Abnormal function of endocrine pancreas and anterior pituitary in Friedreich's ataxia. Studies in a family.

A family had three siblings affected with classic Friedreich's ataxia. One sibling died at age 20 with fulminant diabetic ketoacidosis. The other two affected siblings are identical twin sisters without clinical diabetes but with an abnormality in the metabolism of exogenously administered glucose. These twins also have abnormal hypothalamic-pituitary control of prolactin and possibly of growth-hormone secretion. This study extends the previous reports of endocrine deficienceis associated with Friedreich's ataxia. The mechanisms underlying this association are undetermined but could represent pleiotropic effects of the Friedreich's ataxia gene or secondary manifestations of the primary central nervous system degeneration, or both.     

Application of the IML Resistograph to the infield assessment of basic density in plantation eucalypts

Average bark-to-bark resistance of the IML Resistograph PD400 (hereafter referred to as ‘Resi’) was found to provide strong linear correlations with the basic density of 12-mm-diameter increment cores taken from standing plantation eucalypt trees. Relationships between Resi values and approximately 2 000 cores (predominantly Eucalyptus globulus but some E. nitens) were examined across seven studies (representing samples from nine distinct sites) in Tasmania, Victoria and Western Australia. Custom-written software was developed to process the Resi traces to automatically perform a linear baseline correction of the trace, and extract:

• over-bark and under-bark diameter

• bark thickness

• average resistance of the bark-to-bark (under-bark) trace

• average resistance of the outer 50 mm on the entry and exit side of the traces.

Baseline correction was needed to counter the variable effects among trees of needle drag across the diameter, largely a function of tree diameter and wood density.

Individual traces were collected in less than 20 s tree^?1. The sampling conditions of 150 cm min^?1 speed of forward movement (feed speed) and 3 500 revolutions per minute (rpm) were identified as optimal for the plantation eucalypts studied. The relationship between different feed speeds and rpm were linear and coefficients determined to allow average Resi resistance to be converted to a common set of sampling conditions. A simple linear regression was identified in each study to define a slope and intercept to convert the Resi values to basic density and determine the variance between them. Resi traces from different studies were not always collected using the same instrument and this is believed to explain most of the between-study variance in slope and intercept.

Trace processing software was built into a web-based package that is available to make trace processing easy, with defined variables downloadable for use in routine plantation assessment. Users can change the default slope and intercept values to suit their individual instruments or species as required. Further work is required to fully define the effects of instrument, site and species on these relationships.

The IML Resistograph PD400 was found to be an accurate and quick (40–70 trees hour^?1 person^?1) infield tool for estimating diameter and wood density in standing trees. When combined with automated, web-based processing software the methodology is among the lowest cost options conceivable for wood density assessment of plantation eucalypts.     

Use of an ammonia electrode for rapid quantification of Helicobacter pylori urease: its use in the endoscopy room and in the assessment of urease inhibition by bismuth subsalicylate.

The use of an ammonia electrode to quantify ammonia liberated by urease from Helicobacter pylori was assessed in an in vitro study. It was found to be highly sensitive (down to 0.7 ppm NH3) and highly reproducible (coefficient of variation 6.0%). Inhibition of urease by bismuth subsalicylate was evaluated as urease testing is often used to assess clearance of H. pylori in patients treated with bismuth. Concentrations of bismuth subsalicylate up to 5 mg/ml had no inhibitory effect but bismuth subsalicylate at 50 mg/ml resulted in 21% inhibition of the urease activity of an ultrasonicated H. pylori suspension. As a preliminary study, the ammonia electrode was assessed in the endoscopy room in comparison with conventional techniques for H. pylori diagnosis. Antral biopsies from 39 patients attending for routine diagnostic endoscopy were subjected to culture, histology, detection of urease activity with a commercially available slide test (CLO) and with the ammonia electrode to detect ammonia liberated from samples placed in urea solution. 21 patients were positive after 1 h with the ammonia electrode, compared to only 17 with the commercially available slide test. 20 were positive on histology and 19 by culture. All samples positive with the ammonia electrode were either positive by culture or by histology. The ammonia electrode offers a quick, sensitive, quantitative and cheap method for the detection and quantification of H. pylori.     

Asymptomatic glomerulonephritis after nonstreptococcal upper respiratory infections.

Two hundred forty previously healthy military personnel with nonstreptococcal upper respiratory infections were prospectively studied to define the incidence and clinicopathologic characteristics of possible virus-associated glomerulonephritis. Nine patients without preceding streptococcal infection had erythrocyte casts on urinalysis and glomerulonephritis on biopsy. Of these nine, four had a reduction in total hemolytic complement and five had serologic evidence of infection with adenovirus, influenza A, or influenza B. Initial renal biopsy showed either focal or diffuse mesangial proliferation in all nine, with mesangial C3 deposits in six specimens. Repeat biopsy in three showed histologic improvement or loss of immunofluorescent staining, or both. Sequential creatinine clearances were reduced to 74 to 90 mL/min.1.73 m2 in five patients for the duration of follow-up. We conclude that nonstreptococcal upper respiratory infection is frequently associated with glomerulonephritis and that abnormal glomerular structure and decreased creatinine clearances may persist for at least 2 to 8 months.     

CD52 antibodies for prevention of graft-versus-host disease and graft rejection following transplantation of allogeneic peripheral blood stem cells

Graft-versus-host disease (GVHD) is a major cause of mortality and morbidity after allogeneic bone marrow transplantation, but can be avoided by removing T lymphocytes from the donor bone marrow. However, T cell depletion increases the risk of graft rejection. In this study, two strategies are used to overcome rejection: (1) use of high doses of stem cells obtained from peripheral blood (PBSC), (2) admixture with a CD52 monoclonal antibody in order to deplete both donor and residual recipient lymphocytes. Two antibodies are compared: CAMPATH-1G (rat IgG2b) and its humanized equivalent CAMPATH-1H (human IgG1). A total of 187 consecutive patients at six centers received PBSC transplants from HLA-matched siblings between 1997 and 1999. A wide spectrum of diseases, both malignant and non-malignant, was included. The recovery of CD34+ cells after antibody treatment was close to 100%. The risk of acute GVHD (grade 2 to 4) was 11% in the CAMPATH-1G group and 4% in the CAMPATH-1H group (P = NS). The risk of chronic GVHD (any grade) was 11% in the CAMPATH-1G group and 24% in the CAMPATH-1H group (P = 0.03) but the risk of extensive chronic GVHD was only 2%. The overall risk of graft failure/rejection was 2%, not significantly different between the two antibodies. Antibody treatment was equally effective at concentrations between 10 microg/ml and 120 microg/ml and it made no significant difference to the outcome whether the patients received post-transplant immunosuppression or not (87% did not). Transplant-related mortality in this heterogenous group of patients (including high-risk and advanced disease) was 22% at 12 months. It is proposed that treatment of peripheral blood stem cells with CAMPATH-1H is a simple and effective method for depleting T cells which may be applicable to both autologous and allogeneic transplants from related or unrelated donors. Special advantages of this approach are the simultaneous depletion of donor B cells (which reduces the risk of EBV-associated lymphoproliferative disease) and the concomitant infusion of CAMPATH-1H to deplete residual recipient T cells and thus prevent graft rejection.     

Metformin increases insulin sensitivity and basal glucose clearance in Type 2 (non-insulin dependent) diabetes mellitus

Abstract The effects of metformin on glycaemia, insulin and c-peptide levels, hepatic glucose production and insulin sensitivity (using the euglycaemic, hyperinsulinaemic clamp) were evaluated at fortnightly intervals in 9 Type 2 diabetic patients using a stepwise dosing protocol: Stage 1 - no metformin for four weeks; stage 2 - metformin 500mg mane; stage 3 - metformin 500mg thrice daily; stage 4 – metformin 1000mg thrice daily. Results are expressed as Mean ± SEM. Fasting blood glucose decreased from basal values (9.7 ±1.0 mmol/L) by 13% at stage 2, 34% at stage 3 and 41% at stage 4 (p<0.02 vs basal for all stages; p<0.02 stage 2 vs stage 3). Post-prandial glycaemia was significantly improved only with metformin 3000mg/day (p<0.05). Fasting, meal-stimulated and total insulin and c-peptide levels showed no change. Hepatic glucose output did not change significantly with metformin. Insulin sensitivity, measured as total glucose utilisation during hyperinsulinaemia, increased from stage 1 (10.3 ± 2.1 μmoL/kg/min) by 23% at stage 3 (p < 0.05) and by 29% at stage 4 (p < 0.02). Basal metabolic clearance of glucose increased compared to stage 1 (1.69 ±0.16 mL/kg/min) by 30% at stage 2, 53% at stage 3 and 44% at stage 4 (all p <0.02). This study demonstrates that improved efficiency of glucose utilisation, both basally and under conditions of euglycaemic hyperinsulinaemia, is the basis of metformin's antihyperglycaemic action.