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Biomedical subjects

D Cook

Publications and source records attributed to D Cook.

At least 127 records · Page 7Linked to original sources

Relaxant effects on iloprost in canine cerebral artery.

Iloprost caused relaxation of rings of canine cerebral arteries precontracted with prostaglandin F2 alpha or the thromboxane A2 analogue U46619, but it was without effect on arteries precontracted with potassium chloride. Pretreatment with iloprost did not significantly affect the concentration-response curve to any agent. Contractile responses to oxyhemoglobin were completed relaxed by iloprost. In arteries from animals with moderate cerebrovascular spasm, the response to prostaglandin F2 alpha was also reduced by iloprost. The observation that iloprost relaxes the response to oxyhemoglobin to prostaglandin F2 alpha in spastic arteries may be of interest in the management of cerebral vasospasm.

Animals↗

Respiratory muscle training in chronic airflow limitation: a meta-analysis.

The purpose of this study was to determine the effect of respiratory muscle training on muscle strength and endurance, exercise capacity, and functional status in patients with chronic airflow limitation. Computerized bibliographic data bases (MEDLINE AND SCISEARCH) were searched for published clinical trails, and an independent review of 73 articles by two of the investigators identified 17 relevant randomized trials for inclusion. Study quality was assessed and descriptive information concerning the study populations, interventions, and outcome measurements was extracted. We combined effect sizes across studies (the difference between treatment and control groups divided by the pooled standard deviation of the outcome measure). Across all studies, the effect sizes and associated p-values were as follows: maximal inspiratory pressure 0.12, p = 0.38; maximal voluntary ventilation 0.43, p = 0.02; respiratory muscle endurance 0.21, p = 0.14; laboratory exercise capacity -0.01, p = 0.43; functional exercise capacity 0.20, p = 0.15; functional status 0.06, p = 0.72. Secondary analyses suggested that endurance and function may be improved if resistance training with control of breathing pattern is undertaken. Overall, there is little evidence of clinically important benefit of respiratory muscle training in patients with with chronic airflow limitation. The possibility that benefit may result if resistance training is conducted in a fashion that ensures generation of adequate mouth pressures may be worthy of further study.

Breathing Exercises↗

Time course of changes in concentration of intracellular free calcium in cultured cerebrovascular smooth muscle cells exposed to oxyhemoglobin.

A culture of smooth muscle cells obtained from monkey middle cerebral arteries was developed to allow quantitative assessment of intracellular calcium and immunofluorescence analysis after various periods of exposure to oxyhemoglobin. Intracellular calcium concentration was examined for up to 7 days after a single exposure to oxyhemoglobin. Intracellular calcium concentrations were measured with the fluorescent dye fura-2 and were significantly elevated for 7 days after exposure to oxyhemoglobin (P less than 0.01). Less than 2 minutes after application of oxyhemoglobin, there was marked elevation of intracellular calcium from the control value of 75 +/- 2 nmol/L to 240 +/- 28 nmol/L (P less than 0.01 by analysis of variance). Intracellular calcium concentration of cells exposed for 24 hours to oxyhemoglobin and then grown in normal oxyhemoglobin-free medium fell close to normal levels on Days 3 and 7. On Day 3, the increase in intracellular calcium that followed repeated daily exposure to oxyhemoglobin was greater than that resulting from a single application of oxyhemoglobin (P less than 0.01 by Student's t test), but by Day 7 the elevation produced by these different approaches was similar. Smooth muscle cells exposed to oxyhemoglobin showed a reduction in immunoreactivity to alpha-actin. These data support the hypothesis that disruption of intracellular calcium regulation and calcium overloading may be important in the process of cell injury, which results in vasoconstriction and sometimes cell death, after exposure to oxyhemoglobin.

Actins↗

Quality of life instruments in the evaluation of new drugs.

The importance of measuring changes in a patient's quality of life when evaluating the efficacy of new drugs is increasingly recognised. In this paper, we review the steps associated with this process--recognising the opportunity and the need to include quality of life instruments during the investigation, choosing the most suitable instrument(s) and interpreting the results. To be useful in clinical trials, quality of life measures must be both responsive (able to detect all important differences) and valid. Generic instruments are applicable to a wide variety of populations but may lack responsiveness. Disease-specific instruments are more likely to be responsive and are directly relevant to patients and clinicians. The approach to measurement in a specific clinical trial should be dictated by the goals of the investigators.

Data Interpretation, Statistical↗

Effects of phenothiazine on contractions induced by prostaglandin F2 alpha and 5-hydroxytryptamine in normal and spastic canine cerebral artery.

We have investigated the effect of phenothiazine, a compound known to inhibit calmodulin, on the responses of normal and spastic cerebral arteries, using the canine "two hemorrhage" model of cerebrovascular spasm. Ring preparations from control vessels or vessels removed three or seven days after injection of blood, were contracted with either 5-hydroxytryptamine (5-HT) or prostaglandin F2 alpha (PGF2 alpha) and then exposed to increasing concentrations of phenothiazine. In normal arteries, low concentrations of phenothiazine enhanced the response to PGF2 alpha, while higher concentrations caused relaxation. Responses to 5-HT were inhibited by all concentrations of phenothiazine tested. When normal arteries were compared with arteries from animals injected with blood, in the case of 5-HT, phenothiazine was a less effective antagonist at low doses, but equieffective at higher doses. Similar experiments conducted with PGF2 alpha showed that phenothiazine was a more effective antagonist in spastic vessels. We conclude that 5-HT and PGF2 alpha have significant differences in the mechanism by which they produce contraction of cerebral vessels, that phenothiazine has secondary effects on contraction independent of inhibition of calmodulin, and, finally that the effects of phenothiazine in clinical vasospasm may be insufficient to reverse the condition, despite the observation that vessels in spasm may be more sensitive to this agent.

Animals↗

Glibenclamide relaxes vascular smooth muscle constriction produced by prostaglandin F2 alpha.

The present study has demonstrated: (1) glibenclamide can reduce resting tension in canine cerebral arteries but has no effect on resting tension in the rat aorta; (2) glibenclamide can relax prostaglandin F2 alpha-induced contractions in the rat aorta, and in canine femoral, mesenteric, renal, coronary, basilar and middle cerebral arteries; (3) the relaxation produced by glibenclamide in rat aorta is comparable to that of glyceryl trinitrate and stronger than that of papaverine; (4) canine femoral arteries are less sensitive to glibenclamide than the other arteries; (5) in cerebral arteries glibenclamide was as effective as papaverine, but less effective than glyceryl trinitrate; (6) the actions of glibenclamide on cerebral arteries are not mediated by cGMP as they were not blocked by methylene blue, an inhibitor of guanylate cyclase; (7) the effects of glibenclamide are not endothelium-dependent. The mechanism by which glibenclamide produces relaxation is not clear; while the drug is known to block ATP-dependent potassium channels, in vascular smooth muscle this would cause contraction, not dilation. The action of glibenclamide may be at the level of the receptor or the signal transduction process.

Animals↗

The use of subtractive hybridization to obtain a DNA probe specific for Pseudomonas solanacearum race 3.

Pseudomonas solanacearum, the causal agent of bacterial wilt, has been classified into three races based on host range and into five biovars based on physiological properties. Strains of race 3 belong exclusively to biovar 2 and primarily affect potatoes. Although this race is thought to have originated in the Andean highlands, it has unusual physiological properties that make it a potential threat to potatoes grown at the cooler latitudes worldwide. Consequently, there is need for a rapid and sensitive method for detection of race 3 strains. We have used subtractive hybridization to enrich for race 3-specific DNA sequences in total race 3 genomic DNA, and thereby obtained a 2 kb clone homologous to DNA from all 28 race 3 strains tested, but with only five of 90 non-race 3 strains. In addition, two larger regions of the genome, containing a minimum of 23 kb of DNA, are also specific for race 3. Deletion of this DNA did not affect virulence. This race 3-specific DNA is a potentially useful diagnostic tool for the detection of race 3 strains.

Blotting, Southern↗

Genetic and biochemical characterization of a Pseudomonas solanacearum gene cluster required for extracellular polysaccharide production and for virulence.

Infection of host plants by Pseudomonas solanacerum results in wilting, which is thought to be due largely to the occlusion of xylem vessels by the P. solanacearum extracellular polysaccharide (EPS) that primarily consists of N-acetylgalactosamine (GalNAc). By means of Tn3 mutagenesis, we identified a 6.5-kb gene cluster that contains five complementation units required for EPS production and virulence in this bacterium. There was positive correlation between the amount of EPS produced in culture and (i) in planta growth and (ii) virulence. Based on analysis of beta-glucuronidase-gene fusions, these genes are expressed both in broth cultures and in planta and may be constitutive. Both wild-type and mutant strains contained similar amounts of UDP-GalNAc, the predicted primary substrate for EPS synthesis. Thus, the EPS mutants we obtained should be useful in the analysis of steps in the assembly of the polysaccharide and how this process is related to virulence.

Cloning, Molecular↗

Evaluation of a predoctoral clinical psychology internship program by intern graduates.

This investigation is a replication and extension of an earlier study by Stout, Holmes, and Rothstein (1977) of the predoctoral clinical psychology intern graduates at the William S. Hall Psychiatric Institute. The interns were surveyed (N = 63) with regard to how adequately their internship experience prepared them for their current professional work as practicing clinical psychologists. Questionnaire data (n = 44) from graduates are analyzed in terms of the demographics of each intern's work situation, ratings of how well their internship prepared them in the areas of interprofessional relationships, teaching psychodiagnostic evaluations, psychological treatment, administration, consultation, and research. Several recommendations are offered by the intern graduates for refinement of the clinical psychology internship.

Adult↗

The validity of diagnostic systems for common mental disorders: a comparison between the ID-CATEGO and the DSM-III systems.

It is argued that latent trait analysis provides a way of examining the construct validity of diagnostic concepts which are used to categorize common mental illnesses. The present study adds two additional aspects of validity using multiple discriminant analysis applied to two widely used taxonomic systems. Scales of anxiety and depression derived from previous latent trait analyses are applied to individuals reaching criteria for 'caseness' on the ID-CATEGO system and the DSM-III system, both at initial diagnosis and six months later. The first multiple discriminant analysis is carried out on the initial scale scores, and the results are interpreted in terms of concurrent validity. The second analysis uses improvement scores on the two scales and relates to predictive validity. It is argued that the ID-CATEGO system provides a better classification for common mental illnesses than the DSM-III system, since it allows a better discrimination to be made between anxiety and depressive disorders.

Adjustment Disorders↗

LH and FSH secretion and responses to GnRH and TRH in patients with clinically functionless pituitary adenomas.

Serum concentrations of LH and FSH and their response to the separate administration of GnRH (100 micrograms i.v.) and TRH (200 micrograms i.v.) have been studied preoperatively in 12 patients with a clinically functionless pituitary adenoma, of whom nine (3F: 6M) were found to secrete gonadotrophins in vitro. In three patients with a gonadotrophin-secreting adenoma (GSA) the pulsatile release of LH and FSH was also assessed preoperatively. An elevated serum FSH was recorded in six of nine patients with a GSA, and was subnormal in one, whilst an elevated LH was recorded in only two and was subnormal in six. A doubling of LH occurred in only four of the nine patients after GnRH and in three of six after TRH. None of the three patients with a non-GSA was shown to have an aberrant response to GnRH or TRH. In patients with a GSA, pulsatile release of LH and FSH was usually asynchronous and neither hormone demonstrated any regular harmonic pattern. These data show that in patients with a GSA the serum FSH level is usually elevated but this is not invariable, and the LH may well be low. Pathological responses of LH are frequently found following the administration of either GnRH or TRH and these stimulation tests should be performed separately in patients presenting with a clinically 'non-functioning' pituitary tumour to assist in the preoperative diagnosis. The absence of normal LH and FSH pulsing also appears to be a feature of GS adenomas, and suggests that tumorous gonadotrophin secretion is not under physiological control by hypothalamic GnRH.

Adenoma↗

The detection of antibodies to the glycoprotein X antigen of pseudorabies virus.

The persistence of antibodies to glycoprotein X (gpX) in the serum of pigs experimentally infected with pseudorabies virus (PRV) was determined using an anti-gpX enzyme-linked immunosorbent assay (ELISA). Antibodies to gpX were detected for at least 365 days postchallenge in nonvaccinated pigs. Previous sensitization of pigs by vaccination with S/PRV had no apparent effect on the antibody response of pigs to gpX postchallenge. In determining previous exposure of pigs to PRV strains containing the gpX gene, the anti-gpX ELISA was highly specific, but its sensitivity was lower than the standard serological procedures currently used for detecting PRV antibodies.

Animals↗

The influence of social factors on common mental disorders. Destabilisation and restitution.

This study distinguishes between processes that cause individuals to experience symptoms--destabilisation--and those that are associated with loss of symptoms over time--restitution. It is shown that different clinical, social, and personality variables are associated with each of these processes. Where destabilisation is concerned, it is shown that different variables were associated with the development of symptoms of anxiety and those of depression. Different variables were associated with restitution, and they did not show the same relationship with the symptom dimensions of anxiety and depression as those which were associated with destabilisation.

Adaptation, Psychological↗

High-dose intravenous immunoglobulin in the treatment of demyelinating neuropathy associated with monoclonal gammopathy.

We treated 2 patients with IgM monoclonal paraproteinemic demyelinating peripheral neuropathy (PPN) with monthly intravenous human immunoglobulin. Both patients had a steadily progressive course in spite of steroid and other immunosuppressive therapy for 3 years before starting the immunoglobulin therapy. Both had a rapid clinical improvement noticeable 5 to 10 days after the 1st immunoglobulin infusion lasting on the average of 3 to 6 weeks. Retreatment caused improvement after each consecutive infusion. There were no significant adverse side effects. High-dose IV human immunoglobulin can be a useful therapy in the treatment of PPN and warrants a large-scale controlled therapeutic trial.

Aged↗

Strategic plan creates a blueprint for budgeting.

Effective healthcare organizations develop budgets that reflect and support a strategic plan. Senior managers set a framework that expresses the hospital's future strategic objectives. The budget enables executives to determine which specific service lines are profitable or unprofitable. Administrators and clinicians at all levels are involved in the budgeting process.

Budgets↗