Transplantation of human fetal pancreas: experience in thymusaplastic mice and rats and in a diabetic patient.

The aim of the present study was to investigate if thymusaplastic nude mice and rats are favorable as recipients for transplantation of human fetal pancreas. Twenty human fetal pancreases were transplanted subcutaneously to 20 nude mice, and six human fetal pancreases were transplanted to six rats. The xenografts showed histotypical development of islets of Langerhans. Insulin, glucagon, somatostatin, and pancreatic polypeptide immunoreactivities were also seen in very early stages of the transplant development within the monolayered ducts. With the described "epigastric pouch technique" in rats, we co-ld demonstrate a new in vivo method for selective stimulations and simultaneous blood sampling from tissue-isolated xenografts. Transplantation of human fetal pancreas to the brachioradial muscle of an insulin-dependent patient in combination with a kidney transplant revealed that rejection crises of the kidney led to necrosis of the pancreas transplant, whereas rejection of the kidney was overcome by steroid pulse therapy.

[Prevention of postoperative pancreatic complications following duodenopancreatectomy using somatostatin]. / Verhütung von postoperativen pankreatitischen Komplikationen nach Duodenopankreatektomie durch Somatostatin.

Somatostatin was prophylactically administered to 10 patients who had surgery for pancreatic diseases. The postoperative course uncomplicated with no increase in serum amylase levels. Bile induced acute pancreatitis in six beagles was prophylactically treated with somatostatin. The results demonstrate that SRIF not only inhibits basal but also pancreatic-induced blood amylase and enzyme activities in the dog. SRIF-treated animals were in good general condition compared with untreated controls, macroscopic and histologic aspects of the pancreas were significantly improved.

[Adrenal cortex transplantation. Animal experimental models for the human Cushing and Conn syndromes--clinical aspects of adrenal cortex transplantation]. / Transplantation der Nebennierenrinde. Tierexperimentelle Modelle für das Cushing- und Conn-Syndrom des Menschen--Klinische Aspekte der Nebennierenrindentransplantation.

Thymusaplastic mutants of mice (nu/nu) and rats (rnu/rnu) were used as recipients for tissue of one aldosteronoma of a 21-year-old male patient with Conn's syndrome and for tissue of one adenoma of a 28-year-old female patient with Cushing's syndrome. In this animal experimental study we succeeded in demonstrating that congenitally athymic rodents are ideal recipients for xenotransplantation of adrenal cortical tissue. The graft viability was demonstrated by obtaining light and electron micrographs of the biopsied transplants and its endocrine function documented by the measurements of plasma renin, cortisol, and urinary excretion of aldosterone, cortisol, and corticosterone. Fifteen patients are presented who were surgically treated for Cushing's disease. Fourteen patients with adrenocortical hyperplasia underwent total adrenalectomy and two had after adrenalectomy autotransplantation of adrenal tissue in the forearm muscle. One patient was treated with a transsphenoidal, partial hypophysectomy. Our clinical experience with Cushing's disease showed that the initial surgical procedure may be directed to the pituitary and only in unsuccessful surgery to the adrenals. Adrenal autotransplantation after total adrenalectomy is an obsolete procedure.

Effect of pentobarbital anesthesia and bile acids on cysteamine-induced duodenal and gastric ulcers in rats.

Cysteamine given three times within 8 h produced severe duodenal and gastric ulcers in female SIV rats. A pentobarbital anesthesia during the first 10 h prevented gastric ulcer formation without affecting duodenal ulcer. An additional 10 h lasting intragastric infusion with 0.6 ml/h Ringer containing 5 mmol/l of a mixture 3: 1 pure taurocholic and glycocholic acid or 20 and 50 mmol/l pure taurocholic acid in 0.2 N HCl did not reverse the protective effect of pentobarbital, e.g. incidence and intensity of gastric ulcer did not change. Treatment with somatostatin significantly reduced the intensity of duodenal ulcer. The inhibition of cysteamine-induced gastric ulcer formation by pentobarbital does not seem to be due to a possible inhibition of duodenogastric reflux but more likely to an inhibition of central nervous stress reactions by anesthesia.

Individual patient data meta-analysis of trials of self-monitoring of blood glucose in non-insulin treated type 2 diabetes: protocol for a systematic review.

BACKGROUND AND AIM OF THE STUDY: Recent trials have provided differing estimates of the benefits of self-monitoring of blood glucose (SMBG) for non-insulin treated patients with type 2 diabetes. Designing and conducting randomised trials to demonstrate the efficacy of complex interventions is challenging. Variations in the components of the intervention delivered, target population selected, and reporting methods used have limited the conclusions drawn in recent systematic reviews. We will systematically examine these factors within the trials of SMBG to enable further investigation of the data through an individual patient data analysis (IPD). METHODS/DESIGN: The IPD analysis will include data from randomised trials comparing blood glucose self-monitoring and decisions about self-management versus a control group with standardised or routine care. The data requested for each trial will include outcomes (HbA1c, blood glucose and quality of life), potential moderators of effect (e.g. demographic variables, clinical data and psychosocial factors) and intervention descriptors. The primary outcome of interest will be HbA1c. Secondary outcomes include alternative measures of glycaemia, cardiovascular risk factors, persistence with monitoring, and measures of health status, quality of life and psychosocial factors. Analysis of patient sub-groups defined by age at randomisation, gender, prior use of monitoring and health status will be carried out. An intention to treat analysis will be performed and assessed for clinical and statistical heterogeneity. DISCUSSION: With current uncertainty about the extent of benefit from SMBG for non-insulin treated patients with type 2 diabetes, this study will provide the best estimates to date of overall effectiveness, effectiveness within potential target populations, and optimal components of the intervention.

Is remission of Graves' disease regulated by anti-idiotypic antibodies?

Our results show evidence for regulation of Graves' disease remission by anti-idiotypic antibodies in a biologic assay. The polyclonality and functional heterogeneity of thyroid receptor antibodies is most likely the reason why evidence for idiotypic-anti-idiotypic regulation can be demonstrated in the autologous but not consistently in the homologous system.

Clinical effect of dopamine on incidence of peptic ulceration.

Dopamine and its agonists diminish gastric acid secretion and exert a protective effect on experimentally induced peptic ulcers in rats. For treatment of peptic ulcer disease in man, dopamine and dopamine antagonists have been recommended, but clear evidence is not yet available. To answer the question of whether dopamine has any protective effect regarding peptic ulcer formation in man, autopsy reports were evaluated for the incidence of acute peptic ulcerations before and after the introduction of dopamine as a common drug in intensive care units. The analysis showed no change in ulcer incidence, i.e., our retrospective study demonstrated no ulceroprotective action of dopamine in critically ill patients.

Transplantation of human endocrine tissues to nude mice: a suitable in vivo model for the study of pathomechanisms involved in autoimmune thyroid diseases.

After transplantation of human tissue to nu/nu mice the human lymphocytes disappear. In this context, interestingly, the DR-expression is not detectable anymore after transplantation of the tissues from patients with autoimmune thyrotoxicosis and cancer. Neopterin release was only demonstrable when T-lymphocytes from patients with autoimmune thyrotoxicosis or PHA-stimulated lymphocytes were added, independently of the presence of DR-expression in the used culture tissues. These results seem to exclude a functional role of DR-expression as a trigger mechanism of autoimmunity. It is supposed that DR-priming on epithelial cells is mediated by kinine production of activated T-lymphocytes or macrophages.

Evidence for increased endogenous dopaminergic inhibition of aldosterone secretion in prolactinoma.

Aldosterone responsiveness to consecutive i.v. injections of metoclopramide 1 mg, 2.5 mg and 10 mg was studied in 8 patients with prolactinoma and normally preserved adrenal function and in 14 healthy volunteers. In the patients, aldosterone response to metoclopramide 1 mg was blunted. After metoclopramide 10 mg, aldosterone rose to the same levels in patients and volunteers. In the patients, however, percentage rise of aldosterone was enhanced, since the appropriate base line concentration of aldosterone was decreased. Thus, there is evidence for increased endogenous dopaminergic inhibition of aldosterone secretion in prolactinoma.