Operative technique of highly selective (parietal cell) vagotomy.
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Biomedical subjects
Publications and source records attributed to D Johnston.
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Euglobulin lysis time (ELT), tissue plasminogen activator (tPA), and the fast-acting inhibitor of tPA, were measured pre-operatively in 128 patients who underwent elective major abdominal surgery. Deep venous thrombosis (DVT) was detected by 125I-labelled fibrinogen scan in 37 patients (29 per cent) after operation. Pre-operatively, there was diminished euglobulin lysis activity (332 +/- 197 versus 255 +/- 156 min, mean +/- s.d.; P less than 0.025), and tissue plasminogen activator activity (4.2 +/- 9.9 versus 7.7 +/- 14.3 milliunits/ml, mean +/- s.d.; P = 0.094) in patients who subsequently developed postoperative DVT compared with those who did not. There was no significant difference between the two groups in the level of inhibition of tissue plasminogen activator (160.6 +/- 75.4 per cent versus 152.5 +/- 77.5 per cent, mean +/- s.d.; n = 47). Stepwise logistic discriminant analysis of the data obtained preoperatively showed that tissue plasminogen activator, a more specific measure of fibrinolytic activity, was a weaker predictor of DVT than euglobulin lysis time. The results confirm other observations which indicate that lowered fibrinolytic activity is a risk factor for postoperative DVT. In addition, they suggest that this is not due entirely to low levels of activity of tissue plasminogen activator in plasma.
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The results of 48 Roux-en-Y (RY) diversion procedures are reported: 41 were performed as secondary procedures and 7 as part of a primary operation for peptic ulcer. There was no operative mortality, but four patients developed temporary fistulae in the postoperative period and three patients required reoperation. Good clinical results were found when RY diversion was performed as a primary procedure or when the indication for operation was peptic ulceration. The overall results, however, were poor: 24 patients (50 per cent) felt that they had not benefited and 32 patients (67 per cent) remained in Visick grades III or IV. The main cause of failure was gastric stasis, especially of solid food. Gastric emptying studies were carried out after RY diversion in 22 patients, most of whom had symptoms of stasis. Emptying of liquids was found to be normal in most patients, but emptying of solids was delayed, the median t 1/2 for solids being 160 (75-370) min compared with 67 (50-85) min in DU patients. Bilious vomiting improved significantly after RY diversion, but 18 patients (38 per cent) complained of vomiting food and 32 patients (67 per cent) experienced postprandial distress or pain. Loss of the antral mill, vagotomy of the gastric remnant and, perhaps, resistance to gastric emptying by the Roux loop itself may together explain the delay in gastric emptying of solids after RY diversion.
Mucosal proctectomy with endo-anal pull-through anastomosis (MP + PTA) for ulcerative colitis reduces resting anal pressure and low RAP has been found to correlate with minor leakage of faeces or mucus. Our hypothesis was that conservative proctocolectomy with an end-to-end ileo-anal anastomosis (EEA) would result in higher anal pressure and less leakage. Twelve patients were studied after EEA and 24 after MP + PTA: each was in good health several months after operation. After EEA, maximal RAP decreased from a median 90 cmH2O (60-116 cmH2O) to 70 cmH2O (25-104 cmH2O, P less than 0.01), whereas after MP + PTA maximal RAP decreased from 85 cmH2O (70-125 cmH2O) to 40 cmH2O (22-80 cmH2O, P less than 0.003). RAP after EEA was significantly greater than RAP after MP + PTA (P less than 0.001). The pressure profile of the anal sphincter in the EEA group did not differ significantly from that of the pre-operative group at any point from 6 to 1 cm from the anal verge, and the sphincteric high pressure zone averaged 4 cm in length both before and after operation. After MP + PTA, resting anal pressure at stations 1 to 4 cm from the anal verge was significantly less than pre-operative pressure (P less than 0.001) and the sphincteric high pressure zone was only 3 cm in length compared with 4 cm before operation. Anal squeeze pressures were similar in the two groups of patients. After EEA 11 of 12 patients achieved perfect continence, day and night, whereas after MP + PTA 58 per cent of patients experienced minor faecal leakage (P less than 0.01). These findings suggest that the entire anal canal should be kept intact in the course of conservative proctocolectomy for ulcerative colitis.
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The automatic implantable cardioverter-defibrillator (AICD) has been shown to reduce the mortality rate of patients with malignant ventricular tachyarrhythmias. This report describes experience with implantation of 36 automatic implantable cardioverter-defibrillators (AID-B and AID-BR models) in 22 persons over a 44 month patient follow-up period (mean 19.6 months). There were five deaths: two patients died suddenly 22 and 29 months, respectively, after their second implant, one died of congestive heart failure, one died of respiratory failure and one died of catheter sepsis. Although 11 (50%) of the 22 patients never received a countershock for a ventricular tachyarrhythmia and are still alive, the other 11 received one or more spontaneous countershocks. Nine patients (41%) experienced spurious shocks during the follow-up period. Assuming that the first shock for presumed ventricular tachyarrhythmia prevented death, the hypothetical cumulative survival of patients at 42 months would have been 34 +/- 14.1% in the absence of an automatic implantable cardioverter defibrillator rather than the actual survival rate of 59 +/- 16.8%. The cumulative device survival of the 36 AID-B units was 92 +/- 5.62% at 15 months but diminished to 37 +/- 14.4% by 20 months. No unit lasted longer than 22 months. There were 12 battery depletions. The number of shocks emitted did not influence unit longevity. The manufacturer's elective replacement indicator is of uncertain validity. Six units remained active 7 to 17 months after surpassing their replacement indicator. The automatic implantable cardioverter-defibrillator prolongs the life of many patients with otherwise intractable arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)
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Peripheral blood samples from 118 patients with acute leukaemia (68 untreated; 50 treated) were measured with the Technicon H-6000 automated haematology analyser. This instrument provides, in addition to measurements of the classical haematology parameters (i.e. cell counts, haemoglobin concentration, etc.), a differential count on 10(4) WBC effected by means of flow cytochemistry (peroxidase content) and volume (light scatter) discrimination. Disregarding RBC and platelet counts and their volume distribution profiles, the most important diagnostic parameters for leukaemic disease were the WBC count, the WBC differential count, and the proportions of large unstained cells (LUC) and high peroxidase (HPX) cells obtained by the automated differential count as well as the mean value of the WBC peroxidase content distribution (MPA). Granulocytic leukaemias had lower MPA than normal and lymphocytic leukaemias had MPA values above normal. M1 leukaemias were also characterized by large proportions of LUC and low fractions of HPX, while M2 leukaemias showed low LUC with high HPX. M3 leukaemias had low LUC and very high HPX. M4 leukaemias had large LUC and 'monocytic' components and a modest fraction of HPX. M5 leukaemias had very large numbers of LUC, 'monocytes' and 'lymphocytes' and a normal HPX. For M1 leukaemia, the presence of less than 7% LUC following induction treatment was related to morphological changes of normal cells induced by chemotherapy while LUC above 10% usually indicated unsuccessful induction associated with the presence of residual blasts. If treatment was successful, M2 and M3 leukaemias characteristically decreased their HPX population. All M4 leukaemias studied by us failed to enter remission and continued to display high proportions of HPX and LUC. Similarly, most M5 leukaemias had a poor response to treatment and always showed a very high proportion of LUC. Untreated lymphocytic leukaemias demonstrated high LUC, normal HPX and a high proportion of 'lymphocytes'. Hairy cell leukaemias showed almost equal proportions of 'lymphocytes' and LUC. Successful chemotherapy of all lymphoid leukaemia entities was associated with rapid decreases in LUC, slower decrements of 'lymphocytes' and moderate and transient increments in HPX. Thus, flow cytochemistry can assist not only in the segregation of acute leukaemias along with FAB classification with nonmorphologic criteria, but also in the follow up of patients with these diseases.
Using extra- and intracellular recording techniques, we investigated the epileptiform activity induced by low concentrations (5 and 10 microM) of bath-applied 4-aminopyridine (4-AP) in the CA3 subfield of rat hippocampal slices. We also studied the effects of 4-AP on the excitatory and inhibitory synaptic conductance changes in CA3 neurons produced by mossy fiber stimulation. Low concentrations of 4-AP induced spontaneously occurring epileptiform discharges at extracellular potassium concentrations between 1 and 10 mM. In contrast, picrotoxin and bicuculline produced spontaneous epileptiform discharges at extracellular potassium concentrations between 5 and 10 mM. The paroxysmal depolarizing shift (PDS) induced by 4-AP was also investigated. At potentials between -40 and -10 mV, the waveform of the PDS consisted of a depolarizing component enveloped by a hyperpolarizing component. The amplitude of the depolarizing component of the PDS was a monotonic function of the membrane potential, and the mean measured reversal potential was -25.7 mV. Under voltage-clamp conditions, the measured conductance associated with the depolarizing component of the PDS averaged 110 nS, with a reversal potential of -14.1 mV. Application of 5 microM 4-AP produced an increase in the inhibitory synaptic conductance change calculated from currents measured 15 ms following mossy fiber stimulation. The mean value increased from 35.2 to 58.1 nS (P less than 0.05) without a significant change in reversal potential. A concentration of 10 microM 4-AP also produced an increase in this inhibitory synaptic conductance change (from 53.3 to 66.3 nS, P less than 0.05) but caused a significant depolarization of the reversal potential (from -66.5 to -61.6 mV, P less than 0.05). This change in reversal potential may reflect a prolongation of the excitatory synaptic currents produced by 4-AP that contributes to the current measured 15 ms from the stimulus. Following application of either 5 or 10 microM 4-AP, there were no significant changes in the resting potential or input resistance of the neurons studied. Application of 5 microM 4-AP also significantly increased the amplitude of the measured excitatory synaptic conductance change produced by mossy fiber stimulation (from 27.9 to 44.1 nS, P less than 0.05) without producing a change in the reversal potential. In 5 of 21 neurons studied, a long-lasting outward synaptic current was present at holding potentials near rest following mossy fiber stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)
Of 693 elderly patients admitted with suspected hip fractures, 43 had normal radiographs and were investigated by isotope bone scan. The 30 patients (70%) with normal scans were mobilised and none developed a fracture. All 13 of the patients with specific bone scan abnormalities were subsequently proved to have fractures, five of which became displaced. Clearly conventional radiography does not exclude fracture of the femoral neck in elderly patients; bone scanning is advisable in doubtful cases.
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Recombinant human tumor necrosis factor alpha (TNF alpha) effectively inhibits clonal growth of leukemic cells from patients and several cell lines, including the promyelocytic HL-60 cells. Decreased expression of the c-myc oncogene is linked to growth arrest and terminal cellular differentiation. The present study characterizes the effect of TNF alpha on the regulation of the c-myc gene in HL-60 cells. TNF alpha (100 U/mL) rapidly inhibited messenger RNA (mRNA) accumulation of c-myc with a 50% reduction in less than one hour. Dose-response studies showed that a 50% reduction of c-myc mRNA occurred in the range of 15 U/mL. In vitro nuclear run-on experiments showed that this decrease of c-myc-mRNA accumulation was the result of a reduced rate of transcription of c-myc by TNF alpha. Further studies demonstrated that TNF alpha did not post-transcriptionally alter levels of c-myc mRNA, and the inhibitory action of TNF alpha on c-myc expression in HL-60 cells did not depend on new protein synthesis. In the conditions of all the experiments, TNF alpha did not affect cell viability. By contrast, TNF alpha (500 U/mL) did not decrease mRNA levels of c-myc in an HL-60 variant cell line whose growth was not inhibited by TNF alpha; also TNF alpha (500 U/mL) increased c-myc-mRNA levels in normal fibroblasts whose growth is known to be stimulated by TNF alpha. These findings, in concert with prior studies, show a close association between growth inhibition of HL-60 cells and decreased levels of mRNA coding for c-myc.
Immunization to B16 melanoma is known to induce tumor-specific immune responses, yet the identity of the immunogenic antigens on these cells is not known. To answer this question, sera obtained from mice immunized to a partially purified B16 melanoma antigen vaccine that induced tumor-protective immunity were used to immunoprecipitate extracts of radioiodinated B16 melanoma cells. Immunogenic antigens were identified by sodium dodecyl sulfate polyacrylamide gel electrophoresis and autoradiography of immunoprecipitates. Though the vaccine contained a number of different components, only three induced antibody responses in syngeneic mice. These antigens were surface proteins with molecular weights of approximately 90, 200, and 250 + kDa. The three antigens were expressed by B16F1, B16F10, and B16F106-Lr melanoma cell variants but not by several unrelated syngeneic or xenogeneic cancers or by normal murine tissues. Thus, we have been able to identify some of the antigens in B16 melanoma that are immunogenic in syngeneic mice.
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To assess the effect of duodenal ulcer surgery on Campylobacter pyloridis gastric biopsies were done and fasting bile acid concentrations in gastric aspirates were measured in 35 patients with active duodenal ulceration and 54 who had undergone surgery at some time. Biopsy specimens were assessed blind for the presence of C pyloridis and scored for severity of reflux gastritis by the use of a histological grading system. Among patients who had undergone highly selective vagotomy the proportion who were C pyloridis-positive was similar to that in the unoperated group, but among those who had undergone Billroth I partial gastrectomy, Billroth II partial gastrectomy, or truncal vagotomy and gastroenterostomy it was significantly lower (p less than 0.001). The absence of C pyloridis correlated strongly (p less than 0.001) with high reflux scores and increased bile acid concentrations in the stomach. Reflux scores and bile acid concentrations were significantly higher (p less than 0.01) after Billroth I and Billroth II partial gastrectomies and truncal vagotomy and gastroenterostomy than in the active duodenal ulcer or highly selective vagotomy groups. There was a highly significant correlation (p less than 0.001) between reflux scores and bile acid concentrations. These results suggest that reflux may disrupt mucus and thus cause the death of campylobacters that live beneath it. They also suggest that reflux may produce a reflux-specific gastritis. Highly selective vagotomy may protect against these changes in the gastric mucosa.