Reappraisal of the 5 centimetre rule of distal excision for carcinoma of the rectum: a study of distal intramural spread and of patients' survival.
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Biomedical subjects
Publications and source records attributed to D Johnston.
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Bile acid and lysolecithin concentrations in the stomach were measured in normal subjects and in patients with gastric ulcer (GU) before operation and more than 1 year after highly selective vagotomy, Billroth I partial gastrectomy (PG) and truncal vagotomy and pyloroplasty. Before operation, patients with GU had significantly (P less than 0.001) higher bile acid concentrations in the stomach than normal people. After highly selective vagotomy, bile acid concentrations were significantly lower than in preoperative GU patients and were also significantly lower than in patients after PG, but were still higher than in normal people. Postprandial and peak lysolecithin concentrations after highly selective vagotomy were significantly lower than after partial gastrectomy. The therapeutic effect of highly selective vagotomy in the surgical treatment of GU may be due not only to reduced acid-peptic 'attack' on the gastric mucosa, but also to reduced duodenogastric reflux of 'bile'.
The quality of life for patients with carcinoma of the lower two-thirds of the rectum (5-12 cm from the anal verge) treated by abdominoperineal resection (APER, n = 38) was compared with that of a similar group of patients treated by low sphincter saving resection (SSR, n = 40). Assessment was by questionnaire conducted a minimum of one year after operation. Thirty patients (75 per cent) after SSR were entirely continent and ten patients (25 per cent) had occasional episodes of incontinence. Each patient with a colostomy was incontinent and 25 (66 per cent) had leaks from their appliance (12 frequent; 13 occasional). Patients after APER avoided more items in the diet and took more medication to control their bowel habit than patients after SSR. Fifteen of the 18 patients (83 per cent) who were employed before SSR returned to work after operation; only 6 of 15 patients (40 per cent) returned to work after APER (P less than 0.05). Sexual function was impaired in 6 of 20 men (30 per cent) after SSR and in 12 of 18 men (67 per cent) after APER (P less than 0.06). Depression was significantly more prevalent after APER than after SSR. Patients with low rectal cancer who are treated by modern sphincter saving resection have a quality of life superior to those who are treated by APER.
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Metalloendoproteases have been implicated in the calcium-dependent exocytosis of histamine from mast cells and in the calcium-dependent fusion of myoblasts. Because metalloendoproteases have also been identified in nervous tissue, we investigated the possibility that these proteases may be involved in neurotransmitter release at mammalian synapses. End-plate potentials were recorded intracellularly from mouse diaphragm/phrenic nerve preparations in vitro. The amplitude of the endplate potentials were reduced by as much as 90% during bath application of phosphoramidon, a specific inhibitor of metalloendoproteases, and by carbobenzoxy-dipeptide-amide synthetic substrates for metalloendoproteases. Only those synthetic dipeptides in which the amino group of the peptide bond was provided by a bulky hydrophobic amino acid, such as phenylalanine or leucine, which are substrates for metalloendoproteases, reduced synaptic transmission. Synthetic substrates in which proline or glycine provided the amino group of the peptide bond, which are not metalloendoprotease substrates, had little or no effect on the amplitude of end-plate potentials. The ability of synthetic substrates to reduce synaptic transmission was also dependent on the amino acid that provided the carboxyl group of the peptide bond, with glycine being more effective than tyrosine or serine. In addition, synthetic dipeptides with free carboxyl or amino termini, which have a low affinity for metalloendoproteases, also had little effect on synaptic transmission. The inhibition of synaptic transmission by phosphoramidon and the synthetic substrates occurred within 2 to 3 min and was completely reversible. Neither phosphoramidon nor the synthetic substrates altered the dose-response characteristics of the postsynaptic membrane to bath-applied carbachol. These results suggest that synaptic transmission requires the activity of a metalloendoprotease in the presynaptic nerve terminal and that proteolysis may be an important step during neurotransmitter exocytosis.
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Breathlessness, exercise tolerance, and spirometry were measured in 12 patients whose major symptom was breathlessness, secondary to severe chronic airflow limitation, during a double-blind crossover comparison of inhaled salbutamol in two dosages (200 micrograms 4-hourly and 200 micrograms 2-hourly) with placebo. Daily visual analogue scores of breathlessness, exercise tolerance and spirometry were all significantly improved with salbutamol in both dosages compared to placebo. The 2-hourly regimen was superior to the 4-hourly regimen only in terms of exercise tolerance. Walking distance had deteriorated significantly 2 hours after salbutamol on the 4-hourly regimen and was usefully increased by an extra dose of salbutamol on the 2-hourly regimen at the equivalent time, without side-effects. Salbutamol provided considerable symptomatic relief in addition to spirometric improvement in patients with chronic airflow limitation.
An earlier study of cholesterol metabolism in HeLa cells has provided evidence for the inhibitory effect of glucocorticoids on de novo cholesterol synthesis. To extend this observation to other regulatory pathways involving cholesterol, we have now determined the effects of dexamethasone on the cell-associated low density lipoprotein (LDL) assumed to represent a normal source of exogenous cholesterol. It was found that HeLa cells internalized LDL by low affinity as well as high affinity saturable processes. Since cell-associated LDL was reduced by dexamethasone to 20-60% of the control value, we have made further attempts to examine the nature of this observation. The kinetics of LDL-cell association and the binding studies performed at 4 C indicated that dexamethasone did not affect the immediate binding of LDL to HeLa cells, whereas 25-hydroxycholesterol, which is known in other cells to inhibit LDL binding by reducing the number of LDL receptors, had the same effect in HeLa cells. The nature of the dexamethasone effect appeared to be related to interference with processing of bound LDL after its internalization. Further evidence that dexamethasone did not affect the initial binding of LDL was provided by the experiments in which chloroquine completely abolished the inhibitory action of dexamethasone.
In this study, 95 patients with laparotomy-staged I and II nonmediastinal Hodgkin's disease were treated with involved fields (41 patients), mantle (17), extended fields (26), or involved fields followed by 6 cycles of MOPP (11). Eighty-five patients had upper torso presentations. Seventy had Stage I disease and 25 had stage II. Pathologic findings were nodular sclerosing, 33; mixed cellularity, 41; lymphocyte predominance, 20; and unclassified, one. Five-year overall survivals were excellent regardless of stage, pathologic findings, or treatment: 98% for involved fields or mantle, and 100% for both extended fields and involved fields followed by 6 cycles of MOPP. Corresponding disease-free survivals were 77%, 82%, and 86%, respectively. For patients with upper torso presentations, disease-free figures for the mantle (94%) were better than those for involved fields alone (67%). In addition, regression analysis proved involved fields to be a prognostic factor for a lower disease-free survival. No difference between extended fields or mantle radiotherapy could be detected using this model. Relapses usually occurred in nonirradiated upper torso sites. Only three of the 36 patients treated with involved fields and one of 21 treated with extended fields relapsed in the abdomen alone. Most patients in relapse were salvaged. Rescue treatment was most often radiotherapy and adjuvant combination chemotherapy. Based on this study, the use of mantle radiotherapy is recommended in treating laparotomy-staged I and II patients with nonmediastinal presentations, and the use of extended fields or adjuvant chemotherapy as primary prevention is not recommended.
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The effect on bladder function of protectomy for colitis or Crohn's disease was studied by means of a questionnaire and by pressure/flow cystometry. Thirty-seven patients who had undergone protectomy for inflammatory bowel disease were compared with 34 control patients who had undergone bowel resection without protectomy. Symptoms of urinary dysfunction were found to be significantly more common in patients after protectomy than in controls (P less than 0.05). Straining at micturition (P less than 0.05) and a sensation of incomplete emptying of the bladder (P less than 0.02), in particular, were significantly more common after protectomy. Evidence of denervation of the bladder, as shown by the finding of capacious bladders with poor detrusor function, was found in 6 patients after protectomy but in none of the controls (P less than 0.05). The residual volume of urine in the bladder after micturition was significantly greater in patients after protectomy than in controls (P less than 0.02). Thus, the bladder is at risk of denervation in the course of protectomy for inflammatory bowel disease even when dissection is kept close to the rectum.
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The performance of two high-speed 8-parameter automated hematology analyzers (Coulter Counter S-plus and ELT-8) were compared with that of reference instruments (Coulter Counter S Sr and Technicon Autocounter). The precision, linearity, and lack of carry-over of both instruments were superior over that of existing equipment. The especially noteworthy feature of the instruments was their excellent performance in the range of extreme values of both white blood cells and platelets. This enhanced performance, and the fact that all presently known relevant hematologic parameters can be measured by a single instrument on a single sample, make the contribution of these two flow cytometric-based instruments a significant advance in the field of automated laboratory medicine.
The effect of highly selective vagotomy on pancreatic exocrine function and the release of gastrin and cholecystokinin was studied in 10 patients with endoscopically-proven duodenal ulceration. Cholecystokinin and gastrin concentrations in serum both increased significantly after highly selective vagotomy. Amylase concentration in the duodenal aspirate increased significantly after vagotomy, but trypsin concentration remained unchanged. The expected reductions in gastric acid secretion were noted. Thus highly selective vagotomy reduces acid secretion effectively in patients with duodenal ulcer without impairing the exocrine function of the pancreas.
Duodenogastric reflux of bile acids and lysolecithin in the course of a standard test meal was measured in normal people and in patients with duodenal ulcer before operation and more than one year after highly selective vagotomy, Polya partial gastrectomy, truncal vagotomy and pyloroplasty, and truncal vagotomy and gastrojejunostomy. Before operation, duodenal ulcer patients had significantly higher fasting, post-prandial, and peak bile acid concentrations in the stomach than had normal subjects. After Polya partial gastrectomy, fasting, post-prandial, and peak concentrations of bile acids and lysolecithin were significantly higher than in preoperative duodenal ulcer patients. After highly selective vagotomy, in contrast, bile acid concentrations in the stomach were significantly lower than in preoperative duodenal ulcer patients and post-prandial and peak lysolecithin concentrations were less than half (NS) those recorded in preoperative duodenal ulcer patients. After highly selective vagotomy, bile acid concentrations were also significantly lower than bile acid concentrations after Polya partial gastrectomy, truncal vagotomy and pyloroplasty, and truncal vagotomy and gastrojejunostomy; and post-prandial and peak lysolecithin concentrations were significantly lower than after Polya partial gastrectomy and truncal vagotomy and gastrojejunostomy. Thus, when used in the treatment of patients with duodenal ulcer, highly selective vagotomy keeps ;bile' out of the stomach, probably through its effect on gastric smooth muscle, combined with the preservation of an intact antropyloroduodenal segment. In contrast, Polya partial gastrectomy, truncal vagotomy and gastrojejunostomy, and truncal vagotomy and pyloroplasty all lead to a significant increase in reflux of bile acids and lysolecithin into the stomach. The clinical importance of these findings is that both gastritis and, in the long term, gastric carcinoma may prove to be less common after highly selective vagotomy than after partial gastrectomy or vagotomy with a drainage procedure.