Strain-dependent oxidant release in articular cartilage originates from mitochondria.

Mechanical loading is essential for articular cartilage homeostasis and plays a central role in the cartilage pathology, yet the mechanotransduction processes that underlie these effects remain unclear. Previously, we showed that lethal amounts of reactive oxygen species (ROS) were liberated from the mitochondria in response to mechanical insult and that chondrocyte deformation may be a source of ROS. To this end, we hypothesized that mechanically induced mitochondrial ROS is related to the magnitude of cartilage deformation. To test this, we measured axial tissue strains in cartilage explants subjected to semi-confined compressive stresses of 0, 0.05, 0.1, 0.25, 0.5, or 1.0 MPa. The presence of ROS was then determined by confocal imaging with dihydroethidium, an oxidant sensitive fluorescent probe. Our results indicated that ROS levels increased linearly relative to the magnitude of axial strains (r(2) = 0.87, p < 0.05), and significant cell death was observed at strains >40%. By contrast, hydrostatic stress, which causes minimal tissue strain, had no significant effect. Cell-permeable superoxide dismutase mimetic Mn(III)tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride significantly decreased ROS levels at 0.5 and 0.25 MPa. Electron transport chain inhibitor, rotenone, and cytoskeletal inhibitor, cytochalasin B, significantly decreased ROS levels at 0.25 MPa. Our findings strongly suggest that ROS and mitochondrial oxidants contribute to cartilage mechanobiology.

Investigation of quality of life and family burden issues during insulin pump therapy in children with Type 1 diabetes mellitus--a large-scale multicentre pilot study.

AIMS: To investigate psychosocial aspects of continuous subcutaneous insulin infusion (CSII) therapy in children with Type 1 diabetes and to identify relevant and sensitive measures. METHODS: We performed a multi-centre prospective pre-/post-study with children (53 girls, 64 boys, age 10.5 +/- 3.7 years, mean +/- sd) with Type 1 diabetes and their main carer from 18 German diabetic centres. Twenty-five children aged 8-11 years and 63 adolescents aged 12-16 years and their parents, plus 29 parents of children aged 4-7 years completed standardized questionnaires on generic and diabetes-specific quality of life (QOL), generic parenting stress, mealtime behaviour, fear of hypoglycaemia and family conflict immediately before and 6 months after transition to CSII. RESULTS: After transition to CSII, diabetes-specific QOL of children increased significantly (P < 0.001) in all age groups, with moderate to large effect sizes (children aged 4-7 years: Cohen's effect sized = 1.3; 8-11 years: d = 0.9, adolescents 12-16 years: d = 0.6). Parents reported reduced frequency (P < 0.01, d = 0.4-0.7) and difficulty (P < 0.01, d = 0.3-0.6) of overall parenting stress and decreased worries about hypoglycaemia (P < 0.01, d = 0.4-0.6). Parents of younger children (4-7 years) reported reduced problems with nutrition management (frequency: P < 0.001, d = 1.1; difficulty: P < 0.05, d = 0.7). CONCLUSIONS: CSII may have substantial psychosocial benefits. Controlled studies are needed.

Comparison of continuous subcutaneous insulin infusion (CSII) and multiple daily injections (MDI) in paediatric Type 1 diabetes: a multicentre matched-pair cohort analysis over 3 years.

AIMS: To conduct a multicentre, matched-pair cohort analysis comparing glycaemic control and adverse events of continuous subcutaneous insulin infusion (CSII) with multiple daily injections (MDI) in paediatric patients. METHODS: Using standardized computer-based prospective documentation, HbA(1c), insulin dose, body mass index-standard deviation score (BMI-SDS), rate of hypoglycaemia, rate of diabetic ketoacidosis (DKA) and intensity of care were analysed in 434 matched pairs during a follow-up period of 3 years after initiation of MDI or CSII. RESULTS: HbA(1c) was significantly lower in the CSII group during the first year of new regimen (CSII 7.5 +/- 0.05 vs. MDI 7.7 +/- 0.06; P < 0.05), but rose to the same level as in the MDI group during year 3. Insulin requirement remained significantly lower in the CSII group. The BMI-SDS increased in both study groups, with no significant difference. The rate of severe hypoglycaemia decreased significantly after the change of regimen (CSII 17.87 +/- 2.85 vs. MDI 25.14 +/- 3.79; P < 0.05) and during year 3 of the regimen, particularly when compared with baseline (-21% vs. -16%). The rate of DKA was lower at baseline in the CSII group and remained significantly lower over all 3 years. Intensity of care was the same in both subsets. CONCLUSIONS: Employing a large cohort, this matched-pair analysis has demonstrated over a 3-year study period that CSII is a safe form of intensive insulin therapy with similar glycaemic effects, but with significantly reduced rates of hypoglycaemia and DKA and a lower insulin requirement when compared with MDI.

Leukemic infiltration of the testes in acute nonlymphocytic leukemia.

Two children with ANLL in complete remission developed testicular relapse 18 and 34 months after diagnosis. Their clinical presentation was similar to that observed in patients with ALL. Although the testicular leukemia responded to between 2,400 and 3,000 rads, bone marrow relapse occurred within 4 months and death within 6 months of the testicular relapse. This points out the need for surveillance of the testicles in males with ANLL, and raises the question of need for testicular biopsy among long-time male survivors.

Correlation of the FAB morphologic criteria and prognosis in acute lymphocytic leukemia of childhood.

The bone marrows at the time of initial diagnosis of 101 children with acute lymphocytic leukemia diagnosed from April 1969 to December 1974 were evaluated employing the FAB morphologic classification. The group with L1 morphology and a significantly improved duration of first remission and survival when compared to the L2--L3 morphologic groups. Both groups were similar in age and initial level of WBC, indicating that the morphologic classification has prognostic significance in childhood ALL when age and initial WBC were considered together as prognostic risk factors. The L1 morphologic groups survival for the low- and moderate-risk groups was significantly better than for the L1 high-risk group and for the L2--L3 groups.

Lack of correlation between blast cell size and length of first remission in acute lymphocytic leukemia in childhood.

The bone marrow from 55 children with acute lymphocytic leukemia diagnosed from April 1969 to June 1973 were evaluated for blast cell morphology and size. Sixteen marrows contained a predominance of macrolymphoblasts (greater than 12 mu), while the remainder contained mainly microlymphoblasts. There was no correlation between blast cell size and the known front-end prognostic indicators of age and initial white blood count, nor could blast cell size be used to predict the length of initial bone marrow remission.

Portal hypertension in infants and children with histiocytosis X.

Histiocytosis X describes a disease characterized by histiocytic infiltration of the reticuloendothelial system, skin, bones, and pituitary gland. The disseminated form frequently occurs in infants and children. Chemotherapy has significantly improved the prognosis in this disorder. Sixty-three per cent of survivors, however, have some residual disability related to fibrosis of tissues previously infiltrated by histiocytes. In instances of liver involvement, healing by fibrosis may result in cirrhosis with portal hypertension and bleeding esophageal varices. Clinical findings include hepatosplenomegaly, jaundice, ascites, hypoalbuminemia, prolonged prothrombin time, and Bromsulphalein retention. Histologic examination of the liver shows a characteristic dense "macronodular" periportal cirrhotic pattern. Three children with portal hypertension and bleeding varices due to healed histiocytosis X were sucessfully managed by portosystemic shunt procedures. Portacaval, mesocaval, and central splenorenal shunts were equally effective in relieving poral hypertension. These children had neither recurrence of bleeding nor evidence of encephalopathy. Two children remain well whereas in one patient a primary hepatoma developed fourteen years posthung and he died of pulmonary metastases. Portosystemic shunt procedures effectively relieve the threat of potentially fatal variceal hemorrhage and improve the opportunity for long-term survival in children with cirrhosis and portal hypertension due to healed histiocytosis X.