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Biomedical subjects

A Foster

Publications and source records attributed to A Foster.

At least 163 records · Page 9Linked to original sources

Biliary and urinary excretion of peptide leukotrienes in the domestic pig.

The metabolism of leukotriene (LT)C4 and its major routes of elimination in vivo have been studied in four anesthetized domestic pigs administered intravenous [3H]-LTC4 (0.5 microCi/kg). The kinetic profile of LTC4 in the blood was followed for 60 min after administration while the biliary and urinary excretion of LTC4 and its metabolites were determined over a 120 min interval. The total recovery of radioactivity in bile and urine was 45% +/- 1 (n = 3) and 18% (n = 2) respectively. Examination of the radioactive metabolites in bile showed LTD4 (44% of biliary content) and LTE4 (21% of biliary content) as the major identified lipoxygenase products at t 1/2 (27 min). The only identified cysteinyl leukotriene observed in the urine was LTE4 (13% of urinary content). In both bile and urine substantial amounts of radioactivity were detected at the solvent front of the reverse phase chromatographic system indicating the presence of additional unidentified metabolites. We suggest that measurement of metabolites using these sampling methods may be useful for the detection and measurement of peptide leukotriene production in vivo.

Animals↗

Corneal ulceration, measles, and childhood blindness in Tanzania.

One hundred and thirty Tanzanian children with corneal ulceration were clinically examined to determine the cause of the ulceration. 37% of the ulcers were associated with recent measles infection and 38% of the children had bilateral ulceration. Herpes simplex virus infection was the commonest cause of ulceration in the series, but vitamin A deficiency was the major cause of bilateral ulceration, subsequent blindness, and mortality in this series. Other significant causes of childhood corneal ulceration were the use of traditional eye medicines, confluent measles keratitis, and ophthalmia neonatorum. We discuss the various mechanisms by which measles causes corneal ulceration, and the priorities in prevention and management of corneal ulceration in African children.

Blindness↗

Comparative effects of leukotrienes on porcine pulmonary circulation in vitro and in vivo.

The present study examined the effect of leukotrienes on porcine pulmonary vasculature both in vivo and in vitro. In vitro studies using isolated vascular strips demonstrated that pulmonary arterial smooth muscle contracted to leukotriene C4 (LTC4), whereas pulmonary vein smooth muscle did not. Pulmonary arterial contraction was due to both the direct action of LTC4 and secondarily generated thromboxane A2 (TxA2). In vivo, LTC4 injection caused a pronounced but transient increase in pulmonary arterial pressure and pulmonary arterial wedge pressure (Ppw), with a smaller effect on left ventricular end-diastolic pressure. Effects of LTD4 were smaller with comparable pressure changes at all three sites, suggesting a primary cardiac effect. Like LTC4, histamine caused a disproportionate increase in Ppw vs. left ventricular end-diastolic pressure. These observations suggest that LTC4 causes pulmonary venoconstriction in vivo despite its lack of effect on pulmonary vein smooth muscle in vitro. This discrepancy may be due to venoconstrictor effects of TxA2 generated from upstream pulmonary arterial vessels.

Animals↗

Cataract blindness in Africa.

Of the estimated 17 million blind from cataract in the world, two to three million live in Africa, where manpower and material resources are inadequate to meet the increasing backlog of treatable blindness. The training of primary health care workers to screen rural Africans for cataract, and of eye auxiliaries and general doctors to select patients and perform surgery, is essential. Motivation for surgery will increase if eye services are made more accessible and reliable. This requires more motivated trained staff and appropriately equipped static eye facilities.

Africa↗

Trachoma: evaluation of a new grading scheme in the United Republic of Tanzania.

A new simplified grading system for trachoma, which is based on the presence or absence of five selected key signs, has been assessed. The level of inter-observer variation and of variation for individual observers (intra-observer variation) showed that the system had good reproducibility following a training period that included interactive clinical teaching. The grading scheme was quickly learned by experienced ophthalmologists and auxiliary health personnel (ophthalmic nurses). The scheme should therefore be suitable for widespread application in field surveys of trachoma.

Allied Health Personnel↗

Immune abnormalities in patients with autism.

We have begun an investigation on the immune systems of patients with autism in attempt to determine if immune mechanisms are involved in the development of this severe developmental disorder. A study of 31 autistic patients has revealed several immune-system abnormalities, including reduced responsiveness in the lymphocyte blastogenesis assay to phytohemagglutinin, concanavalin A, and pokeweed mitogen; decreased numbers of T lymphocytes; and an altered ratio of helper to suppressor T cells. Immune-system abnormalities may be directly related to underlying biologic processes of autism, or these changes may be an indirect reflection of the actual pathologic mechanism.

Adolescent↗

Histamine releases PGI2 from human pulmonary artery.

Histamine caused a triphasic response of human pulmonary artery strips in vitro, consisting of a small initial contraction followed by pronounced relaxation preceding a second contractile response. These characteristics were not seen with other contractile stimuli including 5-hydroxytryptamine, leukotriene D4, and KCl. The relaxant component of this response was ablated by removal of endothelium from the vascular strips or by pretreatment of the tissue with 1 microM indomethacin. Measurement of the PGI2 degradation product 6-keto-PGF1 alpha in supernatants from histamine-challenged tissues confirmed the synthesis of PGI2. Supernatants from unstimulated or leukotriene-challenged tissues contained no detectable amounts of 6-keto-PGF1 alpha. The histamine H1 antagonist diphenydramine inhibited both the contractile and relaxant responses to histamine whereas the H2 antagonist cimetidine affected neither component. The released PGI2 significantly altered the dose-response curve to histamine without inhibiting the maximal contractile responses. We conclude that histamine induces PGI2 formation from pulmonary arterial endothelium via an H1 receptor.

Dose-Response Relationship, Drug↗

The synthesis of N-acetyl-leukotriene E4 and its effects on cardiovascular and respiratory function of the anesthetized pig.

The effects of the putative biliary metabolite of the peptido-leukotrienes, N-acetyl-leukotriene (LT) E4 has been investigated in the anesthetized pig. Intravenous bolus doses of synthetic N-acetyl-LTE4 produced minimal respiratory and cardiovascular actions in the pig. N-acetyl-LTE4 was approximately 100-fold less active than LTC4. The actions of N-acetyl-LTE4 were not blocked by pretreatment of the animals with indomethacin (5 mg/kg iv) or with a selective LTD4 antagonist L-649,923 (5 mg/kg plus 2 mg/kg/hr iv). In summary, N-acetyl-LTE4 exerts weak actions in the pig which is consistent with the acetylation process being a mechanism of detoxification.

Animals↗

Childhood blindness from corneal ulceration in Africa: causes, prevention, and treatment.

Corneal scarring is responsible for approximately 70% of blindness in children in African countries. Recent studies confirm that measles infection is a common predisposing factor and that vitamin A deficiency is responsible for the majority of bilateral corneal ulceration. Herpes simplex keratitis (caused by human (alpha) herpesvirus types 1 and 2), ophthalmia neonatorum, and the use of traditional eye medicines also constitute significant causes of corneal ulceration in children in Africa. Intervention strategies, the management of corneal ulceration in children, and areas for future investigation are discussed.

Africa↗

A simple surveillance system for xerophthalmia and childhood corneal ulceration.

A simple cost-effective surveillance system is described for reporting cases of xerophthalmia and childhood corneal ulceration. The system is suitable for use by ophthalmic auxiliaries in developing countries.Presented are the results of a 2-year surveillance involving 15 hospitals in 11 areas of the United Republic of Tanzania. Cases of xerophthalmia in its early stages (characterized by night blindness or Bitot's spots) were found in all areas surveyed. Of almost 300 cases of unilateral and bilateral corneal ulceration, 46% and 79%, respectively, followed a recent infection with measles. The single most important cause of bilateral corneal ulceration was vitamin A deficiency. The surveillance system has proved to be particularly useful as a first step in defining the type and distribution of serious corneal disease in children.

Child↗

Differential activity of leukotrienes upon human pulmonary vein and artery.

Responses to leukotrienes B4, C4, D4 and E4 were examined in human pulmonary artery and pulmonary vein preparations from surgical specimens. Leukotrienes C4 (LTC) and D4 (LTD) were potent contractants of pulmonary vein over the dose range of 10(-10) M to 10(-6) M, whereas they produced minimal contractions of human pulmonary artery only at concentrations of 10(-8) M or greater. Leukotriene E4 was less potent than LTC or LTD, and leukotriene B4 (LTB) at concentrations up to 10(-6) M had no effect upon either pulmonary veins or pulmonary arteries. Contractions of pulmonary vein by LTD were inhibited in a competitive manner by FPL 55712. Dose response characteristics of LTD and inhibition by FPL 55712 were similar for pulmonary venous and bronchial smooth muscle. We conclude that pulmonary vein smooth muscle has leukotriene receptors comparable to those of bronchial smooth muscle whereas pulmonary artery does not.

Dose-Response Relationship, Drug↗

In vitro responses of human asthmatic airway and pulmonary vascular smooth muscle.

Airway and pulmonary vascular smooth muscle was obtained from the surgically resected lobe of a human asthmatic allergic to grass pollen who presented with an endobronchial carcinoid tumor. Grass antigen induced sustained contractions of bronchial and pulmonary vein, but not pulmonary artery tissue. Capsaicin did not alter the bronchial response to grass antigen. Contractions to leukotrienes B4, C4, D4 and E4 and methacholine were equivalent to those seen in nonasthmatic human lung tissue, whereas those to histamine were strikingly greater and disproportionate to methacholine. The C3a octapeptide Ala-Ala-Ala-Leu-Gly-Leu-Ala-Arg produced contractions of pulmonary vein and pulmonary artery. These findings are compared with those obtained using human lung samples from nonasthmatic individuals.

Allergens↗