Gastric Acid Secretion in Chronic Uraemia and after Renal Transplantation

In 45 patients with chronic uraemia the basal acid output was the same as in 22 controls. Maximal acid output in uraemic patients was less than in the controls but not significantly so. In uraemia the maximal acid output was directly related to the duration of uraemia and inversely related to both haemoglobin level and age; it was not related to the height of the blood urea. Neutralization of gastric acid by ammonia probably occurred in the basal juice, but not when acid secretion was maximally stimulated. The presence of secondary hyperparathyroidism was associated with a 50% increase in the maximal acid output, but the increase may have been due to the younger age of this group.Successful renal transplantation was followed in two out of seven patients by a considerable increase in acid output and both patients showed evidence of peptic ulceration.     

Further Studies of Gastric Hypersecretion in Chronic Renal Failure

The effect of medical treatment has been studied in four patients with end-stage renal failure who suffered from severe spontaneous gastric hypersecretion, associated with very low levels of intraduodenal pH in two cases. Atropine decreased the overnight gastric acid output, but the residual acid secretion and duodenal content of acid remained dangerously high in one of the patients. Secretin inhibited the basal gastric secretion of acid in all cases and converted the pH of the duodenal contents to alkaline. While atropine cannot be used to control the gastric hypersecretion, secretin may prove to be valuable in the therapeutic management of the gastric hypersecretion of patients with chronic renal failure.     

Hypergastrinaemia in Chronic Renal Failure

Fasting serum gastrin was measured by radioimmunoassay in 89 patients with chronic renal failure. When the serum creatinine level was used as an index of the degree of renal impairment serum gastrin rose proportionately with the degree of renal failure. Haemodialysis did not significantly alter serum gastrin levels but renal transplantation tended to return them towards normal. This study indicates that the kidney has a role in the degradation of gastrin.     

Insulin Infusion Test of Gastric Acid Secretion

In view of the disadvantages of the standard insulin test for completeness of vagotomy a continuous insulin infusion test has been developed. Twenty-six tests were carried out on 12 healthy male volunteers. A dose of 0·04 unit of soluble insulin/kg/hr was found to produce the highest acid secretion with the least severity of symptoms of hypoglycaemia. The pattern of response was a plateau of acid secretion and of hypoglycaemia, and repeated studies in six subjects showed that the results were reproducible. Evaluation of this test after vagotomy and comparison with the standard insulin test are now required.     

Peritoneal Dialysis in Chronic Renal Failure

The long-term results of intermittent peritoneal dialysis in long-term treatment of renal disease have yet to equal those of intermittent hemodialysis. However, further exploration and refinement of this technique is justified.Performed in acute stages of disease, both peritoneal dialysis and hemodialysis relieve the symptoms of uremia and specifically “buy time” for the patient so that proper medical or surgical therapy may be instituted. In acute situations, peritoneal dialysis is the procedure of choice, and is an important adjunct to more conventional treatment for chronic renal disease. It may be useful sometimes even in chronically hemodialyzed patients—for example, when the hemodialysis cannula for one reason or another is inaccessible because of clots, replacement, or infection. It is especially valuable when the hemorrhagic complications of uremia contraindicate hemodialysis treatment.Its use in chronic uremia remains sharply limited in time, but for brief periods chronic peritoneal dialysis appears to be a reasonably satisfactory means of prolonging life while awaiting homotransplant or decision for maintenance hemodialysis therapy.     

E-type Prostaglandins and Gastric Acid Secretion in the Rat

IT is known that prostaglandins of the ? series (PGEs) inhibit gastric acid secretion^1–4, but the relative potencies of prostaglandin E₁ and prostaglandin E₂ have not been evaluated. We report observations which indicate that orally administered PGE₂ has a considerably longer duration of action than an equipotent oral dose of PGE₁ in inhibiting pentagastrin-induced gastric acid secretion in the rat and that this inhibitory action appears to be due to a local action on the gastro-intestinal wall rather than to absorption of prostaglandins into the systemic circulation.     

Intermittent Hemodialysis in Terminal Chronic Renal Failure

Seven patients with chronic renal failure underwent intermittent hemodialysis for five to 37 months (111 patient-months on a twice-weekly basis) employing arteriovenous Teflon-Silastic cannulas and the modified two-layer Kiil hemodialyzer. A single-pass 37° C. dialysate system has been used. One patient died of an indirectly related cause. All other patients have been successfully rehabilitated and now carry on normal activity of moderate sedentary type. Complications included recurring infection and clotting of arteriovenous cannulas. Hypertension and anemia were common complications requiring careful control. Peripheral neuropathy was noted in five of the seven patients but was of clinical significance in only one patient. Metastatic calcification, osteoporosis and urolithiasis also occurred in this patient. Peptic ulcers with hemorrhage developed in two patients. The degree of rehabilitation and psychological adjustment achieved by this group of patients strongly indicates the need for expansion of dialysis facilities and further research into the medical and economic aspects of dialysis.     

Pharmacodynamics of Practolol in Chronic Renal Failure

Plasma levels of practolol were measured in advanced chronic renal failure. The plasma half life was found to be markedly prolonged. During haemodialysis considerable shortening of the half life occurred. Therapeutic blood levels of practolol can be achieved in maintenance haemodialysis patients by the administration of 200 mg of the drug by mouth at the beginning and end of each dialysis.     

Gastric Acid Secretion and Diagnosis of Zollinger-Ellison Syndrome

One hundred and fifty patients suspected of having Zollinger-Ellison syndrome were investigated. High plasma gastrin levels were found in 23 and in 16 a diagnosis of Zollinger-Ellison syndrome was confirmed. Measurement of the basal and maximal acid outputs showed that these simpler investigations have considerable value as screening tests for the selection of those patients in whom gastrin studies are indicated.     

High Dosage Metolazone in Chronic Renal Failure

Metolazone is a modified quinazolinesulphonamide and in a dose of between 4 and 7·5 mg is an effective diuretic in man with normal renal function. Fourteen patients with non-oedematous stable chronic renal failure (creatinine clearance ranging from 1·2 to 12 ml/min) were given metolazone in doses ranging from 20-150 mg. A noticeable increase in urine flow and sodium excretion occurred, free water clearance increased, and there was a small but significant increase in potassium excretion. No side effects were noted.     

Chronic Hemodialysis for Terminal Renal Failure

Ten terminal uremic patients seen over the period of one and one-half years have been kept alive by repeated hemodialysis using a modification of the Seattle system, carried out for the most part by nurses and technicians. All the patients had creatinine clearance values below 5 ml./min., and blood urea nitrogen values which ranged between 156 and 453 mg. % before beginning the first dialysis.Selection was based on their ability to co-operate with and to tolerate the regimen. Nine patients were fully rehabilitated.The major complications were those related to shunt-site infections, including septicemia, bacterial endocarditis, septic arthritis, septic pulmonary embolism and mycotic aneurysm.Nevertheless, all patients except one were rehabilitated and resumed their full-time occupations and have continued to lead happy and useful lives.     

Peritoneal Dialysis in Acute and Chronic Renal Failure

Clinical experience with peritoneal dialysis in eight cases of acute and four cases of chronic renal failure is presented. Seven of the acute cases survived but in some of these hemodialysis was also employed. The relatively simple technique of peritoneal dialysis was found to be effective, although slower than hemodialysis. In three of the cases it was selected in preference to hemodialysis. Its main advantages are that it does not require elaborate arrangements, or the use of blood or anticoagulants. The authors conclude that when the peritoneum is intact the method can be employed whenever the use of a temporary kidney substitute is indicated.     

Gap Junctional Channels Regulate Acid Secretion in the Mammalian Gastric Gland

Gap junction channels are regarded as a primary pathway for intercellular message transfer, including calcium wave propagation. Our study identified two gap junctional proteins, connexin26 and connexin32, in rat gastric glands by RT-PCR, Western blot analysis, and immunofluorescence. We demonstrated a potential physiological role of the gap junctional channels in the acid secretory process using the calcium indicator fluo-3, and microinjection of Lucifer Yellow. Application of gastrin (10⁻⁷ m) to the basolateral membrane resulted in the induction of uniphasic calcium signals in adjacent parietal cells. In addition, single parietal cell microinjections in intact glands with the cell-impermeant dye Lucifer Yellow resulted in a transfer of dye from the injected cell to the adjacent parietal cell following gastrin stimulation, demonstrating gastrin-induced cell-to-cell communication. Both calcium wave propagation and Lucifer Yellow transfer were blocked by the gap junction inhibitor 18α-glycyrrhetinic acid. Our studies demonstrate that functional gap junction channels in gastric glands provide an effective means for rapid cell-to-cell communication and allow for the rapid onset of acid secretion. Received: 4 December 2000/Revised: 5 June 2001     

A Survey of Chronic Renal Failure in Southeastern Ontario

A survey of all physicians in southeastern Ontario was conducted to determine the potential number of patients with chronic uremia who would be candidates for a chronic dialysis program. Four hundred and sixty-four replies were received from the 1391 physicians who received the questionnaire. With the data provided it was calculated that the period prevalence rate of persons suffering from chronic uremia in the area surveyed ranged from 2.2 to 3.3/100,000 population. On the basis of these figures it was estimated that dialysis facilities might be required for six new patients each year in this area.     

Drug Intoxication and Neurological Episodes in Chronic Renal Failure

Of 178 episodes of neurological derangement in 103 patients with renal failure, only about 40% were due to known causes such as hypertension or electrolyte failure. One-third were due to drug intoxication and no definite aetiology was found for the remainder. Drug intoxication is due partly to the accumulation of a drug normally excreted by the kidney and partly to a greater susceptibility of the central nervous system in uraemic patients. The prognosis is favourable.     

Effects of Haemodialysis on Bone in Chronic Renal Failure

Quantitative histological studies have been done on 80 sequential bone biopsies taken at yearly intervals from 37 patients with chronic renal failure on long-term haemodialysis treatment. Twenty-three patients were studied at the start of dialysis, and in about half the bone was abnormal. During dialysis mean osteoid area and the maximum number of unmineralized osteoid lamellae increased, and mineralized bone area decreased. The loss of bone during dialysis was also reflected in reduction of the width of individual trabeculae. These trends were less obvious in patients already established on dialysis at the time of the initial biopsy. The course of osteitis fibrosa appeared to be unaffected by dialysis.