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Biomedical subjects

G Williams

Publications and source records attributed to G Williams.

At least 721 records · Page 40Linked to original sources

Subcutaneous aprotinin causes local hyperaemia. A possible mechanism by which aprotinin improves control in some diabetic patients.

Local changes in blood flow at the subcutaneous injection site of the proteinase inhibitor aprotinin and its diluent were measured by photoelectric plethysmography. Aprotinin, but not its diluent, caused local hyperaemia in five normal subjects and in five stable and five brittle insulin-dependent diabetic patients, local blood flow increasing by 80%-180%. The duration of the hyperaemic response was shorter in the brittle diabetic patients than in the other two groups, but there was wide individual variation. Aprotinin is known to enhance subcutaneous insulin absorption in normal subjects and in some brittle diabetic patients. The basis for this might be through increasing blood flow near the injection site rather than by inhibition of insulin breakdown.

Adult↗

Activity of neurons in the ventral tegmental region of the behaving monkey.

To investigate the functions of neurons in the ventral tegmental area, recordings were made of the activity of 257 single neurons in this area in the behaving monkey. Four main types of neuronal response were found in the ventral part of the tegmentum. First, neurons with activity phasically related to mouth or arm movements were found. Most of these were located relatively far lateral, close to the junction of the midbrain reticular formation with the zona incerta, or were in the substantia nigra, pars reticulata. Second, neurons were found which responded differentially in a visual discrimination task on trials on which the monkey had to initiate a licking response compared with trials on which he did not, and which also altered their firing rate tonically while mouth movements were being made in other situations (differential motor neurons). These were found mainly in the midbrain reticular formation, consistent with the view that populations of neurons in these regions are involved in the execution of movements. Third, neurons which also responded differentially in the visual discrimination task, but did not respond when the same movements were made in other situations, were found in the ventral tegmental area, in a region medial to and in some cases immediately dorsal to the substantia nigra pars compacta. Fourth, neurons which responded to cues such as a tone which enabled the monkey to prepare for performance on each trial of the visual discrimination task were found in the ventral tegmental area close to the midline. These third and fourth types of neurons were thus found in the region where neurons of the mesocortical and mesolimbic pathways are located. Their responses are similar to those of neurons found in the striatum, and it is suggested that they are important in enabling the animal to prepare for and then to engage in particular behavioral responses.

Animals↗

Can people move bureaucratic mountains? Developing primary health care in rural Indonesia.

Banjarnegara, a regency with a population of 678,000 located in a poor, mountainous region of Central Java, has become a focus of attention because of its Primary Health Care (PHC) programme. Since 1972, three-quarters of Banjarnegara's 279 villages have established a wide range of community-based health activities. Yet it is difficult to describe and analyse this programme, which has never had a specific design or master plan. Nor have there been large injections of funds from Indonesian government or international agencies. The programme runs on a modest budget, relying on an element that eludes many carefully planned, heavily funded development efforts--the voluntary participation of large numbers of local people. Some 4000 unpaid volunteers are largely responsible for planning, implementing and evaluating the programme. This article attempts to describe and assess the programme's achievements, limitations and possible wider relevance.

Community Health Services↗

Medical research council trial of antilymphocyte globulin in renal transplantation. A multicenter randomized double-blind placebo controlled clinical investigation.

A total of 173 patients who received live donor or cadaveric primary or secondary renal transplants at five British hospitals were entered into a randomized double-blind controlled clinical trial of equine antilymphocyte globulin (ALG) administered prophylactically to prevent rejection. The ALG was prepared in the early 1970s and used cultured human lymphoblasts as antigen. Following transplantation all patients were treated with a standard immunosuppressant regimen of steroids and azathioprine and, in addition, were given either 30 mg/kg ALG or placebo daily for 10 days by intravenous infusion. In comparison with more recently produced materials, the ALG employed in this study was of moderate potency in prolonging skin graft survival in monkeys. Primary graft failure occurred in 27 patients (15/86 ALG and 12/87 placebo). At three to five years after transplantation 50 of the remaining patients had died, almost all from diseases relating to their renal condition, and 25 more had suffered complete graft failure. No significant differences were found between patients treated with ALG and placebo in the numbers with functioning grafts during the 3 years following transplantation, in the time between transplantation and the first rejection episode, or in the number of episodes during the first six months after transplantation. This applied whether live or cadaveric grafts were employed. Within the first 6 months of operation, infection was given as a major contributory cause of death in 12 patients treated with ALG and in 5 who received placebo (P greater than 0.1). Infections were also slightly more common during the two weeks following transplantation in those receiving ALG (13/86 ALG, 10/87 placebo). As expected, graft survival was significantly better in patients who received live donor grafts (P = 0.001) and in patients with the least donor-recipient histocompatibility mismatches (P = 0.008). The results of this multicenter trial show no therapeutic benefit to renal graft recipients from the administration of ALG, and suggest that the risks of fatal infection may have been aggravated. Use of such equine ALG in similar dose regimens is therefore, not, justified in renal transplantation, especially if some part of the apparent effects on fatal infections is real. It is stressed that these findings are relevant only to the equine ALG used in this study, which was raised with cultured human lymphoblasts as the antigen, and to ALG prepared in a similar way and of similar potency. It should not be inferred that these results are applicable to ALG prepared in other ways.

Adolescent↗

Combined bipedal lymphangiography, CT scanning and transabdominal lymph node aspiration cytology for node staging in carcinoma of the prostate.

Forty-two patients with carcinoma of the prostate have been studied by bipedal lymphangiography, abdominal CT scanning and percutaneous transabdominal lymph node aspiration cytology to try to increase the accuracy of lymph node staging. The use of two independent radiologists to report the lymphangiograms did not improve the accuracy of reporting. CT scanning was of value only in patients in whom the lymph nodes were not opacified on lymphangiography. Aspiration cytology was positive in 8 of the 40 patients who were studied. There was no morbidity. Six of these 8 patients had MO disease, three had TO tumours and were not on treatment. A poor correlation was found between the presence of lymph node metastases and the Gleason score. Percutaneous transabdominal lymph node aspiration cytology is a safe procedure. When positive, it avoids the need for a staging lymphadenectomy and so helps to identify those patients for whom local treatment is not applicable.

Biopsy, Needle↗

Prostatic cancer: treatment with long-acting LHRH analogue.

Fifteen patients with advanced carcinoma of the prostate were treated with a luteinising hormone releasing hormone agonist ICI 118 630. Three of 5 patients who had failed conventional hormone therapy have had a marked alleviation of bone pain, though no objective evidence of disease regression. Nine of 10 patients previously untreated have shown objective evidence of disease response. This drug appears to have advantages over conventional hormone therapy.

Aged↗

Primary hyperparathyroidism unmasked by donor nephrectomy.

A patient who was normocalcaemic before donation of a kidney to her son developed hypercalcaemia in the immediate postoperative period, which was subsequently found to be due to a parathyroid adenoma. It is assumed that the hypercalcaemia was unmasked by the reduction in glomerular filtration rate following the nephrectomy.

Adenoma↗

Testicular venography in impalpable testis.

77 venographic studies of impalpable testes have been reviewed. All patients subsequently underwent surgical exploration. In 28 studies a pampiniform plexus was identified and in 27 a testis was present at the site of the pampiniform plexus. In 20 studies the testicular vein was blind-ending and in only 1 was testicular tissue present at the site of the blind-ending vein. Testicular tissue was absent in the remaining 19. There were 29 technical failures or an inability to identify the full length of the testicular vein because of patent valves. Testicular venography is most useful in localising the position of an impalpable testis but does not determine in all cases whether testicular tissue is present.

Cryptorchidism↗

Changes in blood flow close to subcutaneous insulin injection sites in stable and brittle diabetics.

Photoelectric plethysmography (PPG) was used to investigate blood flow changes close to superficial subcutaneous injection sites. As a validation procedure, the PPG response to subcutaneous injection of a known hyperemic agent, prostaglandin E1 (10(-5) M), was shown to correlate strongly with subcutaneous blood flow changes estimated by the established technique of 133Xe washout. Changes in blood flow over the subcutaneous injection sites of insulin (Actrapid) and insulin diluent were measured by photoelectric plethysmography in six nondiabetics and in six stable and seven brittle insulin-dependent diabetics. In all subject groups, an acute increase in local blood flow was seen within 2 min of both insulin and diluent injections, probably caused by injection trauma. At diluent injection sites, this acute hyperemia faded rapidly, blood flow returning to preinjection levels within 15-20 min, and there was no further increase in blood flow in any of the subjects. Insulin injected into the nondiabetics and stable diabetics caused a pronounced increase in local blood flow, sustained for at least 60 min after injection. In the brittle diabetics, however, there was no prolonged local hyperemia, the response being significantly less than that seen in both the nondiabetics and the stable diabetics. Insulin-related hyperemia close to injection (or infusion) sites may be important in subcutaneous insulin absorption. Its near-absence in brittle diabetics may contribute to the impaired response to subcutaneous insulin characteristic of these patients.

Adult↗

Activity of the auditory system in rats habituated to a test chamber: a 2-deoxyglucose study.

In a number of species, quantitative 2-deoxyglucose method revealed that the auditory system is much more active than any other-neural system. We tested the hypothesis that stressful experimental conditions may be responsible for this hyperactivity. Three rats received transcatheteral injections of [14C] 2 deoxyglucose while exposed to a wide band noise in a sound-shielded chamber in which they had previously spent 17 habituation sessions. In autoradiograms of these animals the auditory system appeared as intensely labelled (active) as in control animals. We conclude that the high activity of the auditory system in the rat does not seem to result from presumably stressful normal laboratory conditions.

Animals↗

1H NMR studies of the electron exchange between cytochrome c and iron hexacyanides. Definition of the iron hexacyanide binding sites on cytochrome c.

Binding of [Fe(CN)6]3-, [Cr(CN)6]3-, [Co(CN)6]3- and [Cr(C2O4)3]3- to horse, tuna and Candida krusei cytochromes c has been studied by high-resolution 1H NMR spectroscopy. All the reagents bind at the same sites. There are at least two binding sites, and probably three, on horse cytochrome c at pH 7. One of the sites is only a weak binding site and is far from the haem group, whereas the other site(s) is(are) at the haem crevice. Ka for binding of [Fe(CN)6]3- to trimethyllysine-72 of C. krusei ferricytochrome c is 140 +/- 15 M-1 at 27 degrees C and pH 7.

Animals↗

1H NMR studies of eukaryotic cytochrome c. Resonance assignments and iron-hexacyanide-mediated electron exchange.

1H NMR resonance assignments in the spectra of horse, tuna, Neurospora crassa and Candida krusei cytochromes c are described. Assignments have been made using NMR double-resonance techniques in conjunction with electron-exchange experiments, spectral comparison of related proteins, and consideration of the X-ray structure of tuna cytochrome c. Resonances arising from 11 residues of horse cytochrome c have been assigned.

Animals↗