In vitro susceptibilities in lymphocytes from mothers and cord blood to the monofunctional alkylating agent EMS

It has been reported that children may experience different levels of chemical exposures than adults and that their sensitivities to chemical toxins may be increased or decreased when compared to adults. The perinatal period is one period in which these susceptibilities may be examined. Midwives at the Bradford Royal Infirmary collected venous blood samples from mothers at the time of birth and venous cord blood post-delivery. Lymphocytes were isolated from both blood types and examined in the alkaline comet assay using the monofunctional alkylating agent ethyl methanesulphonate (EMS). There were no biologically significant differences when subjects were categorized into subgroups based on lifestyle habits and physical characteristics, and overall there were no statistically significant differences in levels of DNA damage in mothers (n=22) and babies (n=22), except at the basal level (P<0.05), but mean values in babies were always lower over the EMS dose range. Whole blood was used in the micronucleus (MN) assay, and there was a significantly (P<0.05) higher rate of MN in mothers (n=17), per 1000 binucleates, as compared with lymphocytes from their offspring (n=17) at the basal level. This may be accounted for by age and endogenous factors. Overall, this current study cannot provide statistically significant evidence that children have either increased or decreased levels of susceptibility to a chemical toxin in comparison to adults when EMS is examined in vitro.     

Relationship between Optimum Mini‐doses of Glucagon and Insulin Levels when Treating Mild Hypoglycaemia in Patients with Type 1 Diabetes – A Simulation Study

Hypoglycaemia remains the main limiting factor in type 1 diabetes management. We developed an insulin‐dependent glucagon dosing regimen for treatment of mild hypoglycaemia based on simulations. A validated glucose–insulin–glucagon model was used to describe seven virtual patients with insulin pump‐treated type 1 diabetes. In each simulation, one of ten different and individualized subcutaneous insulin boluses was administered to decrease plasma glucose (PG) from 7.0 to ≤3.9 mmol/l. Insulin levels were estimated as ratio of actual to baseline serum insulin concentration (se/ba‐insulin), insulin on board (IOB) or percentage of IOB to total daily insulin dose (IOB/TDD). Insulin bolus sizes were chosen to provide pre‐defined insulin levels when PG reached 3.9 mmol/l, where one of 17 subcutaneous glucagon boluses was administered. Optimum glucagon bolus to treat mild hypoglycaemia at varying insulin levels was the lowest dose that in most patients caused PG peak between 5.0 and 10.0 mmol/l and sustained PG ≥ 3.9 mmol/l for 2 hr after the bolus. PG response to glucagon declined with increasing insulin levels. The glucagon dose to optimally treat mild hypoglycaemia depended exponentially on insulin levels, regardless of how insulin was estimated. A 125‐μg glucagon dose was needed to optimally treat mild hypoglycaemia when insulin levels were equal to baseline levels. In contrast, glucagon doses >500 μg were needed when se/ba‐insulin >2.5, IOB >2.0 U or IOB/TDD >6%. Although the proposed model‐based glucagon regimen needs confirmation in clinical trials, this is the first attempt to develop an insulin‐dependent glucagon dosing regimen for treatment of insulin‐induced mild hypoglycaemia in patients with type 1 diabetes.     

Reference limits for GAD65 and IA-2 autoantibodies by chemiluminescence immunoassay in Northern European adults and children

The GAD65 and IA-2 antibodies (Abs) are biomarkers of the development of type 1 diabetes mellitus (T1DM) in both children and adults. The upper reference limit for the autoantibodies made by the manufacture was established on an adult Chinese population. Here, we established upper reference limits for Northern European adults and children in accordance with the Clinical and Laboratory Standards Institute (CLSI) guidelines. Serum samples from healthy Danish children (0–18 years) and adults (18–70 years) were analysed for GAD65Ab and IA-2Ab using MAGLUMI 800 Chemiluminescence Immunoassay (CLIA). The Kruskal–Wallis test was used for evaluating differences between gender and age groups. No gender or age differences were found for neither GAD65Ab nor IA-2Ab, and a combined upper reference limit for both children and adults could be established. An upper reference limit of 5.1?IU/mL was defined for GAD65Ab and 11.5?U/mL for IA-2Ab. Our results showed a substantial discrepancy with the reference limits established by the manufacturer.     

Early blindness results in a degraded auditory map of space in the optic tectum of the barn owl.

The optic tectum of the barn owl (Tyto alba) contains a neural map of auditory space consisting of neurons that are sharply tuned for sound source location and organized precisely according to their spatial tuning. The importance of vision for the development of this auditory map was investigated by comparing space maps measured in normal owls with those measured in owls raised with both eyelids sutured closed. The results demonstrate that owls raised without sight, but with normal hearing, develop auditory space maps with degraded precision and with aspects of topography that are abnormal.     

Toxicity in standard melphalan-prednisone therapy among myeloma patients with renal failure--a retrospective analysis and recommendations for dose adjustment

Haematological and infectious toxicity was correlated to renal function in 272 newly diagnosed myeloma patients given standard dose melphalan-prednisone (MP) as initial treatment without dose adjustment for renal impairment. The glomerular filtration rate (GFR) was estimated by calculated creatinine clearance. Haematological toxicity was found to be significantly related to renal dysfunction. Haematological toxicity World Health Organization (WHO) grades 3-4 after the first MP course was seen in 18%, 28% and 36% of patients with a creatinine clearance of >50, 30-50 and <30 ml/min respectively. WHO grades 3-4 infections occurred in 6% and were not significantly related to renal function. We conclude that MP therapy can be used for initial therapy in myeloma patients with renal impairment but suggest that reduction of the melphalan dose should be considered in patients with a GFR of <30 ml/min. As only 2% of our patients had a clearance of < or =10 ml/min no conclusions can be drawn for this subgroup.     

Thyroid structure and size and two-year follow-up of solitary cold thyroid nodules in an unselected population with borderline iodine deficiency

OBJECTIVE: Multinodular goitre has been found with a high prevalence in iodine-deficient areas, but less frequently in iodine-replete areas; the iodine intake sufficient to prevent goitre has not been established, however. METHODS: We report data from an ultrasonic investigation of the thyroid glands of 2656 randomly selected subjects aged 41 to 71 years in an area with borderline iodine deficiency. RESULTS: Median iodine concentration in spot urine samples was 70microg/l. Multinodular thyroid structure was found in 23% of the population, increasing in women from 20 to 46% with increasing age, and in men from 7 to 23%. Solitary, scintigraphically cold, thyroid nodules >10mm were found in 2.4% of the population with the same prevalence in the different age and sex groups. Two years of follow-up of these cold nodules revealed no signs of malignancies. Median thyroid volume was 11.0ml. Thyroid enlargement (>18ml for women and >25ml for men) was found among 13. 1% of the women and 6.2% of the men, and the prevalence increased with age. The presence of thyroid nodules was related to positive anti-thyroperoxidase antibody (TPO Ab) titres, whereas thyroid enlargement was associated with iodine excretion <50microg/day. CONCLUSIONS: Thyroid enlargement was associated with low iodine excretion and median thyroid volume was slightly increased compared with iodine-replete areas. Multinodular thyroid structure was found with a high prevalence and was associated with TPO Ab >200kU/l. Cold thyroid nodules were moderately prevalent, with no cases of detected malignancies during 2 years of follow-up.     

Postoperative survival of patients with potentially curable cancer of the colon

The association between histopathologic findings and postoperative survival in 442 patients with potentially curable carcinomas of the colon has been analyzed using Cox's regression model. The prognostic variables included in the study were age, sex, stage of disease according to Dukes' classification and Broders' grading, as well as presence/absence at the time of operation of venous and nerve invasion. The overall five-year postoperative survival rate was 46.6 percent. Using a model including all prognostic factors, sex and Dukes' classification were not found to be associated with survival. Broders' grading and/or nerve invasion yielded only a borderline statistical significance in the model that included all factors. The invasion of veins was almost always associated with invasion of nerves.