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Biomedical subjects

M Clark

Publications and source records attributed to M Clark.

At least 91 records · Page 5Linked to original sources
PubMed1997

Effect of long-term treatment with salmeterol on asthma control: a double blind, randomised crossover study.

OBJECTIVES: To determine the effect of adding salmeterol 50 micrograms twice daily for six months to current treatment in subjects with asthma who control their inhaled corticosteroid dose according to a management plan. DESIGN: A double blind, randomised crossover study. SETTING: Nottingham. SUBJECTS: 101 subjects with mild or moderate asthma taking at least 200 micrograms twice daily of beclomethasone dipropionate or budesonide. INTERVENTIONS: Salmeterol 50 micrograms twice daily and placebo for six months each, with a one month washout. Subjects adjusted inhaled steroid dose according to guidelines. MAIN OUTCOME MEASURE: Reduction in inhaled steroid use, exacerbations of asthma, and use of oral steroids. RESULTS: Data were available for 87 subjects. When compared with placebo salmeterol treatment was associated with a 17% reduction in inhaled steroid use (95% confidence interval 12% to 22%) with no significant difference in the number of subjects who had an exacerbation (placebo 25%, salmeterol 16%) or use of oral steroids. For secondary end points salmeterol treatment was associated with higher morning and evening peak expiratory flow and forced expiratory volume in one second; a reduction in symptoms, bronchodilator use and airway responsiveness to methacholine; and no effect on serum potassium concentration, 24 hour heart rate, or the final forced expiratory volume in one second achieved during a salbutamol dose-response study. CONCLUSIONS: In subjects who adjusted their inhaled steroid treatment according to guidelines the addition of salmeterol 50 micrograms twice daily was associated with a reduction in inhaled steroid use and improved lung function and symptom control.

Administration, Inhalation↗
PubMed1997

End-of-life decisions in Australian medical practice.

OBJECTIVE: To estimate the proportion of medical end-of-life decisions in Australia, describe the characteristics of such decisions and compare these data with medical end-of-life decisions in the Netherlands, where euthanasia is openly practised. DESIGN: Postal survey, conducted between May and July 1996, using a self-administered questionnaire based on the questionnaire used to determine medical end-of-life decisions in the Netherlands in 1995. PARTICIPANTS: A random sample of active medical practitioners from all Australian States and Territories selected from medical disciplines in which there were opportunities to be the attending doctor at non-acute patient deaths, and hence to make medical end-of-life decisions. MAIN OUTCOME MEASURE: Proportion of Australian deaths that involved a medical end-of-life decision, using ratio-to-size estimation based on the sampled doctors' responses to the questionnaire. The response rate was 64%. RESULTS: The proportion of all Australian deaths that involved a medical end-of-life decision were: euthanasia, 1.8% (including physician-assisted suicide, 0.1%); ending of patient's life without patient's concurrent explicit request, 3.5%; withholding or withdrawing of potentially life-prolonging treatment, 28.6%; alleviation of pain with opioids in doses large enough that there was a probable life-shortening effect, 30.9%. In 30% of all Australian deaths, a medical end-of-life decision was made with the explicit intention of ending the patient's life, of which 4% were in response to a direct request from the patient. Overall, Australia had a higher rate of intentional ending of life without the patient's request than the Netherlands. CONCLUSIONS: Australian law has not prevented doctors from practising euthanasia or making medical end-of-life decisions explicitly intended to hasten the patient's death without the patient's request.

Adult↗
PubMed1997

Amygdala-kindled seizures increase the expression of corticotropin-releasing factor (CRF) and CRF-binding protein in GABAergic interneurons of the dentate hilus.

Kindling, a model of temporal lobe epilepsy, induces a number of neuropeptides including corticotropin-releasing factor (CRF). CRF itself can produce limbic seizures which resemble kindling in some aspects. However, tolerance to the convulsant effects of CRF develops rapidly. Hypothetically, this could be explained should seizures also induce the CRF-binding protein (CRF-BP), which has been postulated to restrict the actions of CRF. Therefore, in the present study, we used in situ hybridization to examine the effects of amygdala-kindled seizures on the mRNA levels of CRF and CRF-BP. Kindled seizures markedly elevated CRF and CRF-BP in the dentate gyrus of rats. CRF and CRF-BP were induced almost exclusively in GABAergic interneurons of the dentate hilus. The CRF and CRF-BP interneurons also expressed neuropeptide Y but not cholecystokinin. CRF appeared to have an excitatory role in the dentate gyrus as it decreased the afterhyperpolarization of dentate granule neurons. These results suggest that CRF may contribute to the development of amygdala kindling. However, the compensatory induction of CRF-BP may serve to limit the excitatory effects of CRF in the dentate gyrus.

Amygdala↗
PubMed1997

A comprehensive management system for heart failure improves clinical outcomes and reduces medical resource utilization.

The effectiveness of heart failure management in clinical practice is limited by physicians' suboptimal utilization of effective medications, patients' poor adherence to dietary sodium limitation and optimal drug therapy, and the lack of systematic monitoring of patients after hospitalization. The present study evaluated the feasibility and safety of MULTIFIT, a physician-supervised, nurse-mediated, home-based system for heart failure management that implements consensus guidelines for pharmacologic and dietary therapy using a nurse manager to enhance dietary and pharmacologic adherence and to monitor clinical status by frequent telephone contact. Fifty-one patients with the clinical diagnosis of heart failure were followed for 138 +/- 44 days. Daily dietary sodium intake fell by 38%, from 3,393 to 2,088 mg (p = 0.0001); average daily medication doses increased significantly (lisinopril: 17 to 23 mg, p <0.001; hydralazine: 140 to 252 mg, p = 0.01). Functional status and exercise capacity improved significantly (p = 0.01). Compared with the 6 months before enrollment and normalized for variable follow-up, the frequency of general medical and cardiology visits declined by 23% and 31%, respectively (both p <0.03); emergency room visits for heart failure and for all causes declined 67% and 53%, respectively (both p <0.001). Hospitalization rates for heart failure and for all causes declined 87% and 74%, respectively (p = 0.001), compared with the year before enrollment. The MULTIFIT system enhanced the effectiveness of pharmacologic and dietary therapy for heart failure in clinical practice, improving clinical outcomes and reducing medical resource utilization.

Aged↗
PubMed1997

Sequence and developmental expression of AmphiTob, an amphioxus homolog of vertebrate Tob in the PC3/BTG1/Tob family of tumor suppressor genes.

Tob is a member of the PC3/ BTG1/Tob family of vertebrate tumor suppressor genes; its expression is known to inhibit proliferation of cells in vitro, but its possible roles during normal development have not been investigated previously. The present study concerns the structure and developmental expression of AmphiTob in an invertebrate chordate, amphioxus. This is the first investigation of any Tob gene during embryological development. The 311 amino acid AmphiTob protein is similar to vertebrate Tob but lacks the C-terminal PQ-rich domain of the latter. In early embryos of amphioxus, in situ hybridization first reveals AmphiTob expression in the hypoblast at the gastrula stage on the likely dorsal side of the embryo. During subsequent development, expression is seen in several tissues of the ectoderm, mesoderm, and endoderm. The most striking expression domains are in the developing somitic musculature and dorsal nerve cord. In the medial wall of each somite, AmphiTob is expressed strongly by cells destined to differentiate into the axial trunk muscles; this pattern persists until late in the larval stage, evidently because undifferentiated cells are continually becoming myogenic as the muscles grow. Nerve cord cells conspicuously transcribe AmphiTob from the late neurula until the early larval stage: Expression occurs in a few cells scattered along the nerve cord and in a group of cells located in the cerebral vesicle (in a region presumably homologous to the vertebrate diencephalic forebrain). During development, an intense and transitory transcription of AmphiTob may be an early event in cells exiting the cell cycle in preparation for differentiation.

Amino Acid Sequence↗
PubMed1997

Uterine carcinosarcomas: incidence and trends in management and survival.

Our study's aim was to determine the incidence of uterine sarcomas in New York City (NYC) and evaluate trends in frequency, treatment, and survival of carcinosarcomas in two Brooklyn hospitals. Population-based cancer registry data for 1976-1985 were used to calculate the incidence of uterine sarcomas in NYC women. Medical records and histology slides of carcinosarcomas at two central Brooklyn hospitals from 1960 to 1995 were reviewed. The incidence of uterine sarcomas in black and white women in NYC was 33.4 and 17.0 per million (P < 0.01). Among 97 women with carcinosarcomas diagnosed in 1960-1995, 75% were diagnosed preoperatively, 82% had a hysterectomy, and 45% of those in clinical stage I were upstaged. Predictors of mortality included the presence of extrauterine extension, deep myometrial invasion, vascular space invasion, and gross residual disease, with only the first two being independent predictors of survival in a multivariate analysis. Adjunctive therapy shifted from radiation in 1960-1969 to cisplatin-based chemotherapy after 1980. In surgical stage III, survival increased significantly between 1960-1979 and 1980-1995, but improvement could not be ascribed to particular therapies. The incidence of uterine sarcomas in black women was twice that in white women. Surgical staging including omentectomy is recommended in the management of carcinosarcomas. Modern medical care may have improved the short-term prognosis of carcinosarcomas.

Adult↗
PubMed1997

The germinal center kinase gene and a novel CDC25-like gene are located in the vicinity of the PYGM gene on 11q13.

Multiple endocrine neoplasia type 1 (MEN1) is tightly linked to the muscle-type glycogen phosphorylase (PYGM) gene in 11q13. This region of the human genome contains additional disease-related loci implicated in the development of insulin-dependent diabetes mellitus, familial paraganglioma type 2, spinocerebellar ataxia type 5, Bardet-Biedl syndrome and translocation t(11;17) described in B-cell non-Hodgkin's lymphoma. We approached cloning of candidate disease genes from 11q13 by large-scale genomic sequencing. We obtained > 106 kb of sequence around the PYGM gene and established a transcriptional map that includes: (i) two genes previously localized to 11q13, PYGM and a zinc-finger protein (ZFM1) gene; (ii) the germinal center kinase (GCK, human B-lymphocyte serine/threonine protein kinase) gene; (iii) a novel human CDC25-like (HCDC25L) gene; (iv) a dystrophia myotonica protein kinase-like (DMPKL) gene; and (v) a novel ubiquitously expressed gene of unknown function (germinal center kinase- neighboring gene, GCKNG).

Amino Acid Sequence↗
PubMed1997

Development and evaluation of a computer-based system for dietary management of hyperlipidemia.

OBJECTIVE: To describe the development of a computer-based system for dietary management of hyperlipidemia and to evaluate its efficacy for lowering plasma cholesterol level. DESIGN: Using a stepwise approach, we developed and tested a three-part self-management system in five consecutive clinical studies. Each study assessed plasma cholesterol levels before and after dietary intervention using the system. These studies enabled progressive refinement of (a) a food frequency questionnaire used to assess food intake in the preceding month; (b) computer-generated progress reports, based on questionnaire responses, offering dietary change subgoals and strategies for change; and (c) a dietary workbook providing detailed information on how to achieve goals. SUBJECTS/SETTING: Persons with hyperlipidemia (n=814) were enrolled from worksite and clinical settings in the San Francisco Bay area of California. The attrition rate after randomization was 5%. INTERVENTION: Elements of the dietary intervention evolved in response to the results of five clinical studies. In each study, patients underwent a form of baseline assessment of dietary intake followed by counseling/instruction by various means. Follow-up dietary assessments were provided at specific intervals to facilitate subjects' progress toward their dietary goals. A dietary workbook provided the detailed instruction required to implement the recommendations contained in the periodic progress reports. STATISTICAL ANALYSES PERFORMED: Changes in plasma cholesterol level were measured by paired and unpaired t tests. The relationship between the reported reduction in dietary fat and cholesterol level assessed by food frequency questionnaires and the directly measured change in plasma cholesterol level was measured by multiple linear regression. RESULTS: The three major elements of the final computerized system (food frequency questionnaires, computer-generated progress reports, and dietary workbook) were developed and refined in the course of the five clinical studies. Reductions in total plasma cholesterol level of 5.0% to 6.5% achieved by participants in all five studies were consistent with self-reported reductions in intake of dietary saturated fat and cholesterol. Therefore, the computerized self-management system appears to be an effective tool for reducing plasma cholesterol levels. APPLICATIONS/CONCLUSIONS: A computer-based system for dietary self-management of hyperlipidemia, implemented by mail, was effective in short-term studies. This self-management system can potentially provide health-promoting services to large numbers of people at low cost.

Adult↗
PubMed1997

Visual-imitative dissociation apraxia.

Liepmann posited that, in right handers, the left parietal lobe contains movement formulas or representations. Therefore, performance failures may be induced by degraded representations, a failure of these representations to influence motor systems or a failure of stimuli to fully access these representations. Imitation may help the performance of subjects with degraded representations. However, patients who have impaired visual access to movement representations may perform more poorly with imitation than to verbal command. Trajectories of repetitive 'slicing' gestures made by a previously reported subject (Raymer et al.) with an infarction in the left visual association cortex (left occipital and inferior temporal lobe) that spared the parietal lobe were contrasted with those of three apraxic subjects with lesions that included the left parietal lobe and four non-brain-damaged control subjects. All subjects were asked to produce the gesture to verbal command and to imitation. Movements of the left hand, wrist, elbow and shoulder were digitized from neighboring views, reconstructed in three dimensions, and analysed graphically and numerically. The apraxic subjects with left parietal damage were unable to maintain the proper linearity and spatiotemporal attributes of their wrist motions and showed interjoint coordination deficits. Their deficits were most pronounced to verbal command, with their movements improving though remaining poorly performed when they imitated. The subject with the left occipital and inferior temporal lesion that spared parietal cortex, however, showed an opposite pattern. This subject exhibited close to normal performance when producing the movement to verbal command, but significant deficits when imitating.

Aged↗
PubMed1997

Cervical cancer as an AIDS-defining illness.

OBJECTIVE: To evaluate the importance of cervical cancer in the spectrum of human immunodeficiency virus (HIV)-related diseases at a single high-risk institution and to compare disease characteristics in HIV-infected women with cervical cancer and those with other AIDS-related malignancies. METHODS: We retrospectively reviewed data on cervical cancer and AIDS in women registered through the New York City Department of Health and institutional tumor registries from 1987 through 1995. RESULTS: During the study period, cervical cancer was diagnosed in 28 HIV-positive women. In 26, cervical cancer was the initial AIDS-defining illness, representing 4% (26 of 725) of the subjects, and it was the sixth most common initial AIDS-defining illness in women. Cervical cancer was the most common AIDS-related malignancy among women, representing 55% of the cases, followed by lymphoma (29%) and Kaposi sarcoma (16%). In 71% of the women with cervical cancer, HIV infection was diagnosed at the time of cancer presentation by routine testing, whereas in women with other malignancies, HIV diagnosis preceded cancer diagnosis (70%) by a mean of 2.7 years. Patients with other malignancies had greater immunosuppression (mean CD4 count 153/microL) than those with cervical cancer (mean CD4 count 312/microL). The recurrence rate for women with cervical cancer was 88%. Although the interval from cancer diagnosis to death was similar in all three groups (9.1-12.4 months), cancer was the cause of death in 95% of HIV-infected women with cervical cancer, compared with 60% of those with other AIDS-related malignancies. CONCLUSION: In urban populations at increased risk for both diseases, cervical cancer is an important AIDS-defining illness and may be the most common AIDS-related malignancy in women.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Dissolution testing of soft shell capsules-acetaminophen and nifedipine.

The problem of pelliculation of soft gelatin capsules on aging has been studied. Pelliculation frequently differs in soft shell capsules from hard shell capsules because of the larger mass of gelatin in the softshell dosage form. Two batches of nifedipine soft shell capsules are described. One batch failed in vivo testing and the other batch did not, after storage at 25 degrees C, yet both batches failed dissolution testing by the USP apparatus II method. The USP dissolution apparatus III-method, however, distinguished correctly between the batches. The study reported here was carried out with acetaminophen and was set up to establish whether the USP apparatus III testing method would be more suitable, and if so, what the most desirable dissolution medium should be. To create controlled pelliculation, samples were made with 0, 20, and 80 ppm of formaldehyde. The resulting capsules were subjected to ambient and accelerated storage and dissolution testing was carried out. It was found that the USP apparatus III method best reflected distinction between acceptable and substandard capsules.

Acetaminophen↗
PubMed1997

Gastrin effects on growth and exocrine secretion in the neonatal rat pancreas.

In adult rats, cholecystokinin (CCK) binds to pancreatic CCK-A receptors and stimulates exocrine secretion and pancreatic growth. In newborn rats there is very little mature intestinal CCK and few pancreatic CCK-A receptors. However, there is an abundant source of the related peptide gastrin, and in addition, there are pancreatic CCK-B/gastrin receptors. In this study, we have explored the hypothesis that gastrin may "deputise" for CCK in the neonate and cause pancreatic exocrine secretion, growth, and maturation. Newborn rats were injected intraperitoneally with the gastrin antagonist, C1-988, or placebo for 5 days and sacrificed on day 6. Body weight (CI-988, 8.25 +/- 0.48 g; placebo, 10.17 +/- 0.93 g) and pancreatic weight (19.41 +/- 1.5 vs. 21.58 +/- 1.72 mg) were the same. Protein (1,202 +/- 78 vs. 1,254 +/- 56 micrograms), amylase (22.3 +/- 0.9 vs. 19.2 +/- 1.00 U), RNA (117 +/- 7 vs. 126 +/- 5 micrograms), and DNA (95 +/- 8 vs. 100 +/- 7 micrograms) contents of the pancreas were similar in the two groups. The weight of the stomach was reduced (p = 0.04) in the treated group (50.8 +/- 2.5 mg) compared to the placebo group (59.8 +/- 3.7 mg). In both neonates and adults, CCK-8 was approximately 1,000 times more potent than gastrin-17 in stimulating amylase release from isolated pancreatic acini. This suggests that enzyme release is probably mediated by the same receptors in both adults and neonates, and in adults previous work has shown this to be the CCK-A receptor. In conclusion, these data show that gastrin has very weak effects on neonatal pancreatic exocrine secretion, and furthermore, gastrin is not essential for growth and maturation of the neonatal pancreas. The role of gastrin and CCK-B/gastrin receptors in the neonatal pancreas remains speculative.

Amylases↗
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↗