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Biomedical subjects

P Howard

Publications and source records attributed to P Howard.

At least 73 records · Page 4Linked to original sources
PubMed1994

Histamine induced pulmonary vasodilatation in the rat: site of action and changes in chronic hypoxia.

Histamine constricts postcapillary lung vessels and also causes dilatation, site unknown. In chronically hypoxic rats, pulmonary arterioles are muscularized and histamine-containing mast cells increase. We wanted to determine a) whether vasoreactivity to histamine changes in chronic hypoxia; b) whether dilatation is due to H2 receptors; and c) which vessels dilate. We perfused isolated lungs of normal (C) and chronically hypoxic (CH) rats. Histamine was tested during hypoxic vasoconstriction. To examine effects on arteries alone, we raised alveolar (inflation) pressure above outflow pressure; during inflation, pressure/flow (P/Q) lines were measured during normoxia, and hypoxia, and after histamine during continued hypoxia. Dose-related dilatation was seen, which was abolished by cimetidine and enhanced in CH rats. A mast cell-discharging agent, but not exogenous histamine, caused constriction, which was abolished by chlorpheniramine. P/Q lines differed in C and CH rats in a manner which suggests that hypoxia constricts larger "extra-alveolar" vessels in C rats, but mainly muscularized arterioles exposed to alveolar pressure in CH rats. Histamine restored the P/Q line to nearly its normoxic position; it therefore dilated those vessels which constrict in hypoxia in each rat group. It is concluded that histamine has a strong H2 dilator effect, enhanced in chronic hypoxia, which might be an important attenuating factor in hypoxic pulmonary hypertension.

Animals↗
PubMed1994

Hypothesis: exposure to solvents may cause fibrosing alveolitis.

The incidence of fibrosing alveolitis, which can be caused by many agents, is increasing. In a proportion of patients, the aetiology is unknown (cryptogenic fibrosing alveolitis), but it has been suggested that environmental factors may play an important, but unrecognized, role in its pathogenesis. A review of the literature suggests that there may be a link between exposure to solvents, widespread occupational pollutants, and fibrosing alveolitis. Experimental work in animals has shown that exposure to solvents produces changes in the lung similar to those found in fibrosing alveolitis. Occupational exposure to a wide number of solvents has been associated with the development of systemic sclerosis. Pulmonary involvement in systemic sclerosis is morphologically indistinguishable from fibrosing alveolitis, and a close relationship between the two diseases seems to exist. This close relationship and the experimental work linking solvent exposure to fibrosing alveolitis suggest that solvent exposure may be one cause of cryptogenic fibrosing alveolitis. Determination of any occupational exposure of patients with cryptogenic fibrosing alveolitis may help in the understanding and prevention of this disease.

Acute Disease↗
PubMed1993

Endothelial control of the pulmonary circulation in normal and chronically hypoxic rats.

1. The effect of blockade of nitric oxide synthesis in pulmonary endothelium by two L-arginine analogues was tested in isolated blood-perfused lungs of normal rats and rats exposed chronically to 10% O2. 2. In both groups of rats the analogues (N-monomethyl-L-arginine (L-NMMA) and N-nitro-L-arginine methyl ester (L-NAME)) enhanced hypoxic vasoconstriction. In normal rats, with rare exceptions, these analogues had little or no effect on pulmonary artery pressure (Ppa) at constant blood flow during normoxia. However, chronically hypoxic rats have pulmonary hypertension and in these rats the analogues always raised Ppa; the rise in Ppa after L-NMMA but not L-NAME could be partially reversed by L-arginine. L-NAME was more potent than L-NMMA. 3. To see whether the difference between rat groups was due to the high Ppa in chronically hypoxic rats, in control rats we raised Ppa passively by lung inflation to values higher than found in chronically hypoxic rats. L-NAME did not alter the effects of lung inflation on Ppa. 4. Ppa was also raised passively by plotting pressure-flow lines up to high flow rates; the lines were changed minimally by both analogues in control rats but in chronically hypoxic rats the lines were raised to higher pressures and steepened substantially. 5. In control rats, during vasoconstriction caused by hypoxia, endothelin 1 and almitrine, L-NAME caused further rises in pressure. We conclude that a stimulus for nitric oxide release in control rats is the narrowing of vessels caused by vasoconstriction rather than passive increases in intravascular pressure. 6. In chronically hypoxic rats arterioles are narrowed by growth of new muscle and there is some muscle tone even in normoxia. Thus narrowing of the vascular lumen is the stimulus common to both groups of rats which leads to nitric oxide synthesis and attenuation of Ppa by a negative feedback process. Narrowing is associated with a large increase in shear stress due to two factors; the pressure drop along a vessel segment is increased and the surface area of the lining of the affected segment is decreased. 7. Atrial natriuretic peptide caused dose-dependent pulmonary vasodilation in both rat groups but had a greater effect in chronically hypoxic rats. The action persisted and was enhanced after blockade of NO synthesis.

Almitrine↗
PubMed1993

Attenuation of chronic hypoxic pulmonary hypertension in rats by cyclooxygenase products and by nitric oxide.

We wanted to assess the respective roles of arachidonic acid products and nitric oxide in the modulation of pulmonary hypertension in chronically hypoxic rats. In isolated blood-perfused lungs, the effects of arachidonic acid before and after treatment with the cyclooxygenase inhibitor, meclofenamate, were compared in control (C) rats and rats exposed for two weeks to 10% oxygen (chronic hypoxia CH). Arachidonic acid caused mixed dilator and constrictor effects during both normoxia and hypoxia; dilatation was more prominent in chronically hypoxic rats. Meclofenamate abolished both dilator and constrictor actions of arachidonic acid; it raised baseline, normoxic pulmonary artery pressure, in chronically hypoxic but not control rats, which suggests that dilator products of arachidonic acid are released in the pulmonary hypertension of chronic hypoxia and attenuate pulmonary artery pressure. As shown previously, the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) raised pressure in chronically hypoxic but not control rats. Meclofenamate and L-NAME given in sequence both raised pulmonary artery pressure in chronically hypoxic rats and the combined rise was substantial (+13 mmHg). We conclude that, in the conditions of our experiment, both nitric oxide and dilator prostanoids are released in hypoxic pulmonary hypertension in rats. Thus, two synthetic processes, both possibly endothelial dependent, may modulate hypoxic pulmonary hypertension.

Amino Acid Oxidoreductases↗
PubMed1993

Occupational siderosis and welders' lung: a review.

Siderosis of the lung is generally assumed to be a benign condition, not associated with respiratory symptoms. A review of the literature suggests that this assumption may be incorrect, and that siderosis may lead both to symptomatic and functional changes. It is known that iron ore miners have a raised lung cancer mortality, but this has been attributed to smoking, or exposure to tars or radon. Mortality studies among iron workers (haematite miners, welders, iron foundry and steel workers) show, however, that an association exists between working with iron and death, both from lung cancer and other respiratory causes. A number of surveys have examined respiratory function and symptoms among welders. These indicate that welding is associated with obstructive airways disease. The effect of the welding fume on respiratory function and symptoms can be as great as that of smoking. Iron has also been shown to cause fibrosis in some cases. Small functional changes of restriction and loss of lung compliance are often due to iron alone. The fibrosis may be enhanced by associated silica exposure. A number of constituents of welding fume could, along with iron, contribute to pulmonary changes. The presence of siderosis may act as a good marker of exposure to fume and any resulting disability.

Adult↗
PubMed1993

Low prevalence of human papillomavirus types 16 and 18 in cervical adenocarcinoma in situ, invasive adenocarcinoma, and glandular dysplasia by polymerase chain reaction.

Using the polymerase chain reaction on paraffin blocks for human papillomavirus (HPV) types 16 and 18, a positive result was seen in three of 20 cases of invasive adenocarcinoma, 15 of 36 cases of adenocarcinoma in-situ, and one of five cases of glandular dysplasia of the uterine cervix. Types 16 and 18 were found with equal frequency. In adenocarcinoma in situ there was no age difference between HPV-positive and or HPV-negative cases. Concomitant squamous dysplasia was slightly more frequent in HPV-positive adenocarcinoma in-situ. HPV positivity rates are lower than most of those previously reported. Possible reasons for this are discussed.

Adenocarcinoma↗
PubMed1993

The carotid body: a review of its anatomy, physiology and clinical importance.

The carotid body is a peripheral chemoreceptor that monitors arterial blood gas tensions and pH. Its main function is to contribute to the regulation of breathing although there is evidence for a reflex influence on the pulmonary circulation and the kidney. The carotid body's acute response to hypoxia is a rapid increase in breathing. The chronic response to hypoxia such as would occur at high altitude or as a consequence of COPD, includes growth of the organ, both hyperplasia and hypertrophy, modification of amine content and an attenuation of its hypoxic sensitivity. It is the latter aspect that may cause severe problems of management of COPD for the clinician. It is postulated that the attenuated hypoxic sensitivity may play a role in the deterioration of the COPD patient.

Carotid Body↗
PubMed1993

Hyperinflation, trapped gas and theophylline in chronic obstructive pulmonary disease.

Assessment of patients with chronic airflow limitation traditionally involves the measurement of airway obstruction by forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), as well as hyperinflation by residual volume (RV). Patients often claim reduction of breathlessness during theophylline therapy, without change of spirometry. In severe airflow limitation there is often a difference in lung volumes measured by helium dilution and plethysmography. The latter is thought to measure the absolute amount of gas in the lungs at functional residual capacity (FRC), whereas helium dilution measures only air in rapid communication with the mouth. The difference between the two is considered to represent poorly-ventilated areas of the lung, and is termed trapped gas volume. Twenty two patients with "irreversible" airflow limitation, mean (SD) FEV1 1.15 (0.52) l, FVC 2.57 (0.88) l, were studied. Uniphyllin Continus tablets (Napp Laboratories) were given at a dose to provide a mean steady-state plasma level of 14 mg.l-1, in a placebo-controlled, double-blind, cross-over study. The measurements made were FEV1, FVC, static lung volumes, 6 min walking distance (6WD), breathlessness after exercise assessed by visual analogue scales (VAB), and arterial blood gases. No significant correlation was found between changes in VAB and changes in RV measured by the helium dilution technique (RV (He)), FEV1 or FVC, but there were good correlations with trapped gas volume (r = 0.61, p < 0.01). The plethysmographic element of the calculated trapped gas volume reflects change in the sensation of breathlessness, and is affected by treatment with theophylline.

Aged↗
PubMed1993

Methods and prognosis of non-invasive ventilation in neuromuscular disease.

Ventilatory failure is the commonest terminal event in many neuromuscular disorders. Increasingly, non-invasive methods of ventilation, employing both negative and positive pressure techniques, have been used, with the aim of prolonging life and reducing morbidity. The use of non-invasive ventilation is reviewed in three main groups of neurological diseases, and the degree of success assessed. It is concluded that non-invasive methods can be effective in reducing morbidity in selected patients, especially those with more slowly progressive disorders. A reduction in mortality is suggested by comparison with historical controls. The institution of ventilatory support is a major undertaking for the medical team, patient and family, and should only be initiated after a full and frank discussion of the overall prognosis, in terms of both mortality and quality of life. The patient and principal caregivers can then make an informed decision as to the desirability of home ventilation.

Home Care Services↗
PubMed1992

Squamous cell carcinoma of the cervix: HPV 16 and DNA ploidy as predictors of survival.

In this study, the hypothesis that DNA ploidy and the presence of HPV 16 and HPV 18 DNA affects survival of patients with squamous cell carcinoma of the cervix was tested. Archival paraffin blocks from biopsy and surgical specimens were obtained from 127 women diagnosed in 1977-1984. Determination of DNA ploidy was by flow cytometry and HPV 16 and HPV 18 DNA status by polymerase chain reaction with subsequent dot-blot hybridization. For each patient, age, stage, treatment modality, and 5-year survival were correlated with ploidy and HPV status. HPV 16 DNA was present in 53% of the tumors. HPV 18 was not detected in this population. HPV 16 DNA was found twice as often in Stages IB and IIA than in advanced-stage disease (III and IV). These advanced-stage tumors were more commonly aneuploid. Neither HPV status nor DNA ploidy were predictive of survival for any stage of disease or therapeutic modality.

Adult↗
PubMed1992

Interactions between hypoxic and almitrine-induced vasoconstriction in the rat lung.

1. To test whether almitrine might improve the arterial partial pressure of O2 in patients with chronic obstructive airways disease by improvement of ventilation-perfusion matching, we looked at the interaction between hypoxic and almitrine-induced vasoconstriction in isolated rat lungs perfused with blood at constant flow. Increases in pressure represented increases in resistance. 2. Almitrine, given in increasing doses between challenges with 2% O2, enhanced hypoxic vasoconstriction at low doses but attenuated it at high doses. 3. Stimulus-response curves to hypoxia of increasing severity gave a sigmoid curve. 4. Almitrine solvent caused small changes in pulmonary artery pressure and shifted the stimulus-response curve slightly in a parallel fashion. 5. Small doses of almitrine enhanced the action of mild to moderate hypoxia, medium doses attenuated moderately severe hypoxia, whereas high doses depressed vasoconstriction due to all degrees of hypoxia. 6. These effects of almitrine on hypoxic vasoconstriction were compared with the effect of solvent by analysis of variance; the results substantiated significant enhancement of hypoxia by small doses and attenuation by large doses. 7. In patients, if similar effects apply, small doses of almitrine would assist ventilation-perfusion matching, but large doses might worsen it. 8. Almitrine-induced vasoconstriction was attenuated by a fall in perfusate temperature in a similar manner to hypoxic vasoconstriction. It was also attenuated by three drugs, chlorpheniramine, propanolol and diethylcarbamazine, all of which also decrease hypoxic vasoconstriction. The similarity between hypoxic and almitrine-induced pulmonary vasoconstriction is further confirmed.

Almitrine↗
PubMed1992

The use of ethnography and structured observations in the study of risk factors for the transmission of diarrhea in highland Papua New Guinea.

Methods that combine anthropological and epidemiological data are needed for the study of behavioral risk factors in communicable diseases, but as yet remain undeveloped. Ethnography is often undervalued as both the preliminary and integrative step in the design and execution of such studies. The analysis of critical methodological issues emerging from a case-control study of the behavioral and environmental risk factors for the transmission of childhood diarrhea in both urban and rural highland Papua New Guinea suggests that focused ethnographic assessments, complemented by structured observations performed by nonprofessionals, may provide a viable research design. In highland Papua New Guinea, significant risk factors include non-usage of latrines and sleeping with pigs; the latter is a factor that could have important implications regarding women's roles in a changing economy.

Anthropology, Cultural↗