HLA-B27 in juvenile chronic arthritis

The prevalence of HLA-B27 in 88 patients with juvenile chronic arthritis was 22/88 (25%) with little variation among the 3 commonly recognized onset types. This was significantly more frequent than the prevalence of 9.4% in a Danish reference population. A strong association was found between the HLA-B27 antigen and 3 subgroups of patients: (1) boys with pauciarticular and late onset disease; (2) girls with apophyseal joint fusion; (3) a group of patients in whom the clinical picture was compatible with reactive arthritis or incomplete Reiter's syndrome. When these 3 subgroups were excluded from the total patient population, only 8 of the remaining 63 patients carried the B27 antigen, i.e., 13%, which was not significantly different from the prevalence in the reference population. Thus, the 3 subgroups account completely for the increase of B27 in the entire group of patients.     

Pharmacokinetics and metabolism of trimethoprim in neonatal and young pigs

The pharmacokinetics and metabolism of trimethoprim (TMP) was studied in newborn, 1 and 8-week-old piglets after intravenous administration of 5 mg/kg. Kinetic parameters were calculated using a two-compartment open model. Steady-state volume of distribution increased from 0.78 L/kg at birth to 1.32 L/kg at 1 week, and 1.83 L/kg at 8 weeks due to changes in plasma protein binding and tissue accumulation. Elimination half-life decreased from 485 minutes at birth to 224 minutes at 1 week, and 120 minutes at 8 weeks leading to a rise in body clearance from 1.18 to 11.8 ml/min/kg during the same period. Urinary excretion data indicated that the increase in body clearance reflects maturational changes in both metabolic capacity and renal function. Metabolism was the main contributor to the elimination of TMP at all ages, although the major metabolic pathway, O-demethylation and subsequent conjugation, was only slightly developed at birth. The capacity to form conjugates with either glucuronic acid or sulphate appeared to be at least as high as the capacity for O-demethylation since more than 90% of the metabolites were excreted as conjugates in all groups.     

The bioavailability of thyroxine and 3,5,3'-triiodothyronine in normal subjects and in hyper- and hypothyroid patients

A new method for the estimation of the bioavailability of thyroxine (T4) and 3,5,3'-triiodothyronine (T3) is described based on gel separation followed by antibody extraction of labelled T4 and T3 from serum, and using the area under the curve of disappearance of the tracer (AUC) for the calculations. The peak serum concentrations of radioactive labelled T4 and T3 were reached approximately 90 min after oral administration of both tracers. The relative difference of duplicate estimations was below 10% (n = 3). The bioavailability of T4 in 6 euthyroid controls was in median 65% (range 64-75%), and it was significantly increased both in hyperthyroidism (88% (75-99%), n = 6, P less than 0.01) and hypothyroidism (84% (67-100%), n = 6, P less than 0.02). The bioavailability of T3 in 6 euthyroid controls was in median 78% (69-99%) and significantly greater than that of T4 (P less than 0.02). The bioavailability was unaffected by hyperthyroidism (79% (61-98%), n = 9) and hypothyroidism (77% (66-97%), n = 7). No significant difference between T4 and T3 bioavailabilities was found in hyper- or hypothyroidism. The clinical implication of the present study is that the bioavailability of T4 and T3 is almost identical and approximately 80% in patients with severe hypothyroidism.     

Detection by ELISA of IgG-subclass-specific antibodies in primary respiratory syncytial (RS) virus infections

The IgG-subclass specific antibody response was investigated in primary RS-virus infections in infants and small children by using an ELISA with monoclonal antibodies against the four human IgG subclasses. When 78 serum samples obtained from 21 patients during the first 3-4 mo following the onset of illness were studied, only IgG-1 and IgG-3 antibodies could be detected. Both of these subclass specific antibodies appeared during the second week following the beginning of illness. Approximately 4 wk after the onset of illness, IgG-1 antibodies reached maximum levels, which persisted during the following months. Approximately 3 wk after the onset of illness, IgG-3 antibodies reached maximum levels, which decreased during the following months. Both IgG-1 and IgG-3 antibodies showed neutralizing capacity.     

Neurological disease among women with silicone breast implants in Denmark

OBJECTIVES: To investigate the risk of neurological disease among women with cosmetic breast implants. MATERIAL AND METHODS: We identified 1,653 women who had undergone breast implant surgery at private clinics in Denmark and a comparison cohort of 1,736 women who underwent other types of cosmetic surgery at the same clinics. Ratios of observed-to-expected numbers of hospitalizations for neurological disease in the private implant and comparison cohorts were calculated, separately and combined with data from updated public hospital cohorts. RESULTS: The occurrence of neurological disease in the private clinic implant cohort was comparable to that in the general population. A similar risk pattern was observed in the private clinic comparison cohort. When data for these private clinic cohorts were combined with updated data for public hospital cohorts, excess risks for neurological disorders were seen in both implant and comparison cohorts, reaching statistical significance only in the comparison cohort. CONCLUSION: Our findings indicate no causal association between silicone breast implants and neurological disease.     

Capsular contracture after cosmetic breast implant surgery in Denmark

The authors investigated the association between the occurrence of capsular contracture and implant and patient characteristics. All women with breast implants from 1977 to 1997 were identified from the files of two private plastic surgery clinics in Denmark. Information on implant and patient characteristics, surgical procedure, and complications was obtained through medical records and self-administered questionnaires. Of 754 women (1,572 implants), average age at implantation was 32 years. Implant types were silicone double lumen, textured, 31.2%; silicone single lumen, textured, 27.8%; silicone single lumen, smooth, 24.5%; silicone double lumen, smooth, 0.8%; and other or missing, 15.7%. Placement was submuscular for more than 90% of implants. Capsular contracture occurred in 7.9% of implanted breasts, on an average of 621 days postoperatively, with 51.6% being bilateral. Overall, 66.1% of capsular contractures were recorded within the first 12 months postoperatively, and 79.0% were recorded within 24 months. Double-lumen implants were associated with a significantly (p < 0.01) reduced occurrence of capsular contracture. In summary, capsular contracture typically occurs within the first 2 years of implantation. Host factors may be important because more than half the capsular contractures in the current study were bilateral. Occurrence of capsular contracture did not appear to be associated with implant surface or placement, occurrence of local complications, or patient characteristics, although these findings should be interpreted cautiously.     

Genetic and environmental factors in epilepsy: a population-based study of 11900 Danish twin pairs

The contribution of genetic and environmental factors to the occurrence of epilepsy was examined in an unselected sample of twins recruited from the population-based Danish Twin Registry. Information on the occurrence of epilepsy in both members of a twin pair was obtained from 11900 pairs whose ages ranged from 12 to 41 years. Concordance rates, odds ratios and tetrachoric correlations were used to quantify the similarity of monozygotic (MZ) and dizygotic (DZ) twins. The sample was stratified by sex and separated into two age cohorts for analysis. Significantly higher probandwise concordance rates were found for MZ compared with DZ twins (0.37 and 0.08, P<0.01). Odds ratios and tetrachoric correlation showed similar pattern. An etiological model including additive genetic and individual specific environmental factors provided the best overall fit to the data, with 70 and 88% of the liability to develop epilepsy being accounted for by genetic factors in the younger and older cohorts, respectively. Individual specific environmental factors explained the remaining 30 and 12%, respectively. In conclusion, this study has confirmed the substantial impact, which genetic factors have in the etiology of epilepsy. The heritability of epilepsy is high and seems to increase with age.     

HIV and other predictors of serum folate, serum ferritin, and hemoglobin in pregnancy: a cross-sectional study in Zimbabwe

BACKGROUND: Folate and iron status and hemoglobin concentrations are important to maternal and infant health. OBJECTIVE: Our goal was to identify predictors of serum folate, serum ferritin, and hemoglobin. DESIGN: This was a cross-sectional study of 1669 pregnant women (22-35 wk of gestation) in Harare, Zimbabwe, who were receiving prenatal care. The statistical effects of age, season, gestational age, gravidity, HIV-1 infection, malaria parasitemia, and serum alpha1-antichymotrypsin (ACT) on serum folate, serum ferritin (log10 transformed), and hemoglobin were estimated by using multiple linear regression analyses. RESULTS: Serum folate (x: 11.4 micromol/L) was 0.52-nmol/L (95% CI: 0.04, 1.0) lower in HIV-infected women than in uninfected women and 0.65-nmol/L (0.014, 1.28) lower in weeks 25-35 than in weeks 22-25. Serum ferritin (geometric x: 11.6 microg/L) was 0.93 times (0.86, 0.99) lower in HIV-infected women and 2.25 times (1.41, 3.61) higher in women with malaria parasitemia than in uninfected women. Similarly, serum ferritin was 0.71 times (0.63, 0.79) higher in weeks 32-35 than in weeks 22-25 and 1.21 times (1.12, 1.29) higher in gravida > or =3 than in gravida 1. Elevated serum ACT was a strong predictor of serum folate, serum ferritin, and hemoglobin. HIV infection was associated with a 12.9-g/L (8.9, 16.8) lower hemoglobin concentration in women with nondepleted iron stores but low serum retinol and a 7-8-g/L lower hemoglobin concentration in women with other combinations of serum ferritin and retinol (P for interaction = 0.038). Season, age, gestational age, and gravidity were not significant predictors of hemoglobin. Low serum folate, ferritin, and retinol were associated with low hemoglobin. CONCLUSIONS: HIV was associated with lower serum folate, serum ferritin, and hemoglobin. HIV infection was also associated with lower hemoglobin, particularly in women with stored iron and low serum retinol. Low serum folate, ferritin, and retinol were associated with low hemoglobin.     

The relationship between cognitions and panic attack intensity

OBJECTIVE: To investigate the relationship between panic attack intensity, catastrophic belief and cognitions. METHOD: Data from 540 panic diaries were collected from 42 patients with panic disorder with agoraphobia. RESULTS: When we controlled for individual variation, effects of treatment and number of symptoms, catastrophic belief contributed significantly to more intense panic attacks (r2 change = 0.10, P<0.0001). There were no significant differences in panic attack intensity between primary and secondary cognitions. CONCLUSION: Our results indicate that catastrophic belief is a reliable predictor of panic attack intensity.     

Is cytochrome P450 CYP2D activity present in pig liver?

The presence of CYP2D in pig livers has been studied using different strains of pig, different CYP2D test substrates and monoclonal and polyclonal antibodies. The results of the studies lacked consistency, therefore the aim of this study was to identify the reasons for these inconsistencies. Liver microsomes isolated from conventional pigs and minipigs were tested in Western blotting using both monoclonal and polyclonal antibodies against human CYP2D6. The microsomes were also incubated with three different CYP2D tes t substrates.'The immunoblotting only gave a positive response when hybridised with polyclonal antibody. The pig microsomes did not metabolise debrisoquine, but metabolised two other test substrates, dextromethorphan and bufuralol. No correlation was found between the two enzyme assays and CYP2D apoprotein level. On the other hand positive correlations were found between dextromethorphan and bufuralol metabolism and the CYP2B immunochemical protein level, indicating that the CYP2B isoenzyme may be involved in the metabolism of these substrates. Further, assays using immunoinhibition and chemical inhibition of these reactions were performed. No response was obtained in the immunoinhibition assay. When using chemical inhibition, however, an average inhibition percentage of 83 were obtained with orphenadrine, a human CYP2B inhibitor. Average Ki values of 26.9 microM and 43.6 microM for orphenadrine indicate that it was a potent inhibitor. A rat and a mouse CYP2B inhibitor, resveratrol and pilocarpine, inhibited the reaction with an average of 40 and 70 percentage respectively. Orphenadrine did not inhibit CYPIA, CYP2A, CYP2E and CYP3A activities up to more than maximum 12 percentage, showing that it was almost selective for dextromethorphan metabolism. These results indicate that dextromethorphan and bufuralol metabolism may be catalysed by CYP2B and not CYP2D.