[Immunosuppression with cyclosporin induces clinical remission and improved beta cell function in patients with newly diagnosed insulin-dependent diabetes. A national and international multicenter study]. / Immunosuppression med ciklosporin inducerer klinisk remission og forbedret beta-cellefunktion hos patienter med nykonstateret insulinkraevende diabetes. En national og international multicenterundersøgelse. The Canadian-European Randomized Control Trial Group.

A prospective, randomized, double-blind, placebo-controlled international multicenter trial including 188 newly diagnosed insulin-dependent diabetic (IDDM) patients was undertaken with the aim of investigating whether immunosuppression for one year with ciklosporin (Cs) could induce and maintain clinical remission and improvement of beta-cell function. The relative odds for non-insulin-requiring remission at one year were increased approximately five times in the Cs-treated group. After three months Cs-treated patients achieved more than a doubling of beta-cell function compared to baseline than did placebo-treated patients, and the Cs-treated group maintained this improvement in beta-cell function for 12 months, whereas the placebo-group lost beta-cell function during the same period. Short duration of disease (less than or equal to six weeks of symptoms, less than or equal to two weeks of insulin treatment) was associated positively with remission, as was an elevated proinsulin/C-peptide ratio, especially in patients with the tissue-type HLA-DR 3,4; 4,X and X,X. Cs-treatment inhibited the formation of antibodies against insulin and islet cell components, but islet cell antibody status at entry was not predictive of remission. Cs-treatment caused a reversible decrement of kidney function as measured with serum creatinine and the calculated creatinine clearance, but studies of renal physiology and kidney biopsies performed on a limited subset of patients indicated that Cs treatment in IDDM patients for one year induced a slight chronic nephropathy in some of these.(ABSTRACT TRUNCATED AT 250 WORDS)

Circulating immune complexes, insulin antibodies, and deposits of immunoglobulins in the skin in diabetes.

Sixty-five insulin-dependent diabetes mellitus (IDDM) patients at the Steno-Memorial Hospital entered the present study. Of these, 43.1 percent had one or more late diabetic complication, 19.3 percent had circulating immune complexes (CIC)--there was a tendency for CIC to be related to late diabetic complications (P = 0.1) - and 16.9 percent had elevated total S-IgG. Elevated S-IgG values were related neither to CIC, to complications, nor to IgG deposits in the skin. Three patients had elevated total S-IgM, IgD and, IgE, respectively. No patients had elevated total S-IgA. Insulin antibodies were present in 41.9 percent. They were related to neither CIC nor clinical complications. No patients had rheumatoid factors (RF) or granulocyte-specific antinuclear antibodies (ANA). 12.3 percent had a low titre of organ non-specific ANA. No relationship could be established between ANA and complications or CIC. As regards skin deposits IgG was present at the dermo-epidermal junction zone (DEJ) and/or in the dermal vessels in 75.4 percent of the patients; IgA was present in 35.4 percent; and IgM in 32.3 percent. IgD and IgE were absent in all patients. Fibrinogen deposits were found in 80 percent and complement C3 in 32.3 percent. No correlation was found between skin deposits and CIC, on one hand, or clinical complications, on the other. From the present work, we conclude that humorally mediated immunological processes are active in IDDM. However, the exact role of this activity still remains to be defined.

Treatment of malignant pleural effusion with drainage, with and without instillation of talc.

In order to determine whether pleural drainage with talc instillation was better than pleural drainage alone, in the treatment of malignant effusion, the present trial was initiated. Thirty-one patients with malignant pleural effusion and progressive disease, resistant to conventional therapy, were included. All patients had pleural drainage applied. After re-expansion of the lung, half of the patients had talc instilled through the chest tube. Twenty-one of the 31 treated patients were evaluable. After pleural drainage with talc instillation, all of 9 treated patients obtained complete resolution of the effusion and subjective improvement. After pleural drainage alone, 7 of 12 patients obtained complete resolution of the malignant effusion. If it is possible to re-expand the lung during pleural drainage in patients with a malignant pleural effusion, pleurodesis can be obtained in 60% of the treated patients with pleural drainage alone. This study showed a statistically significant improvement in the treatment associated with instillation of talc into the pleural cavity and this was achieved without causing increased discomfort to the patient.

Diagnostic thoracoscopy.

During a 5-year period, diagnostic thoracoscopy was attempted in 566 patients and successfully performed in 556. No deaths due to thoracoscopy occurred and complications were few. In patients with malignant disease of the pleura, positive biopsies were obtained in 95 of 137 patients (69%). A positive culture for tubercle bacilli was obtained from pleural biopsy in 27 of 36 patients (75%) with bacteriologically confirmed pleural tuberculosis. Thoracoscopy improved the diagnostic accuracy in these conditions. In patients with benign tumours as well as anatomical abnormalities thoracoscopy was diagnostic. In other conditions thoracoscopy was rarely able to give a positive diagnosis, but it proved very helpful in ruling out malignant disease and tuberculosis. The number of false positive was small, about 3% in this series.

Basophil histamine release by nuclear components in chronic bronchitis and bronchial asthma of intrinsic type.

The involvement of an allergic reaction directed against nuclear components and aggregated IgG was examined by basophil histamine release technique in chronic bronchitis (CB) in the intrinsic type of bronchial asthma (IA). In the group of 21 CB patients, seven responded to RNA, DNA or histone and three responded to aggregated IgG. In the other group of seven IA patients one responded to RNA and histone. In comparison with healthy blood donors the prevalence of smooth muscle antibodies was increased in CB patients and antinuclear antibodies were increased in both groups of patients. The findings suggest an involvement of an allergic reaction directed against RNA, DNA, histone, and aggregated IgG in some patients with CB and IA. This may play some role in the reversible airway obstruction of these diseases.

Fluorescein angiography in diabetic children.

In 63 diabetic children, aged 10--14 years, with normal ophthalmoscopy, fluorescein angiography revealed slight diabetic retinopathy in maximally three, aged 12--14 years. These findings are discussed in relation to the controversial results published in a few other fluorescein angiographic studies on diabetic children. It is concluded that normal ophthalmoscopy does not exclude the presence of diabetic retinopathy and that fluorescein antiography is a valuable method in the early diagnosis of diabetic retinopathy.

Oesophageal varices as a late complication to neonatal umbilical vein catheterization.

Three recent cases are presented. Haematemesis in children with splenomegalia and a history of neonatal umbilical vein catheterization should involve careful examination for oesophageal varices due to portal hypertension.

Insulin secretion in insulin-requiring diabetics before and during insulin treatment.

Endogenous insulin secretion after different stimuli was determined in insulin requiring diabetics without circulating insulin antibodies. Four groups of non-obese diabetics were investigated and compared with 111 controls. Group I: 14 patients with mild diabetes, not yet requiring insulin; diagnosis before the age of 30 years. Group II: 19 ketonuric patients just before being started on insulin treatment. Group III: 18 patients during remission after an average of 16.5 months' insulin treatment. Group IV: 13 patients with no remission period or relapse after an average of 19.5 months on insulin treatment. Blood glucose and immunoreactive insulin were measured during fasting and after iv secretin, iv tolbutamide, iv GTT, and oral GTT, followed by combined iv tolbutamide and glucagon stimulation. A considerable insulin secretion could be demonstrated in group I, whereas in group II only a very low insulin peak was obtained after secretin and the combined injection of glucagon and tolbutamide. In group III considerable insulin secretion was demonstrated, whereas in group IV only a very low insulin peak was obtained. A significant correlation between the degree of metabolic control and endogenous insulin secretion was found.

Secretin-induced insulin response. I. Cubital insulin concentration in normal, obese and pancreatectomized patients, including portal insulin concentration in normals after secretin.

Intravenous injection of the gastro-intestinal hormone secretin elicits an increase in the insulin concentration in the cubital vein. In 10 normal weight non-diabetics and 10 obese non-diabetics the latter group gave a hypernormal insulin response. By the simultaneous determination of the insulin concentration in the cubital and portal veins and also by an investigation of 2 pancreatectomized patients, it was demonstrated that an increase in the cubital insulin concentration following intravenous injection of secretin was due to an altered secretion from the pancreas and not to an altered elimination of insulin.

Secretin-induced insulin response. II. Dose-response relation.

Twenty-four patients--5 normals, 5 obese subjects, 9 normal weight maturity-onset diabetics and 5 obese maturity-onset diabetics--were subjected to stimulation with the gastro-intestinal hormone secretin (GIH, Stockholm, Sweden). Secretin was administered by rapid intravenous injection 6 times every 30 min in doses increasing from 0.9-90 pmol/kg body weight. Radioimmunological insulin assay and blood glucose determination were carried out. The secretin-induced maximum insulin response rose in all groups with increasing doses. D50 (16 pmol/kg body weight) was identical in all 4 groups. Thus, the diabetic B cells exhibited the same sensitivity to secretin as the normals. Obese subjects already showed a significant insulin response after 0.9 pmol secretin/kg, whereas the response of normal weight subjects did not rise until the dose was 3.6 pmol/kg. This, combined with the normal D50, indicates an increased B cell mass in obese subjects.