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Biomedical subjects

R Walker

Publications and source records attributed to R Walker.

At least 361 records · Page 20Linked to original sources

Selection of morphologically abnormal sperm by human cervical mucus.

The important role of cervical mucus from a reproduction standpoint is the transport and selection of spermatozoa. The study of the fertilizing ability of human spermatozoa by the use of zona-free hamster oocytes has shown that morphologically abnormal sperm can fuse with the zona-free hamster oocyte. The high proportion of morphologically abnormal spermatozoa present in human semen is significantly reduced after sperm migration through cervical mucus. The mucus, while a favorable environment for sperm survival, does not seem to contribute to the occurrence of sperm capacitation and acrosome reaction.

Animals↗

N-terminal tryptic fragment of big gastrin. Metabolism and failure to influence gastrin 17-evoked acid secretion in humans.

The metabolism and some biological properties of the N-terminal 1-17 sequence of human big gastrin (G-34) were studied during infusion in 5 human volunteers. Radioimmunoassay of the 1-17 fragment in plasma indicated rapid clearance (t1/2, 2.4 min). In doses of 75-1000 pmol X kg-1 X h-1, 1-17 G-34 did not, however, influence basal acid output or G-17-stimulated acid output. Gel filtration of plasma samples taken during the infusion indicated the presence of the 1-17 fragment of G-34, together with three other immunoreactive species. Two of these correspond to N-terminal G-34 immunoreactive forms previously found in human peripheral circulation. A fourth immunoreactive component that eluted late on Sephadex G50 was identified for the first time. This component also occurred in fasting human plasma, where it was the only detectable form of N-terminal G-34 immunoreactivity; its concentration increased during infusion of 1-17 G-34. The identification of this fragment and its concentrations in human circulation after feeding deserves further study. Because the fragments of 1-17 G-34 do not occur in antral extracts, and are not produced when G-34 or its N-terminal fragments are incubated in plasma in vitro, they are presumed to be generated from the 1-17 sequence by the action of peptidases found on capillary walls. The elucidation of the mechanisms involved is essential for an understanding of the metabolic pathways of gastrin.

Adult↗

Deaths in early childhood in west Cumbria.

Investigation of deaths in early childhood is one method of assessing the quality of child care in a district. This paper describes a study carried out in one health district, on children in the age group one week to five years: 28 deaths occurred over a two-year period, 25 of these in the first year of life. The deaths are classified according to potential preventable factors. The study gave a more detailed picture of mortality patterns in the district than was previously available. Parents found the home interview in the study helpful in allowing them to explore their worries about the child's death.

Child, Preschool↗

Transient neurologic disturbances, brain tumors, and normal computed tomography scans.

During a 4-year period, four patients presented with transient disturbances in neurologic function that were diagnosed as seizures in two and transient ischemic attacks in the other two. Computed tomography (CT scan), both with and without contrast, was normal in all four patients. Isotopic brain scans (3 patients), cerebral angiograms (4 patients), and lumbar punctures (4 patients) were normal. Electroencephalograms (EEG) were normal in two patients and abnormal in two patients (consisting of focal slowing). Within 4.5 months, all patients developed symptoms and signs of a brain tumor, and in all four, CT scan now revealed a large mass lesion which at surgery was shown to be a malignant astrocytoma. These four patients constituted 4% of the total number of patients with malignant astrocytomas that were seen at the NYU Medical Center during this same time period. It is stressed that the CT scan may be normal early in the course of patients with brain tumors, particularly if they present with a transient disturbance in neurologic function. The first evidence of the tumor in such patients may be a slow-wave abnormality on the EEG. Patients who are suspected of having a brain tumor should, if the initial CT scan is normal, have the scan repeated later.

Adult↗

Bromocriptine and lisuride in Parkinson disease.

Lisuride was compared with bromocriptine in 25 parkinsonian patients in whom the response to levodopa had diminished; 19 had "wearing off," "on-off" phenomena, or both. At the time bromocriptine was added to levodopa, the mean age of the patients was 62.7 years and mean disease duration was 8.9 years. Disability decreased by 34% in the on period and by 20% in the off period, and the number of hours the patients were on increased from 9.6 to 12.8. All these changes were significant (p less than or equal to 0.01 to 0.05). Bromocriptine, however, had to be discontinued in 11 patients because of adverse effects. In the remaining 14 patients, bromocriptine was eventually discontinued because of decreased efficacy. Mean dose of bromocriptine was 55 mg (range, 20 to 100 mg). At the time lisuride was added to levodopa the patients were older (65.4 years), had had the disease longer (11.4 years), and were more disabled. Nonetheless, disability decreased in the on period by 33% and in the off period by 17%, and the number of hours the patients were on increased from 3.9 to 8.9. All these changes were significant (p less than or equal to 0.01 to 0.05). The mean dose of lisuride was 2.8 mg (range, 0.6 to 5.0 mg). Lisuride was discontinued in 8 patients because of adverse effects. Both bromocriptine and lisuride are useful in managing patients with advanced Parkinson disease whose response to levodopa has diminished. While it is presently not possible to state which of the drugs is more effective, ultimately their usage will probably be determined by their relative cost.

Aged↗

Metabolism of 3-deoxy-4-sulphohexosulose, a reaction product of sulphite in foods, by rat and mouse.

The excretion of single intragastric doses of 14C-labelled 3-deoxy-4-sulphohexosulose (DSH) was studied in male CF1 mice and male and female Wistar albino rats. Urine and faeces were collected 6, 12, 24, (36), 48 and 72 hr after administration of 2100 mg [14C]DSH/kg body weight (to mice), 1700 mg/kg (to male rats) and 100 and 500 mg/kg (to male and female rats). After 72 hr, plasma and total carcass levels were determined in some experiments. In mice 29% of the administered radioactivity was excreted in the urine, 50% in the faeces and some 13% in cage washings. In rats, faecal excretion varied between 58.5 and 73%. Urinary excretion varied between 16.5 and 31% and was slightly higher in male than in female rats. No radioactivity was detected in expired air of rats, and carcass levels in rats and mice after 72 hr were less than 0.1% of the dose. TLC analysis of urine extracts revealed only unchanged [14C]DSH. In similar studies, male rats and mice were given 35S-labelled DSH in a dose of 6500 mg/kg or 10,700 mg/kg, respectively. Urinary activity accounted for 19.5% of the dose in rats and 27.5% in mice by 72 hr and no 35S-labelled sulphate was detectable in the urine. Organ analyses at nine intervals from 0.25 to 24 hr after intragastric administration of 1600 and 1800 mg [14C]DSH/kg to male rats and mice, respectively, showed that at all times most of the 14C activity was associated with the gastro-intestinal tract in both species. Maximum tissue levels were 2.16% of the dose in the rat liver 0.5 hr after dosing and 1.57% in the mouse kidney after 0.25 hr. Significant amounts of activity (greater than 0.25% of the dose) occurred transiently also in the pancreas and lungs of both species, in the rat testes and in the mouse bladder. Maximum plasma levels were 0.09% of the dose/ml in rats 0.5 and 1 hr after dosing and 0.34%/ml in mice at 0.25 hr.

Animals↗

Acute toxicity of 3-deoxy-4-sulphohexosulose in rats and mice, and in vitro mutagenicity in the Ames test.

3-Deoxy-4-sulphohexosulose (DSH) is formed in sulphited foods by the interaction of SO2 and intermediates of the Maillard reaction. The acute intragastric toxicity of DSH has been studied in rats and mice, and the LD50 was found to exceed 5 g/kg body weight in both species. The only adverse effect seen in a 14-day post-dosing period was a transient diarrhoea in the first 24 hr. DSH was shown to be non-mutagenic in four strains of Salmonella typhimurium in the Ames test, with and without metabolic activation by S-9 mix from Aroclor-treated rats.

Animals↗

Further studies with lisuride in Parkinson's disease.

Lisuride was administered to 63 patients with advanced Parkinson's disease (PD) who were no longer satisfactorily responding to levodopa. The group included 40 patients with 'on-off' phenomena. Lisuride alone (13 patients) or combined with levodopa (50 patients) resulted in a 34% decrease in PD disability as assessed in the 'on' period, a 16% decrease in disability as assessed in the 'off' period, and a 96% increase in the numbers of hours in which patients were 'on' (from 5.5 to 10.8 h). All of these changes were significant (p less than or equal to 0.001). 37 of the 63 patients (59%) improved at least one-stage on lisuride. The major adverse effect limiting the use of lisuride was the occurrence of an organic confusional syndrome. This was related, in part, to the presence of an underlying dementia and to the concurrent use of anticholinergic drugs.

Aged↗

Comparative efficacy of pergolide and bromocriptine in patients with advanced Parkinson's disease.

Treatment with pergolide was compared with bromocriptine in 25 patients, all of whom were also receiving levodopa and in all of whom the response to levodopa had diminished. All 25 patients had "on-off" phenomena. At the time bromocriptine was added to levodopa, the mean age of the patients was 61.8 years, mean duration of disease was 9.0 years, and mean duration of levodopa treatment was 6.1 years. For the group as a whole, disability as determined in the "on" period decreased by 36%, from 28.7 to 18.5; and 11 patients improved at least one stage. Disability as determined in the "off" period decreased by 25%, from 59.5 to 44.4. The number of hours in which patients were "on" increased by 62%, from 7.1 to 11.5. All of these changes were significant (p less than or equal to 0.05). Bromocriptine had to be discontinued in nine patients (eight because of mental changes). In the remaining 16 patients, bromocriptine was eventually discontinued because of diminishing efficacy. Mean dose of bromocriptine was 50 mg (range, 10-100 mg), and mean duration of treatment was 23 months (range, 2-65 months). At the time of their treatment with pergolide, the patients were older, 65.5 years, had the disease longer, 12.7 years, and were more disabled. Nonetheless, for the group as a whole, disability score as determined in the "on" period decreased significantly by 40%, from 43.5 to 26.3, and 14 patients improved at least one stage. Disability as determined in the "off" period decreased significantly by 21%, from 69.0 to 54.8. The number of hours in which patients were "on" increased significantly by 224%, from 3.4 to 11.0 hr. The mean dose of pergolide was 2.1 mg (range, 0.1-10.0 mg), and the mean duration of treatment was 6.2 months (range, 0.5-20 months). Pergolide was discontinued in eight patients: three because of asymptomatic tachyarrhythmias of unknown clinical significance (detected only by Holter monitoring); two because of orthostatic hypotension; and two because of mental changes. Although pergolide appears to be more potent than bromocriptine because of its greater effect in a larger number of patients at a more advanced stage of their disease, both drugs are useful, and both enhance our ability to manage patients with PD.

Aged↗

Focal glomerulosclerosis--another familial renal disease?

Of 179 consecutive patients with glomerulonephritis 27 (15 percent) had focal glomerulosclerosis (FGS). Two of these 27 patients with FGS were sisters whose mother died of renal failure at 27 years of age. The father of another of these 27 patients with FGS died from renal failure at a young age. The third family included four members who reached end-stage failure. The findings from these three families suggested that FGS may be a familial or hereditary disease.

Adult↗

A continuous spectrophotometric determination of hepatic microsomal azo reductase activity and its dependence on cytochrome P-450.

1. A continuous spectrophotometric determination of rat hepatic microsomal anaerobic azo reductase activity has been developed. 2. The addition of soluble flavins (riboflavin, FMN or FAD) greatly increased this NADPH-dependent activity towards a number of azo substrates. 3. Investigations with amaranth as substrate gave an apparent Km of 34 microM and Vmax. of 4 nmol/min per mg of microsomal protein. The inclusion of a fixed concentration of FMN increased Vmax. and greatly decreased Km, the magnitude of these changes reflecting the concentration of flavin present. 4. Investigations using a fixed amaranth concentration over a range of flavin concentrations gave biphasic double-reciprocal plots with two apparent Km and Vmax. values. 5. Pretreatment of animals with cobaltous chloride, 2-allyl-2-isopropylacetamide, carbon tetrachloride, phenobarbitone and 3-methylcholanthrene altered azo reductase activity in parallel with changes in cytochrome P-450 content. 6. The significance of these results is discussed in terms of the electron-transfer components present in the hepatic microsomal fraction.

Amaranth Dye↗

Adult celiac disease and recurrent pericarditis.

Three patients presented with acute pericarditis. No cause was found and, in each case, the pericarditis was recurrent. Investigation revealed evidence of malabsorption due to adult celiac disease. Two of the patients responded to a gluten-free diet and cortiscosteroid therapy. The third patient responded to a gluten-free diet alone and remains well. Celiac disease is a multisystem disorder in which extraintestinal involvement is common. Recurrent pericarditis may be such a manifestation.

Acute Disease↗

The use of pergolide, a potent dopamine agonist, in Parkinson's disease.

Pergolide, a semisynthetic ergoline and a potent long-acting adenylcyclase-linked dopamine agonist, was given to 40 patients with advanced Parkinson's disease whose response to levodopa had diminished considerably. The group included 31 patients with marked diurnal oscillations in performance ("wearing off" and/or "on-off" phenomena). Pergolide alone (7 patients) or combined with levodopa (33 patients), resulted in a reduction in disability (P less than or equal to 0.01) as assessed in both the patients' "on" and "off" periods. Pergolide also resulted in an increase (P less than or equal to 0.001) in the number of hours in which patients were on from 3.8 (+/-0.4) to 11.9 (+/-0.9). The mean daily dose of pergolide was 2.4 mg (range 0.1 to 10.0). The mean duration of the study was 12 mo (range 1 to 24). Pergolide is effective in Parkinson's disease and will change the management of patients whose response to levodopa has diminished.

Adult↗