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Biomedical subjects

R Hill

Publications and source records attributed to R Hill.

At least 253 records · Page 14Linked to original sources

L-Glutaric acidemia: investigation of a patient and his family.

A 5-month-old infant had an unusual combination of clinical signs and symptoms. These consisted of irritability, dystonia, lack of head control, grimacing, opisthotonos, choreoathetoid movements, delayed development, and severe metabolic acidosis. Metabolic investigation by gas-liquid chromatography/mass spectrometry detected urinary organic acids. This confirmed the diagnosis of L-glutaric aciduria. The concentration of L-glutaric acid in the patient's plasma was 2.5 mg/dl (normal range, 0 to 0.1 mg/dl), and in the patient's urine was 4.6 mg/mg of creatinine (normal range, 0 to 0.05 mg/mg of creatinine), but the concentration was not elevated in the plasma and urine of the infant's parents nor of two other family members. No glutaryl-CoA dehydrogenase activity was found in leukocytes taken from the patient. Three of the four family members, including the parents, demonstrated 38%, 42%, and 42% activity, respectively, compared with the activity of normal controls. These findings are consistent with an autosomal recessive disorder involving the metabolism of glutaryl-CoA to crotonyl-Co-a. Dietary restriction was instituted on two separate occasions. First, a low protein diet of 1.6 gm/kg of body weight per day was given, then a low lysine intake of 50 mg/kg/day. These dietary manipulations caused a decrease in the plasma and urine concentrations of L-glutaric acid and beta-hydroxyglutaric acid. However, no effect on the clinical manifestations of the disease was noted.

Amino Acid Metabolism, Inborn Errors↗

Haematological, serological and pathological effects in chicks of one or more intravenous injections of Salmonella gallinarum endotoxin.

Abnormalities appeared a few hours after groups of 14-day-old chicks (Gallus domesticus) were injected intravenously with 15 mg/kg of endotoxin (LPS) from Salmonella gallinarum. Clinical illness without mortality was accompanied by significant (P less than 0.05) falls in body temperature, bursa weight, the main haematological parameters, serum iron (SI) and transferrin saturation (TS) and a significant increase in unsaturated iron-binding capacity. All responses, apart from bursa weight, SI values and total and differential white-cell counts, returned to normal within 24 to 48 h. LPS given daily for three consecutive days did not cause changes in the main haematological parameters during the 48 h period following the third injection. However body and bursa weight and heterophil counts were significantly depressed, whereas body temperature, SI and TS were affected biphasically, being first depressed and then raised above normal. Chicks injected with LPS daily for six consecutive days showed broadly similar responses but a persistent microcytosis was also present.

Animals↗

Effect of repeated injections of iron dextran on the haematological, serological and pathological changes in experimental avian tuberculosis.

Eight intramuscular injections of 200 mg/kg of iron (DFe), given as iron dextran twice weekly in the week before and the three weeks after intravenous infection with about 10(7.5) colony-forming units of Mycobacterium avium, significantly prolonged (by about 11 days) the mean 'time-to-death' of immature male fowl (Gallus domesticus) compared with corresponding regimes using dextran (Dx) only or saline, When a proportion of the birds were examined 21 days after infection many of the abnormalities associated with the disease, including a marked hypochromic anaemia, were less severe in DFe-treated than in the Dx- or saline-treated chicks and there were about 10- to 85-fold fewer viable tubercle bacilli in the liver and spleen of the DFe-treated birds.

Animals↗

Comparisons of the starch equivalent (SE) and metabolisable energy (ME) systems in feeding cattle.

Rations were formulated for dairy cows and for growing and fattening cattle by the starch equivalent (SE) and the new metabolisable energy (ME) system, to show in quantitative terms the differences that are recognised between the two systems. For a low-yielding cow, rations formulated by both systems are very similar, but for a high-yielding cow the SE system greatly underestimates energy requirement: at a production of 40 kg (8.8 gal) milk daily an extra 2 kg (4.4 lb) of a barley-soyabean concentrate is needed daily to meet the energy requirement according to the ME system. For a particular rate of gain in young newly weaned animals and in older animals gaining weight at a moderate rate on a high roughage diet, the energy level recommended by the ME system is lower than that by the SE system. The difference corresponds in each case to about 0.5 kg of a barley-soyabean concentrate daily. For older animals gaining weight rapidly on a high concentrate diet the ME system requires slightly more energy for a given weight gain, than the SE system.

Animal Feed↗

Does long term treatment with amitriptyline alter the monoamine oxidase of rat brain?

Amitriptyline, at a concentration of 10(-5) M, inhibits the oxidative deamination of phenylethylamine, tyramine and tryptamine (by 40, 16, and 8 percent, respectively) by rat brain MAO. After the long term administration of amitryptyline, even at a dosage of 20 mg per kg body weight twice daily, there was no detectable influence on the biochemical properties of MAO. These findings indicate that the full antidepressive effect, which only appears after the first 3 weeks of long term treatment, cannot be caused by the inhibition of MAO.

Amitriptyline↗

The influence of protein source and basal dietary component on survival in acute experimental fowl typhoid in the chick (Gallus domesticus).

1. The influence of diet on the survival of chicks inoculated orally at 15 d of age with Salmonella gallinarum was determined, and in the first experiment the numbers of salmonellae were counted in blood 5 or 7 d after inoculation to assess their value in predicting survival. 2. Significantly more chicks survived among those given beef powder as the protein supplement in a starch-based diet than among those where fish flour replaced beef powder. The number of salmonellae in blood was significantly higher in chicks given the fish-flour diet than in those given the beef-powder diet, but the relationship between the number of viable organisms in blood and the final survival rate was not close. 3. Whale meat and soya-bean protein gave high survival rates, similar to that given by beef powder, and casein plus gelatin was slightly poorer in this respect. 4. For each high-protein food the level of survival from the acute disease was significantly greater with wheat than with starch as the basal component of the diet. 5. The addition of either condensed beef extract or fish solubles to a standard diet did not influence survival.

Animals↗

Bioassay of kinship in northwestern Europe.

Kinship of Barra (Outer Hebrides) is bioassayed as 0.0096 relative to northwestern Europe, in reasonable agreement with prediction of 0.008 relative to Britain. The exponential decline of kinship with distance is similar to Scandinavia. Kinship of larger populations is consistent with predictions from isolates. Kinship is largely due to local drift rather than Norse admixture, the estimate of which is obscured by drift and appears highly unreliable. Other populations in northwest Europe, including Iceland, Lewis and Orkney, give estimates of kinship which reflect drift and geography, but also do not provide reliable estimates of admixture. Bioassay of kinship from gene frequencies gives observations to be explained in terms of migration and drift, but contributes nothing to the question of whether polymorphism in the species is maintained by neutral mutation or selection. Although the latter is on various grounds more likely, no calculations based on gene frequency distribution can provide critical evidence.

Emigration and Immigration↗

Survival in lung cancer.

Analysis was carried out according to stage and tissue type of 392 consecutive cases of lung cancer diagnosed at David Grant Medical Center between 1960 and 1974. Biphasic survival curves were described with a variable primary phase and a constant (1.1 percent per month) secondary phase. Survival was found to correlate both to histology and stage. The best survival was found in stage I bronchoalveolar carcinoma. Even in the more favorable categories a leveling off of survival was not found. This study strongly suggests that surgical treatment of lung cancer, while beneficial, cannot expect to be considered as a curative procedure in more than 10 percent of cases. Radiotherapy did not prolong survival.

Adenocarcinoma↗

Increased survival from acute Salmonella gallinarum infection in chicks given diets with high levels of some forms of iron.

Amounts exceeding 100 ppm of extra dietary iron as the ferric salts of ethylenediaminetetra-acetic acid (FeE) or nitrilotri-acetic acid (FeN) produced highly significant increases in survival among chicks infected with 10(6.4) living Salmonella gallinarum strain 9. Additional dietary iron (400 ppm) as the sulphate or chloride salts (or as ferric fructose) lacked activity comparable with FeE or FeN except when 0.2 per cent of NaE was also present in the diet. FeE iron (600 ppm) also diminished the severity of several of the pathological reactions which occur in chicks during the acute stage of experimental fowl typhoid. The enhanced survival and decreased severity of the pathological changes in infected chicks were associated with large reductions in the numbers of viable salmonellae in the spleen at the height of the acute infection.

Animals↗

Experimental fowl typhoid in chicks impaired immunologically by treatment with cyclophosphamide.

Male chicks were injected intramuscularly with 6 mg of cyclophosphamide daily for three consecutive days, the initial dose being given on the day of hatching. This treatment impaired bursal development and lymphopoiesis and no circulating antibodies appeared after such chicks were injected with Salmonella gallinarum antigens at 19 and again at 26 days of age. In impaired chicks which were infected orally when 15 days old with S gallinarum the level of mortality was essentially the same as that in unimpaired animals. Impairment did not affect the lower mortality that accompanies feeding with a nutritionally adequate diet containing meat meal as the sole protein supplement in comparison with fish meal as the supplement. An anaemia was present in chicks examined seven days after infection. This anaemia was microcytic to a degree that either exceeded or approached statistical significance. As antibody-mediated hypersensitivity reactions involving the erythrocytes were absent in the impaired chicks, the anaemia must have differed in pathogenesis from the macrocytic anaemia of immunopathological orgin reported by others in adult females with acute fowl typhoid. A disturbance of iron metabolism could have accounted for the anaemia in the diseased chicks.

Anemia↗

Enhancement of survival in acute experimental fowl typhoid in chicks by the administration of iron dextran.

Chicks aged 15 days were infected orally with 10(6-4) living Salmonella gallinarum. Iron from iron dextran or ferric ammonium citrate (DFe and CFe respectively), in doses of 2-0 or 0-4 mg/kg given intramuscularly at the time of infection, had no effect on subsequent mortality compared with infected controls. Increasing the amount of CFe to the maximum (20 mg/kg) that was non-toxic intramuscularly was also ineffective but when the dose of DFe was increased to 20 or 50 mg/kg the survival rate rose sharply. If given at other times in relation to the time of infection, or more frequently, 50 mg/kg or more of DFe was less active. The increased survival rate among infected chicks given 50 mg/kg of DFe at the time of infection was accompanied by decreases in the severity of the morbid changes in the disease, and by reductions of between c 10- to 100-fold in the numbers of viable S gallinarum in the liver, spleen or blood at the height of the acute infection. DFe (50 mg/kg) given at the time of infection also eliminated the difference in the survival rate noted previously between infected chicks fed respectively with diets containing fish or meat meal as the sole source of supplementary protein.

Anemia↗

Altered absorption and regulation of iron in chicks with acute Salmonella gallinarum infection.

Chicks aged 15 days were infected orally with Salmonella gallinarum. During the six-day period immediately following infection the absorption of 59Fe from the gut fell progressively to be eventually about half that in noninfected chicks. This reduced uptake was accompanied by a shift in the distribution of the 59Fe absorbed, more occurring in the spleen and less in the liver and blood. During the eight-day period that immediately followed infection in another experiment, serum iron concentration on day 4 and 6 in infected chicks was significantly lower than that in noninfected birds. In the infected chicks also the transferrin saturation was significantly lower and the unsaturated ironbinding capacity higher, on days 4, 6, and 8 after infection. These findings show that there is a major disturbance in iron regulation in acute systemic bacterial infection in the immature fowl and suggest that the mild anaemia which occurs in chicks during acute S gallinarum infection a shortage of iron in the body.

Animals↗

Population structure of Barra (Outer Hebrides).

Historical demography, surname concordance (isonymy), migration, and genealogy give a consistent description of population structure. The census size has averaged about 1400 over the last five centuries. Conjoined with an effective migration rate of 3-05 per generation as estimated by three different methods, this gives an evolutionary size of 638, random kinship of 0-008 and inbreeding of 0-007 relative to the rest of Britain. The population structure of Barra is similar to other British isolates in the recent past, but an order of magnitude less inbred than slash-and-burn agriculturalists and Pacific Islanders. Some consequences for rare genes and polymorphisms are discussed.

Emigration and Immigration↗