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Biomedical subjects

A Oesterle

Publications and source records attributed to A Oesterle.

3 recordsLinked to original sources

Continuous subcutaneous insulin infusion. A new way to lower risk of severe hypoglycemia, improve metabolic control, and enhance coping in adolescents with type 1 diabetes.

OBJECTIVE: Recommendations from the Diabetes Control and Complications Trial (DCCT) indicate that adolescents with type 1 diabetes should be treated with intensive therapy involving multiple daily injections (MDI) of insulin or insulin pump therapy (continuous subcutaneous insulin infusion [CSII] to help obtain better metabolic control and prevent later complications. Interest has thus focused on insulin pump therapy to help adolescents meet this challenge. The purpose of this study was to examine responses to CSII and MDI in a large group of adolescents with established type 1 diabetes during a 12-month period and to determine whether either treatment regimen more favorably affected clinical and psychosocial outcomes. RESEARCH DESIGN AND METHODS: One-third of 75 youths aged 12-20 years who were candidates for intensive therapy chose CSII as their mode of treatment. Patients received intensive treatment and education as described by the DCCT investigators. Psychosocial data (e.g., quality of life, depression, self-efficacy, and coping) were collected at baseline and at 6-month intervals, and clinical data (e.g., HbA1c levels, adverse events) were collected every 4-6 weeks. RESULTS: Although both MDI- and CSII-treated adolescents initially exhibited improved metabolic control, this level of control was more difficult to sustain for 12 months in the MDI group (at 6 months HbA1c = 8.1, at 12 months HbA1c = 8.3), whereas average HbA1c levels in the CSII group continued to decrease during the 12 months of treatment (at 6 months HbA1c = 7.7, at 12 months HbA1c = 7.5). Despite lower HbA1c levels in CSII-versus MDI-treated patients, the rate of severe hypoglycemic events was reduced by almost 50% in the CSII group (P = 0.01). Self-reported questionnaires demonstrated that there was improvement in self-efficacy, depression, and quality of life in both MDI- and CSII-treated patients. Finally, adolescents using CSII found coping with diabetes to be less difficult than adolescents using MDI did. CONCLUSIONS: CSII is an alternative means to lower HbA1c levels and reduce the risk of hypoglycemia without adversely affecting psychosocial outcomes in adolescents with type 1 diabetes.

Adaptation, Psychological↗

Initial hepatic removal of chylomicron remnants is unaffected but endocytosis is delayed in mice lacking the low density lipoprotein receptor.

Two endocytic receptors, the low density lipoprotein (LDL) receptor (LDLR) and the LDLR-related protein (LRP), are thought to act in concert in the hepatic uptake of partially metabolized dietary lipoproteins, the chylomicron remnants. We have evaluated the role of these two receptors in the hepatic metabolism of chylomicron remnants in normal mice and in LDLR-deficient [LDLR (-/-)] mice. The rate of chylomicron remnant removal by the liver was normal up to 30 min after intravenous injection of chylomicrons into LDLR (-/-) mice and was unaffected by receptor-associated protein (RAP), a potent inhibitor of ligand binding to LRP. In contrast, endocytosis of the remnants by the hepatocytes, measured by their accumulation in the endosomal fraction and by the rate of hydrolysis of component cholesteryl esters, was dramatically reduced in the absence of the LDLR. Coadministration of RAP prevented the continuing hepatic removal of chylomicron remnants in LDL (-/-) mice after 30 min, consistent with blockade of the slow endocytosis by a RAP-sensitive process. Taken together with previous studies, our results are consistent with a model in which the initial hepatic removal of chylomicron remnants is primarily mediated by mechanisms that do not include LDLR or LRP, possibly involving glycosaminoglycan-bound hepatic lipase and apolipoprotein E. After the remnants bind to these alternative sites on the hepatocyte surface, endocytosis is predominantly mediated by the LDLR and also by a slower and less efficient backup process that is RAP sensitive and therefore most likely involves LRP.

Analysis of Variance↗

Differences in outer membrane characteristics between gallstone-associated bacteria and normal bacterial flora.

Previous studies with scanning electron microscopy (SEM) have suggested that pigment gallstones contain bacteria. We set out to culture these bacteria and to study their membrane characteristics. We studied gallstones from 54 patients (36 men, 18 women; mean age 55.4 years) admitted consecutively to two hospitals for cholecystectomy. SEM detected bacteria in all of 14 brown pigment stones, 2 of 14 black pigment stones, and in the pigmented centres of 9 of 19 mixed cholesterol stones; no bacteria were detected in 14 pure cholesterol stones or within the cholesterol portions of mixed stones. We were able to culture bacteria from all gallstones with bacteria seen on SEM and for which sufficient material was available (n = 16). 20 bacterial species were recovered from these stones. Gallstones containing bacteria were associated with clinical sepsis and cholangitis. All bacteria obtained from gallstones agglutinated human O P1 erythrocytes, which reflects the presence of P1-specific fimbriae. 5 strains were positive for Forssman-antigen-specific fimbriae. None showed evidence of mannose-specific fimbriae. All of the organisms bound anti-Gal, a ubiquitous naturally occurring IgG specific for alpha-galactosyl residues. The presence of P1 fimbriae and alpha-galactosyl residues and the absence of mannose-specific fimbriae distinguish these organisms from gut flora. We postulate that possession of these unusual properties may enhance the ability of bacteria to colonise the biliary tree and initiate pigment gallstone formation.

Adolescent↗