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D Johnston

Publications and source records attributed to D Johnston.

At least 271 records · Page 15Linked to original sources
PubMed1988

Muscarinic depression of long-term potentiation in CA3 hippocampal neurons.

Behavioral studies have suggested that muscarinic cholinergic systems have an important role in learning and memory. A muscarinic cholinergic agonist is now shown to affect synaptic plasticity in the CA3 region of the hippocampal slice. Long-term potentiation (LTP) of the mossy fiber-CA3 synapse was blocked by muscarine. Low concentrations of muscarine (1 micromolar) had little effect on low-frequency (0.2 hertz) synaptic stimulation but did significantly reduce the magnitude and probability of induction of LTP. Experiments under voltage clamp showed that muscarine blocked the increase in excitatory synaptic conductance normally associated with LTP at this synapse. These results suggest a possible role for cholinergic systems in synaptic plasticity.

Animals↗
PubMed1988

The case for low dose diuretics in hypertension: comparison of low and conventional doses of cyclopenthiazide.

In a double blind placebo controlled randomised parallel study the antihypertensive activity and adverse biochemical effects of three doses of cyclopenthiazide were evaluated in patients with mild essential hypertension that had been recently diagnosed or was being treated with a single drug. After a four week placebo washout period 53 patients with diastolic blood pressures between 90-110 mm Hg were randomly assigned to 50, 125, or 500 micrograms cyclopenthiazide or matching placebo for an eight week period of treatment. Blood pressure was measured in the patients' homes by the same observer every two weeks. Serum urea, electrolytes, urate, and creatinine concentrations and 24 hour urinary sodium excretion were monitored every four weeks and serum magnesium concentration and plasma renin activity at the end of the washout and treatment periods. After eight weeks of treatment systolic and diastolic blood pressures were significantly reduced in patients taking 125 and 500 micrograms cyclopenthiazide when compared with those taking placebo. The decrement in serum potassium concentration (0.6 mmol/l) and increase in serum urate concentration 0.06 mmol/l) were greatest with the 500 micrograms dose, the increase in serum urate concentration alone being significant. No change in serum magnesium concentration or 24 hour urinary sodium excretion was noted with any dose of cyclopenthiazide. Only the 500 micrograms dose of cyclopenthiazide significantly increased the mean plasma renin activity (1.8 (95% confidence interval 0.2 to 3.4)-5.4 (3.9 to 6.8) nmol angiotensin I/l/h); the other doses like the placebo had no effect. Cyclopenthiazide 125 micrograms, a dose lower than is currently marketed, produced a similar hypotensive response to 500 micrograms of the drug without upsetting the biochemical profile.

Aged↗
PubMed1988

Highly selective vagotomy and duodenal ulcers that fail to respond to H2 receptor antagonists.

A study was conducted to see whether patients with duodenal ulcers that failed to heal in response to H2 receptor antagonists had a higher incidence of recurrent ulceration after highly selective vagotomy than patients whose ulcers healed with these drugs. Between 1977 and 1983, 157 patients had a highly selective vagotomy for uncomplicated duodenal ulcer; in 57 patients the ulcer had failed to heal despite treatment with H2 receptor antagonists (refractory group), 19 patients had developed recurrent ulceration while receiving maintenance treatment, 67 patients had remained healed while taking H2 receptor antagonists but suffered frequent relapses when treatment was stopped, and 14 patients had not been given these drugs before operation. The overall incidence of recurrent ulceration was 6% after two years and 11% after five years of follow up. In the refractory group, however, the incidence of recurrent ulceration was 18% at two years and 34% after five years, whereas the incidence of recurrence was only 1.5% at two years and 3% after five years in patients whose ulcers had healed with H2 receptor antagonists. Resistance to H2 receptor antagonists was not related to preoperative basal or peak acid output but was related to cigarette smoking. Factors associated with recurrent ulceration after highly selective vagotomy were basal acid outputs before and after operation, cigarette smoking, and the surgeon who performed the operation. Duodenal ulcers that fail to respond to H2 receptor antagonists represent a more severe ulcer diathesis, for which highly selective vagotomy is less effective.

Adolescent↗
PubMed1988

A prospective comparison of the effects of placebo, ranitidine and highly selective vagotomy on 24 h ambulatory intragastric pH in patients with duodenal ulcer.

Twenty-four hour ambulatory intragastric pH (24 h IGpH) recording, a highly reproducible technique, was used to compare the effects of ranitidine and highly selective vagotomy (HSV) in 20 patients who had been referred for surgical treatment of duodenal ulcer. The 24 h IGpH was recorded when they were taking either placebo or ranitidine 300 mg at 10 pm, and again 4 to 13 weeks after elective HSV. Median 24 h IGpH and 24 h hydrogen ion activity (24 h [H+]) were calculated for each patient. Median (quartile) 24 h IGpH was 1.4 (1.3-1.6) with placebo, 2.2 (1.8-2.7) after ranitidine and 2.6 (1.8-3.7) after HSV. IGpH was significantly higher after both ranitidine (P less than 0.0001) and HSV (P less than 0.0001) than after placebo, but IGpH after ranitidine did not differ from IGpH after HSV (0.5 greater than P greater than 0.4). HSV reduced 24 h [H+] by a median 68 per cent (quartiles, 47-82 per cent) whereas ranitidine reduced it by only 50 per cent (34-69 per cent, 0.1 greater than P greater than 0.05). The 24 h pH recording was then analysed as two distinct periods; 'daytime' (8 am to midnight) and 'night-time' (midnight to 8 am). HSV reduced daytime [H+] by a median 77 per cent (59-93 per cent) whereas ranitidine reduced it by only 30 per cent (13-45 per cent, P less than 0.0001). HSV reduced night-time [H+] by a median 57 per cent (40-83 per cent) but ranitidine reduced it by a median 92 per cent (78-98 per cent, P less than 0.01). Thus, HSV inhibits gastric acidity more during the day than at night, whereas ranitidine given at 10 pm effectively suppresses night-time acidity but is much less effective in suppressing daytime acidity. However both HSV and ranitidine will heal more than 90 per cent of duodenal ulcers. Hence, contrary to Dragstedt's teaching, suppression of nocturnal acidity is not of crucial importance for the healing of duodenal ulcers.

Adult↗
PubMed1988

Anal sensation after restorative proctocolectomy for ulcerative colitis.

The hypothesis that anal sensation might be better after restorative proctocolectomy with end-to-end ileoanal anastomosis than after mucosal proctectomy with endo-anal anastomosis was tested in this study. Anal sensation was measured in 14 patients before operation, 16 patients after restorative proctocolectomy with end-to-end anastomosis (RP + EEA) and 13 patients after mucosal proctectomy with endo-anal anastomosis 1 cm above the dentate line (MP + EAA). Threshold electrosensitivity was measured in the upper, mid and lower anal canal by means of a bipolar constant current stimulator probe. The 'recto'-anal inhibitory reflex was tested, and the patients' ability to discriminate between flatus and faeces and to release flatus 'safely' was assessed by interview. In the upper anal canal, threshold sensitivity was significantly greater in patients who had undergone MP + EAA than in patients who had undergone RP + EEA (P less than 0.05). In the mid and lower anal canal, electrosensitivity in the three groups of patients did not differ significantly. Twelve patients (75 per cent) regained the 'recto'-anal reflex after RP + EEA, but after MP + EAA only three patients (23 per cent) did so (P less than 0.02). Thirteen patients after RP + EEA could release flatus safely without fear of faecal leakage, compared with only four after MP + EAA (P less than 0.02). The proportions of patients in these two groups who said they were able to discriminate flatus from faeces did not differ significantly. Anal sensation and discriminatory function are significantly better after end-to-end ileoanal anastomosis than after mucosal proctectomy with endo-anal anastomosis.

Adult↗
PubMed1988

Endoluminal ultrasound and computed tomography in the staging of rectal cancer.

Pre-operative staging of rectal cancer might define patients with disease confined to the rectal wall without lymph node metastases, in whom local excision might be appropriate, or patients with extrarectal spread, who might benefit from pre-operative radiotherapy. With these objectives, 36 consecutive patients with rectal cancer were studied by endoluminal ultrasound: 17 of them also underwent computed tomography (CT) of the pelvis. The results were correlated with the findings at operation and subsequent pathological examination. Endoluminal ultrasound correctly predicted invasion of the tumour through the rectal wall in 86 per cent of patients, with a sensitivity of 96 per cent and specificity of 50 per cent, but correctly identified lymph node metastases in only 61 per cent of patients (sensitivity 57 per cent; specificity 64 per cent). CT correctly predicted invasion through the rectal wall in 94 per cent of cases, with a sensitivity of 100 per cent and specificity of 67 per cent and correctly identified lymph node metastases in 70 per cent of patients (sensitivity 25 per cent; specificity 85 per cent). These findings indicate that both endoluminal ultrasound and CT may be helpful in selecting patients for pre-operative radiotherapy. Neither technique, however, can reliably identify lymph node metastases and therefore cannot be used to select patients who would be suitable for local excision.

Aged↗
PubMed1988

Tumorigenic and molecular characterization of novel phorbol ester-resistant and -sensitive lines of mice.

Two outbred lines of CD-1 mice were developed using males and females in an initiation (dimethylbenz[a]anthracene; DMBA), promotion (12-O-tetradecanoylphorbol-13-acetate; TPA) challenge, posttumorigenesis breeding protocol. Our results indicate that the phorbol ester-sensitive (PESTI) line developed tumors at a rate 4.1 times faster than the CD-1 parental line, while the phorbol ester-resistant (PERTI) line developed tumors at a rate 36 times slower than the CD-1 parents. The average number of tumors per mouse reached levels of 27.5 at 12 wk in the PESTI line, 0.1 at 16 wk in the PERTI line, and 6.7 at 16 wk in the CD-1 line. Biochemical tests showed that the PESTI line had both a high basal level and an enhanced epidermal ornithine decarboxylase (E.C. 4.1.1.17) response to TPA, the latter being nine times that of the PERTI line at their maximum dosages. An autoradiographic analysis of in vivo epidermal cell protein phosphorylation indicated marked differences in basal protein phosphorylation profiles (with high phosphate incorporation, PERTI, 112.7, 95.5, 64.4, 40.8, 18.6, 17.4, and 12.3 kDa; PESTI, 64.4, 40.8, 31.8, and 12.3 kDa) as well as TPA-dependent changes in these profiles (difference from basal levels, PERTI, 31.8 and 12.8 kDa; PESTI, 139.6, 126.3, 37.2, and 18.6 kDa). These heterogeneous profiles indicate strong genetic segregation of these protein kinase C target substrates.(ABSTRACT TRUNCATED AT 250 WORDS)

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1988

Chemoresistance is not a cause of the apparent failure of adjuvant chemotherapy in postmenopausal women.

Chemotherapeutic regimens used for the adjuvant treatment of breast carcinoma are less effective when applied to postmenopausal women than when applied to premenopausal women. Differences in growth fraction or altered chemosensitivity of tumors are potential causes of the differential effects of chemotherapy in younger and older patients. We have attempted to identify the presence of these putative causes by measuring size of clonogenic cell fraction and drug sensitivity of progenitor cells on the tumors from pre- and postmenopausal women. We found that the chemosensitivity of tumors was similar for patients of all ages. We further observed that the clonogenic cell fraction of tumors from women older than 65 years tended to be smaller compared to those of all other patients, while the hormone-sensitivity of tumors from these patients was higher. Our observations thus suggest that drug resistance related to inherent metabolic characteristics of tumor cells may not be a major contributing cause of failure of adjuvant chemotherapy in the treatment of postmenopausal women.

Adult↗
PubMed1988

Glutamate and dynorphin release from a subcellular fraction enriched in hippocampal mossy fiber synaptosomes.

A procedure is described for the isolation of intact hippocampal mossy fiber synaptosomes. Electron microscopic examination revealed numerous synaptosomal profiles which are clearly of mossy fiber origin, indicated by their large size (2-6 micron diameter) and characteristic morphology. Furthermore, this fraction is enriched in zinc and dynorphin B which appear to be concentrated in mossy fiber terminals in vivo. Synaptosomes isolated by this procedure accumulated 2-deoxyglucose and retained 88% of total lactate dehydrogenase activity after incubation at 30 degrees C for 60 minutes, indicating a high degree of membrane integrity. Oxygen consumption was stimulated 4-fold by veratridine (0.1 mM) and inhibited 90% by ouabain (1 mM), suggesting that synaptosomal metabolism remained tightly coupled to ouabain-sensitive ATPase activity. Potassium-stimulated (45 mM) release of dynorphin B was completely dependent upon the presence of extrasynaptosomal calcium, while only 30% of the evoked release of glutamate was calcium-dependent. D-aspartate, which exchanges glutamate out of the cytoplasmic pool, virtually eliminated the calcium-independent component of glutamate release. This synaptosomal preparation will be useful in identifying the factors that modulate the release of amino acid and opioid neurotransmitters from hippocampal nerve terminals and in the investigation of their presynaptic mechanisms of action.

Animals↗
PubMed1988

Selection of resistance to gentamicin and netilmicin in the faecal flora following prophylaxis for colo-rectal surgery.

The selection of aminoglycoside-resistant bowel flora, following the administration of either gentamicin or netilmicin in combination with metronidazole for prophylaxis, during colo-rectal surgery in 88 patients has been examined. Both antibiotic regimens resulted in the selection of an aminoglycoside-resistant flora in a total of 57 (65%) of patients: in half of the patients there was a net gain in the aminoglycoside-resistant flora, and in 13 (15%) one aminoglycoside-resistant strain present prior to prophylaxis was displaced by another following operation. Three patients (3%) lost aminoglycoside-resistant strains after prophylaxis. Most of the resistant organisms selected were considered to be of little importance as potential pathogens, at least in the short term. In only a small minority (5%) of patients were aminoglycoside-resistant enterobacteria isolated. Aminoglycoside-resistant Staphylococcus aureus was not isolated. Of the resistant enterobacteria, only one strain, an isolate of Enterobacter cloacae selected in a patient receiving gentamicin, carried a resistance determinant which was self-transmissible to Escherichia coli.

Clinical Trials as Topic↗
PubMed1988

Effect of low versus conventional dose cyclopenthiazide on platelet intracellular calcium in mild essential hypertension.

Platelet free intracellular calcium levels were measured during a double-blind, placebo-controlled parallel study to investigate the antihypertensive activity of 50 micrograms, 125 micrograms, and 500 micrograms cyclopenthiazide, in mild essential hypertension. Cytosolic free calcium levels were significantly higher in established hypertensive patients (135 +/- 28 nmol/l, P less than 0.001) but not in borderline hypertensive patients (123 +/- 26 nmol/l) compared with normotensive controls (111 +/- 9 nmol/l). A positive correlation between platelet free calcium level and systolic and diastolic blood pressure was confirmed (n = 68; r = 0.309 P = 0.01; r = 0.405 P less than 0.001, respectively). The 125-micrograms and 500-microgram doses of cyclopenthiazide produced mean decrements in blood pressure of 18/10 mmHg and 23/8 mmHg, respectively, (P less than 0.05 for both), after 8 weeks of therapy. The 50-microgram dose displayed no useful antihypertensive activity. Platelet free calcium levels fell by a similar amount in the four groups. The fall in blood pressure produced by the 125 and 500-microgram doses of cyclopenthiazide did not correlate with changes in platelet [Ca2+]i (r = 0.166 systolic and r = 0.169 diastolic). These findings do not support the hypothesis that changes in platelet cytosolic calcium levels are determined by the same factors that control blood pressure.

Blood Platelets↗
PubMed1988

Survival of patients with the automatic implantable cardioverter defibrillator.

Between May 1982 and May 1988, 37 patients (28 males and 9 females, mean age 57.6, range 16-76 years) of approximately 600 evaluated for sustained ventricular tachycardia and/or fibrillation (VT/VF) were treated with an automatic implantable cardioverter defibrillator (AICD). Twenty-eight of the patients had coronary artery disease, 7 had nonischemic cardiomyopathy, 1 had amyloid heart disease, and 1 had rheumatic heart disease. The mean ejection fraction was 32.2 +/- 12.9% (range, 9-64%). Eleven patients have died at a mean of 16.7 months after implantation. The cumulative survival rate was 81% at 1 year, 77% at 2 years, 68% at 3 years, and 53% at 4, 5, and 6 years. Considering only sudden deaths, the survival was 97% at 1 and 2 years, 90% at 3 years, and 80% at 4, 5, and 6 years. Twenty-one of the 37 patients received spontaneous shocks. If the first shock marks the time to death in the absence of an AICD, the cumulative survival rate would have been 56% at 1 year, 42% at 2 years, 29% at 3 years, and 14% at 4, 5, and 6 years. The maximum amount of time to a first appropriate shock was 39.7 months. Thirty-nine devices have been explanted: 28 for battery depletion; 5 for infections; 3 for improper sensing; 2 for electronic failure; and 1 at the time of cardiac transplantation. The average time to failure of the 28 units removed for battery depletion was 19.8 +/- 6.9 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗
PubMed1988

Noradrenergic enhancement of long-term potentiation at mossy fiber synapses in the hippocampus.

1. We tested several hypotheses related to the modulation of long-term potentiation (LTP) by norepinephrine (NE) at the mossy fiber synapses in the rat hippocampal slice preparation using extracellular and intracellular recording techniques. 2. NE exerted frequency-dependent effects on mossy fiber synaptic transmission. It had little effect on extracellular population excitatory postsynaptic potentials (pEPSPs) sampled during low-frequency stimulation, whereas it had marked effects on the duration, magnitude, and probability of induction of LTP at these synapses. 3. The beta-adrenoceptor agonist isoproterenol mimicked all of the effects of NE, whereas the beta-adrenoceptor antagonists propranolol and timolol reversibly blocked the induction of LTP, suggesting the effects of NE are mediated by a beta-adrenoceptor and that beta-adrenoceptor activation may be an important constituent for the expression of LTP at these synapses. 4. Frequency-dependent effects of NE and isoproterenol on mossy fiber pEPSPs were also observed in the presence of the gamma-aminobutyric acid (GABA) antagonist, picrotoxin, suggesting that NE can enhance LTP by a mechanism that does not depend on intact inhibition. However, propranolol did not block LTP in these disinhibited slices and did not affect LTP magnitude. 5. The adenylate cyclase activator forskolin augmented pEPSPs sampled during low-frequency stimulation in disinhibited slices and significantly enhanced LTP. Forskolin, however, did not produce LTP in the absence of tetanic stimulation. This supports the hypothesis that NE and isoproterenol augment features of LTP by stimulating adenosine 3',5'-cyclic monophosphate (cAMP) production and that cAMP plays a modulatory role in the induction of LTP. 6. The postsynaptic injection of the cAMP analogue 8-bromoadenosine 3',5'-cyclic monophosphate (8-bromo-cAMP) significantly increased the probability of induction of LTP measured intracellularly under voltage-clamp conditions with intact inhibition. An analysis of the inhibitory synaptic slope conductance during these experiments indicated that changes in this measure could neither account for the increase in mossy fiber synaptic slope conductance in those cells that displayed it nor account for the group differences in this variable. 7. The amplitude and duration of the postsynaptic depolarization during tetanic stimulation in the cells that displayed LTP in the 8-bromo-cAMP-injected group were significantly greater than in the cells that did not display LTP in the adenosine 5'-monophosphate-injected group.(ABSTRACT TRUNCATED AT 400 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1988

Gastrin-producing ovarian mucinous cystadenomas: a cause of the Zollinger-Ellison syndrome.

An ovarian gastrinoma would appear to be an extremely rare cause of the Zollinger-Ellison syndrome. Nevertheless, two consecutive cases of Zollinger-Ellison syndrome seen at our institution each proved to be caused by a gastrin-producing ovarian mucinous cystadenoma. That the ovarian tumor was the source of gastrin production was established by preoperative and postoperative gastrin and gastric secretory studies and by specific immunocytochemistry of the excised tissue. After oophorectomy, each patient was apparently cured of the disease. Ovarian gastrinomas may not be as uncommon as is generally believed and should be considered as a possible cause of the Zollinger-Ellison syndrome in any female patient in whom a primary gastrointestinal or pancreatic tumor cannot be located.

Adult↗