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Biomedical subjects

P Scott

Publications and source records attributed to P Scott.

At least 181 records · Page 10Linked to original sources

Impaired macrophage leishmanicidal activity at cutaneous temperature.

Temperature is one of the primary influences upon the pathogenesis of cutaneous leishmaniasis. In this study, we measured the temperature of murine leishmanial lesions and determined the ability of lymphokine (LK) activated macrophages to kill Leishmania major at these temperatures. The temperature of leishmanial lesions in BALB/c and C3H/HeN mice ranged from 27 degrees C to 32 degrees C. We found that LK activated resident or inflammatory macrophages exhibited significantly less leishmanicidal activity in vitro at temperatures closer to those measured in vivo. The decrease in microbicidal activity was not due to the enhanced growth of the parasites at lower temperatures, since impaired killing was also observed against non-replicating radiation attenuated amastigotes. Finally, the tumoricidal activity of macrophages was found to be significantly depressed at temperatures below 37 degrees C, indicating a generalized impairment of macrophage function at these temperatures. These findings suggest that impaired macrophage microbicidal activity at cutaneous temperatures may contribute to parasite survival, and imply that healing of leishmanial lesions, as well as other cutaneous infections, may require an exceptionally potent local LK response.

Animals↗

The toxicity of Datura stramonium (thorn apple) to horses.

Meal contaminated by Datura stramonium seeds at the rate of 0.5% by weight was fed to two horses. Both horses showed clinical signs of depression, anorexia, weight loss, rapid heart and respiration rates, mydriasis, polyuria, polydipsia and diarrhoea. Both recovered with treatment. Maize screenings contaminated by the seeds had been used in the manufacture of the meal.

Journal Article↗

Biologic effect of 5-fluoro-2'-deoxyuridine incorporation in L1210 deoxyribonucleic acid.

Recent studies have demonstrated that 5-fluoro-2'-deoxyuridine (FdUrd) misincorporates in eukaryotic DNA. We have extended these findings and studied the relationship between DNA incorporation of FdUrd and cell lethality. This required an approach that would distinguish the DNA and RNA effects of this agent. The specific effect of (FdUrd)DNA formation on L1210 clonogenic survival was, therefore, monitored using deoxyuridine (dUrd) to inhibit the metabolism and subsequent incorporation of FdUrd into RNA. The results demonstrated that misincorporation of FdUrd in DNA resulted in lethal cellular events. These observations suggest a new mechanism of action for this cytotoxic and mutagenic agent.

Animals↗

Resistance to macrophage-mediated killing as a factor influencing the pathogenesis of chronic cutaneous leishmaniasis.

Cutaneous leishmaniasis can be either a spontaneously healing or chronic disease, depending upon the strain of parasite and the immunological status of the host. We have investigated parasite factors responsible for the variable pathogenesis observed in leishmanial infections by testing the sensitivity of several leishmanial strains to intracellular killing in lymphokine (LK) activated mouse macrophages. Significant microbicidal activity against Leishmania tropica, a strain which heals in C57BL/6 (B6) mice, was found. In contrast, a strain (Maria) which has previously been shown to induce chronic nonhealing cutaneous lesions in B6 mice was resistant to killing in activated macrophages. This resistance to killing was observed in macrophages activated by LK obtained from either Bacille Calmette-Guérin-, L. tropica, or the Maria strain infected mice. The inability of LK activated macrophages to kill the Maria strain was shown not to be due to parasite induced inhibition of killing mechanisms, since Maria strain infected, LK treated macrophages exhibited tumoricidial activity similar to uninfected macrophages. Furthermore, LK activated macrophages simultaneously infected with the Maria strain and another intracellular pathogen, Toxoplasma gondii, killed Toxoplasma, but not the Maria strain. Temperature was also found to significantly influence the multiplication and killing of Leishmania parasites. As would be expected from their cutaneous nature, L. tropica and Maria strain parasites multiplied better at 35 degrees C than at 37 degrees C. Also consistent with the failure of cutaneous strains to visceralize in immunocompetent mice was the observation that the killing of leishmanial parasites was enhanced at the higher temperature. Thus, the temperature dependent growth capacity and sensitivity to killing of a given leishmanial strain in macrophages may be important factors influencing the pathogenesis of cutaneous leishmaniasis.

Animals↗

Racial variations in tests of fetoplacental function.

Fetoplacental function tests discriminated well between poorly grown and well grown fetuses in European mothers. In contrast, apart from human placental lactogen, the individual values of poorly grown Asian fetuses fell within the well grown range. Haemoglobin values rose in the second trimester in European pregnancies associated with poor growth, whereas the values fell in the Asian pregnancies both with well grown and poorly grown fetuses. These observations imply fundamental differences in the aetiology of intrauterine growth retardation in the two races.

Adult↗

Anthropometric and biochemical changes during pregnancy in Asian and European mothers having well grown babies.

At this hospital, about a third of all mothers are Asian. Although generally they have smaller and lighter babies, many Asian mothers achieve similar standards of intrauterine growth to the European mother. This paper describes the nutritional status of Asian and European mothers having well grown babies. Twenty eight European and 11 Asian mothers, who had a normal past obstetric history and a normal present pregnancy resulting in a well grown baby, were studied throughout pregnancy. At each visit, weight, skinfold thickness, and mid-upper arm circumference were measured and biochemical measurements of nutritional status were performed (serum albumin, transferrin and alkaline ribonuclease, plasma amino acids and nitrogen partition of urine). Asian mothers were fatter than European mothers at booking and put on more fat during the second trimester. At the same time, the biochemical tests suggested that the Asian mothers had a higher plane of nutrition. It seems that if the Asian mothers are well nourished in the second trimester, they can achieve a standard of intrauterine growth comparable to the Europeans.

Adult↗

Curd and whey proteins in the nutrition of low birthweight babies.

Some animals thrive more satisfactorily on a milk that contains whey and curd protein. For this reason human milk protein (which contains about 40% whey) may have some advantages over cows' milk protein (which contains about 15% whey) and so infants feeding formulae based on demineralised whey in which the protein has been modified to achieve a curd:whey ratio similar to that in human milk may also thrive more satisfactorily. As the exact situation in the human newborn is unclear, the effects of feeding a formula containing unmodified cows' milk protein (mainly curd) and one containing the same amount of modified cows' milk protein (curd and whey) were studied in 57 low birthweight babies during the first 3 months of life. During the early weeks of life the curd and whey group grew bigger, absorbed more nitrogen, and excreted proportionately less urea. These results suggest that a curd and whey formula has advantages in the protein nutrition of low birthweight babies, especially the preterm ones. We feel it would be unwise to reduce the protein content of a formula based on cows' milk below 15 g/1 unless it was modified to achieve a larger proportion of whey protein and hence, among other qualities, more cysteine. Although some of the qualities of human milk protein can be mimicked by the use of demineralised whey formulae, others cannot.

Animals↗

Gastric bezoars. A technique of endoscopic removal.

Gastric bezoar formation is an uncommon sequela of gastroduodenal surgery or unusual eating habits. Because they generally produce severe symptoms, their removal is always necessary. Previously, this required surgical extirpation or slow enzymatic dissolution. We present here an endoscopic procedure for bezoar removal utilized successfully in five patients with vegetable-mucus bezoars. This technique employs a jet spray of water under direct vision to mechanically disrupt the bezoar, which may then be removed using a large gastric lavage tube. This procedure is simple, safe, and rapid and is therefore recommended as an alternative to surgical removal or enzymatic dissolution of gastric bezoars.

Bezoars↗

Plasma alkaline ribonuclease (EC 3.1.4.22) and nitrogen retention in low-birth-weight infants.

1. Nitrogen retention was determined by classical N balance techniques in fourteen rapidly growing low-birth-weight infants receiving 3 g protein/kg body-weight and during their 3rd week of life. This was compared with plasma free alkaline ribonuclease (EC 3.I.4.22; RNase) activity and other biochemical measurements of protein nutrition. 2. Plasma RNase showed a significant positive correlation with N retention and a corresponding negative correlation with urine urea-N. These results were unexpected and suggest a different relationship between RNase and N retention in infants compared with that found by other workers in children and adults. 3. The most likely explanation of this apparent anomaly is that in all instances high activities of plasma RNase are associated with a need to conserve N. In the infants studied this may indicate some measure of 'protein economy' and they could therefore benefit from a higher protein intake.

Body Weight↗

Bumetanide and frusemide: a comparison of dose-response curves in healthy men.

1 Log dose-responses for the loop diuretics bumetanide and frusemide in healthy subjects deviated significantly from parallelism as regards urine volume and sodium excretion. Ignoring the nonparallelism the best estimate of natriuretic potency (bumetanide: frusemide) was 46:1 in the bumetanide dose range 0.5-2 mg. 2 For a given natriuresis the urinary potassium excretion following bumetanide was significantly lower than that for frusemide within this dose range. 3 The data illustrate the limitations of studies comparing diuretics at a single dose level. Extrapolation of the observed log dose-response curves provides one possible explanation for the relative potency (bumetanide: frusemide) of 20:1 reported when the drugs are used at high dosage in patients with renal failure.

Adult↗

Milk pH, acid base status, and growth in babies.

Metabolic acidosis is common in babies fed cows' milk-based formulae. Therefore the effects of adding alkaline salts (sodium and potassium citrate) to a demineralised whey formula were studied in vitro and in 26 low birthweight babies fed on the formula or formula plus citrate. The alkali altered the pH and titratable acidity to a value nearer human milk but it increased the buffering capacity to a value further away. This may effect the bacterial flora of the intestine. The babies fed on formula plus citrate did not make greater gains in weight, length, head circumference, skinfold thickness, or midarm muscle circumference, although they had a greater blood base excess. Some of these babies developed a mild metabolic alkalosis and 3 had hyponatraemia despite their increased sodium intakes. These babies also had lower levels of plasma transferrin but showed no differences in urea, albumin, cholesterol, and calcium levels. No baby fed on the demineralised whey formula without added citrate had a base deficit exceeding 5 mmol/l; late metabolic acidosis is less common in babies fed on this formula and the routine addition of alkali can have untoward metabolic effects.

Acid-Base Equilibrium↗

Effect of gestational age and intrauterine nutrition on plasma transferrin and iron in the newborn.

Plasma concentrations of transferrin and iron were measured in the cord blood of babies of varying gestational age and birthweight. Tranferrin and iron concentrations rose with gestational age; values in light-for-dates babies did not differ from those in babies of appropriate weight. In the last trimester of pregnancy plasma transferrin and iron concentrations in the fetus are affected by the maturity of the pregnancy but are independent of the nutritional status of the fetus. The low transferrin levels, particularly in preterm babies, may caution the use of iron especially by the parenteral route in the neonatal period, but we are wary of abandoning on this evidence alone the well tried clinical custom of giving oral iron to preterm babies who are not breast fed.

Fetal Blood↗