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Biomedical subjects

D Johnston

Publications and source records attributed to D Johnston.

At least 307 records · Page 17Linked to original sources
PubMed1986

Pre-operative identification of patients at high risk of deep venous thrombosis after elective major abdominal surgery.

Eighteen items of clinical and laboratory information were measured on the day before operation in 85 patients who underwent elective major abdominal surgery. Postoperatively, deep venous thrombosis (DVT) was detected by 125I-fibrinogen scan in 23 patients. Stepwise logistic discriminant analysis was used to identify factors which predicted DVT. Seven such factors were identified, which were then used to construct a predictive index. In descending order of predictive power, they were: age, euglobulin lysis time (ELT), previous abdominal surgery, varicose veins, antithrombin III concentration, cigarette smoking, and platelet count. Pre-operatively, the predictive index correctly identified 91% of the patients in whom DVT developed, and wrongly allocated to the high-risk group 19% of those in whom it did not. A shortened version of the predictive index based only on age and ELT (I = -11.5 + 0.133 age + 0.006 ELT) was 91% sensitive and 63% specific in the prediction of DVT. In a prospective study of 43 patients, this shortened predictive index correctly identified pre-operatively 93% of patients in whom DVT developed, and wrongly allocated to the high-risk group only 17% of those in whom it did not.

Abdomen↗
PubMed1986

Comparison of the function of triplicated and duplicated pelvic ileal reservoirs after mucosal proctectomy and ileo-anal anastomosis for ulcerative colitis and adenomatous polyposis.

Among 39 consecutive patients who underwent colectomy, mucosal proctectomy and ileo-anal anastomosis, a triplicated pelvic ileal pouch was constructed in 17, and a duplicated pouch in 22 patients. There was no mortality, but complications such as anastomotic dehiscence and pelvic sepsis led to removal of the pouch in seven patients (18 per cent). The functioning of the pouch and anal sphincter was assessed in 31 patients 6 months, and in 22 patients 12 months after closure of the diverting ileostomy. By 6 months, all patients were either completely continent or experienced only minor leakage and defaecation could be deferred for more than 15 min by 81 per cent of patients and flatus distinguished from faeces by 90 per cent of patients. No significant differences between triplicated and duplicated pouches were discernible at 6 months. At 12 months defaecation was significantly less frequent (P less than 0.05) in patients with triplicated pouches (median, 5 times in 24 h) than in patients with duplicated pouches (7 times in 24 h). All patients with triplicated pouches and all except one with duplicated pouches were able to defaecate spontaneously, without needing to intubate the reservoir. Thus, provided the early postoperative problems can be overcome, most patients achieve good anal function after mucosal proctectomy combined with a pelvic ileal reservoir. No evidence was found in this study that the functional results of duplicated pouches were superior to those of triplicated pouches; in fact, the triplicated pouches proved to be slightly superior.

Adolescent↗
PubMed1986

Factors influencing bowel function after ileal pouch-anal anastomosis.

Seventeen patients were studied 3-31 months (median 6.4 months) after mucosal proctectomy and ileal pouch-anal anastomosis for ulcerative colitis (n = 15) or adenomatous polyposis (n = 2). Seven had a triplicated pouch, and ten a duplicated pouch. Clinical bowel function was determined by detailed questionnaire, and correlations sought between clinical end-points such as frequency of defaecation, urgency of defaecation and continence, and the results of laboratory investigations, comprising anal manometry, capacity and compliance of the pouch, completeness of emptying, faecal bacteriology and mucosal inflammation. Frequency of defaecation was found to be inversely correlated with both the capacity (rs = -0.66, P less than 0.01) and the compliance (rs = -0.53, P less than 0.05) of the pouch. Patients who could postpone defaecation for greater than 30 min had higher anal squeeze pressures (P less than 0.05) than patients who had greater urgency of defaecation. Patients with perfect anal continence had higher resting anal pressure (P less than 0.05) and emptied the pouch more completely (P less than 0.01) than patients who experienced minor leakage. The faecal flora of the pouches showed a greater predominance of anaerobes (P less than 0.01) and increased numbers of bacteroides (P less than 0.01) compared with the faecal flora of ileostomies, but the changes in the flora did not correlate with any aspect of bowel function. The best clinical results (i.e. perfect continence, low frequency of defaecation and little urgency) were associated with high anal pressure and with large volume, high compliance and complete emptying of the pouch. The completeness of emptying was similar for both designs of pouch, but the capacity and compliance of triplicated pouches were greater than the capacity and compliance of duplicated J pouches (P less than 0.05), and this was associated with a better clinical result in the triplicated pouches.

Adolescent↗
PubMed1986

Blind total gastrectomy for massive bleeding from the stomach.

The source of massive haemorrhage from the stomach cannot always be identified even with the use of fibreoptic endoscopy and angiography. Six patients with massive, continuing, non-variceal haemorrhage from the stomach are described in whom total gastrectomy was eventually required. Three patients were shown to have bled from submucosal arteriovenous malformations, two from erosive gastritis and one from a vessel in an ulcer at the oesophagogastric junction. One patient died as a result of surgery and another died later of disseminated malignant disease. The functional results in the remaining patients were surprisingly good and rebleeding has not occurred. Total gastrectomy is a satisfactory 'last resort' treatment for life-threatening gastric haemorrhage for which no cause can be found.

Adult↗
PubMed1986

Gastric inhibitory effects of CM57755. A new histamine H2 receptor antagonist.

The gastric inhibitory effects of CM57755, a new histamine H2 receptor antagonist, have been compared in ten healthy male volunteers with the actions of an equal dose of cimetidine and with placebo. The inhibitory effect of CM57755 was virtually identical with, and not significantly different from the effects of cimetidine on nocturnal gastric secretion of acid, while neither drug influenced the secretion of pepsin. Neither drug, administered in the evening, influenced the intragastric pH and acidity during the following day, from breakfast onwards. The therapeutic impact of the new drug is likely to resemble that of cimetidine and clinical application will depend on the safety profile.

Adolescent↗
PubMed1986

Lack of correlation between mutagen-induced chromosomal univalency and aneuploidy in mouse spermatocytes.

Aneuploidy represents the predominant type of chromosomal abnormality found in human newborns with birth defects. The concern that environmental agents may cause aneuploidy in germ cells has prompted development of assay systems for detection of potentially aneuploidy-producing agents. One of the most frequently used methods involves cytogenetic analysis of murine spermatogenic cells at the stages of meiotic metaphases. However, criteria for aneuploidy induction have not been standardized in this test system. Many investigators consider the ability of an agent to induce univalents an appropriate measure of its potential to induce aneuploidy. In the present study, the relationship between univalency and aneuploidy was examined in mouse spermatocytes after various mutagen treatments. 45 Swiss mice were treated with 4 different agents; viz., adriamycin, vinblastine sulfate, cytosine arabinoside, and radiation (cobalt 60) and 10 untreated animals served as controls. From each animal, 50-200 MIs were examined for both sex-chromosomal and autosomal univalency (X-Y U and AU), and equal numbers of MIIs were examined for aneuploidy (hyperhaploidy). No significant correlations between univalency (either X-Y U or AU) and aneuploidy were found in the mutagen-treated mice; nor were they found in the untreated animals. These results indicate that induction of univalents by a mutagen is not necessarily predictive of the aneuploidy-inducing ability of this agent.

Aneuploidy↗
PubMed1986

Lymphokine activated killing of fresh human leukaemias.

The relative susceptibility of 10 human leukaemias comprising acute phase leucocytes from 5 acute myeloid and 5 lymphoid neoplasms, and 2 immunoblastic lymphomas to killing by peripheral blood mononuclear cells (PBMC), before and after target cell treatment with phytohaemagglutinin (PHA), and by interleukin-2 (IL-2) activated peripheral blood lymphocytes (PBL) was investigated in short term 51Cr release assays using effector cells from 10 allogeneic donors. Optimal lectin-dependent cellular cytotoxicity (LDCC) was verified against K562 and L1210 cells and lymphokine-activated killing (LAK) against K562 and Daudi cells. Under these conditions, the majority of the leukaemias tested revealed only a finite sensitivity to any of the cytotoxic mechanisms, which was dependent on the donor origin of the effectors. The leukaemias were more consistently susceptible to LDCC than LAK and removal of adherent cells to enrich for the latter activity in effector populations, was ineffective. Lymphocytes from a patient in long term (greater than 5 yr) remission exhibited LAK against the autologous target E84, a natural killer (NK)-sensitive acute myelomonocytic leukaemia. These cells failed to cross-compete for lysis of K562 by LAK cells, suggesting the existence of different recognition structure(s) on the two targets.

Cell Line↗
PubMed1986

Reflux gastritis: distinct histopathological entity?

A total of 98 patients who had either undergone gastric surgery (23) or who had peptic ulcers (56), or who had normal endoscopic findings (19), all underwent gastric biopsy, together with measurement of pH and total bile acid concentration in their fasting gastric juice. The biopsy specimens were graded "blind" for the presence of foveolar hyperplasia; oedema and smooth muscle fibres in the lamina propria; vasodilation and congestion of superficial mucosal capillaries; and a paucity of both acute and chronic inflammatory cells in the brief that these features constituted a distinctive histological picture related to reflux of alkaline duodenal content into the stomach. We found a strong association between severe grades of each of these histological variables and both hypochlorhydria (pH greater than or equal to 4) and increased bile acid concentrations in the stomach. Furthermore, when the individual grades were added together to give a composite "reflux score," there was a significant difference in the incidence of hypochlorhydria (p less than 0.01) and raised bile acid concentrations (p less than 0.005) between those patients with a reflux score above and below 10. Although we do not claim that reflux is invariably accompanied by a distinctive histological picture, we suggest that recognition of this hitherto poorly documented combination of features as reflux gastritis may assist in the selection of patients for specific treatment and minimise the overdiagnosis of premalignant dysplasia (with which the lesion may be confused) in the postoperative stomach.

Adult↗
PubMed1986

Conductance mechanism responsible for long-term potentiation in monosynaptic and isolated excitatory synaptic inputs to hippocampus.

The biophysical mechanisms underlying long-term potentiation (LTP) were investigated in identifiable and monosynaptic excitatory inputs to hippocampal neurons. The results provide the first insights into the conductance changes that are responsible for the expression of LTP. Both current- and voltage-clamp measurements of the mossy fiber synaptic response in pyramidal neurons of region CA3 were made with a single-electrode-clamp system. The excitatory postsynaptic response was pharmacologically isolated by bathing hippocampal slices in saline containing 10 microM picrotoxin, which blocks the synaptic inhibition that normally accompanies the experimentally evoked mossy fiber response. LTP was induced by tetanically stimulating the mossy fiber input for 1 s at 100 Hz. Before and 20 min to 1 h after inducing LTP, we attempted to measure the mean excitatory postsynaptic potential (EPSP) amplitude, intrasomatic current-voltage relationship to a step (RN) or alpha function (AN) current waveform, membrane time constant (tau m), spike threshold (T50), peak excitatory postsynaptic current amplitude (IP), synaptic conductance increase (delta G), and synaptic reversal potential (VR); but adequate assessments of all eight of these were not always obtained for every cell that was studied. The induction of LTP increased the mean (+/- SE) EPSP amplitude form 10.5 +/- 1.4 mV during the control period to 16.8 +/- 2.4 mV after the induction of LTP (n = 14; P less than 0.05). This change was not accompanied by increases in the mean value of RN (63 +/- 11 M omega before and 61 +/- 11 M omega after induction; n = 8; P greater than 0.05); AN, which approximates the effective synaptic input resistance at the soma (10.0 +/- 1.50 M omega before and 10.5 +/- 1.60 M omega after; n = 10; P greater than 0.05); or tau m (22 +/- 2 ms before and 20 +/- 2 ms after; n = 8; P greater than 0.05). There was no significant change in T50, which was also assessed with an alpha function current waveform (1.48 +/- 0.11 nA before and 1.49 +/- 0.10 nA after; n = 6; P greater than 0.05). The mean value of IP increased from 1.1 +/- 0.2 nA during the control period to 1.8 +/- 0.3 nA after inducing LTP (n = 15; P less than 0.05). Similarly, delta G increased from 30 +/- 4 nS before to 47 +/- 4 nS after induction (n = 10; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Voltage-clamp analysis of synaptic inhibition during long-term potentiation in hippocampus.

The excitatory synaptic response evoked by stimulating the mossy fiber synaptic input to hippocampal CA3 neurons in normally accompanied by concomitant feedforward or recurrent inhibition. The purpose of the present study was to determine whether a decrease in the inhibitory conductance of this mixed synaptic response contributes to the enhanced synaptic efficacy observed during long-term potentiation (LTP). Intracellular recordings were made from CA3 neurons of rat hippocampal brain slices. Current- and voltage-clamp measurements of the mixed excitatory/inhibitory evoked synaptic response were made, using a single-electrode clamp system. Outward and inward rectification were reduced, respectively, by intracellular injection and bath application of Cs+. Biophysical analysis of the evoked synaptic conductance sequence was performed before and 15 min to 1 h after inducing LTP. As expected, measurements made in the early part of the conductance sequence, which represents primarily the monosynaptic excitatory input, demonstrated an increase in the slope conductance during LTP. Measurements made later in the conductance sequence, when the excitatory component appeared to have declined to a negligible value, revealed no decrease in the slope conductance of the inhibitory component of the mixed response. We conclude that a decrease in the conductance associated with the inhibitory component of the mixed synaptic response plays little or no role in the increase in synaptic efficacy observed during LTP of this synaptic system.

Animals↗
PubMed1986

Arbovirus infections in several Ontario mammals, 1975-1980.

Serological studies for arboviruses were conducted on 725 animal sera collected in 22 Ontario townships between 1975 and 1980 including 44 coyote (Canis latrans), 277 red fox (Vulpes vulpes), 192 raccoon (Procyon lotor) and 212 striped skunk (Mephitis mephitis). Hemagglutination inhibition antibodies to two flaviviruses, namely St. Louis encephalitis and Powassan were found in 50% of coyote, 47% of skunk, 26% of fox and 10% of raccoon sera. Similarly, hemagglutination inhibition antibodies to a California serogroup virus, snowshoe hare, were found in 12% of fox, 7% of skunk, 7% of raccoon and 5% of coyote sera. No antibodies were detected to two alphavirus, namely eastern equine encephalitis and western equine encephalitis, antigens. This study affirms the endemic presence of Powassan and snowshoe hare virus and further delineates the scope of St. Louis encephalitis activity in Ontario.

Animals↗
PubMed1986

Use of growth-stimulatory hormones to improve the in vitro therapeutic index of doxorubicin for human breast tumors.

Tumor-specific growth factors that increase the proliferative rate of tumor cells should, in theory, enhance the efficacy of cytotoxic drugs that have cell-cycle-dependent activity. To test this hypothesis, we measured the cytotoxicity of doxorubicin for clonogenic breast tumor cells in the presence and the absence of hormones that stimulate their in vitro growth (17 beta-estradiol, epidermal growth factor, hydrocortisone, and insulin). These growth factors increased the sensitivity to doxorubicin of the clonogenic cell populations from 20 of 25 breast tumors. Their effect was greatest on tumors from hormone-responsive patients. In contrast, these hormones increased the clonogenicity and sensitivity to doxorubicin of bone marrow progenitor cells to a much lesser degree. Hence, under the effect of these growth factors, the in vitro therapeutic index of doxorubicin improved for most of the tumors tested, while tamoxifen citrate, a tumor growth-inhibitory hormone, had the opposite effect. We conclude that tumor tissue-specific growth-stimulatory hormones can improve the in vitro efficacy of cell cycle-active anticancer drugs.

Bone Marrow↗
PubMed1986

Control theory applied to neural networks illuminates synaptic basis of interictal epileptiform activity.

A brief historical account is presented of the formulation of two hypotheses that have been proposed to explain the mechanisms underlying the paroxysmal depolarizing shift (PDS) in experimental epilepsy. The two hypotheses are called the giant EPSP hypothesis and the endogenous burst hypothesis. The giant EPSP hypothesis states that the PDS (the intracellular correlate of the interictal discharge) is comprised of a larger-than-normal-strength excitatory synaptic input, whereas the endogenous burst hypothesis states that the PDS is an endogenous burst triggered by an excitatory postsynaptic potential of normal strength. Two sets of four experimentally testable predictions, which were derived from these two hypotheses for the PDS, are presented. These predictions describe the expected behavior of the PDS in response to changes in membrane potential and under conditions of voltage clamping. With the advent of single-electrode current- and voltage-clamp techniques and improved intracellular recording conditions, the testing of these predictions has become possible. Experiments are described in which each of the predictions from the two hypotheses were tested. The results strongly support the giant EPSP hypothesis and are not easily reconciled with the endogenous burst hypothesis. Because the PDS is a network-driven event, it is important to understand the properties of the neuronal network responsible for the genesis of the PDS. Others have proposed that there are three necessary conditions for epileptiform activity in any neuronal network: endogenous bursting, disinhibition, and recurrent excitatory synapses. Using control theory as a frame of reference, we argue that it is premature to raise these three phenomena to the level of general theoretical requirements for interictal activity. Insufficient quantitative information exists about the properties of neurons, synapses, and connectivity patterns in any cortical neuronal network to conclude that the three preposed requirements are necessary and sufficient general conditions for epileptiform activity. Because all of the key predictions of the giant EPSP hypothesis have now been experimentally verified, we conclude that the PDS is a large, network-driven EPSP. The current challenge to neurophysiologists is to describe is detail the properties of neurons and synapses in a cortical neuronal network and then to evaluate the relative contributions of network and individual neuronal properties to the expression of interictal epileptiform activity.

Animals↗
PubMed1986

Gastroesophageal reflux is not increased by highly selective vagotomy.

In an attempt to determine whether or not highly selective vagotomy leads to increased gastroesophageal reflux, 20 patients were studied after vagotomy (ten underwent highly selective vagotomy and ten, truncal vagotomy and drainage) and ten patients with duodenal ulcer disease were studied preoperatively by history, esophageal manometry, basal pH studies, standard acid reflux tests, acid perfusion tests (Bernstein tests), acid clearance tests and endoscopy with biopsy. Nine of ten patients had either no or minimal reflux symptoms after highly selective vagotomy were contrasted with five of ten preoperative patients who underwent truncal vagotomy and four of ten patients with duodenal ulcer disease. No significant differences in the three patient groups studied were found by esophageal manometry, pH tests, acid perfusion tests, acid clearance tests or endoscopic and histologic examinations. Our results add support to the view that gastroesophageal reflux is not increased after vagotomy (including highly selective vagotomy).

Adult↗