Islet autotransplantation and total pancreatectomy.

The goal of IAT is the preservation of beta-cell mass at the time of pancreatectomy. The majority of recipients have significant endogenous beta-cell function with positive blood C-peptide after surgery, even if only approximately one third achieve insulin independence. In appropriately selected patients, total pancreatectomy combined with IAT achieves relief of pain and improves quality of life with relatively easier-to-manage glycemic control and avoidance of hyper- and hypoglycemic episodes. Current research is focused on improving techniques of islet isolation and engraftment as well as long-term survival of autografted islets.

From pancreatic extracts to artificial pancreas: History, science and controversies about the discovery of the pancreatic antidiabetic hormone. II: Nicolae C. Paulescu: The discovery of pancreine

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[Primary sclerosing cholangitis with chronic pancreatitis]. / Primär-sklerosierende Cholangitis mit chronischer Pankreatitis.

HISTORY AND CLINICAL FINDINGS: A 68-year old man with insulin dependent diabetes mellitus was admitted to hospital because of diarrhoea, general weakness and 10 kg weight loss over the preceding 3 months. Biliary tract enzymes were markedly elevated (alkaline phosphatase > 1000 U/l, gamma-glutamyl transferase > 300 U/l). Computed tomography (CT) was suggestive of a space occupying lesion in the head of the pancreas. INVESTIGATIONS: CT confirmed the space-occupying lesion and biopsy revealed chronic fibrosing pancreatitis. Radiology showed the typical picture of primary sclerosing cholangitis (PSC), in addition to inflammatory changes in the pancreatic duct. TREATMENT AND COURSE: Administration of ursodeoxycholic acid and substitution therapy for the exocrine and endocrine pancreatic insufficiency normalised the laboratory values. The patient gained 5 kg and the changes in the biliary tract and pancreatic ducts markedly regressed. CONCLUSION: PSC is rarely associated with inflammatory pancreatic changes, which cause severe functional changes. Ursodeoxycholic acid improves both the biochemical changes and the histological lesions of the biliary tract and the pancreatic ducts.

Spontaneous hypoglycaemia in a noninsulin-dependent diabetes mellitus patient with disseminated pancreatic carcinoma.

A 52-year-old-woman with non-insulin-dependent diabetes mellitus developed carcinoma of the pancreas and had a Whipple's resection performed. She required pancreatic exocrine supplements and insulin post-operatively. Five years later metastatic disease became apparent, and was accompanied by episodic spontaneous hypoglycaemia necessitating the cessation of insulin therapy. Hormonal analysis was performed, off insulin, at a time of hypoglycaemia (glucose 0.9 mmol l-1) and showed negligible insulin concentrations (< 2 mU l-1) but raised IGF-II together with low IGF-I concentrations (1.85 and 0.1 U ml-1, respectively). The association between diabetes and pancreatic carcinoma, and the pathogenesis of non-islet cell tumour induced hypoglycaemia (NICTH) are discussed.

[Factors with insulin-like effects: IGF-I and GLP-1]. / Pusobky s inzulinovým úcinkem: IGF-I a GLP-1.

In the submitted review the author discusses two substances secreted into the circulation which can similarly as insulin lower the blood sugar level. These substances are IGF-I (insulin-like growth factor I) and GLP (glucagon-like peptide). While in case of the former it is not certain whether it participates in the glucose homeostasis, this is beyond doubt in the latter. IGF-I prepared by the recombinant technique can be used therapeutically in cases of insulin resistance caused by a receptor or postreceptor disorder, because it may act via its own receptor. Side-effects after larger doses are a problem. GLP-1, the use of which would be useful in type 2 diabetics as it stimulates insulin secretion, is not used so far in therapy because hitherto prepared preparations have a very short period of a effectiveness.

Treatment with growth hormone-releasing hormone (GHRH) 1-44 in children with idiopathic growth hormone deficiency: a randomized double-blind dose-effect study. The GHRH European Multicenter Study (GEMS) Group.

One hundred and eleven pre-pubertal children (70 boys, 41 girls, aged 2.5 to 14.3 years) with growth failure (height 2 SD below the mean for chronological age (CA) and height velocity (HV) below the 10th percentile for bone age) due to idiopathic growth hormone deficiency (peak plasma GH < 20 mUI/1 to two standard provocative tests) were treated with GHRH 1-44 NH2. Patient stratification in two classes was performed according to body weight; in each class, patients were randomly allocated to one of seven GHRH doses, from 30 to 300 micrograms/day. GHRH was injected subcutaneously, every evening, for six months in a double-blind fashion. No relationship was found between the absolute or incremental HV during treatment and the dose (range from 1.3-23.1 micrograms/kg/day) of GHRH. However, HV (cm/year) increased from 3.8 +/- 0.1 (mean +/- SEM) before treatment to 6 +/- 0.2 during six months treatment and 47 patients (42%) increased their HV up to at least the mean normal HV for bone age (catch-up growth). Low titer antibodies to GHRH were found in 19 patients (17.1%) at six months; no adverse effect was observed. Our results suggest that patients showing catch-up growth were older, had a height closer to the mean for chronological age and a slower pre-treatment height velocity. Failure to demonstrate a relationship between GHRH dose and changes in growth velocity might be explained by the combination of a placebo effect, insufficient frequency of GHRH administration and heterogeneity of the population.

Postischemic liver damage in rats: effect of some therapeutic interventions on survival rate.

The aim of this paper is to elucidate the cause of death after 90 min of normothermic partial (2/3) ischemia of the liver and to examine the effects of glucagon, somatostatin, insulin, prednisolone and oral administration of polymyxin B (PB). The animals 24 hr after partial ischemia for 90 min were divided into two groups; namely, animals with normal appearance and those with moribund state. There were no significant differences in the plasma level of S-GOT, S-GPT, amino acids, NH3 or insulin, or in morphometrically estimated volume ratio of necrotic hepatocytes between the two groups of rats. The blood glucose level, however, was significantly decreased (31 +/- 28 mg/100 ml, n = 6) in the moribund rats with a higher incidence of positive Limulus gelation tests as compared with the rats with normal appearance (149 +/- 19, n = 5). The 1-day and 1-week survival rates of the animals were 42/62 (69%) and 32/61 (53%), respectively. A glucagon injection (1.5 mg/kg, after ischemia) was effective to elevate the 1-day survival rate (14/14), but failed to increase the 1-week survival rate (11/14). On the other hand, a somatostatin injection (100 micrograms/kg, after ischemia) or PB treatment (15 mg/kg/day x 5-9, before ischemia) succeeded to increase the 1-week survival rate (20/22 p less than 0.01 and 17/17 p less than 0.01, respectively), although no significant amelioration in transaminase levels or volume ratio of necrosis was demonstrated. It could be seen that a moribund state after partial ischemia was accompanied by severe hypoglycemic shock, and that the injection of somatostatin after ischemia or the annihilation of gram-negative bacteria by means of oral administration of polymyxin B before ischemia prevented the occurrence of the hypoglycemic shock.