Biomedical subjects
A Foster
Publications and source records attributed to A Foster.
Measles, corneal ulceration and childhood blindness: prevention and treatment.
Explore the source record for details and available documents.
Treatable blindness: cataract.
Explore the source record for details and available documents.
[The diabetic foot: importance of a center for specialized care].
Explore the source record for details and available documents.
Parallel pathways can conduct visual CS information during classical conditioning of the NM response.
Single and combined lesions were made to the lateral geniculate nucleus (LGN), the superficial layers of the superior colliculus (SC), and the pretectal nuclei (Ptc) prior to conditioning of the nictitating membrane (NM) response in rabbit with a visual conditioned stimulus (CS). Due to technical considerations, lesions of the dorsal LGN were accompanied by lesions of the visual cortex, the only output of the dorsal LGN, in order to render the dorsal LGN nonfunctional. Single lesions to any one of the 3 target systems (LGN, SC, Ptc) did not alter the rate of conditioning. Furthermore, double lesions to any 2 of the systems did not prevent conditioning, although LGN + SC lesions significantly retarded acquisition. When all 3 systems were lesioned, however, animals never acquired to the visual CS, although they successfully conditioned to an auditory CS. The results indicate that in rabbit there are parallel visual pathways individually capable of supporting the acquisition of conditioned NM responses.
Evidence of in-vivo omega-oxidation of peptide leukotrienes in the rat: biliary excretion of 20-CO2H N-acetyl LTE4.
In a previous study in our laboratory it was observed that after [3H] LTC4 administration (luCi/kg i.v.) to the anesthetized rat, significant amounts of injected radioactivity (approximately 25%) were associated with previously unidentified biliary polar metabolite(s). In the present study we describe the isolation and characterization of the predominant polar metabolite. Rats were injected with synthetic LTC4 (20 microgram/kg i.v.) and bile collected over 30 min. After extraction and purification (2 step RP-HPLC procedure), the retention time of the metabolite was compared (plus coinjections) and found to be identical with synthetic 20-CO2H N-Ac LTE4 in two RP-HPLC systems. Also, the UV spectrum of the biologically derived metabolite was compared and found identical to the synthetic material, giving a characteristic conjugated triene absorption in the UV with a max of 281 nm and shoulders at 270 and 290 nm. Further, the trimethyl ester derivative of the metabolite showed identical chromatographic behaviors in 2 reverse and 2 normal phase HPLC systems compared with synthetic 20-CO2H N-Ac LTE4 trimethyl ester. We conclude omega-oxidation of peptide leukotrienes occurs in the rat and that 20-CO2H N-Ac LTE4 is an in vivo product of LTC4 metabolism.
Metabolism and excretion of peptide leukotrienes in the anesthetized rat.
The metabolism and excretion of the peptide leukotrienes C4, D4, E4 and N-acetylleukotriene E4 have been studied in the anesthetized rat. The intravenous administration of [3H]leukotriene C4 (2.6 X 10(-11) mol/kg) showed a rapid clearance of radioactivity from the blood and a time-related biliary excretion, recovering 69 +/- 1.6% (n = 6) over 60 min. Less than 1% of total radioactivity was recovered in the urine over the same time period. Similarly, the intravenous administration of [3H]leukotriene D4 (2.5 X 10(-11) mol/kg), [3H]leukotriene E4 (2.5 X 10(-11) mol/kg) and N-acetyl[3H]leukotriene E4 (2.1 X 10(-11) mol/kg) showed a 62 +/- 7.5% (n = 4), 52 +/- 1.5% (n = 4) and 37 +/- 4.6% (n = 5) biliary recovery of radioactivity, respectively, after 60 min. Examination of bile identified leukotriene D4 and N-acetylleukotriene E4 as the main products, although substantial radioactivity, which probably represents unidentified polar products, was present at the solvent fronts of the reverse-phase HPLC. Time course studies indicated a relatively rapid conversion of leukotriene C4 to leukotriene D4, while leukotriene D4 metabolism appeared to be much slower. Leukotriene E4 was a minor product, suggesting that the N-acetylation process is rapid. Incubation of [3H]leukotriene C4 in rat plasma and whole blood in vitro resulted in a slow conversion of leukotriene C4 to leukotriene D4 and leukotriene E4 only. These data suggest that the majority of the leukotriene metabolism and excretion in vivo in the anesthetized rat occurs predominantly in the hepatic system. We conclude that this model is suitable for the measurement of in vivo production of peptide leukotrienes.
Vitamin A supplements and mortality related to measles: a randomised clinical trial.
One hundred and eighty children admitted with measles were randomly allocated to receive routine treatment alone or with additional large doses of vitamin A (200,000 IU orally immediately and again the next day). Baseline characteristics of the two groups were virtually identical for age, severity of measles, and vitamin A and general nutritional states. In 91% of the children serum vitamin A concentrations were less than 0.56 mumol/l. Of the 88 subjects given vitamin A supplements, six (7%) died; of the 92 controls, 12 (13%) died (p = 0.13). This difference in mortality was most obvious for children aged under 2 years (one death out of 46 children receiving supplements versus seven deaths out of 42 controls; p less than 0.05) and for cases complicated by croup or laryngotracheobronchitis. Mortality was several times higher in marasmic than in better nourished children, regardless of study allocation (p less than 0.01).
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.
Reduced natural killer cell activity in autism.
Explore the source record for details and available documents.
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.
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.
Diagnosis of primary open angle glaucoma by doctors and medical auxiliaries.
Explore the source record for details and available documents.
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.
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.
World blindness--a challenge to all doctors.
Explore the source record for details and available documents.
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.
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.