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Biomedical subjects

R E Phillips

Publications and source records attributed to R E Phillips.

At least 19 recordsLinked to original sources
PubMed1992

Effects of reproductive status, ovariectomy, and photoperiod on vasoactive intestinal peptide in the female turkey hypothalamus.

Vasoactive intestinal peptide (VIP) appears to be a physiologically relevant prolactin (PRL)-releasing factor during the avian reproductive cycle, yet little is known of the factors involved in modulating the hypothalamic concentrations of this neuropeptide. A heterologous chicken VIP radioimmunoassay was developed to examine the effects of reproductive status, ovariectomy, and photoperiod on hypothalamic VIP immunoreactivity in the female turkey. VIP concentrations were highest in the median eminence/infundibular nuclear complex (ME/INF) relative to other subregions of the hypothalamus and changed only in this region during the reproductive cycle. Quiescent, nonphotostimulated hens subjected to stimulatory photoperiod exhibited a 1.6-fold increase in VIP in the ME/INF (quiescent 59.9 +/- 6.0 vs photostimulated 95.8 +/- 7.1 pg/microgram protein). An additional 2-fold increase in ME/INF VIP concentrations was observed in laying hens (183.0 +/- 28.5 pg/microgram protein). Coincident increases in plasma PRL were also observed. In contrast, during incubation and the photorefractory stage, a dissociation between hypothalamic VIP and plasma PRL occurred. No changes were observed in VIP in incubating hens, yet a 6-fold increase in PRL was noted, compared to layers. In addition, ME/INF VIP concentrations exhibited no change during the photorefractory stage, whereas a 28-fold decrease in plasma PRL occurred. VIP concentrations in the ME/INF of laying hens were unaffected by ovariectomy, whereas exposure to short photoperiod reduced VIP by 44%. The inhibitory effects of short photoperiod could not be reversed by administration of exogenous steroids, while steroid treatment reduced VIP concentrations by 45% in the ovariectomized hens. These results provide additional correlative evidence for a modulatory role of VIP in PRL secretion and suggest that the expression of this neuropeptide in the INF may serve as a neural link between photoperiodic mechanisms and PRL release during the avian reproductive cycle.

Animals↗
PubMed1992

Anaemia of Plasmodium falciparum malaria.

The pathophysiology of the anaemia of falciparum malaria is both complex and multifactorial, and results in a condition which is a major cause of mortality and morbidity in patients, especially children and pregnant women, living in malarial endemic areas. The importance of anaemia as a cause of death in malaria may well be underestimated because of difficulty in diagnosis, especially where parasitaemia may be low and the clinical picture may be confused with other causes of anaemia. Two clinical presentations predominate: severe acute malaria in which anaemia supervenes, and severe anaemia in patients in whom there have been repeated attacks of malaria. The major mechanisms are those of red cell destruction and decreased red cell production. Potential causes of haemolysis include loss of infected cells by rupture or phagocytosis, removal of uninfected cells due to antibody sensitization or other physicochemical membrane changes, and increased reticuloendothelial activity, particularly in organs such as the spleen. Decreased production results from marrow hypoplasia seen in acute infections, and dyserythropoiesis, a morphological appearance, which in functional terms results in ineffective erythropoiesis. The role of parvovirus B19 as a possible cause of bone marrow aplasia in a few cases is postulated. Finally, there is now evidence which points to genetic factors, HLA associated, which may protect against the development of malarial anaemia and which has become common in areas endemic for malaria.

Anemia↗
PubMed1991

Human immunodeficiency virus genetic variation that can escape cytotoxic T cell recognition.

In a longitudinal study of HIV seropositive patients, there were fluctuations in the specificity of cytotoxic T cells for the virus. This was matched by variability in proviral gag DNA epitope sequences in the lymphocytes of these patients. Some of these viral variants are not recognized by autologous T cells. Accumulation of such mutations in T-cell antigenic targets would provide a mechanism for immune escape.

Amino Acid Sequence↗
PubMed1991

Involvement of dopamine in prolactin release induced by electrical stimulation of the hypothalamus of the female turkey (Meleagris gallopavo).

Controversy exists regarding the role of dopamine (DA) in the regulation of avian prolactin (PRL) secretion. Consequently, we injected apomorphine, a DA agonist, and pimozide, a DA receptor blocker, into laying and nest-deprived incubating turkeys and studied their effect on PRL secretion before (-20, -10, 0 min), during (5, 10, 20, 30 min), and after (5, 15, 30 min) electrical stimulation in the ventromedial nucleus of the hypothalamus. Apomorphine (10 mg/kg, ip) completely abolished the electrical stimulation-induced PRL increase in both laying and nest-deprived incubating hens. Pimozide (2 mg/kg, ip) potentiated electrical stimulation-induced PRL secretion in laying hens. In the two pimozide experiments, peak responses were 10.9-fold for the pimozide-treated group vs 2.9-fold for the control group, and 5.4-fold for the pimozide-treated group vs 2.6-fold for the control group. In nest-deprived incubating hens, PRL response to electrical stimulation was unaffected by pimozide treatment. These data support the concept that DA is inhibitory to the neuroendocrine system which stimulates PRL secretion in laying hens. In incubating hens, the dopaminergic inhibition is diminished, allowing for the increased PRL level observed during incubation.

Analysis of Variance↗
PubMed1991

Exogenous prolactin delays photo-induced sexual maturity and suppresses ovariectomy-induced luteinizing hormone secretion in the turkey (Meleagris gallopavo).

A direct effect of prolactin (Prl) on gonadotropin secretion has been suggested but not convincingly demonstrated. The secretion of LH in response to photostimulation (phs) and ovariectomy (ovx) was evaluated in adult female turkeys that had received injections of ovine Prl (124 IU/bird/day for 14 days). In experiment 1, oPrl administration initiated on the day of ovx and phs in reproductively quiescent birds suppressed (p less than 0.05) the elevated LH from a peak level of 11.7 +/- 3.5 ng/ml to 5.1 +/- 0.8 ng/ml in ovx hens. The photo-induced LH increase was unaffected by the oPrl treatment in intact birds. In experiment 2, the oPrl treatment was initiated 7 days before ovx and/or phs. This treatment blunted the peak increase in LH level that follows phs in intact (p less than 0.05) and in ovx (p less than 0.05) hens. In both experiments, onset of lay following phs was delayed (p less than 0.05) in the oPrl-treated groups (29.4 +/- 0.9 days vs. 22.3 +/- 0.9 days; 34.8 +/- 0.5 days vs. 25.0 +/- 0.9 days). In experiment 3, administration of oPrl after ovx of laying hens suppressed the LH rise at essentially all sampling times tested. At the end of the experimental period, 6 of the 7 sham-operated, oPrl-treated laying hens, but none of the sham controls, displayed incubation behavior and had Prl levels of 1020 +/- 370 ng/ml compared to 34 +/- 7 ng/ml in vehicle-treated controls. The results suggest a role for Prl in incubation behavior and LH secretion in the turkey.

Animals↗
PubMed1991

Intracranial prolactin perfusion induces incubation behavior in turkey hens.

Intracranial perfusion of ovine prolactin (oPrl) via osmotic pump in laying turkey hens caused a sudden onset in incubation behavior, defined as an increase in nest visits. The hens also displayed a gradual decrease in egg laying during the time they were receiving oPrl, another indicator of the onset of incubation. Circulating immunoreactive turkey Prl levels fell during the perfusion period, even though the hens were displaying persistent nesting activity and reduced egg laying. No effects on serum LH were noted. Perfusion of oPrl during the first 14 days of photostimulation delayed the onset of egg laying by several days. No effects on serum Prl or serum LH were noted. It is suggested that incubation behavior is facilitated by central levels of Prl.

Animals↗
PubMed1990

Cerebral malaria in children.

Cerebral malaria is a rapidly progressive encephalopathy with up to 50% mortality. A cardinal feature is the massing of red cells containing mature Plasmodium falciparum within the cerebral capillaries. Adhesion of these parasitised red cells to endothelium, an event which may initiate cerebral malaria, is being studied at the molecular level. However, the relevance of these studies to the pathophysiology and treatment of human cerebral malaria is uncertain. Although chloroquine is still widely used to treat falciparum malaria, resistance has spread to most of the endemic zone. Quinine is emerging as the only effective treatment for cerebral malaria, though resistance to this drug threatens to become a problem. Alternative drugs are urgently needed.

Adult↗
PubMed1990

Oxygen-dependent modulation of erythropoietin mRNA levels in isolated rat kidneys studied by RNase protection.

Using oligonucleotide primers complementary to conserved regions in the mouse erythropoietin (Epo) gene, a portion of the rat Epo gene was amplified by the polymerase chain reaction to produce a probe suitable for assay of rat Epo mRNA by RNAse protection. The assay, which has sufficient sensitivity to measure to Epo mRNA in unstimulated rat kidneys, was used to demonstrate high amplitude in vitro modulation of Epo mRNA levels in response to changes in perfusate flow rate and oxygen tension in isolated kidneys, thus providing clear evidence that all the necessary events linking changes in oxygen delivery to the modulation of Epo mRNA levels can occur intrarenally.

Animals↗
PubMed1990

Hypoglycemia during diarrhea in childhood. Prevalence, pathophysiology, and outcome.

To determine the frequency and outcome of hypoglycemia during diarrhea in childhood, we screened 2003 consecutive patients less than 15 years of age who were admitted to a diarrhea treatment center in Dhaka, Bangladesh. Hypoglycemia, defined as a blood glucose concentration less than 2.2 mmol per liter, was found in 91 patients (4.5 percent), 39 (42.9 percent) of whom died. We also measured the plasma concentrations of glucoregulatory hormones and gluconeogenetic substrates in 46 of the patients with hypoglycemia who were 2 to 15 years old and in 25 normoglycemic patients matched with them for age and weight. The patients with hypoglycemia had had diarrhea for less time than the normoglycemic patients (median, 12 vs. 72 hours; P less than 0.05), and their last feeding had been 18 hours before admission, as compared with 9 hours for the normoglycemic patients (P less than 0.05). The groups were similar in terms of nutritional status, the proportion of patients who had fever, and the types of pathogens recovered from stool samples. The plasma C-peptide concentrations were low (less than 0.30 nmol per liter) in all the hypoglycemic patients. As compared with the normoglycemic patients, the patients with hypoglycemia had elevated median plasma concentrations of glucagon (44 vs. 11 pmol per liter; P = 0.001), epinephrine (3400 vs. 1500 pmol per liter; P = 0.012), norepinephrine (7500 vs. 2900 pmol per liter; P = 0.002), and lactate (3.5 vs. 2.1 mmol per liter; P = 0.020) and similar alanine and beta-hydroxybutyrate concentrations. Eighteen hypoglycemic patients with severe malnutrition had been ill longer than 26 better-nourished patients with hypoglycemia (median duration of illness, 18 vs. 10 hours; P = 0.023) and had lower median plasma concentrations of lactate (1.9 vs. 3.9 mmol per liter; P = 0.021) and alanine (173 vs. 293 micromol per liter; P = 0.040). We conclude that hypoglycemia is a major cause of death in association with diarrhea. Because the glucose counterregulatory hormones were appropriately elevated in the children with diarrhea and hypoglycemia, whereas the gluconeogenetic substrates were inappropriately low, we further conclude that the hypoglycemia observed in such patients is most often due to the failure of gluconeogenesis.

Adolescent↗
PubMed1990

Pharmacokinetics of three commercial antivenoms in patients envenomed by the Malayan pit viper, Calloselasma rhodostoma, in Thailand.

The pharmacokinetics of 3 monospecific antivenoms were compared in patients envenomed by the Malayan pit viper, Calloselasma rhodostoma. There was a biphasic decline in serum concentrations following intravenous administration. The initial rapid decline was attributable to the formation of venom-antivenom complexes, as the fall in antivenom during this phase was positively correlated with the initial venom concentration (P = 0.045). The total apparent volume of distribution for each antivenom was 1.5-3 times larger than that of the central compartment, which suggests some tissue distribution in addition to complex formation. This was marked for antivenom from the Government Pharmaceutical Organization of Thailand which contained mostly F(ab)2 fragments. The terminal elimination half time was shorter for Twyford antivenom of caprine origin. Systemic clearance was lower for Thai Red Cross antivenom. In 8 of the 26 patients who experienced recurrence of non-clotting blood after initial response to antivenom, serial measurements of plasma venom and antivenom concentrations revealed that recurrence of venom antigenemia and non-clotting blood bore no direct relation to the elimination half-life of the antivenom used, but non-clotting blood recurred when serum antivenom levels fell below 10-20% of the total given. There is no substitute for close monitoring of envenomed patients so that indications for further antivenom can be detected promptly.

Adolescent↗
PubMed1990

Plasmodium falciparum hyperparasitaemia: use of exchange transfusion in seven patients and a review of the literature.

During the last 15 years, at least 35 patients with severe falciparum malaria or babesiosis have recovered following treatment by exchange of up to 10 l of blood. In a patient treated in Manchester, a parasitaemia of 2.10 X 10(6) microliters (42 per cent) was virtually eliminated over eight hours by a 3.5 litre exchange blood transfusion. However, the equipment and amounts of compatible blood required for total exchange are rarely available in areas endemic for malaria and the risks of the procedure, including transfusion-related infections, are high. Partial exchange transfusion with one to two litres of blood carried out over two to seven hours, reduced Plasmodium falciparum parasitaemias of 0.33-1.48 X 10(6)/microliters (13-38 per cent) to 0.11-0.81 X 10(6) (4-17 per cent) in six Thai patients who were receiving intravenous quinine. The reduction in parasitaemia ranged from 0.13-0.67 X 10(6) microliters (9-12 per cent) within six hours. During the same period, parasitaemia in 13 patients with cerebral malaria treated with chemotherapy alone showed little reduction from initial levels of 0.20-1.74 X 10(6)/microliters (11-42 per cent). One of the patients who were treated with exchange transfusion died with intractable hypotension before the procedure could be completed and two others developed oliguric renal failure which was controlled by peritoneal dialysis. Partial exchange transfusion is a promising and practical alternative to total exchange where facilities are limited. It deserves further assessment in the rural tropics.

Adolescent↗
PubMed1989

Failure of interferon alfa and tribavirin in rabies encephalitis.

OBJECTIVE: To test the effect of interferon alfa and tribavirin (ribavirin) in patients with rabies encephalitis. DESIGN: An open trial of chemotherapy and intensive care in patients with early rabies. SETTING: The intensive care unit of a Bangkok hospital. PATIENTS: Four conscious men with clinical rabies encephalitis. INTERVENTIONS: Rapid virological diagnosis of rabies. Treatment with intravenous and intraventricular injections of high doses of lymphoblastoid interferon alfa in three patients and tribavirin in one patient. Intensive care was given throughout. MAIN OUTCOME MEASURES: Rabies infection confirmed by antigen detection and virus isolation. Rabies neutralising antibody and specific IgM sought in serum and cerebrospinal fluid. Interferon concentrations monitored before and during treatment in three patients. RESULTS: Interferon alfa treatment produced high concentrations in serum and cerebrospinal fluid. All four patients died after 5 1/2 to 12 1/2 days of treatment with no evidence of virostatic or clinically beneficial effects from either treatment. CONCLUSION: Interferon alfa treatment is not effective in rabies encephalitis. The use of tribavirin warrants further study, possibly combined with new therapeutic methods.

Adolescent↗
PubMed1989

Contribution of focal haemorrhage and microvascular fibrin deposition to fatal envenoming by Russell's viper (Vipera russelli siamensis) in Burma.

In Burma, clinicopathological studies were carried out in three young farmers who died 15, 52 and 36 h after being bitten by Russell's vipers. Clinical features included local swelling, spontaneous systemic bleeding, defibrination, shock, cardiac arrhythmia, hypoglycaemia, coma and oliguria. On admission to hospital, 15, 48 and 21 h after the bites, serum venom antigen concentrations ranged from 50 to 130 ng/ml. Autopsies revealed widespread congestion and bleeding in the lungs, gastrointestinal and renal tracts, adrenals, heart, brain and anterior pituitary. There was histopathological evidence of focal haemorrhage and fibrin deposition at the site of the bite and in the pituitary, lungs and kidneys and acute tubular necrosis. Deposition of fibrin microthrombi results from the action of venom procoagulants. Shock was attributed to increased capillary permeability, revealed clinically by conjunctival oedema. Acute pituitary/adrenal failure in one case was explained by fibrin deposition and haemorrhage in the anterior pituitary--resembling Sheehan's syndrome. Acute tubular necrosis resulted from ischaemia caused by fibrin deposition and to prerenal factors. An intractable cardiac tachyarrhythmia may have been caused by subendocardial and myocardial haemorrhages.

Adolescent↗
PubMed1989

Vernal increases in prolactin levels of nonbreeding male and female canvasbacks (Aythya valisineria).

Serum levels of prolactin were determined in nonbreeding male and female canvasbacks (Aythya valisineria) from mid-April to late June to evaluate the temporal changes occurring during spring. During this time interval, serum prolactin levels increased 1.5- to 2-fold in both males and nonlaying females (P less than 0.01). Serum prolactin levels of males and females exposed to natural lighting and temperature at Delta, Manitoba (50 degrees 11'N, 98 degrees 19'W), steadily increased from mid-April when the daylength was 14 hr light and peaked in mid-June when daylength was 16.25 hr light. Administration of exogenous estradiol via slow-release subdermally implanted capsules in females with intact reproductive systems had a marginal effect on reducing the seasonal increase in prolactin. Exogenous testosterone in similar slow-release capsules implanted subdermally in males had no influence on circulating prolactin levels.

Animals↗
PubMed1989

Effects of preoptic and hypothalamic lesions in female turkeys during a photoinduced reproductive cycle.

Prolactin (Prl) is released by electrical stimulation in the turkey hypothalamus and preoptic area (POA). Possible trajectories for POA efferents to the median eminence (ME) were tested by placing lesions in the POA, the lateral hypothalamus (LHy), or the ventromedial nucleus of the hypothalamus (VMN) of reproductively quiescent turkey hens, then subjecting them to long photoperiods while monitoring their blood Prl levels and nesting activities. In addition, lesions were made in the VMN of a group of incubating hens to learn whether the lesions would cause the elevated Prl levels to fall or interfere with incubation behavior. Lesions in medial POA, LHy, or VMN prevented the onset of incubation and prevented the large rise in Prl associated with it. However, these lesions did not interfere with the initial, more gradual Prl rise caused by increasing daylengths. Lesions in LHy or VMN appeared to interfere with a pathway lying laterally from POA to ME. Electrical stimulation in medial POA, which caused an increase in circulating Prl, failed to do so in hens with LHy or VMN lesions. Lesions in the VMN of incubating hens caused them to leave the nest and suffer a large decline in Prl, both within 48 h. It is tentatively suggested that incubation behavior and its associated elevated Prl are prevented by the POA lesions and that lesions in LHy or VMN, which mimic POA lesion effects, interfere with POA efferents projecting to ME.

Animals↗