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Biomedical subjects

R Hunt

Publications and source records attributed to R Hunt.

At least 19 recordsLinked to original sources

Increased lymphatic pumping ability in pregnant ewes.

OBJECTIVE: Daily the lymphatic system returns several liters of fluid to the systemic circulation. Unlike blood, lymph is pumped against a pressure gradient. Because vessels in the systemic circulation are hyporesponsive to vasoconstrictor hormones during pregnancy, we decided to assess whether lymphatic pumping ability was decreased during pregnancy. STUDY DESIGN: Ten pregnant ewes were chronically catheterized in the left thoracic duct and jugular vein. Four days after surgery thoracic duct pumping ability was determined by measuring the lymph flow rate as a function of outflow pressure by varying the height at which lymph flow drains in an open-flow system. RESULTS: Lymph flow was plotted against outflow pressure, and the value at which lymph flow decreases is defined as the "breaking point." The outflow pressure at which lymph flow equals zero is the "stopflow" pressure; this value defines the pumping ability. The pregnant ewes had a breaking point of -1 +/- 2.7 versus 14.4 +/- 3.0 mm Hg (mean +/- SD) for the nonpregnant sheep. Stopflow pressures were 62 +/- 7.3 versus 23.9 +/- 4.7 mm Hg (mean +/- SD) for the nonpregnant ewes (p < 0.05). CONCLUSIONS: The ability of the lymphatic system to generate pressure is increased during pregnancy, but the breaking point is diminished. Alterations of lymphatic pumping ability could explain fluid retention under pathophysiologic conditions.

Animals

Glucose turnover and its regulation during intense exercise and recovery in normal male subjects.

Intense exercise to exhaustion is expected to be associated with rapid and large changes in glucose production (Ra) and utilization (Rd). To quantify these, and to determine their mechanisms and those of the prolonged postexercise hyperglycemia, we measured circulating metabolic regulators and glucose kinetics, the latter by the method of enriched tracer [3-3H] glucose infusion during exercise. Eighteen fit, lean young male subjects exercised to exhaustion at 80% of maximal workload (approximately 100% VO2max) on a cycle ergometer. Plasma glucose was 4.90 +/- 0.08 mM/L at rest, increased during exercise, then abruptly to 6.91 +/- 0.40 mM/L at 4 min recovery then gradually declined. Plasma insulin was constant during exercise, then doubled to 162 +/- 28 pmol/l until 20 min recovery, before declining. Plasma glucagon increased by 71 +/- 11 pg/mL. Plasma norepinephrine increased 18-fold and epinephrine 14-fold, both declining by 20 min recovery. Ra increased 7-fold by exhaustion to 13.0 +/- 1.18 mg/kg/min, then decreased to 2.43 +/- 0.24 mg/kg/min by 9 min, then to about 2 mg/kg/min the rest of recovery. Rd rose 3-fold (6.61 +/- 0.70 mg/kg/min), and remained lower than Ra to 7 min recovery, but thereafter declined more slowly. Thus, the rapid and extremely large increase in Ra was not matched by the increment in Rd during exercise and early recovery. We suggest that unlike in exercise of lesser intensity, the major mediators of both the increase in Ra and the restraint of the increase in Rd are the catecholamines. The post exercise hyperglycemia and hyperinsulinemia are appropriate to muscle glycogen repletion.

Adult

Detection of breast abnormalities on teleradiology transmitted mammograms.

The authors conducted an observer performance study to compare breast lesion detection of conventional mammography (CM) with teleradiology (TE) transmitted mammograms. One hundred four abnormal, single-projection mammographic images were transmitted by teleradiology. Abnormalities included 11 cases with skin thickening or retraction, 48 cases with microcalcifications, and 52 with parenchymal masses. The CM and TE images were reviewed by four mammographers who indicated the type and location of abnormalities and a level of confidence for their diagnostic decisions. For each of three detection tasks--skin and nipple abnormalities, microcalcifications, and masses--receiver operating characteristic curve analysis was performed for individual readers and all readers as a group. For detecting skin and nipple abnormalities, readers performed significantly better with CM than with TE (z = 2.05, P = less than 0.04). However, no significant differences were found among readers for detection of either microcalcifications or masses. Further improvements in hardware and imaging parameters may improve detection of soft tissue abnormalities. Further evaluation is necessary to determine whether teleradiology might be applicable to breast cancer screening.

Breast Neoplasms

Staphylococcus aureus enterotoxin B challenge of monkeys: correlation of plasma levels of arachidonic acid cascade products with occurrence of illness.

Arachidonic acid cascade products have been shown to be increased in vitro in Staphylococcus aureus enterotoxin B (SEB)-treated epithelial cell cultures in our laboratory. In order to confirm that these products were clinically related to SEB intoxication, monkeys were administered SEB by nasogastric intubation. It caused emesis in five of six monkeys (less than 4 h), and the sixth monkey showed signs of mild illness. The monkeys which vomited continued to display signs of gastrointestinal illness beyond 8 h but were without any apparent signs of illness by 24 h. Blood samples were collected prior to SEB administration, upon first indication of illness, and at twice that time interval. One week prior to SEB treatment, the same monkeys were administered saline by nasogastric intubation and in every way handled similarly in order to serve as their own controls. Blood samples were taken from the control animals at 0, 4, and 8 h. The plasma concentrations of prostaglandin E2 (PGE2), leukotriene B4 (LTB4), and 5-hydroxyeicosatetraenoic acid (5-HETE) did not vary significantly throughout the 8-h experiment for saline-treated controls, nor did they differ from the concentrations found in the plasma of monkeys just before administration of SEB. When the SEB-treated monkeys showed the first indication of illness (less than 4 h), the mean of the concentration in plasma of PGE2 increased 1.44-fold, that of LTB4 increased 2.23-fold, and that of 5-HETE was essentially unchanged. At twice the time interval of the first display of illness (less than 8 h), PGE2 was still elevated (1.48-fold), LTB4 had decreased slightly to 1.66-fold, and 5-HETE had soared (3,45-fold), suggesting a divergence in the enzymatic utilization of the parent compound of the latter two metabolites, 5-hydroperoxyeicosatetraenoic acid. These studies suggest that arachidonic acid cascade metabolites were a consequence of SEB intoxication and may provide a logical site for metabolic interference in SEB-induced toxicity.

Animals

Early postnatal administration of 5,7-dihydroxytryptamine: effects on substance P and thyrotropin-releasing hormone neurons and terminals in rat brain.

Substance P, thyrotropin-releasing hormone (TRH) and serotonin are putative neurotransmitters which have been proposed to co-exist in some brain neurons. Our previous immunocytochemical and biochemical studies have demonstrated that 85-100% of all serotonin neurons are destroyed following neonatal 5,7-dihydroxtryptamine (5,7-DHT) treatment. In this study, we have determined the effect of neonatal 5,7-DHT and desipramine (DMI) treatment on the biochemical content and immunocytochemical localization of substance P and TRH throughout the brain. Interestingly, we have observed that virtually all substance P- and TRH-immunoreactive cells in the ventral pons-medulla are destroyed by the neurotoxin. However, peptide-containing neurons in other regions were not affected. Additionally, we measured the peptide content and found that TRH is significantly decreased in the spinal cord (-50%) and pons-medulla (-20%), but not in other brain regions. Substance P content was not significantly altered in any region, even after a greater than 90% reduction of serotonin. These data indicate that the co-localized substance P and TRH forms a small proportion of the total peptide in brain.

5,7-Dihydroxytryptamine

An influence of diet on transplantation immunity.

It was discovered by chance that mice raised under otherwise entirely conventional conditions of husbandry but fed upon autoclaved diet (diet A) had stronger cell-mediated immune reactions than those of mice raised under the same conditions but with an unmodified diet (diet B) : skin allografts were rejected more quickly, transplantation tolerance was more difficult to procure and fibrosarcomas induced by the injection of methylcholanthrene (MCA) arose more slowly and less often. Analysis showed that these findings could be explained at least in part by the discovery of Mertin & Hunt (1976, p. 928) that a partial deprivation of polyinsaturated fatty acids led to an intensification of cell-mediated immunity; on the other hand, experiments with dietary mixtures made it seem unlikely that this was the whole explanation and pointed towards some positive immunopotentiation by an ingredient of autoclaved diet. This, it was proposed, might be a compound of unknown composition resulting from the interaction of vitamin A with other dietary constituents. This interpretation was not supported by direct evidence but by confirming that retinol derivatives, especially retinyl acetate, could exercise an immunopotentiation of the kind and degree under investigation: retinyl acetate could counteract the immunosuppressive action of linoleic acid, though retinyl methyl ether was ineffective. Although retinyl derivatives may protect against MCA tumours by impeding its metabolic conversion to an oncogenic form, the effects of an autoclaved diet upon skin allograft survival, the induction of tolerance and the formation of tumours is probably mediated through an immunological mechanism.

Animals

Prolonged apnea of an oral surgery patient after administration of succinylcholine.

To properly diagnose the presence of a genetic pseudocholinesterase variation, the family history is important. Furthermore, the DN and pseudocholinesterase tests are most useful, but if facilities for these are not available, one should be wary of patients with abnormal liver function tests. Certainly medical history, family medical history, laboratory evaluation, and knowledge of the disease processes should avoid unnecessary complications.

Adolescent

Reduction by linoleic acid of the severity of experimental allergic encephalomyelitis in the guinea pig.

This paper reports the effects of supplementation of the diet with linoleic acid on the severity of experimental allergic encephalomyelitis (EAE) in guinea pigs. Clinical signs of disease (e.g. paresis, paraplegia, urinary incontinence), weight loss, frequency of perivascular lesions in the central nervous system and ability of isolated lymph node cells to respond to myelin basic protein in vitro were all reduced by linoleic acid supplementation. Linoleic acid was effective when fed at a dose of 0.5 ml/day from 7 to 21 days after sensitization of the animals with basic protein, i.e., before and during the time in which clinical signs normally appeared. The same daily dose fed from 7 days before to 7 days after sensitization, i.e., ceasing about 7 days before the normal time of appearance of clinical signs, produced no significant effect. Feeding linoleic acid to normal guinea pigs significantly altered the fatty acid composition of their serum and lymph nodes, but not of their brain. Of several possible explantations for the protective effect of lineolic acid in EAE, we considered action by this essential fatty acid on the immune system most likely.

Animals

Cardiopulmonary manifestations of systemic lupus erythematosus.

Nine of 17 patients (52%) with systemic lupus erythematosus participating in a controlled prospective study were found to have maximal mid-expiratory flow rates suggestive of obstructive or obstructive and restrictive pulmonary disease. Cigarette smokers with systemic lupus erythematosus had significantly lower (P less than .05) maximal mid-expiratory flow rates than either non-smokers with systemic lupus erythematosus or smokers with degenerative joint disease. By echocardiography, pericardial thickening was seen in six of 17 patients (41%) and mitral valvular abnormalities were noted in four of 17 (24%) patients with systemic lupus erythematosus. Echocardiography was found to be an effective means of detecting pericardial disease in patients with systemic lupus erythematosus.

Adolescent

Preclinical toxicological study of phosphonoacetic acid: determination in blood by selected ion monitoring.

Confirmed observations of the inhibition of oncogenic viruses by phosphonoacetic acid led to preclinical trials in animal model systems. Circulating phosphonoacetic acid was detected in the blood of mouse, rabbit and monkey after oral or subcutaneous administration of the drug. Phosphonoacetic acid is quantified in blood, after removing proteins and lipids, as the trimethylsilylated derivative, by monitoring the intensity of the protonated molecular ion and also that of phosphonopropionic acid (internal standard) using chemical ionization mass spectrometry combined with gas chromatography. The detection limit is 20 ng ml-1 when 0.2 ml serum is analyzed. A dosage of 230 mg kg-1 day-1 by continuous infusion is proposed for therapeutic trials in monkeys. This dose is well tolerated and results in slowly increasing blood levels of phosphonoacetic acid which reach a maximum of approximately 50 microgram ml-1 in a four day infusion, and decrease to 2 microgram ml-1 24 h after termination.

Animals