Calorimetric determination of dissolution enthalpy with a novel flow-through method

A new calorimetric flow-through system for determining the enthalpies of dissolution with small amount of solids (<1 mg) was developed. The system was designed to be used as an add-on cell with a 4 ml twin heat conduction calorimeter 2277 TAM but the principle is adoptable also for other heat conduction calorimeters. The system was tested with two salts (NaCl, KCl), sucrose and different polymorphic forms of theophylline at 25 °C and 40 °C by using water as the solvent. The system gave more accurate and precise results at 25 °C. The precision was not affected by the extent of the dissolution enthalpy. The accuracy was dependent on the calibration utilized but even the normal electrical calibration gave acceptable values. The results obtained at 40 °C were also acceptable but not as good as at 25 °C due to heat leaks. The effect of heat leaks can be minimized by heating the inflowing solvent outside the calorimeter prior to entering the flow-through cell.     

Spatial assessment of articular cartilage proteoglycans with Gd-DTPA-enhanced T1 imaging.

In Gd-DTPA-enhanced T(1) imaging of articular cartilage, the MRI contrast agent with two negative charges is understood to accumulate in tissue inversely to the negative charge of cartilage glycosaminoglycans (GAGs) of proteoglycans (PGs), and this leads to a decrease in the T(1) relaxation time of tissue relative to the charge in tissue. By assuming a constant relaxivity for Gd-DTPA in cartilage, it has further been hypothesized that the contrast agent concentration in tissue could be estimated from consecutive T(1) measurements in the absence or presence of the contrast agent. The spatial sensitivity of the technique was examined at 9.4 T in normal and PG-depleted bovine patellar cartilage samples. As a reference, spatial PG concentration was assessed with digital densitometry from safranin O-stained cartilage sections. An excellent linear correlation between spatial optical density (OD) of stained GAGs and T(1) with Gd-DTPA was observed in the control and chondroitinase ABC-treated cartilage specimens, and the MR parameter accounted for approximately 80% of the variations in GAG concentration within samples. Further, the MR-resolved Gd-DTPA concentration proved to be an even better estimate for PGs, with an improved correlation. However, the linear relation between MR parameters and PG concentration did not apply in the deep tissue, where MR measurements overestimated the PG content. While the absolute [Gd-DTPA] determination may be prone to error due to uncertainty of relaxivity in cartilage, or to other contributing factors such as variations in tissue permeability, the experimental evidence highlights the sensitivity of this technique to reflect spatial changes in cartilage PG concentration in normal and degenerated tissue.     

Good perinatal outcome in selective vaginal breech delivery at term

BACKGROUND AND AIM: To compare perinatal outcome in groups of planned vaginal breech delivery, elective cesarean section with the fetus in breech presentation, and planned vaginal delivery with the fetus in cephalic presentation in a university hospital with a tradition of managing breech deliveries by the vaginal route. METHODS: A cohort study from a 7-year period 1995-2002, including 590 planned vaginal deliveries with a term (> 37 weeks) singleton fetus in breech presentation, 396 elective cesarean sections with a term singleton fetus in breech presentation, and 590 control women intending vaginal delivery with a singleton term fetus in cephalic presentation. RESULTS: The Apgar scores were lower in the group of planned vaginal breech delivery, but in other outcome measures there were no significant intergroup differences. The overall neonatal morbidity was small (1.2% vs. 0.5% vs. 0.3% in the respective study groups) if compared to a recently published randomized multicenter study. CONCLUSIONS: Selective vaginal breech deliveries may be safely undertaken in units having a tradition of vaginal breech deliveries.     

Cow milk is not responsible for most gastrointestinal immune-like syndromes--evidence from a population-based study

BACKGROUND: Gastrointestinal hypersensitivity to cow milk (CM) may be more common among school-aged children and young adults than previously thought. OBJECTIVE: The objective was to study various gastrointestinal complaints and the immunologic mechanisms associated with food-related, especially CM-related, gastrointestinal disorders in young adults. DESIGN: Of 827 subjects aged 16-21 y who completed a questionnaire on food-related gastrointestinal symptoms, 49 symptomatic subjects agreed to a clinical examination, including an interview, blood tests, a lactose-maldigestion test, a blinded CM challenge and, in severely symptomatic subjects (n = 12), an endoscopic examination. Twenty-nine subjects served as controls. RESULTS: Approximately 10% of the subjects reported having major gastrointestinal symptoms, mainly food-related (n = 70 of 86), during the preceding year. Specific organic disease was found in 2 symptomatic subjects: 1 case of celiac disease and 1 of colitis. The result of the lactose-maldigestion test was positive in 16 of the remaining 47 symptomatic subjects, but only 4 carried the C/C(-13910) genotype for adult-type hypolactasia. The symptomatic subjects had restricted their consumption of certain foods, particularly CM. However, in a blinded challenge, CM-induced symptoms were rare. The symptomatic subjects had higher plasma soluble intercellular adhesion molecule 1 (P = 0.007) and lower granzyme A (P = 0.001) concentrations than did the control subjects. Duodenal biopsy samples tended to have higher intraepithelial CD3(+) cell counts (P = 0.065) and a higher expression of transforming growth factor beta (P = 0.073) and interleukin 12p35 messenger RNA (P = 0.075) than did the control subjects. CONCLUSIONS: In an unselected cohort of young adults, 8% reported food-related gastrointestinal symptoms. The finding of immunologic activity implied the existence of a food-related gastrointestinal syndrome but not one induced by CM.     

Impaired Wisconsin card sorting test performance in first-episode schizophrenia: resource or motivation deficit?

Patients with first-episode schizophrenia (n = 27) and age- and education-matched healthy controls (n = 27) were administered the standard version of the Wisconsin Card Sorting Test (WCST), the Wechsler Adult Intelligence Scale-Revised (WAIS-R), and the Rorschach according to the Comprehensive System (CS). Schizophrenic patients achieved a significantly lower full-scale IQ and made more perseverative responses and achieved fewer categories on the WCST than the healthy control group. No significant associations were observed between effort or motivation and WCST performance. Schizophrenic patients who made more perseverative responses tended to be impoverished in terms of available resources, and functioned in a simplistic way when attending to details of the stimulus field. First-episode schizophrenics are able to generate motives and initiate goal-directed activity, but some of them fail to achieve their goals because the cognitive abilities and available resources required for effective planning, purposeful action, or effective performance are impaired.     

Maternal, fetal and aminiotic fluid ACTH, cortisol and prolactin in association with medical beta-adrenergic stimulation

In view of observations indicating accelerated fetal pulmonary maturation after tocolytic therapy with beta-adrenergic agonists, this study was undertaken to determine whether the phenomenon is related to enhanced maternal or fetal ACTH, cortisol or prolactin secretion. The concentrations of ACTH, cortisol and prolactin in maternal venous blood, umbilical arterial and venous blood, and amniotic fluid were similar after short-term maternal intravenous infusion of isoxsuprine, fenoterol or isotonic saline, and they did not increase in the maternal venous blood during these treatments or during long-term treatment with intravenous ritodrine. These results suggest that the accelerated fetal pulmonary maturation induced by beta-adrenergic stimulation is not mediated by ACTH, cortisol or prolactin.     

Genetic polymorphisms of DNA repair and xenobiotic-metabolizing enzymes: role in mutagen sensitivity

Mutagen sensitivity, measuring the extent of chromosome damage induced by an in vitro treatment of peripheral lymphocytes with bleomycin, has been associated with an increased risk of various human cancers. Sensitivity to bleomycin appears to have high heritability and is usually considered to reflect individual capacity to repair DNA lesions. Another potential contributor to variation in bleomycin sensitivity could be inherited differences in the metabolism of bleomycin. We assessed whether genetic polymorphisms of DNA repair and xenobiotic-metabolizing enzymes (XMEs) could explain bleomycin sensitivity. Frequencies of bleomycin-induced chromatid breaks per cell (b/c) were determined for 80 healthy Caucasians. Genotypes of DNA repair genes XRCC (X-ray repair cross-complementing) 1 and 3 and XME genes bleomycin hydrolase (BLHX), glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) and N-acetyltransferase 2 (NAT2) were analyzed from leukocyte DNA using methods based on polymerase chain reaction. The mean number of chromatid b/c was increased in individuals with XRCC1 codon 280 variant allele (P = 0.002; two-sided Mann-Whitney test). Smokers carrying BLHX codon 1450 variant allele showed a decrease in the mean number of chromatid b/c (P = 0.036). In multiple linear regression models including adjustment for age, sex, smoking and genotype, the adjusted relative risks (and 95% confidence intervals) were 1.18 (0.98-1.41) and 0.84 (0.69-1.00) for carriers of XRCC1 codon 280 and BLHX codon 1450 variant alleles, respectively. XRCC1 codon 280 polymorphism had a significant effect (P = 0.012) in predetermining whether the individual was classified as non-sensitive, sensitive or hypersensitive to bleomycin. Although based on relatively few individuals, our results suggest that bleomycin sensitivity is partially explained by genetic polymorphisms affecting DNA repair (XRCC1) and in vitro metabolism of bleomycin (BLHX).     

Manganese superoxide dismutase genotypes and asbestos-associated pulmonary disorders

Manganese superoxide dismutase (MnSOD) activity is highly elevated in the biopsies of human asbestos-associated malignant mesothelioma. We therefore examined if polymorphism in the mitochondrial targeting sequence of the MnSOD gene modified individual susceptibility to this malignancy or related asbestos-associated pulmonary disorders. The study population consisted of 124 male Finnish asbestos insulators who were all classified as having been exposed to high levels of asbestos; 63 of the workers had no pulmonary disorders and 61 either had malignant mesothelioma or the non-malignant pulmonary disorders asbestosis and/or pleural plaques. No significant associations were found between the MnSOD genotypes and these ill-health. This study therefore suggest no major modifying role for the MnSOD polymorphism in development of asbestos-associated pulmonary disorders.     

Endarteriectomy of the femoral tripod: long-term results and analysis of failure factors]

STUDY AIM: The aim of this retrospective study was to report immediate and long term results of endarteriectomies of the common femoral artery (CFA) and/or femoral tripod and to analyse predictive factors of failure. PATIENTS AND METHODS: Between 1982 and 1995, 110 endarteriectomies were performed in 101 patients, 52% of them in limb salvage situation. The arteriogram showed a thrombosis or stenosis of the common femoral artery in 100% of cases. There was a stenosis of the deep femoral artery (DFA) in 79% of cases. The superficial femoral artery (SFA) was thrombosed in 40% of cases. One artery only of the lower leg was permeable in 43.3% of cases. Run off was judged bad in 38% of patients. RESULTS: The endarteriectomy could be realised in 93 patients (84.5%). It concerned the only common femoral artery in 20% of cases (patch angioplasty in 55% of cases), common and deep femoral arteries in 50.5% of cases (82% of patch), CFA, DFA and SFA at its origin in 29.1% of cases (93% of patch). Perioperative mortality rate was 1%. Local morbidity rate was 21.6% with 18% of minor complications and 3.6% of complications requiring a second operation. There were 2% of vascular complications (1 thrombosis and 1 false-aneurysm). Mean follow-up was 43 months in 90 patients. There were restenosis or thrombosis (5.5%), false-aneurysms (2.2%) and amputations (6.6%). Femoro-popliteal (10%) and iliac complementary bypasses (6.6%) were necessary. Permeability was 94.9% at 3 years and 88.8% at 5 years. Clinical results were considered good in 80.7% of the cases at 3 years and in 71.7% at 5 years. With univariate analysis, the predictive factors for failure were: limb salvage (P < 0.01), altered popliteal run off (P < 0.03) and extended distortion of the deep femoral artery (P < 0.05). CONCLUSION: Isolated endarteriectomy of the femoral tripod is a low risk and effective technique. A femoropopliteal revascularisation should be associated in case of a major alteration of the deep femoral artery.