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Biomedical subjects

M Fitzpatrick

Publications and source records attributed to M Fitzpatrick.

At least 55 records · Page 3Linked to original sources
PubMed1997

SEB is cytotoxic and alters EC barrier function through protein tyrosine phosphorylation in vitro.

We studied whether Staphylococcal enterotoxin B (SEB) has direct effects on endothelial cells (EC) in the absence of effector cells or their products. Bovine or human pulmonary artery EC were grown to confluence on filters mounted in chemotaxis chambers. Barrier function was assessed by placing [14C]bovine serum albumin in the chamber and sampling the lower well for 14C activity. SEB exposures induced a significant (P < 0.001) dose- and time-dependent increase in albumin flux across both bovine and human EC monolayers. Albumin flux was temperature dependent, and cycloheximide pretreatment of the monolayers did not block the SEB-induced increase in permeability. Preincubation of SEB with trypsin or anti-SEB antibody significantly (P < 0.0001) reduced the effect, whereas pretreatment with polymyxin B did not. SEB at > or = 10 micrograms/ml significantly (P < 0.03) increased EC injury as measured by 51Cr release in a dose- and time-dependent manner. Herbimycin and genistein, inhibitors of protein tyrosine kinases, each protected against SEB-induced cytotoxicity, barrier dysfunction, and intercellular gap formation. We conclude that SEB perturbs endothelial barrier function and viability in the absence of effector cells or their mediators.

Animals↗
PubMed1996

Critical care medicine: opportunities and strategies for improvement.

BACKGROUND: Like other areas of health care, critical care faces increasing pressure to improve the quality while reducing the cost of care. Strategies drawn from the literature and the authors' experiences are presented. STRATEGIES AND OPPORTUNITIES FOR IMPROVEMENTS: Ten process- or structure-related areas are targeted as strategically important focuses of improvement: (1) restructuring administrative lines to better suit key processes; (2) physician leadership in critical care units; (3) management training for critical care managers; (4) triage; (5) multidisciplinary critical care; (6) standardization of care; (7) developing alternatives to critical care units; (8) timeliness of care delivery; (9) appropriate use of critical care resources; and (10) tracking quality improvement. TIMELINESS OF CARE DELIVERY: Whatever the root cause(s) of unnecessary delays, the result is inefficient use of critical care resources-and ultimately either a need for more resources or longer wait times. Innovations designed to reduce wait times and waste, such as the establishment of a microchemistry stat laboratory, may prove valuable. APPROPRIATE USE OF CRITICAL CARE RESOURCES: Possible strategies for the appropriate use of critical care resources include better selection of well-informed patients who undergo procedures. Reduction in variation among physicians and organizations in providing therapies will also likely lead to a reduction in some high-risk procedures offering little or no benefit, and therefore a reduction in need for critical care services. Better preparation of patients and families should also make end-of-life decisions easier when questions of "futility" arise. Better information on outcomes and cost-effectiveness and consensus on withdrawal of critical care treatments represent two additional strategies.

Critical Care↗
PubMed1996

Complete ring melanoma of the choroid.

BACKGROUND: Ring melanoma of the uvea is a term generally applied to elongated, circumferentially oriented malignant melanomas of the iris and ciliary body; a complete ring melanoma involving almost exclusively the choroid is extremely uncommon. METHODS: The authors present a case report and clinicopathologic correlation of complete ring melanoma of choroid managed by enucleation. RESULTS: A 74-year-old woman was found to have a diffuse, melanotic thickening of the midzonal to peripheral choroid circumferentially for 360 degrees and an associated subtotal serous retinal detachment with shifting subretinal fluid in her left eye. The thickest portion of the mass measured only 2.3 mm by ultrasound biometry. The eye was enucleated, and histopathologic analysis confirmed a diffuse malignant melanoma composed predominantly of spindle B cells. CONCLUSIONS: A complete ring melanoma of the choroid is a rare and unusual variant of diffuse uveal malignant melanoma. The pertinent differential diagnosis of choroidal ring melanoma includes diffuse choroidal melanocytoma, choroidal melanocytosis associated with ocular melanocytosis, bilateral diffuse uveal melanocytic proliferation associated with systemic carcinoma, and diffuse uveal lymphocytic infiltration.

Aged↗
PubMed1995

Oxygen desaturation during sleep and exercise in patients with severe chronic obstructive pulmonary disease.

Patients with chronic obstructive pulmonary disease (COPD) have varying degrees of arterial oxyhaemoglobin desaturation during sleep, which have been shown to correlate with awake oxygen levels. We wished to ascertain if exercise desaturation was a better predictor of nocturnal oxygen desaturation than daytime blood gases. We studied 25 COPD patients with PaO2 < 10 kPa (mean = 8.6 kPa), 12 of whom were normocapnic (PaCO2 < or = 6 kPa, Group A), and 13 of whom were hypercapnic (PaCO2 > 6 kPa, Group B), by means of overnight oximetry and maximum treadmill exercise testing. The overall group desaturated significantly more during sleep than exercise [12.9 +/- 10.5 fall in nocturnal oxygen saturation (SaO2) vs. 4.5 +/- 3.7, P < 0.01]. Group B had a lower minimum SaO2 during sleep than Group A (74.3 +/- 13.4 vs. 84.6 +/- 5.8, P < 0.05), despite very similar pre-sleep SaO2 (91.9 +/- 3.2 vs. 92.8 +/- 2.9, P = n.s.). Awake SaO2 correlated well with both mean values (r = 0.7, P < 0.001), and minimum sleep SaO2 (r = 0.44, P < 0.05), but not with the fall in sleep SaO2 (r = 0.21, P = n.s.). Minimum sleep and exercise SaO2 were also significantly correlated (r = 0.44, P < 0.05), but the fall in SaO2 during sleep and exercise was not (P = n.s.). We conclude that exercise studies add no extra information to awake blood gas analysis in predicting the likelihood of nocturnal oxygen desaturation in patients with COPD.

Aged↗
PubMed1994

Testes size and testosterone levels in a model for weightlessness.

The purpose of this study was to test whether the lack of testicular growth found in suspended rats would affect testosterone production in a way that might have consequences on muscle atrophy and function studies. Body and testes weight, food consumption, and testosterone levels in testes and plasma were measured at the beginning of the experiment and after 1, 3 or 8 weeks of suspension. Suspended animals ate more but gained less weight than their pair-fed controls. Testes testosterone concentration (microgram/g tissue) was increased at 3 and 8 weeks, but total tissue testosterone (microgram/testes) was not. Up to 3 weeks of suspension, tissue concentration was dependent on testes size and independent of treatment. Plasma testosterone was increased only after 8 weeks of suspension. At 8 weeks, plasma levels correlated with total testes testosterone. Our results show that use of the Morey-Holton rat tail-suspension model up to 3 weeks did not induce testosterone changes of consequence to a skeletal muscle study. For long term studies consideration should be given to possible hormonal effects as tissue and plasma testosterone levels increase after 8 weeks of suspension.

Animals↗
PubMed1993

Reversible hypercapnia in acute exacerbations of chronic obstructive pulmonary disease (COPD).

We prospectively studied emergency hospitalizations due to acute exacerbations of chronic obstructive pulmonary disease (COPD) among 74 hypercapnic patients, in order to determine factors which predict reversal to normocapnia as a result of therapy. Clinical, arterial blood gas and pulmonary function data on presentation were compared to predischarge values among those 58 patients who survived the admission. Patients were divided into those who reverted to normocapnia (reversible, 40% of surviving patients), and those who remained hypercapnic (chronic, 60% of surviving patients). Reversible patients had higher admission arterial oxygen tension (PaO2) levels than those with chronic hypercapnia (6.4 +/- 1.3 kPa (mean +/- SD), as compared to 5.7 +/- 1.1 kPa) better pulmonary function (forced expiratory volume in one second (FEV1) 35 +/- 16% predicted, as compared to 26 +/- 7.9), and a lower prevalence of cor pulmonale (30% as compared to 63% of patients). No admission variable(s) distinguished individual patients as reversible or chronic hypercapnic, and, in particular, admission arterial carbon dioxide tension (PaCO2) and pH levels were similar in both groups. Furthermore, there were no differences between survivors and those 16 patients who died during the admission, apart from a higher urea level among those who died. These findings suggest that reversible patients have milder underlying disease than those with chronic hypercapnia. Our data establish the high prevalence of reversible hypercapnia among patients hospitalized with exacerbations of COPD, and, furthermore, indicate that patients who are normocapnic in the stable state can develop similar levels of hypercapnia during exacerbations as those with chronic hypercapnia.

Acute Disease↗
PubMed1992

Validation and reproducibility of bidirectional laser Doppler velocimetry for the measurement of retinal blood flow.

Bidirectional laser Doppler velocimetry (BLDV) for the measurement of retinal blood flow was validated in six anaesthetised minipigs, by comparing BLDV derived results with those obtained using radioactively labelled microspheres (RLM). The mean velocity of blood (Vmean) was calculated from the maximum red blood cell velocity measured by BLDV. Volumetric flow rate was determined from Vmean and vessel diameter, measure from monochromatic fundus photographs. Total retinal blood flow (TRBF) was calculated by summating flow values obtained for each retinal vein draining into the optic disc. A significant correlation was found between the TRBF results obtained by the two techniques (r = 0.99, p less than 0.001). The BLDV results were between 3-35 microliters/min lower than the corresponding RLM results (p = 0.05). Values of 57 +/- 24 microliters/min and 76 +/- 34 microliters/min were obtained for TRBF using the BLDV and RLM techniques respectively. Reproducibility studies with BLDV were also performed in six anaesthetised pigs over three hours and in six normal human volunteers over two hours and two weeks. No significant difference between measurements was found with time. Ninety five percent confidence limits of +/- 9.8% for the six pigs and +/- 8.9% for the six human volunteers were found for measurements on the same day and at two weeks. We conclude that with a sample size of six, changes in flow of approximately 20% can be detected using BLDV and monochromatic fundus photography.

Adult↗
PubMed1991

Cognitive-behavioral therapy for panic: an open study.

This paper reports results of an open prospective study of 26 patients who met DSM-III criteria for panic disorder or agoraphobia with panic attacks. Cognitive-behavioral treatment alone produced clinically and statistically significant improvement in panic symptoms, including both full-blown and limited symptom episodes. In addition, the treatment produced improvement in associated symptoms of phobic avoidance and generalized anxiety. This work provides further preliminary indication of the usefulness of cognitive-behavioral strategies as an alternative to medication in symptom-oriented treatments.

Adult↗
PubMed1991

Vulnerability to sodium lactate in panic disorder patients given cognitive-behavioral therapy.

Six patients with panic disorder who had panicked during sodium lactate infusion were given cognitive-behavioral treatment for 12-24 weeks. After treatment they underwent another lactate infusion, and four patients were rates as having no panic, suggesting that reduced vulnerability to lactate accompanies remission of panic. Controlled trials of cognitive-behavioral therapy and use of lactate infusion as a measure of remission are recommended.

Adolescent↗
PubMed1990

Does intensive medical therapy influence the outcome in unstable angina?

Three hundred and forty-six patients of all ages and both sexes were admitted to coronary care with documented unstable angina. Management was conservative, without the routine use of beta-blockers or calcium antagonists. Mortality was 3.2%, and the nonfatal myocardial infarction rate was 10.1% during the first 28 days. After one year, coronary mortality was 10.5% with a nonfatal infarction rate of 13.1%. Twenty-six patients were subjected to coronary artery bypass surgery, eleven during the first 28 days and fifteen subsequently. No patient underwent coronary angioplasty. The factors influencing immediate and long-term prognosis in these patients were studied. Persistence of pain in hospital, previous chronic angina, and age had an adverse effect on outcome. A total of 143 patients complained of persistent pain lasting for 24 hours or more. The use of beta blockers or calcium antagonists in patients with persistent pain exceeding five days did not appear to influence outcome. The current widespread adherence to "intensive medical treatment," including the routine use of beta blockers and calcium antagonists, is questioned.

Adrenergic beta-Antagonists↗
PubMed1990

Cellular interactions with biomaterials: in vivo cracking of pre-stressed Pellethane 2363-80A.

The phenomenon of stress cracking of Pellethane 2363-80A (PEU) was investigated using the cage implant system. A cytotoxic polyvinylchloride (PVC) and a silicone rubber containing an anti-inflammatory steroid were used to create inflammatory environments in which the biostability of the pre-stressed PEU was tested. These coimplants provided alternative in vivo environments to study in vivo polymer interactions. The inflammatory responses to the implanted cages were monitored by analyzing the exudates aspirated from the cages at different implantation times over 21 days. The pre-stressed PEU specimens were retrieved after 5, 10, and 15 weeks postimplantation and examined by optical microscopy (OM) and scanning electron microscopy (SEM). The results support the conclusion that in vivo cracking of stressed (strained) Pellethane 80A is related to cell-polymer interactions. Severe cracking or rupture of the implanted PEU specimens was observed as early as 5 weeks postimplantation. Molecular chain degradation of the implanted specimens was evident from molecular weight measurements. Neither surface cracking nor degradation of macromolecules was found on the pre-stressed PEU specimens with the added cytotoxic PVC implanted over 15 weeks. No cracking was observed on the pre-stressed specimens in the presence of steroid silicone rubber, even after 10 weeks implantation.

Animals↗
PubMed1990

Knowledge, attitudes and behavior related to sexuality in adolescents with chronic disability.

This study explored the level of knowledge, attitudes and activity related to sexuality in a group of adolescents and young adults with myelomeningocele, a group of matched controls and a group of adolescents with cystic fibrosis. Slightly more than half of the study sample were female, the mean age was 17.2 years, and their backgrounds were mainly middle-class. 28 per cent of the myelodysplastic group reported previous sexual activity, compared with 60 per cent of the control group and 43 per cent of the group with cystic fibrosis. Most of the disabled adolescents expressed a desire to marry and have children, but fewer than 20 per cent had sought information regarding their sexual or reproductive function from their physician. Among those sexually active, 60 per cent of the controls and 67 per cent of those with cystic fibrosis had used contraception, compared with 16 per cent of the myelodysplastic group. The authors conclude that sex education and screening for contraceptive need is indicated for adolescents with chronic disabilities.

Adolescent↗