Carbonic anhydrase IX expression, hypoxia, and prognosis in patients with uterine cervical carcinomas.

PURPOSE: Hypoxia is associated with adverse outcome for a number of solid tumors, including cervical carcinomas. Direct pO(2) measurement requires specialized equipment and expertise that is not generally available. Immunohistochemical measurement of intrinsic tissue markers of hypoxia is an alternative approach. Recent studies suggest that carbonic anhydrase IX (CA IX), which is regulated via hypoxia-inducible factor 1, is a useful intrinsic marker of tumor hypoxia. EXPERIMENTAL DESIGN: Biopsies were obtained from 110 patients with locally advanced cervical carcinoma treated with radiotherapy or chemoradiotherapy. Tissue sections were labeled using an immunofluorescence technique and CA IX expression in the viable tumor area measured using a semiautomated fluorescence image analysis technique. Results were compared with direct pO(2) values obtained using an Eppendorf probe and to patient outcome. Intratumoral heterogeneity of CA IX expression was examined in a subgroup of patient who underwent multiple biopsies. RESULTS: The median percentage of tumor area staining for CA IX was 3.56 (range, 0.01-58.85). CA IX staining did not correlate with the Eppendorf pO(2) measurements. Whereas the latter values were predictive of patient outcome, the CA IX levels were not. Measurement of CA IX in multiple biopsies indicated that intratumoral heterogeneity accounted for 41% of the total variance in the data set. CONCLUSIONS: In contrast to some recent studies, we did not find significant associations between CA IX expression and tumor pO(2) levels or patient outcome in locally advanced carcinomas of the cervix. Probable explanations relate to the problems of sampling error using single biopsies and the existence of biological factors other than hypoxia that influence CA IX levels.     

The efficacy of acarbose in type 2 diabetes mellitus in Jamaica

The efficacy and tolerability of acarbose was studied in type 2 diabetic patients eating a typical Jamaican diet. The study was an open label parallel group study without placebo control. Of the 51 subjects recruited, five (9.8%) did not complete the study and were excluded from further analysis. Six (13%) of the remaining 46 had adverse side effects and did not complete the protocol. Of the remaining 40 (Gp A), acarbose was added to their previous regime of diet alone (n = 15), [Gp B], oral hypoglycaemic agents, OHAs (n = 17), [Gp C], or insulin (n = 8), Gp D]. In addition, during the run-in period all subjects had one session each with a dietitian and a diabetes educator. Over a 3-month period, significant reductions in average glucose (mmol) were observed in Gp B 10.5 +/- 1.1 to 8.4 +/- 0.9 (p < 0.027) and, from 11.0 +/- 1.0 to 8.7 +/- 0.7 (p < 0.01) in Gp C. Similarly, total glycosylated haemoglobin fell from 14.8 +/- 1.1% to 12.2 +/- 1.0% (p < 0.016) in Gp B, from 14.9 +/- 1.1 to 11.9 +/- 1.1% (p < 0.002) in Gp C, and from 14.1 +/- 1.4 to 11.8 +/- 1.4 (p < 0.02) in Gp D. Twenty-three per cent (23%) of the patients experienced flatulence; 7.5%, changes in bowel habits and 5%, abdominal cramps and discomfort. Acarbose is effective as monotherapy and as combination therapy with oral hypoglycaemic agents or insulin. Side effects were common, but tolerable.     

Infants born to narcotic dependent mothers: Physical growth patterns in the first 12 months of life

Objectives: To describe the physical growth patterns of infants born to narcotic dependent mothers (INDM) over a 12 months period and, if possible, to relate the growth to drug taking patterns during pregnancy.
Methodology: The growth of a cohort of 43 INDM was measured during the first 12 months of life. Weight and length measurements were compared with percentile charts and converted to Z scores. Questionnaire data about drug taking practices, demographic variables and the neonatal period (including withdrawal scores) were obtained.
Results: Twenty-four (55.8%) of INDM had evidence of neonatal drug withdrawal requiring treatment with phenobarbitone. At birth, Z scores for weight and length indicated relative intrauterine growth retardation. By 12 months, there had been some catch up growth, but Z scores for weight and length were still below zero. Persistent weight retardation at 12 months was correlated with methadone dosage during pregnancy, but not the need for phenobarbitone therapy.
Conclusions: The growth patterns of INDM in the first 12 months of life indicated that at birth there was evidence of intrauterine growth retardation, but by 12 months the growth was little different from the rest of the community. There appears to be some influence of narcotic agents taken while pregnant on subsequent growth of INDM.     

Are boys better than girls at building a tower or a bridge at 2 years of age?

This study was designed to look at the differences in visuospatial abilities between boys and girls before they can speak fluently. At the mandatory two year follow up visit, children were given the opportunity to build a tower and a bridge. In children whose birth weight was > or = 2500 g, the capacity for erecting a tower was the same in both sexes, but for building a bridge striking differences were noted according to their sex. Among the 376 children of this category, 41 out of 199 boys (21%) were able to build a bridge in comparison with 15 out of 177 girls (8%). This difference is highly significant. In children whose birth weight was < or = 2500 g, no differences were noted either for building a tower or a bridge. By showing that boys outnumber girls among the most skilled toddlers in spatial abilities, this work confirmed the action of a male related factor on cerebral lateralisation.     

Sonographic measurements of fetal parts to predict pulmonary maturity among twins and singletons

To determine if sonographic examination of fetus can be readily utilized to predict a mature lecithin/sphingomyelin (L/S) ratio among twins and singletons. Twins (n = 36) undergoing amniocentesis for assessment of pulmonary maturity were matched with singleton (1:2) for maternal demographics, gestational age (GA), and indications for procedure. At the time of amniocentesis, twins and singletons with mature L/S ratios differed significantly in mean GA (33.2 +/- 2.7 vs 34.5 +/- 4.6 wks, p = 0.01), biparietal diameter (BPD), abdominal circumference (AC), femur length (FL) and estimate of birth weight (EFW). Based on ten receiver operating characteristics curves constructed, the following diagnostic thresholds predicted a mature L/S ratio with a true positive rate of 100% among twins and singletons, respectively: 1) BPD $84 and $92 mm; 2) head circumference $315 and $320 mm; 3) AC $295 and $350 mm; or 4) FL $64 and $72 mm; or 5) EFW $2400 and $3200 g. Using any one of these five criteria correctly identified pulmonary maturity among 59% of twins and 28% of singletons (p = 0.001). Sonographic measurement of fetal parts or EFW may be a noninvasive method to predict a mature L/S ration among twins as well as singletons.     

Mortality and prehospital thrombolysis for acute myocardial infarction: A meta-analysis

CONTEXT: Early administration of thrombolysis for acute myocardial infarction (AMI) may improve survival if safely and appropriately delivered. No systematic reviews that have comprehensively examined this topic exist in the literature. OBJECTIVE: To perform a meta-analysis of randomized controlled trials of prehospital vs in-hospital thrombolysis for AMI measuring in-hospital mortality. DATA SOURCES: The Cochrane search strategy was used to search MEDLINE, EMBASE, and the Science Citation Index (1982-1999); Dissertation Abstracts (1987-1999); and Current Contents (1994-1999) for the terms thrombolysis, thrombolysis therapy, prehospital, and acute myocardial infarction. In addition, text and journal article bibliographies were hand searched, the National Institutes of Health Web site was reviewed, and primary authors and thrombolytic drug manufacturers were contacted for unpublished studies. STUDY SELECTION: Randomized controlled trials of prehospital vs in-hospital thrombolysis for AMI measuring all-cause hospital mortality were included. Two authors independently reviewed 175 citations by title, abstract, or complete article. After exclusion of 30 duplicate citations, 145 studies remained, of which 6 studies and 3 follow-up studies met the inclusion criteria. DATA EXTRACTION: Independent data abstraction by 2 reviewers blinded to the journal, title, and author was confirmed by consensus. Trial quality was independently assessed by 2 other coauthors, blinded to the author, title, journal, introduction, and discussion. DATA SYNTHESIS: The results of the 6 randomized trials (n=6434) were pooled and indicated significantly decreased all-cause hospital mortality among patients treated with prehospital thrombolysis compared with in-hospital thrombolysis (odds ratio, 0.83; 95% confidence interval, 0.70-0.98). Results were similar regardless of trial quality or training and experience of the provider. Estimated (SE) time to thrombolysis was 104 (7) minutes for the prehospital group and 162 (16) minutes for the in-hospital thrombolysis group (P=.007). CONCLUSIONS: Our meta-analysis suggests that prehospital thrombolysis for AMI significantly decreases the time to thrombolysis and all-cause hospital mortality. JAMA. 2000;283:2686-2692.     

Hypoglycémie hyperinsulinémique persistante du nouveau-né et du nourrisson

Persistent hyperinsulinemic hypoglycaemia of infancy (PHHI) is the most frequent cause of hypoglycaemia in infancy. Clinical presentation is heterogeneous, with variable onset of hypoglycaemia and response to diazoxide, and presence of sporadic or familial forms. Underlying histopathological lesions can be focal or diffuse. Focal lesions are characterised by focal hyperplasia of pancreatic islet-like cells, whereas diffuse lesions implicate the whole pancreas. The distinction between the two forms is important because surgical treatment and genetic counselling are radically different. Focal lesions correspond to somatic defects which are totally cured by limited pancreatic resection, whereas diffuse lesions require a subtotal pancreatectomy exposing to high risk of diabetes mellitus. Diffuse lesions are due to functional abnormalities involving several genes and different transmission forms. Recessively inherited PHHI have been attributed to homozygote mutations for the beta-cell sulfonylurea receptor (SUR1) or the inward-rectifying potassium-channel (Kir6.2) genes. Dominantly inherited PHHI can implicate the glucokinase gene, particularly when PHHI is associated with diabetes, the glutamate dehydrogenase gene when hyperammonaemia is associated, or another locus.     

The efficacy of the ketogenic diet-1998: a prospective evaluation of intervention in 150 children

OBJECTIVE: The ketogenic diet is a high-fat, low-protein, low-carbohydrate diet developed in the 1920s for the treatment of children with difficult to control seizures. Despite advances in both the pharmacotherapy and the surgery of epilepsy, many children continue to have difficult-to-control seizures. This prospective study sought to determine the ketogenic diet's effectiveness and tolerability in children refractory to today's medications. METHODS: One hundred fifty consecutive children, ages 1 to 16 years, virtually all of whom continued to have more than two seizures per week despite adequate therapy with at least two anticonvulsant medications, were prospectively enrolled in this study, treated with the ketogenic diet, and followed for a minimum of 1 year. Seizure frequency was tabulated from patients' daily seizure calendars and seizure reduction calculated as percentage of baseline frequency. Adverse events and reasons for diet discontinuation were recorded. RESULTS: The children (mean age, 5.3 years), averaged 410 seizures per month before the diet, despite an exposure to a mean of 6.2 antiepileptic medications. Three months after diet initiation, 83% of those starting remained on the diet and 34% had >90% decrease in seizures. At 6 months, 71% still remained on the diet and 32% had a >90% decrease in seizures. At 1 year, 55% remained on the diet and 27% had a >90% decrease in seizure frequency. Most of those discontinuing the diet did so because it was either insufficiently effective or too restrictive. Seven percent stopped because of intercurrent illness. CONCLUSIONS: The ketogenic diet should be considered as alternative therapy for children with difficult-to-control seizures. It is more effective than many of the new anticonvulsant medications and is well tolerated by children and families when it is effective.