Search PubMed⌕ Search

Biomedical subjects

D Johnston

Publications and source records attributed to D Johnston.

At least 235 records · Page 13Linked to original sources
PubMed1991

Reversal of postmortem degeneration of mouse oocytes during meiotic maturation in vitro.

The developmental capacity of oocytes matured in vitro following isolation at the germinal vesicle stage from freshly killed mice (control) was compared with that of oocytes isolated from the carcasses of mice killed 3, 6, 9, and 12 hr earlier. The yield of intact, cumulus cell-enclosed oocytes decreased as the interval between death of the animal and removal of the ovary increased. After 15-16 hr of culture of medium containing follicle-stimulating hormone, the frequency of germinal vesicle breakdown, extrusion of a polar body, and cumulus expansion was equivalent in oocytes of all groups. The frequency of development of inseminated ova to 2-cell stage embryos in the control, 3, and 6 hr postmortem groups was the same but declined markedly in the 9 and 12 hr groups. There was also no difference in the frequency of blastocyst development from 2-cell stage embryos between the control, 3, 6, and 9 hr postmortem groups, but the 2-cell embryos in the 12 hr postmortem group did not develop to blastocysts. Thirty-six percent of the 2-cell stage embryos from the 6 hr postmortem group developed to live young after transfer to foster mothers. Follicles of 6 hr postmortem ovaries showed degeneration manifested as prominent crystalline inclusions within the oocytes and many pyknotic granulosa cells. The crystals disappeared within 1 hr of culture and the secondary oocytes appeared normal. The cultured oocyte-cumulus cell complexes, therefore, reversed degenerative changes induced by the death of the animal. This study demonstrates the feasibility of recovering developmentally competent oocytes from valuable recently deceased zoological, agricultural, and endangered mammals.

Animals↗
PubMed1991

In vivo proton magnetic resonance spectroscopy studies of human brain.

In vivo localized proton magnetic resonance spectroscopy (MRS) studies of brain were performed on eighteen normal subjects using the stimulated echo (STE) sequence. The absolute concentrations and proton relaxation times of N-acetyl aspartate (NAA), total creatine (Cr) and choline (Cho) were estimated. The MRS data was quantitatively analyzed for repeatability and intersubject variability. Quantitative analysis indicates excellent spectral repeatability. Significant intersubject variations in [NAA] and [Cr] have been observed while the intersubject variability in [Cho] has been found to be fairly small. Significant intensity distortions have been observed for mixing times longer than 50 msec.

Adult↗
PubMed1991

Photostability testing of drug substances and drug products in UK pharmaceutical laboratories.

Results of a survey on photostability testing of drug substances and products by UK pharmaceutical laboratories are presented. The results indicate diverse practices in the form of presentation of the product and particularly in exposure to light (as measured in lx days), although there was more consistency in analytical methods and in the analytical criteria used to classify products as stable or unstable for those laboratories adopting this type of classification. A majority of laboratories use daylight in addition to artificial light sources for tests on drug substances and products. Artificial daylight fluorescent tubes and xenon lamps are the most widely used sources of artificial light and both should provide a reasonable simulation of natural light. All laboratories intend their photostability tests to represent light exposure which exceeds that expected to occur in practice but the tests actually applied vary widely in severity as shown in the wide range in light exposure (8-4500 klx days). Therefore the classification of products as stable or unstable needs to be considered carefully in relation to the severity of the test used. Testing procedures for drug substances are broadly similar to those used for drug products. It is concluded that the variation in testing procedure is the result of differing perceptions regarding product exposure in practical usage and the absence of regulatory guidelines.

Drug Industry↗
PubMed1991

The clinical management of otorrhoea following grommet insertion: a survey of otolaryngologists and general practitioners.

A postal questionnaire of all Consultant Otolaryngologists in the British Isles, and of General Practitioners within the local family practitioner committee area, was designed to compare the current practice in the management of discharge from the ear following grommet insertion. 76% of the Otolaryngologists and 52% of the General Practitioners completed the questionnaire. Between the two groups, statistically significant differences were apparent in the management of this common complication of grommet surgery. A higher proportion of Consultants took a bacteriology swab of the ear as part of their treatment, which was significantly more frequently treated by antibiotic ear drops. Within the Consultant group, significant regional variations in choice of drugs and therefore the cost of treatment were apparent. The General Practitioners more commonly prescribed oral antibiotics. This common complication of grommet surgery is managed differently by General Practitioners and Otolaryngologists without a firm rational basis. Treatment based on current knowledge is discussed. Further evaluation of the efficacy of different treatment regimens by controlled prospective trials is required.

Cerebrospinal Fluid Otorrhea↗
PubMed1991

Fate of explanted ICD patients.

UNLABELLED: Of 56 consecutive patients who underwent an initial AICD implantation at our center, we analyzed eight patients who subsequently had their units explanted and not replaced by other antitachycardia devices. The mean age was 57.8 years, mean ejection fraction was 28.4%; six patients had coronary disease and two had cardiomyopathy. The presenting arrhythmia was sudden death in four patients and sustained ventricular tachycardia in four others. Mean follow-up from implant to explant was 25 +/- 22 months, and 22 +/- 10 months from explant to end of follow-up. Reasons for explantation were: infection in five patients, lead fracture in one patient, battery depletion in one patient, and one patient underwent cardiac transplantation. Devices were not reimplanted because of: patient refusal in three patients, physician discretion in two patients (one recurrent infection, one received no shocks over 24 months), cardiac transplantation in one patient, ablation of VT focus in one patient, and one patient died while being treated for infection. Three patients died 2, 21, and 26 months after device explantation of nonsudden cardiac, sudden cardiac and noncardiac causes, respectively. CONCLUSIONS: Preoperative clinical parameters were not indicative of a lower risk of arrhythmic events in these patients as compared to the general population of AICD implantees. Of eight patients, two received alternate nonmedical therapy, one died while receiving treatment for a device-related infection; of the five remaining patients none died of cardiac causes. Termination of AICD therapy for malignant ventricular arrhythmias does not imply imminent sudden cardiac death for most patients treated by alternate modes of therapy.

Anti-Arrhythmia Agents↗
PubMed1991

Kinetic properties of two anatomically distinct excitatory synapses in hippocampal CA3 pyramidal neurons.

1. We have investigated the kinetic properties of pharmacologically isolated excitatory synaptic currents in hippocampal CA3 neurons. Two distinct anatomic pathways, the commissural/associational (C/A) and the mossy fiber inputs, were compared to test the hypothesis derived from cable theory that distal inputs have slower kinetics than proximal inputs when measured at the soma. 2. Intracellular recordings were made from adult rat hippocampal slices using a single-electrode voltage clamp and low-resistance microelectrodes. A mixture of 10 microM picrotoxin and 10 microM bicuculine was used to block completely fast GABAergic inhibition. The slow inhibitory input was blocked by intracellular cesium. 3. The mean reversal potential of mossy fiber synaptic currents, -2.8 mV, was not significantly different from that of the C/A synaptic current, -1.4 mV. The mean 10-90% rise time of the mossy-fiber synaptic current [1.7 +/- 0.08 (SE) ms], however, was significantly faster than the C/A synaptic current (3.2 +/- 0.16 ms). Both mossy fiber and C/A synaptic-current decays were fit with a single exponential. The decay time constant of mossy fiber synaptic currents was also faster than that of the C/A excitatory postsynaptic current, 6.5 +/- 0.4 versus 10.1 +/- 0.8 ms. The mossy fiber synaptic current decay time constant showed little voltage dependence. 4. A modified shape index plot of synaptic current rise time versus decay time constant, normalized to membrane time constant, yielded a good linear relation for C/A synapses. A poorer correlation was observed for mossy fiber synapses. 5. Both synaptic currents could be fit by alpha functions. A representative value of alpha for the mossy fiber synapse was 295/s, and for the C/A was 172/s. 6. The rise time of the mossy fiber synaptic potential was significantly faster (5.3 ms) than the C/A (7.5 ms). The decay of both mossy fiber and C/A synaptic potentials was slower than the membrane time constant, suggesting that active currents may contribute to their falling phases. This prolongation was voltage dependent but insensitive to 2-amino-5-phosphonovaleric acid. 7. Our data provide a quantitative comparison of a proximal and a more distal synaptic input to CA3 hippocampal neurons. Distal inputs show slower kinetics than proximal synapses, as predicted. However, the voltage dependence of synaptic potential decays suggests that synaptic integration may be affected by active dendritic conductances.

Animals↗
PubMed1991

Effect of daily etidronate on the osteolysis of multiple myeloma.

Progressive bone disease in multiple myeloma frequently leads to osteolysis, bone resorption, pathologic fractures, vertebral compression, and hypercalcemia. We conducted a double-blind study in 173 newly diagnosed multiple myeloma patients of etidronate disodium (EHDP), a diphosphonate compound that reduces bone resorption by inhibiting osteoclastic activity. The patients were randomly assigned to receive oral EHDP 5 mg/kg/d or placebo until death or discontinuation due to intolerance or refusal. The extent of vertebral deformity was measured by a vertebral index as well as height. The frequency of pathologic fractures, hypercalcemia, and bone pain was regularly assessed, as well as size and number of osteolytic lesions. All patients received melphalan and prednisone daily for 4 days every 4 weeks as the primary chemotherapy for their disease. Although the repeated measures analysis showed a significant height loss, there was no difference between treatment arms (P = .98). There was no significant difference in bone pain, episodes of hypercalcemia, or development of pathologic fractures. Patients on EHDP showed less deterioration in their vertebral index, but this difference only approached statistical significance (P = .07). We conclude that EHDP therapy used in this dosage schedule does not have a clinically significant impact in multiple myeloma.

Aged↗
PubMed1990

Single lumen ileum with myectomy: a possible alternative to the pelvic reservoir in restorative proctocolectomy.

An alternative procedure to construction of a pelvic ileal reservoir was assessed which avoids the need for a pouch, while providing an adequate rectal substitute and good continence. Thirty-six female adult beagles were allotted randomly to undergo total colectomy with (a) ileo-anal anastomosis alone, (b) ileo-anal anastomosis with two 15 cm myectomies, (c) ileo-anal anastomosis and myectomy with an ileo-ileal valve, or (d) ileo-anal anastomosis with a duplicated J pouch. The animals were studied before operation and at 4-weekly intervals for 20 weeks after operation. Mortality rates were similar. Ileal compliance was increased significantly by myectomy from 0.64 ml/mmHg (median, interquartile range 0.49-0.78) after ileo-anal anastomosis alone to 1.65 mmHg (1.16-1.93), P less than 0.01, an increase which was maintained. Ileal capacity was also increased both by myectomy and by the J pouch: ileo-anal anastomosis = 85 ml (75-100 ml), ileo-anal anastomosis and myectomy = 139 ml (116-156 ml), ileo-anal anastomosis and myectomy and ileo-ileal valve = 125 ml (range 85-145 ml), ileo-anal anastomosis and J pouch = 130 ml (range 75-165 ml) (P less than 0.01). Bowel function in the other three groups was markedly superior to ileo-anal anastomosis alone. Mean transit time was significantly less after ileo-anal anastomosis, 5.2 h (2.6-8.2 h) than after both ileo-anal anastomosis and myectomy, 10.5 h (9.6-13.9 h), P less than 0.05 and ileo-anal anastomosis and J pouch, 11.0 h (8.4-13.0 h), P less than 0.05, but addition of an ileo-ileal valve did not produce a further increase in transit time, 12.9 h (range 10.5-14.5 h), P = n.s.. Myectomy of single lumen ileum may be a useful alternative to a pelvic ileal reservoir in restorative proctocolectomy.

Anal Canal↗
PubMed1990

The role of azathioprine in the management of ulcerative colitis.

The use of azathioprine in ulcerative colitis is unclear. The authors present the details and outcome of 47 patients who received azathioprine for either a) severe, resistant disease otherwise requiring surgery (28 patients) or b) patients with steroid dependence who have been followed up for at least 12 months (19 patients). Duration of treatment ranged from one week to 66 months (median, 12 months). Of the patients in Group I, 13 (46 percent) achieved remission, 11 of whom had not relapsed during a median follow-up of 22 months (range, 12 to 58 months), and 15 underwent surgery one week to 12 months (median, five weeks) after commencing azathioprine. In Group II, steroids were withdrawn or reduced in 12 (63 percent) patients and three patients required colectomy. Side effects necessitating withdrawal of azathioprine occurred in 12 patients (hematologic effects, 6 patients; gastrointestinal effects, 4 patients; other effects, 2 patients). Two patients required a reduced dose of azathioprine because of leukopenia. The authors conclude that azathioprine is a valuable therapeutic option in selected patients with ulcerative colitis.

Adult↗
PubMed1990

The efficacy of tobramycin in the treatment of ulcerative colitis.

This paper reports a double-blind placebo-controlled trial of oral tobramycin in acute ulcerative colitis. Eighty-four patients with an acute relapse of ulcerative colitis were randomized to receive oral tobramycin or placebo for 1 week as an adjunct to steroid therapy. At endpoint, 31 of 42 (74%) in the tobramycin group achieved complete symptomatic remission compared with 18 of 42 (43%) in the placebo group (P = 0.008). The tobramycin group achieved better histological scores (P less than 0.05) at endpoint. These findings show that treatment with oral tobramycin improves the short-term outcome of patients with ulcerative colitis in relapse.

Adult↗
PubMed1990

The reliability of palpation in the assessment of tumours.

There is now a joint UICC-AJC classification for cervical lymph nodes based mainly on the size of the nodes. There is a recognized error in palpation, not only for detecting the presence of tumour but also its size. This study used an animal tumour model system to compare the ability of 6 independent observers of varying experience to detect and stage superficially transplanted growths. A preclinical medical student was as good as a Consultant ENT Surgeon in predicting the presence of tumour but the ability to stage tumours accurately was related to experience. Whilst the most experienced observers accurately estimated the size of tumours less than 2 cm, they were less accurate for larger (greater than 2 cm) tumours which were constantly understaged. This phenomenon may have important clinical implications particularly related to current nodal staging criteria.

Animals↗
PubMed1990

Towards a state measure of Type A behaviour.

To investigate the feasibility of developing a measure of state Type A behaviour, a random sample of 95 men aged 40-64 years attended a clinic at which Type A behaviour was assessed using the Structured Interview (Rosenman, 1978). Upon completion of the Structured Interview, subjects were administered a 65-item adjective checklist to describe their experience of the interview. Discriminant function analysis of adjective ratings on Structured Interview classification identified 15 adjectives which allowed 83 per cent correct classification. The limitation of these data includes the small sample size and the uniqueness of the Structured Interview situation. Nevertheless, these data provide encouragement that a robust and versatile measure of state Type A could be developed. Comparisons between various measures of trait Type A behaviour are also reported.

Adult↗
PubMed1990

Is antral gastrin important in the resistance of duodenal ulcers to H2 receptor antagonists or in recurrent ulceration after highly selective vagotomy?

Basal serum gastrin, integrated gastrin response to a meal, and integrated gastrin response to insulin induced hypoglycaemia were measured in 60 patients with duodenal ulcer before and after elective highly selective vagotomy to determine whether antral gastrin has a role in resistance to H2 receptor antagonist treatment which the patients had received before surgery or in the development of recurrent ulceration after vagotomy. The basal gastrin, integrated gastrin response to a meal, and the integrated gastrin response to insulin were similar in patients whose ulcers healed after H2 receptor agonist treatment or were refractory to at least three months of this treatment. The same parameters measured before or after highly selective vagotomy were similar in patients who eventually developed recurrent ulceration compared with those who did not. As expected the basal and meal stimulated (but not insulin stimulated) serum gastrin values increased after highly selective vagotomy. Ulcer patients with particularly high gastrin values (whether basal or stimulated) were not more resistant to H2 receptor antagonist treatment or prone to develop ulcer recurrence after highly selective vagotomy. This study suggests that antral gastrin is not important in 'resistance' of duodenal ulceration either to H2 receptor antagonist treatment or to highly selective vagotomy.

Adolescent↗
PubMed1990

High grade dysplasia of the gastric mucosa: a marker for gastric carcinoma.

The natural history of gastric epithelial dysplasia and its relation to gastric cancer are ill defined. A consecutive series of 40 patients with an initial diagnosis of gastric epithelial dysplasia based on examination of endoscopic biopsies has been reviewed to determine the clinical outcome and to evaluate a two tier histological grading system as a predictor of the risk of cancer. On review, only 20 of the 40 patients were considered to have true dysplasia: seven patients had low grade dysplasia and 13 had high grade dysplasia. Of the 13 patients with high grade dysplasia, 11 (85%) were found to have gastric cancer within 15 months. Of the 10 patients with high grade dysplasia who underwent gastrectomy, six were found to have early gastric cancer, three had cancer invading into the muscularis propria, and none had lymph node metastases. High grade dysplasia is thus a marker of gastric cancer. Moreover, the cancers associated with high grade dysplasia are usually pathologically favourable and curable. The finding, by an experienced pathologist, of high grade dysplasia in two separate sets of endoscopic biopsies is therefore an indication for radical surgical treatment, provided that the patient's age and general condition permit such an approach.

Aged↗
PubMed1990

Properties and distribution of single voltage-gated calcium channels in adult hippocampal neurons.

1. The properties of single voltage-gated calcium channels were investigated in acutely exposed CA3 and CA1 pyramidal neurons and granule cells of area dentata in the adult guinea pig hippocampal formation. 2. Guinea pig hippocampal slices were prepared in a conventional manner, then treated with proteolytic enzymes and gently shaken to expose the somata of the three cell types studied. Standard patch-clamp techniques were used to record current flow through calcium channels in cell-attached membrane patches with isotonic barium as the charge carrier. 3. Single-channel current amplitudes were measured at different membrane potentials. Single-channel current-voltage plots were constructed and single-channel slope conductances were found to fall into three classes. These were (approximately) 8, 14, and 25 pS, and were observed in all three cell types. 4. The three groups of channels differed from each other in voltage dependence of activation: from a holding potential of -80, the small-conductance channel began to activate at about -40 to -30 mV, the medium-conductance channel at about -20 mV, and the large-conductance channel at approximately 0 mV. 5. Ensemble averages of single-channel currents during voltage steps revealed differences in voltage-dependent inactivation. The small-conductance channel inactivated completely within approximately 50 ms during steps from -80 to -10 mV or more positive. Steps to less positive potentials resulted in less inactivation. The medium-conductance channel displayed variable inactivation during steps from -80 to 0 mV. Inactivation of this channel during a 160-ms step ranged from virtually zero to approximately 100%. The large-conductance channel displayed no significant inactivation during steps as long as 400 ms. 6. The large-conductance channel was strikingly affected by the dihydropyridine agonist Bay K8644 (0.5-2.0 microM), resulting in a high probability of channel opening, prolonged openings, and an apparent increase in the number of channels available for activation. The medium and small-conductance channels were not noticeably affected by the drug. 7. The large-conductance channel could be induced to open at very negative membrane potentials by holding the patch for several seconds at 20 or 30 mV and stepping to -30 or -40 mV. This process was enhanced by Bay K8644, resulting in prolonged openings at potentials as negative as -100 mV.(ABSTRACT TRUNCATED AT 400 WORDS)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗