of depressive disorders in serious juvenile offenders.

The authors systematically evaluated a selected population of juvenile offenders for the prevalence of affective disorders. Seventy-one (40 male, 31 female) serious juvenile offenders were interviewed using the Schedule for Affective Disorders and Schizophrenia (SADS). They were then diagnosed using the Research Diagnostic Criteria (RDC) and the DSM-III. The Hamilton Rating Scales (HRS), Carroll Self-Rating Scale (CSRS), and Global Rating Scale for Depression (GRS) were also obtained for each subject. Eleven (15%) subjects were diagnosed as having an active major depressive disorder (MDDa), 6 (8%) subjects were diagnosed as having a major depressive disorder in remission (MDDr), and 9 (13%) as having a minor depressive disorder (mDD). The HRS, CSRS, and GRS differentiated the MDDa from the other three groups including MDDr, mDD and all other psychiatric diagnoses. RDC subtypes of depressive disorders were identified in those juvenile offenders with active major depressive disorders (MDDa) and compared to a population of hospitalized adolescents with major depressive disorders. There were significant differences in the distribution of the subtypes identified. Secondary, agitated and endogenous subtypes occurred significantly more often. The diagnostic, prognostic and therapeutic significance of these findings are discussed.

Adolescent↗