Using a double blind controlled clinical trial to evaluate the function of a Diabetes Advisory System: a feasible approach?

This paper assesses the feasibility of using a double blind controlled clinical trial to evaluate the function of a decision support system by applying such a design to the evaluation of a Diabetes Advisory System (DIAS). DIAS is based on a model of the human carbohydrate metabolism and is designed an interactive clinical tool, which can be used to predict the effects of changes in insulin dose or food intake on the blood glucose concentration in patients with insulin dependent diabetes. It can also be used to identify risk periods for hypoglycaemia. and to provide advice on insulin dose. The latter feature was evaluated in the present study. We believe double blind controlled clinical trials are prerequisites for clinical application of many decision support systems, and conclude that the present double blind controlled clinical trial is a suitable evaluation method for the function of DIAS.

[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)

Nephrotoxicity of cyclosporin A in humans: effects on glomerular filtration and tubular reabsorption rates.

The contention that cyclosporin A (CyA) nephrotoxicity may be due to renal afferent arteriolar constriction was inferred from rat studies showing CyA to increase renal vascular resistance, to reduce glomerular filtration rate (GFR) and delivery of tubular fluid from the end of the proximal tubule to the loop of Henle (Vprox), and to increase proximal fractional reabsorption. In order to test whether the mechanism of human CyA nephrotoxicity is similar to its rat analogue, and whether CyA treatment causes prolonged renal malfunction after drug withdrawal, renal function was investigated with clearance techniques including lithium clearance (CLi) as a measure of Vprox. The subjects were patients (n = 11) with previously normal renal function, given CyA in the treatment of ocular manifestation of extrarenal disease, or bone-marrow transplant recipients. Nine out of these eleven patients were investigated before and during CyA treatment: GFR (P less than 0.05) and Vprox (P less than 0.005) decreased while proximal fractional reabsorption increased (P less than 0.01). In six patients investigated before CyA was given, and re-examined a mean of 273 days (range 84-384 days) after CyA withdrawal, CLi was reduced (P less than 0.05) while mean GFR was not significantly lowered (0.5 greater than P greater than 0.2). In one of these six patients GFR was reduced to a subnormal value of 26 ml min-1 (1.73 m2 body surface)-1. In conclusion, human and rat CyA nephrotoxicity have the same pattern of renal functional deterioration. Cyclosporin A nephrotoxicity was evident in patients investigated a mean of 9 months after CyA withdrawal.

Treatment of Graves' ophthalmopathy with cyclosporin A.

Six patients with Graves' ophthalmopathy (2 with acute and 4 with chronic alterations) were treated with cyclosporin A (10 mg/kg/day) for 5 weeks. This treatment had no effect on either the ocular manifestations (protrusion, eye muscle function) or subjective well-being of the patients. In contrast, creatinine clearance decreased from 83.5 to 55.5 ml/min during treatment, but normalized (94.9 ml/min) after cessation of the drug. A transient increase in serum 4-androstenedione was observed in 3 patients. We conclude that cyclosporin A has no convincing effect in the treatment of Graves' ophthalmopathy, but rather exerts serious renal effects.

Malignant mesenchymoma of the heart presenting as mitral stenosis.

Malignant mesenchymoma of the left atrium obstructing the mitral orifice was revealed at autopsy in a 39-year-old woman with a history indicating mitral stenosis. Minor tumour nodules were found in the walls of the right and left ventricle together with a few distant metastases. Clinical findings in primary cardiac tumours and the rarity of primary malignant mesenchymoma of the heart are discussed.

[Abdominal pregnancy. A complication of an intrauterine coil?]. / Abdominal graviditet. En komplikation til spiral?

PIP: A primary abdominal pregnancy was discovered in a 23-year-old woman who had used a Copper-T IUD for 2 years. After complaining about pelvic pain and bleeding disorders, X-rays were taken and the IUD was located in the pelvis minor. After acute pain and bleeding symptoms, a laparotomy was performed and a 3-1/2 month pregnancy with the placenta attached to the peritoneus parietale was discovered and removed without complication. The possible relationship to the IUD perforation is discussed.^ieng

Pulmonary alveolar septal amyloidosis. A scanning- and transmission electron microscopy study.

A case of primary amyloidosis is presented with diffusely involved the alveolar septa. The lung was studied by light microscopy and by transmission and scanning electron microscopy. The fine structure of the amyloid material showed it to be porous, homogeneous, and an acellular substance consisting of interwoven bundles of amyloid fibrils. The fine structure of the amyloid material was considered to explain the normal gas diffusion across the alveolar respiratory membrane. The diagnosis of amyloidosis was first made from a uterine cervical biopsy specimen.