Search PubMed⌕ Search

Biomedical subjects

M Clark

Publications and source records attributed to M Clark.

At least 73 records · Page 4Linked to original sources
PubMed1997

Interventional recovery outside the walls of an intensive care environment.

St. Luke's Episcopal Hospital in Houston, Texas, created a cardiology collaborative practice team to review patient flow, to develop and implement process redesign, and to evaluate the effectiveness of the redesign project. The team focused on the recovery of interventional patients outside the critical care or intensive care unit environment. In December 1993, the team opened an interventional cardiology recovery unit on a cardiovascular telemetry floor. One thousand forty-five patients were recovered in this unit in the first year. Complication rates did not change significantly for low-risk patients; patient and family satisfaction scores improved, and the cost per case was reduced by $1,746. The success of the pilot project has become the standard for implementing new programs within the cardiology services.

Case Management↗
PubMed1996

Bright Spots, Structure, and Magmatism in Southern Tibet from INDEPTH Seismic Reflection Profiling

INDEPTH seismic reflection profiling shows that the decollement beneath which Indian lithosphere underthrusts the Himalaya extends at least 225 kilometers north of the Himalayan deformation front to a depth of approximately 50 kilometers. Prominent reflections appear at depths of 15 to 18 kilometers near where the decollement reflector apparently terminates. These reflections extend north of the Zangbo suture to the Damxung graben of the Tibet Plateau. Some of these reflections have locally anomalous amplitudes (bright spots) and coincident negative polarities implying that they are produced by fluids in the crust. The presence of geothermal activity and high heat flow in the regions of these reflections and the tectonic setting suggest that the bright spots mark granitic magmas derived by partial melting of the tectonically thickened crust.

Journal Article↗
PubMed1996

Characterisation and clinicopathological correlates of serum anti-p53 antibodies in breast and colon cancer.

The humoral immune response to p53 was determined in 54 individuals with colon or breast cancer and 50 healthy subjects, in an attempt to better understand the origin and significance of anti-p53 serum antibodies. The presence of anti-p53 antibodies in serum was determined by enzyme-linked immunosorbent assay using purified recombinant human p53, and results were validated by immunoprecipitation of radiolabelled p53. Immunohistochemical analysis of 28 tumours was performed to detect the accumulation of p53 protein. Antibodies against p53 were significantly more common in patients with colorectal (10 of 42) and breast (2 of 12) cancer than in healthy individuals (2 of 50). They were of both the IgM (7 of 11) and IgG (4 of 11) isotypes. There was no significant difference in prevalence of serum antibodies against p53 with respect to the p53 immunohistochemical status of the tumour or to other pathological features, including the presence of lymph node and distant metastases. These findings provide indirect evidence that, rather than arising as a result of a specific immune response, anti-p53 antibodies in individuals with cancer may represent elevated levels of naturally occurring polyreactive antibodies.

Adult↗
PubMed1996

Toward the construction of integrated physical and genetic maps of the mouse genome using interspersed repetitive sequence PCR (IRS-PCR) genomics.

Using two recently developed techniques, IRS-PCR YAC walking and IRS-PCR genotyping, a framework-integrated physical and genetic map of the mouse genome was constructed. The map consists of 821 contigs, containing 7746 YAC clones originating from three different YAC libraries. Three hundred eighty of the contigs have been anchored to the genetic map. Approximately 16% of the physical length of the mouse genome is estimated to be represented.

Animals↗
PubMed1996

Economic analysis of treating depression with nefazodone v. imipramine.

BACKGROUND: It is estimated that treating diagnosed depression costs 420 pounds million annually in England and Wales. This economic study analyses treatment of major depression with nefazodone v. imipramine. METHOD: The study updates a previously published model using data obtained from the continuation phase of a double-blind one-year placebo-controlled comparison of nefazodone with imipramine. RESULTS: Annual costs for nefazodone are lower than those for imipramine, 218 pounds compared to 254 pounds; the cost per successfully treated patient is also lower for nefazodone than for imipramine, 242 pounds v. 323 pounds. Varying the resources included in the treatment patterns still results in lower costs for nefazodone treatment. CONCLUSIONS: Based on clinical trial data for patients completing six to eight weeks of depression treatment and followed for at least one year, the model shows that the annual costs of nefazodone are lower than those for the less expensive imipramine.

Antidepressive Agents, Second-Generation↗
PubMed1996

Summary of track D: social science: research, policy and action.

SCOPE: This review summarizes the main issues discussed during Track D, which examined the societal impact of HIV/AIDS, and responses to the epidemic by individuals, families, communities and societies worldwide. Micro- and macrolevel issues addressed included the development, implementation and evaluation of programmes for prevention and care; policy development and implementation; structural issues such as the impact of gender relations, development and migration on the development of the epidemic; and the social and economic impact of HIV/AIDS on affected societies and communities. RECURRENT THEMES: Presentations provided strong evidence that peer-led, community-based programmes offer particularly effective ways of working, and that participatory research involving affected communities provides useful results for the design and evaluation of programmes and policies. This is the case across settings, issues, populations and countries. FUTURE DIRECTIONS: Emerging needs include how best to ensure sustainability of national and international responses, how best to scale up successful interventions for wider reach, and how best to work with systematically marginalized, neglected groups and populations. Research priorities include the characterization of the multiple determinants of HIV-related vulnerability, and the evaluation of interventions that take these complex determinants as their starting point. A more coherent and strategic response requires less separation between the different constituencies involved in AIDS work, and the more sustained involvement of people living with HIV/AIDS themselves.

Community Health Services↗
PubMed1995

Contingent tolerance to the anticonvulsant effects of carbamazepine: relationship to loss of endogenous adaptive mechanisms.

Contingent tolerance to the anticonvulsant effects of carbamazepine on amygdala kindled seizures develops when the drug is repeatedly given prior to but not after the electrical stimulation. Such tolerance can be reversed by kindling the rats for several days without drug or even by continuing to give the drug but after each seizure has occurred. Contingent tolerance can be slowed by reducing the electrical stimulus intensity and by chronic continuous (as opposed to repeated paired) drug administration. Contingent cross-tolerance has been demonstrated from carbamazepine to PK11195 (a drug active at peripheral-type benzodiazepine receptors) and valproate, but not to clonazepam and diazepam (two drugs active at central-type benzodiazepine receptors) or phenytoin. Endogenous physiological changes occur in conjunction with contingent tolerance, exemplified by the decrease in seizure threshold that returns to normal upon reversal of tolerance. We suggest that contingent tolerance is associated with a loss of seizure-induced adaptations, since many biochemical changes that occur following seizures (or in non-tolerant animals given drug after seizures) are not observed in tolerant animals. These include a loss of seizure-induced up-regulation of GABAA receptors and a loss of increases in mRNA expression for corticotropin-releasing-factor (CRF), thyrotropin-releasing-hormone (TRH), neuropeptide Y (NPY), glucocorticoid receptors and brain-derived neurotrophic factor (BDNF). Thus, several putative seizure-induced anticonvulsant adaptations, such as increases in GABAA receptors and TRH and NPY mRNA fail to occur in tolerant animals. These findings are consistent with the novel observations that, paradoxically, seizures themselves appear to facilitate the anticonvulsant effects of carbamazepine or diazepam on amygdala kindled seizures. That is, animals given a 'vacation' from seizures show a decreased response to these agents, a phenomenon we have called the 'time-off seizure' effect. Thus, seizures are postulated to induce adaptive changes that influence seizure thresholds and potentiate the anticonvulsant effects of exogenously administered drugs such as carbamazepine and diazepam. Taken together, these data suggest that seizures are associated with endogenous adaptations lasting days to weeks and that a selective failure of some of these to occur during contingent drug administration may underlie the development of contingent tolerance. These observations suggest tht endogenous illness-related mechanisms may participate both in the therapeutic responses of some agents and that their failure to occur could relate to loss of drug efficacy via tolerance; these processes may reveal new potential targets for therapeutic intervention.

Adaptation, Physiological↗
PubMed1995

Incorporation of surface tension into molecular dynamics simulation of an interface: a fluid phase lipid bilayer membrane.

In this paper we report on the molecular dynamics simulation of a fluid phase hydrated dimyristoylphosphatidylcholine bilayer. The initial configuration of the lipid was the x-ray crystal structure. A distinctive feature of this simulation is that, upon heating the system, the fluid phase emerged from parameters, initial conditions, and boundary conditions determined independently of the collective properties of the fluid phase. The initial conditions did not include chain disorder characteristic of the fluid phase. The partial charges on the lipids were determined by ab initio self-consistent field calculations and required no adjustment to produce a fluid phase. The boundary conditions were constant pressure and temperature. Thus the membrane was not explicitly required to assume an area/phospholipid molecule thought to be characteristic of the fluid phase, as is the case in constant volume simulations. Normal to the membrane plane, the pressure was 1 atmosphere, corresponding to the normal laboratory situation. Parallel to the membrane plane a negative pressure of -100 atmospheres was applied, derived from the measured surface tension of a monolayer at an air-water interface. The measured features of the computed membrane are generally in close agreement with experiment. Our results confirm the concept that, for appropriately matched temperature and surface pressure, a monolayer is a close approximation to one-half of a bilayer. Our results suggest that the surface area per phospholipid molecule for fluid phosphatidylcholine bilayer membranes is smaller than has generally been assumed in computational studies at constant volume. Our results confirm that the basis of the measured dipole potential is primarily water orientations and also suggest the presence of potential barriers for the movement of positive charges across the water-headgroup interfacial region of the phospholipid.

Crystallography, X-Ray↗
PubMed1995

Cholecystokinin is a satiety hormone in humans at physiological post-prandial plasma concentrations.

1. Intravenous infusions of the brain/gut hormone, cholecystokinin, have been shown to reduce food intake in a subsequent test meal. However, in previous studies the doses administered were large and likely to have produced plasma concentrations far in excess of the normal post-prandial range. 2. In this study cholecystokinin-8 was infused intravenously to six healthy subjects in doses that reproduced physiological post-prandial concentrations. Plasma concentrations of cholecystokinin were measured using a novel sensitive and specific radioimmunoassay. The effect of cholecystokinin-8 infusion on subsequent food intake in a standard test meal was compared with the effect of saline infusion in the same subjects. 3. Food intake (mean +/- SEM) was significantly less during cholecystokinin (5092 +/- 665 kJ) than during saline infusion (6418 +/- 723 kJ, P = 0.03). During cholecystokinin infusion, plasma concentrations increased from 0.45 +/- 0.06 pmol/l to 7.28 +/- 2.43 pmol/l immediately before the meal. With saline infusion there was no premeal increase in plasma cholecystokinin concentration. 4. This paper describes a novel radioimmunoassay for measurement of plasma concentrations of cholecystokinin. Using this assay we have demonstrated that cholecystokinin is important in control of satiety in humans.

Adult↗
PubMed1995

Clinical experience with CD3 x CD19 bispecific antibodies in patients with B cell malignancies.

In extensive preclinical testing, a CD3 x CD19 bispecific antibody (BsAb) induced killing of malignant B cells by resting T cells even in an autologous situation. In a 14 day clonogenic assay using a CD19+ pre-B cell line (REH), BsAb required repeated administration together with IL-2 to achieve a 5 log kill by resting peripheral blood T cells. Intravenously administered BsAb in an intrapatient dose escalation study of 3 patients with B cell non-Hodgkin's lymphoma showed limited toxicity (WHO grade II fever and chills) due to tumor necrosis factor-alpha (TNF-alpha) release by T cells. Pharmacokinetics with 2.5 mg BsAb showed peak levels of 200-300 micrograms/ml and a t1/2 of 10.5 h. The next patient, with chronic lymphocytic leukemia (CLL), received 0.6 mg BsAb/m2 as an i.v. infusion preceded by 1 MU IL-2/m2 s.c. Improved T cell activation was noted, as indicated by an increase in IFN-gamma, IL-6, IL-8, and IL-10, in addition to high TNF-alpha increases. TNF-alpha increases were highest on the first day. Toxicity remained restricted to grade II fever and chills, observed every day after the infusion of BsAb. No clear clinical effects were seen in this chemotherapy-resistant CLL patient with a high tumor burden. If subsequent patients also show limited toxicity, treatment of patients with a lower tumor load seems to be warranted to evaluate the efficacy of CD3 x CD19 BsAb therapy.

Animals↗
PubMed1995

Personal health benefits of Masters athletics competition.

Questionnaires (750 respondents, 44.4% response rate) examined the long-term health value of endurance exercise training in older age-classed competitors ('Masters Athletes', 551 men and 199 women) over a 7-year period (1985-1992). The majority had initially completed maximal exercise tests. The weekly time devoted to training, competition and exercise-related travel was 10 to 30 h, and the annual expenditure on clothing, equipment and entrance fees was typically in the range Canadian $500-1500. Despite their age (mean(s.d.) 58(10), current range 40-81 years), only 1.4% reported sustaining a non-fatal heart attack and 0.6% had required bypass surgery over the 7-year interval. The majority (90%) were very interested in good health; 76% considered themselves as less vulnerable to viral illnesses than their peers, and 68% regarded their quality of life as much better than that of their sedentary friends. The majority of former smokers had stopped smoking before they began training, but 37% indicated that exercise had helped them in smoking withdrawal. In keeping with their health-conscious attitude, 59% had regular medical check-ups, and 86% obeyed legislation requiring use of a seat-belt when driving. In contrast with many older people, 88% slept well or very well. Slightly over half of the sample (57%) had sustained some injury which had limited their training for one or more weeks over the 7-year study. Although participation in Masters competition appears to carry considerable health benefits, gains may in part reflect an overall healthy lifestyle.

Adult↗
PubMed1995

Using the Multiphasic Sex Inventory with child molesters.

Subjects were 30 white men who denied that they were child molesters at the time of arrest and were court ordered to have a psychological evaluation as part of the pre-sentencing. The Multiphasic Sex Inventory was administered to the subjects during the initial interview and later in therapy sessions they did admit to the offense. When scores for the group were compared with scores for a pretreatment child-molester group (n=140) in a study cited in the manual, the difference was significant on the Child Molest Lie Scale. Implications are discussed.

Adult↗
PubMed1995

Angiotensin II down-regulates the vascular smooth muscle AT1 receptor by transcriptional and post-transcriptional mechanisms: evidence for homologous and heterologous regulation.

The vascular angiotensin II (ANG II) receptor (AT1) is a central component of the renin-angiotensin system; thus, regulation of its expression is likely to be important in cardiovascular responsiveness. We demonstrate that ANG II down-regulates its receptor in rat aortic vascular smooth muscle cells. Incubation for 4 hr with 100 nM ANG II decreased AT1 mRNA and protein by 70% and 35%, respectively. This homologous down-regulation was concentration and time dependent and was blocked by the AT1 antagonist losartan. It did not appear to be mediated by protein kinase C or other protein kinases but was dependent on the sustained signaling pathway sensitive to phenylarsine oxide. Heterologous down-regulation was observed with the agonists alpha-thrombin and ATP and the cAMP-increasing agent forskolin. ANG II inhibited transcription by 50% and destabilized the AT1 mRNA. Down-regulation of AT1 mRNA was blocked by transcription and translation inhibitors, suggesting that it required expression of a protein factor or factors. These results indicate that ANG II down-regulates its vascular receptor by both transcriptional and post-transcriptional mechanisms. Homologous and heterologous down-regulation of the AT1 receptor may participate in the coordinated physiological adaptation of vascular tone to vasoactive hormones.

Adenosine Triphosphate↗