Search PubMed⌕ Search

Biomedical subjects

A U Teuscher

Publications and source records attributed to A U Teuscher.

29 records · Page 2Linked to original sources

[Function of pancreas transplants in increased metabolic stress].

Patients undergoing successful pancreas transplantation have normal glucose levels in the fasting and fed states and normal levels of hemoglobin A1c without use of exogenous inulin or any other medications for diabetes. In some of these patients, these measures have remained stable for more than 10 years. Additionally pancreas transplant recipients recover from short-term hypoglycemia produced by an intravenous pulse of insulin. However, metabolic success has been determined by relatively routine, unsophisticated tests such as oral and intravenous glucose tolerance tests or stimulation with intravenous arginine. These tests may not provide measures of the functional reserve of the pancreas, which is called on during periods of maximal stress. Consequently, we designed studies to ascertain beta and alpha cell performance in recipients of whole pancreas transplants and recipients of a segment of a living related donor. All recipients were recruited from the University of Minnesota Transplant Registry, Minneapolis, Minnesota. Successfully transplanted recipients were subjected to prolonged hyperglycemia to assess insulin secretory reserve using the method of glucose potentiation of arginine induced insulin secretion and to prolonged hypoglycemia to assess glucagon responsiveness and hepatic glucose production using the technique of the hyperinsulinemic hypoglycemic clamp. Our studies show that pancreas transplant recipients have markedly diminished insulin secretory reserve, a defect not evident with conventional tests of beta-cell function. No difference was found between the whole graft and segmental graft recipients. Pancreas transplantation restores the defective glucagon secretory response and enhances hepatic glucose production during prolonged hypoglycemia in subjects with type I diabetes. We conclude that pancreas transplantation does not completely restore beta-cell secretory reserve. This defect might be probably caused in part by cyclosporine and by the procedure involved in transplanting a cadaveric pancreas. Pancreas transplantation normalizes hypoglycemia-induced glucagon secretion and hepatic glucose production, thereby allowing for normalization of glucose recovery from hypoglycemia.

Diabetes Mellitus, Type 1↗

[The effect of long-term cyclosporin and prednisone therapy on insulin secretory reserve].

Insulin secretory reserve assessed by the method of glucose potentiation of arginine induced insulin secretion is decreased in non-diabetic transplant recipients using triple immunosuppressive therapy with prednisone, cyclosporine, and azathioprine. To determine whether this defect is due to the combined therapy or to a single agent, we examined the acute insulin response (AIR) to arginine at 5 levels of glucose (basal and 4 levels achieved by continuous glucose infusions) in 7 normoglycemic arthritis patients (AP) using long term prednisone (10.3 +/- 37 mg for 83 +/- 37 months), and 4 normoglycemic psoriasis patients (PP) using long term cyclosporine (350 +/- 61 mg for 25 +/- 4 months) and compared them with matched healthy controls (CON). Long-term cyclosporine (ANOVA p = 0.016 compared to control subjects) but not prednisone treatment decreased insulin secretory reserve. We conclude that cyclosporine might have an adverse effect on beta-cell function and contribute to posttransplant diabetes.

Adult↗

Insulin-mediated and glucose-mediated glucose uptake following hemipancreatectomy in healthy human donors.

Healthy humans undergoing hemipancreatectomy for the purpose of donation to a family member with IDDM have previously been demonstrated to maintain serum glucose values equal to matched control subjects during short-term glucose infusion despite significant decrements in glucose- and arginine-induced insulin secretion. In order to determine whether humans compensate for hemipancreatectomy by increasing insulin- or glucose-mediated glucose uptake, we measured glucose turnover and insulin sensitivity by three protocols. Insulin-mediated glucose uptake was measured during sequential infusions of insulin at rates of 0.25, 1.0, and 10.0 mU.kg-1.min-1 in 12 donor subjects and 12 matched control subjects maintained at euglycaemia. Both groups displayed similar increases in rates of glucose disappearance and similar decreases in rates of hepatic glucose production. Glucose-mediated uptake was calculated as the difference between the rates of glucose disappearance measured during a hyperglycaemic clamp performed at identical rates of insulin infusion and was also found to be similar in both donor subjects and control subjects. Both groups also had indistinguishable measures of insulin sensitivity and glucose effectiveness as determined by the minimal model technique. Therefore, donor subjects appear to compensate for diminished insulin secretion following hemipancreatectomy by an unidentified mechanism since neither insulin- nor glucose-mediated glucose uptake are increased.

Adult↗

Diminished insulin secretory reserve in diabetic pancreas transplant and nondiabetic kidney transplant recipients.

Although both kidney and pancreas transplantation can restore renal and pancreatic endocrine functions, the accompanying immunosuppression may cause diminished glucose tolerance in some individuals. Therefore, we determined to what extent pancreas transplantation itself and the triple immunosuppressive therapy used in pancreas transplant recipients have adverse effects on insulin secretory reserve. Beta-cell secretory reserve was assessed by the method of glucose potentiation of arginine-induced insulin secretion in 25 normoglycemic pancreas recipients, 12 nondiabetic kidney recipients using the same immunosuppressive therapy, 3 psoriasis patients treated long term with cyclosporine, 5 arthritis patients treated long term with prednisone, and their respective sex-, age-, and body mass index-matched control subjects. Levels of fasting glucose, HbA1c, and glucose disappearance rates were normal in all subjects. During the glucose potentiation study, pancreas recipients had significantly less insulin secretion than control subjects (maximal acute response [ARmax] = 1,083 +/- 93% vs. 3,938 +/- 355%, P < 0.001). Insulin responses were also decreased in kidney recipients (ARmax = 2,296 +/- 290%) vs. control subjects (4,691 +/- 554%, P = 0.001) and in psoriasis patients treated with cyclosporine (ARmax = 2,153 +/- 390%) vs. control subjects (3,962 +/- 88%, P = 0.011), but not as extreme as that seen in pancreas recipients. No abnormalities were observed in arthritis patients treated with steroids. We conclude that normoglycemic pancreas and kidney transplant recipients receiving triple immunosuppressive therapy have diminished beta-cell secretory reserve. Because this defect was present in psoriasis patients treated long term with cyclosporine, but not in arthritis patients treated long term with prednisone, this adverse effect was probably caused in part by cyclosporine.

Adult↗

Predictive value of bronchoalveolar lavage in excluding a diagnosis of Pneumocystis carinii pneumonia during prophylaxis with aerosolized pentamidine.

We assessed the negative predictive value of bronchoalveolar lavage (BAL) for Pneumocystis carinii pneumonia (PCP) during prophylaxis with aerosolized pentamidine. On the basis of the assumption that undiagnosed and untreated PCP would progress and become clinically apparent, for 3 months we prospectively followed 34 consecutive cases in which BAL had not detected PCP. All patients were immunodeficient, had a symptomatic human immunodeficiency virus infection, and were evaluated for possible PCP during prophylaxis with aerosolized pentamidine. No transbronchial biopsies were performed. In 32 of 34 cases, a diagnosis of PCP could be excluded because of other definite diagnoses or improvement during the follow-up. Despite negative results of an examination of their BAL fluid, two patients received empirical treatment that was active against PCP; these patients were regarded as possibly having undiagnosed PCP. Thus, the negative predictive value of BAL alone was at least 94% (32 of 34 cases) in excluding a diagnosis of PCP during prophylaxis with aerosolized pentamidine.

AIDS-Related Opportunistic Infections↗

[Diagnosis and course of patients with HIV infections and exclusion of Pneumocystis carinii pneumonia].

30 patients infected with HIV (20 men, 10 women; mean age 34 [26-54] years), suspected of having Pneumocystis carinii (Pc) pneumonia, had undergone bronchoalveolar lavage which proved negative for Pc. They were then kept under observation for 5 months. No transbronchial biopsy was performed. 27 patients were in stage IV of the HIV infection, and 14 had been on pentamidine prophylaxis. The most frequent diagnosis with the bronchial lavage was bacterial infection (19 patients), next most frequent was mycobacterial infection (6, atypical in 5). A neoplasia (Kaposi sarcoma; non-Hodgkin lymphoma) was found in two, with pulmonary involvement. The diagnosis remained unclear in only three patients who were treated as for Pc pneumonia. The remaining 27 patients did not receive any treatment against Pc. Nonetheless, there were no cases of Pc pneumonia in the 5 months of observation so that bronchoalveolar lavage has a negative predictive value of 90% (27 of 30), high enough to make additional bronchial biopsy unnecessary.

Adult↗

Influence of human insulin on symptoms and awareness of hypoglycaemia: a randomised double blind crossover trial.

OBJECTIVE: To investigate the apparent increased risk of severe hypoglycaemia associated with use of human insulin by comparing the pattern of symptoms of hypoglycaemia with human insulin and porcine insulin. DESIGN: Randomised controlled double blind crossover trial of treatment with human insulin and porcine insulin, with two treatment periods of six weeks. SETTING: Diabetes outpatient department of a university teaching hospital in Berne, Switzerland. PATIENTS: 44 patients (25 men, 19 women) aged 14 to 60 years, with insulin dependent diabetes mellitus. All patients met the following criteria: receiving treatment with fast acting soluble insulin and long acting protamine insulin; performing multiple daily fingerstick blood glucose self measurements; and had stable glycaemic control with about one mild hypoglycaemic episode a week during the preceding two months. INTERVENTION: Patients were randomised to receive either human or porcine insulin for six weeks and were then changed over to the other type of insulin for a further six weeks. MAIN OUTCOME MEASURE: Questionnaire recording "autonomic" and "neuroglycopenic" symptoms that occurred during hypoglycaemic episodes confirmed by a blood glucose concentration less than or equal to 2.8 mmol/l. RESULTS: Insulin doses and blood glucose, glycated haemoglobin A1c, and fructosamine concentrations were similar during the two treatment periods. 493 questionnaires on hypoglycaemia (234 during treatment with human insulin and 259 during treatment with porcine insulin) were analysed. With human insulin patients were more likely to report lack of concentration (52% v 35%, p = 0.0003) and restlessness (53% v 45%, p = 0.004) and less likely to report hunger (33% v 42%, p = 0.016) than during treatment with porcine insulin. The difference in the pattern of symptoms during the two treatments was similar to that between the 12 patients with a history of recurrent hypoglycaemic coma and the 32 patients without such a history. CONCLUSIONS: The pattern of symptoms associated with human insulin could impair patients' ability to take appropriate steps to avoid severe hypoglycaemia. Caution should be exercised when transferring patients from animal insulin to human insulin, and a large scale randomised trial of the two types of insulin may be justified.

Adolescent↗

Ischaemic oculomotor nerve palsy. Clinical features and vascular risk factors in 23 patients.

Of 61 patients with isolated third nerve palsy, 23 (38%) had the characteristic clinical features of an ischaemic oculomotor nerve palsy. The essential sign of this usually painful disorder of acute onset was a marked discrepancy between complete or severe paresis of the extraocular muscles innervated by the third nerve, and sparing of the pupillary sphincter. All patients had completely recovered within 3 months. Fourteen had a history or on follow-up had other cranial mononeuropathies. Except for two patients, all were above the age of 60 years. Of the 23 cases, 11 had diabetes mellitus and 8 an abnormal glucose tolerance test, while in 4 the latter was normal. Almost all had hypertension and were overweight, and half were smokers. In 18 patients, four or five vascular risk factors were present.

Aged↗