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Biomedical subjects

M Fowler

Publications and source records attributed to M Fowler.

At least 37 records · Page 2Linked to original sources
PubMed1996

Perceived self-control of seizures in young people with epilepsy.

Evidence now suggests that some people can exert some degree of control over seizure initiation and inhibition. In order to explore this further, 79 young people with epilepsy, attending specialist residential schools, were interviewed regarding awareness of seizure precipitants; recognition of seizure warnings; attempts at seizure inhibition, and ways of self-inducing seizures. Questionnaires with the same content were completed by residential care staff. Results show that many subjects claimed to identify seizure precipitants (63.3%), experienced warnings (70.9%), and had developed means of trying to inhibit seizure occurrence (50.6%). However, in each instance, staff reports were much lower (56.9%, 47.2%, and 22.2%, respectively), and one-to-one concordance was poor. A larger than expected percentage of self-induction was reported for both subjects (8.9%) and staff (9.7%). The implication of these results for both the investigation and treatment of epilepsy are discussed further.

Adolescent↗
PubMed1996

Carbon Dioxide Gas Embolism in the Experimental Animal

Accidental vascular placement of Veress needle or cannula during laparoscopic insufflation with carbon dioxide gas (CO2) may cause a fatal gas embolism. Deliberate CO2 injection into the vena cava of dogs did not define a safe flow rate or pressure to prevent mortality. We studied incremental increase in pressure at the same maximum rate of gas flow (corresponding to 2.5 L/mm in a 70-kg man, the maximum flow rate possible with a Veress needle) to define the pressure at which pigs did not reversibly tolerate intravenous CO2 insufflation. The right iliac vein was cannulated and CO2 was insufflated at the maximum flow rate but at three pressures, 15, 20, and 25 mm Hg. During each cycle CO2 was insufflated until the elapse of 30 seconds or a change in end tidal CO2 by 50%. Five of the six animals tolerated intravenous CO2 at 15 mm Hg pressure. In one animal, during insufflation at 15 mm Hg the flow rate was accidentally set at twice the standard level, which resulted in immediate and fatal CO2 embolism. During insufflation at 20 mm Hg four pigs died, the last one during insufflation at 25 mm Hg. Transient insufflation of CO2 at low pressure (15 mm Hg) is well tolerated because pressure in the venous system may limit gas flow. However, a decrease in end tidal CO2 should alert the anesthesiologist to stop insufflation immediately. This will allow recovery. When insufflating pressures are in the middle (20 mm Hg) or high range (25 mm Hg), CO2 embolism can be fatal despite its early recognition.

Journal Article↗
PubMed1996

Ultrasound densitometric analysis of carotid plaque composition. Pathoanatomic correlation.

BACKGROUND AND PURPOSE: The components of a carotid artery plaque might affect the risk of ipsilateral stroke. The accuracy of carotid duplex scan in assessing stroke risk reflects the experience of the scan reader. Thus, methods that can enhance ultrasonic evaluation of plaque morphology might allow a more objective means of determining carotid-mediated stroke risk. METHODS: We performed densitometric analysis of B-mode images of carotid plaques in nine patients scheduled for carotid endarterectomy. All patients had preoperative duplex color imaging and cerebral arteriography. The surgical specimen was analyzed histologically to determine the plaque components (soft plaque/organized thrombus, intraplaque hemorrhage/lipid deposition, fibrosis, and calcification). The specimen findings were correlated with the densitometric measurements to determine whether the density analysis would allow a reliable determination of the plaque substratum. RESULTS: With 1.0 as a reference point for the moving column of blood, the mean acoustic densities (+/-SD) were as follows: organized thrombus, 1.8 +/- 0.5; intraplaque hemorrhage/lipid deposition, 5.15 +/- 0.9; fibrosis, 9.51 +/- 2.9; and calcification, 15.5 +/- 8.6. CONCLUSIONS: We conclude that densitometric evaluation allows differentiation of the various possible components of carotid plaque. The determination of plaque composition, based on density measurement, may provide information about its potential for thromboembolization.

Aged↗
PubMed1996

Exercise capacity of heart transplant recipients: the importance of chronotropic incompetence.

BACKGROUND: Maximal exercise capacity is limited in patients after heart transplantation. The extent to which chronotropic incompetence contributes to this intolerance has not been well defined. METHODS: This prospective cross-sectional study examined the heart rate response to exercise and its relation to exercise capacity in 159 heart transplant recipients during progressive, symptom-limited, upright exercise. All prior exercise studies of heart transplant recipients that reported peak oxygen uptake and peak heart rate were also evaluated. RESULTS: Peak oxygen uptake was closely correlated with peak heart rate (r = 0.39, p < 0.001) and maximum increase in heart rate (r = 0.49, p < 0.001) during exercise by our patients. Similar correlations were found in the published studies for peak oxygen uptake versus maximal heart rate (r = 0.54, p < 0.05) and peak oxygen uptake versus increase in heart rate (r = 0.63, p < 0.02). The current study showed that the increase in heart rate from rest to peak exercise was significantly higher and the decline in heart rate after exercise significantly faster for patients 2 or more years after transplantation than for patients less than 2 years after transplantation (46 +/- 2 versus 38 +/- 1.9 beats/min, p < 0.05); the decline in heart rate 4 minutes after exercise was 27 +/- 1.8 versus 16 +/- 1.8 beats/min, respectively ( p < 0.001). CONCLUSION: The reduction in peak oxygen consumption, particularly during the first 2 years, appears to be related in part to chronotropic incompetence. Late after transplantation the heart rate response to exercise is greater and the decline in heart rate after exercise faster, suggesting possible autonomic reinnervation in some patients. Chronotropic incompetence may be an inadequate explanation of oxygen uptake impairment seen late after transplantation, when other factors such as myocardial dysfunction and intrinsic skeletal muscle abnormalities are of increasing importance.

Analysis of Variance↗
PubMed1995

The relationship of granzyme A and perforin expression to cardiac allograft rejection and dysfunction.

The mechanisms underlying contractile dysfunction following heart transplantation are poorly defined. To investigate the role of cytotoxic T cells (CTL) in cardiac transplant rejection, and during episodic contractile dysfunction, we performed a prospective study analyzing the expression of granzyme A and perforin, two functional markers of activated CTL. Sixteen consecutive patients were analyzed during the first year posttransplantation. All patients received induction therapy with OKT-3 and received standard three-drug immunosuppression therapy. Rejection status was monitored using routine surveillance endomyocardial biopsy and graded according to the ISHLT scale. Granzyme A and perforin mRNA were detected by reverse transcription PCR at the time of each routine biopsy. A total of 64/123 biopsies were positive for granzyme expression, while 38/123 samples were positive for perforin expression. LV function was monitored using M-mode derived fractional shortening and Doppler assessment of diastolic function (isovolumic relaxation time [IVRT] and pressure half-time [P1/2]). As expected, the presence of granzyme A message was associated with rejection score (ANOVA, P = 0.001). In addition, granzyme A expression was correlated with a decrease in diastolic function (chi 2 = 6.4, P < 0.02), but was not associated with systolic function. The presence of perforin message was not correlated with functional changes or with rejection grade, but was associated with granzyme expression (chi 2 = 9.11, P = 0.0025). These studies suggest that the presence of granzyme A message may be an important predictor of graft function.

Adolescent↗
PubMed1995

A demonstration of generalization of performance across settings, materials, and motor responses for students with profound mental retardation.

A treatment package, consisting of multiple exemplar training and community-based instruction, was evaluated for its effectiveness in teaching four students with profound mental retardation and multiple disabilities to participate in two sets of community-living tasks. All training took place in community settings, and each student demonstrated improved performance on at least one task set. In addition, all students demonstrated improved performance on a series of tasks selected to assess generalization of performance across settings, materials, and/or motoric responses required to complete the target task. Maintenance of performance over a 4- to 5-month period was assessed and achieved for two of the students. The results of this investigation are discussed in terms of the implications for programming for students with profound mental retardation.

Activities of Daily Living↗
PubMed1994

Potent and selective inhibition of human nitric oxide synthases. Inhibition by non-amino acid isothioureas.

S-Ethylisothiourea was a potent competitive inhibitor of human nitric oxide synthase (NOS), with Ki values of 17, 36, and 29 nM for the inducible (i), endothelial (e), and neuronal (n) isozymes, respectively. Unlike some potent inhibitors of NOS, no time dependence was observed. S-Ethylisothiourea was not a detectable substrate for eNOS. S-Ethylisothiourea was also a potent inhibitor of mouse iNOS (Ki value of 5.2 nM), and its binding perturbed the spectrum of iNOS consistent with its altering the environment of the bound heme. The optimum binding of S-ethyl- and S-isopropylisothiourea relative to 70 other analogs suggested that these alkyl substitutions fit into a small hydrophobic pocket. Most isothioureas were 2-6-fold selective for the human iNOS (Ki for iNOS versus Ki for eNOS), with one being 19-fold selective. The cyclized mimics of S-ethylisothiourea, 2-NH2-thiazoline, and 2-NH2-thiazole, were also competitive inhibitors of human NOS. A third structural class of inhibitors, bisisothioureas, were, in general, the most selective in their inhibition of human iNOS. S,S'-(1,3-Phenylenebis(1,2-ethanediyl))bisisothiourea was 190-fold selective (Ki value of 0.047 microM against iNOS versus 9.0 microM against eNOS). These results demonstrate that potent and selective inhibition of human NOS isozymes is achievable.

Amino Acid Oxidoreductases↗
PubMed1994

Abnormalities of pulmonary function in patients with congestive heart failure, and reversal with ipratropium bromide.

Patients with congestive heart failure (CHF) have baseline restrictive and obstructive abnormalities in pulmonary function. Thus, improvement of respiratory parameters may provide a new method for the treatment of CHF. Ipratropium is an inhaled anticholinergic bronchodilator with no reported cardiac or systemic effect. A pilot study was performed to investigate the acute effects of a 72 micrograms inhaled dose of ipratropium bromide on pulmonary function and pulmonary artery pressures in 18 nonsmokers and 11 smokers with severe (New York Heart Association class 2 or 3), stable CHF who were referred for orthotopic cardiac transplantation. An unmatched group of 10 healthy subjects (5 men and 5 women, mean age 36.8 +/- 1.8 years) were studied with pulmonary function testing alone. Forced expiratory volume in 1 second (FEV1) in 15 of 18 nonsmokers with CHF showed a favorable response with a mean improvement of 5.1% (2.74 +/- 0.20 to 2.89 +/- 0.19 liter after drug treatment; p = 0.0026). Forced expiratory flow between 25 and 75% of the forced vital capacity (FEF25-75) improved by 19% (2.50 +/- 0.25 to 3.09 +/- 0.28 liter/s; p = 0.0013). Eight of 11 smokers with CHF responded with a 9.5% increase in FEV1 (2.32 +/- 0.21 to 2.54 +/- 0.19 liter; p = 0.0006) and a 23.2% increase in FEF25-75 (1.82 +/- 0.38 to 2.37 +/- 0.46 liter/s; p = 0.0029). Pulmonary artery pressures, cardiac output, systemic arterial pressures, and cardiac rate and rhythm were unaffected by administration of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1994

HIV vaccine development and clinical trials.

The magnitude of HIV pandemic has made the development of HIV vaccines an urgent biomedical research priority. Although the biologic problems in designing a vaccine for a chronic viral infection like HIV are formidable, there has been encouraging progress. More than a dozen first generation prophylactic HIV vaccine candidates have completed phase I human trials that have established the safety and immunogenicity of these products in adults. A phase II trial of two HIV subunit envelope vaccines in adults at high risk of HIV infection is underway in the United States, and preparations for phase III efficacy trials have begun. Preliminary studies are under way to evaluate the potential application of active and passive immunization for preventing vertical transmission of HIV. Because of the higher rate of HIV transmission and a more abbreviated time course to disease, it may be more efficient to evaluate the efficacy of HIV vaccines in HIV infected pregnant women and their offspring than in adults who are exposed sexually to HIV.

AIDS Vaccines↗
PubMed1993

Effects of transitory cognitive impairment on psychosocial functioning of children with epilepsy: a therapeutic trial.

The authors report a trial of the use of anti-epileptic medication to treat possible cognitive deficits due to subclinical epileptiform EEG discharges in 10 children with psychosocial and educational problems associated with epilepsy. Medication intended to suppress the EEG discharges was added to the children's existing drug regime. In all instances, epileptiform activity, assessed by 24-hour periods of ambulatory monitoring, was reduced on active medication compared with placebo. In general, there was improvement of psychosocial function on active treatment: eight children improved, there was no change in one and one deteriorated. No psychosocial deterioration attributable to adverse effects of the medication was detected in those completing the trial. Despite possible confounding factors, the findings are in accordance with the view that subclinical EEG discharges can impair psychosocial function, which may be ameliorated by anti-epileptic medication.

Adolescent↗
PubMed1993

Oleic acid-induced mucosal injury in developing piglet intestine.

A role for luminal nutrients, in particular products of lipid digestion, in the pathogenesis of mucosal injury to developing intestine has been postulated. We evaluated changes in mucosal permeability and light and electron microscopic histology induced by luminal perfusion with the long-chain fatty acid oleate in developing piglet intestine as a function of age and concentration of the fatty acid. 51Cr-labeled EDTA plasma-to-lumen clearance was measured in jejunum and ileum of 1-day-, 3-day-, 2-wk-, and 1-mo-old piglets during sequential perfusion with saline control (20 min); 0, 1, 5, and 10 mM oleic acid/10 mM taurocholate in saline (20 min); and normal saline (60 min). The jejunum of piglets < or = 2 wk showed significantly greater increases in mucosal permeability compared with 1-mo-old animals after perfusion with oleic acid. This effect was dependent on the luminal concentration of the fatty acid and was associated with mucosal injury evident under light and electron microscopy. In contrast, the overall response in ileum was more attenuated compared with jejunum. Thus oleic acid, a common dietary fatty acid, induces dose- and age-dependent injury in developing piglet intestine. Investigation of the mechanisms of this injury may provide the basis for dietary modifications directed at decreasing the risk of mucosal injury during enteral feeding in neonatal intestine.

Aging↗
PubMed1993

Pain management at home. Struggle, comfort, and mission.

This article presents findings from an exploratory, descriptive study that investigated the experiences of pain in the home from the perspective of the patient, the primary family caregiver, and the home care nurse. The following research questions are addressed: What are the special problems associated with pain management at home as identified by patients, caregivers, and nurses? What are the similarities and differences among patients, caregivers, and nurses regarding issues of managing pain at home? Qualitative techniques were used to collect and analyze data. The sample included 10 cancer patients with pain and their respective caregivers and nurses. After the in-depth interviews were transcribed, a multidisciplinary research team performed content analysis on the data. Overall, the findings suggest that patients approach pain management with a struggle for control, whereas self-denying caregivers seek to provide comfort, and nurses attempt to fulfill an urgent mission to eradicate pain.

Adult↗