A.E. Read

SCLEROSING PERITONITIS, AN UNUSUAL REACTION TO A β-ADRENERGIC-BLOCKING DRUG (PRACTOLOL)

Abstract Peritoneal disease, apart from the post-operative variety, is rare, but three female patients, who presented with abdominal symptoms and in whom an unusual peritoneal lesion was found at operation, had one factor common to their medical histories—namely, previous treatment with the β-adrenergic-blocking drug practolol. The main finding at laparotomy was a pattern of massive peritoneal adhesions, but one patient had no history of abdominal surgery, and the findings at laparotomy were unusual. Other possible causes of this sclerosing peritonitis can be excluded, and the possible involvement of practolol in these cases is supported by the identification, via the Committee on Safety of Medicines, of four similar cases.

Intravenous administration of diazepam in patients with chronic liver disease.

The EEG response and drug kinetics after intravenous infusion of diazepam at 1-0 mg/min until nystagmus, dysarthria, and moderate sedation developed, has been investigated in five normal subjects and 17 patients with chronic liver disease. Diazepam induced adequate premedication with a similar clinical response in all subjects with no adverse reactions. Maximal response was during or within five minutes of infusion. The dose of diazepam required in liver chronic disease was 17-9 +/- 1-4 mg (M +/- SEM) compared with 27 +/- 5-4 mg in controls (p less than 0-01). Dose correlated significantly with serum albumin (p less than 0-05). Baseline mean dominant frequency (MDF) and slow wave index (SWI) significantly correlated with albumin (p less than 0-01). After diazepam, the MDF decreased and SWI increased. The change was greatest at the time of maximal clinical response. It was greater in liverdisease and was greatest in patients with previous hepaticencephalopathy. In spite of reduced dose requirements in liver disease, there was no significant difference in plasma concentration at the end of drug infusion...

CLOSTRIDIUM DIFFICILE ASSOCIATED DIARRHŒA: A ROLE IN INFLAMMATORY BOWEL DISEASE?

Abstract 56 patients with diarrhœa were screened for the presence of Clostridium difficile toxin in their stool. The test was positive in 9: 5 had severe inflammatory bowel disease and were receiving systemic steroids; 2 were on steroids for other conditions; 1 had been on antibiotics; and in 1 there was no apparent predisposing factor. In each case clearance of the toxin was associated with clinical improvement. Evidently Cl. difficile toxin is not specific for antibiotic-associated diarrhaea, but is associated with diarrhœa of various aetiologies, often unrelated to antibiotic therapy. Cl. difficile may be an important factor in some exacerbations of inflammatory bowel disease.

A RADIOIMMUNOASSAY FOR CHOLECYSTOKININ-PANCREOZYMIN

A sensitive and specific radioimmunoassay for cholecystokinin-pancreozymin (CCK-PZ) has been developed, using rabbit antisera to crude porcine hormone. Highly purified porcine CCK-PZ, labelled with (131)I, and repurified by column chromatography on Sephadex G15, was used as tracer. Separation of free from antibody-bound labelled CCK-PZ was carried out using charcoal, ion-exchange resin, or a double antibody procedure. Non-specific interference with the assay system by serum factors was abolished (as judged by in-vitro and in-vivo recovery studies) by boiling and diluting the serum samples before assay. Ninety-nine per cent pure porcine CCK-PZ (standard), commercial CCK-PZ preparations, caerulein, the C-terminal 8- and 12-amino acid fragments of the CCK-PZ molecule, and endogenous human CCK-PZ all cross reacted in the assay system and showed parallel inhibition curves. No significant cross reaction was found with gastrin, secretin, glucagon, or insulin. The sensitivity of the assay is approximately 5 pg per ml of test solution, which proved adequate for measuring physiological levels of CCK-PZ in peripheral blood in man.The mean immunoreactive CCK-PZ concentration in 50 fasting normal subjects was 60.4 pg per ml. The distribution of individual values was skewed, however, so that the median was much lower (30 pg per ml). Older subjects had higher fasting levels of CCK-PZ than were found in young adults.

Fibreoptic examination of the colon: a review of 255 cases

The results of fibreendoscopy of the colon are described in 255 consecutive examinations. Of the examinations, 26·5% resulted in a diagnosis being made solely by endoscopy. This included 17 cases of carcinoma, 15 patients with polyps, and 25 patients with inflammatory bowel disease. The most common reason for referral was undiagnosed rectal bleeding (75 cases) and endoscopy alone was successful in diagnosing the probable or definitive source of bleeding in 50% of the cases referred. It is not yet clear, however, to what extent this figure may reflect the inadequacy of conventional radiology. A definitive radiological diagnosis was refuted in 11 patients and an unnecessary laparotomy avoided in seven of these. There is no doubt that fibreoptic colonoscopy increases diagnostic accuracy in large bowel disease and is especially helpful in cases where radiology is either negative or equivocal.

Steatorrhea and malignant lymphoma the relationship of malignant tumors of lymphoid tissue and celiac disease

Summary1. Seven patients with celiac disease complicated by malignant lymphoma are presented. Seventeen other cases of steatorrhea and lymphoma, together with 40 cases from the literature, are discussed.2. The commonest mode of presentation of this type of reticulosis is failure of response to treatment for steatorrhea or a recurrence of symptoms in patients who have improved as a result of treatment. Abdominal pain, skin rashes, fever, and an abdominal mass occur frequently. Laparotomy with biopsy gives the best chance of diagnosis.3. When steatorrhea occurs with malignant lymphoma, the tumor is found mostly commonly in proximal small intestine; the incidence of Hodgkins disease is increased; there appears to be a higher than normal incidence among women; the onset of lymphoma is later than usual, and the prognosis is poorer.

Radioimmunoassay of cholecystokinin-pancreozymin.

A sensitive and specific radioimmunoassay for cholecystokinin-pancreozymin (CCK-PZ) has been developed, using rabbit antisera to crude porcine hormone. Highly purified porcine CCK-PZ, labelled with 131I, and repurified by column chromatography on Sephadex G15, was used as tracer. Separation of free from antibody-bound labelled CCK-PZ was carried out using charcoal, ion-exchange resin, or a double antibody procedure. Non-specific interference with the assay system by serum factors was abolished (as judged by in-vitro and in-vivo recovery studies) by boiling and diluting the serum samples before assay. Ninety-nine per cent pure porcine CCK-PZ (standard), commercial CCK-PZ preparations, caerulein, the C-terminal 8- and 12-amino acid fragments of the CCK-PZ molecule, and endogenous human CCK-PZ all cross reacted in the assay system and showed parallel inhibition curves. No significant cross reaction was found with gastrin, secretin, glucagon, or insulin. The sensitivity of the assay is approximately 5 pg per ml of test solution, which proved adequate for measuring physiological levels of CCK-PZ in peripheral blood in man. The mean immunoreactive CCK-PZ concentration in 50 fasting normal subjects was 60·4 pg per ml. The distribution of individual values was skewed, however, so that the median was much lower (30 pg per ml). Older subjects had higher fasting levels of CCK-PZ than were found in young adults.

Neurological disorders and adult coeliac disease

An investigation into the incidence of neurological disorder in 30 patients with adult coeliac disease has shown that three patients had severe depression, two had epileptiform convulsions, and one patient only had signs of involvement of the peripheral nervous system. Motor nerve conduction velocity was low in only one patient. When the nerve conduction velocities of the group on a gluten-free diet were compared with the group who were not on a gluten-free diet, there was no statistically significant difference. Similarly, nerve conduction velocities in patients with a low serum pyridoxal level were not significantly different from those with normal serum pyridoxal levels. Measurements of the serum level of pyridoxal in 30 patients confirmed that pyridoxine deficiency occurs in adult coeliac disease and that the restriction of gluten from the diet appeared to affect pyridoxal levels favourably.

SALINE PURGATIVES ACT BY RELEASING CHOLECYSTOKININ

Abstract Saline purgatives such as magnesium sulphate are generally believed to produce their effects on the gastrointestinal tract by attracting and retaining fluid in the intestinal lumen by osmosis, thereby increasing the volume of the intestinal contents. However, a large body of experimental work demonstrates that these salts have a complex series of actions, both motor and secretory, on the gastrointestinal tract which cannot be explained by a simple osmotic effect. All the known actions of magnesium sulphate on the gut are closely similar to reported actions of the hormone cholecystokinin-pancreozymin (C.C.K.-P.Z.), which is released from the intestinal mucosa in response to magnesium sulphate and other salts. This hypothesis suggests that the action of the saline purgatives is not brought about by osmotic effects but is in large part due to the actions of C.C.K.-P.Z. on the gastrointestinal tract.

Evaluation of colloidal bismuth (De-Nol) in the treatment of duodenal ulcer employing endoscopic selection and follow up

A double-blind, placebo-controlled trial of colloidal bismuth (De-Nol) was performed on 20 patients with active duodenal ulceration employing endoscopic selection and follow up after a treatment period of 28 days. By these means it was shown that healing of ulcers was significant in those patients treated with the active compound. In addition a greater number (9/10) of patients treated with colloidal bismuth showed symptomatic improvement than those receiving placebo (6/10) but this difference did not reach statistical significance. The results of endoscopic and symptomatic assessment of the patients receiving colloidal bismuth were in complete agreement although there was a poor correlation between these results in those receiving the placebo. This supports the results from a previous study that endoscopic assessment of duodenal ulcer healing provides a more objective assessment than do clinical methods.