Effect of atorvastatin and fluvastatin on the metabolism of midazolam by cytochrome P450 in vitro

We have investigated the effects of the statins atorvastatin and fluvastatin on the cytochrome P450 3A4 enzyme (CYP 3A4)-mediated metabolism of midazolam in vitro, using pooled human liver microsomes. Midazolam was metabolised by human hepatic microsomes with a Michaelis-Menten constant (K(m)) of 5.25 (SD 1.2) micromol.l(-1). Atorvastatin was a moderate competitive inhibitor of CYP 3A4 with an inhibitory constant (K(i)) of 12.4 (95% CI 4.65-20.06) micromol.l(-1). Fluvastatin was a weak non-competitive inhibitor of CYP 3A4 with a K(i) of 94.3 (95% CI 55.01-133.5) micromol.l(-1). Both atorvastatin and fluvastatin inhibit the CYP 3A4-mediated metabolism of midazolam in vitro.     

Portable gas analyser Cosmed K4b2 compared to a laboratory based mass spectrometer system

AIM: The purpose of this study was to systematically test the accuracy of an automated, portable, gas analysis system, the Cosmed K4b2 with a laboratory based mass spectrometer system, the Morgan EX670 across a number of gas and ventilation parameters. METHODS: Eight subjects (mean+/-SE) age, 23.7+/-1.1 y, height, 1.78+/-0.01 m, mass, 74.4+/-2.1 kg performed a V.O2max test and a submaximal exercise test at 150, 200, 250 and 300 Watts (W), on an SRM cycle ergometer. The Morgan EX670 system and the K4b2 were randomly connected in series, using the same breath for the calculation of gas and ventilatory parameters. RESULTS: The K4b2 system reads significantly higher than the Morgan EX 670 for both VO2 and V.CO2 at 250 (VO2/V.CO2: p<0.05, p<0.002), and 300 W (VO2/V.CO2: p<0.002, p<0.005). Unsystematic bias between the 2 analysers varies between 1% and 16% and systematic bias between 3% and 8%. CONCLUSION: There are some significant unsystematic and systematic differences between these 2 systems and laboratories should endeavour to utilise either one or the other piece of equipment to test their subjects.     

Extended interval for retrieval of Günther Tulip filters

PURPOSE: To evaluate the Gunther Tulip vena cava filter with regard to ease of placement, complications, and retrieval over long time periods. MATERIALS AND METHODS: In 53 patients (ratio of men to women, 24:29; mean age, 52.8 years) retrievable Gunther Tulip filters (Vena Cava M Reye Filter Set; William Cook Europe, Denmark) were inserted. Indications included planned major surgery with recent pulmonary embolus or high pulmonary embolus risk (n = 16), extensive ilio-femoral thrombus (n = 11), deep vein thrombosis with anticoagulant complications (n = 9), breakthrough pulmonary embolus despite anticoagulant therapy (n = 4), and contraindication to anticoagulant therapy (n = 13). All patients were followed-up for immediate and long-term complications. RESULTS: Fifty-three filters were successfully placed in 52 of 53 patients, yielding a success rate of 98.1%. Nineteen patients underwent attempted retrieval of their filter. Sixteen of 19 retrieval procedures were successful (84%). In three patients, the filter could not be removed on attempted retrieval (extensive filter thrombus in two patients and attachment to the wall in one patient). One patient received two filters, which were both successfully retrieved at a later date. Median implantation time for retrievable filters was 34 days (range, 7-126 days). Mean follow-up for patients with permanent filters was 13 months. Two major complications (pneumothorax and break through pulmonary embolus) and three minor complications (right internal jugular vein thrombosis in two patients and transient Horner's Syndrome in one patient) were recorded. CONCLUSION: Insertion and retrieval of filters is safe and feasible. Preliminary data suggest that Gunther Tulip filter retrieval is feasible over and above the manufacturer's recommended retrieval interval of 14 days.     

Bone mass is recovered from lactation to postweaning in adolescent mothers with low calcium intakes

BACKGROUND: Adolescent mothers may be at increased risk of irreversible bone loss during pregnancy and lactation, particularly when calcium intake is low. OBJECTIVE: Longitudinal changes in bone mass from lactation to postweaning were evaluated in 10 adolescent mothers aged 15-18 y who habitually consumed <500 mg Ca/d. DESIGN: Total-body bone mineral content (TBBMC), total-body bone mineral density (TBBMD), and lumbar spine bone mineral density (LSBMD) were measured at lactation (6-24 wk postpartum) and after weaning (12-30 mo postpartum). Serum hormones (intact parathyroid hormone, estradiol, and prolactin), serum calcium, and markers of bone turnover [urinary N-telopeptide cross-linking region of type I collagen (NTx) and plasma activity of bone alkaline phosphatase] were measured at lactation. RESULTS: TBBMC, total calcium content, TBBMD, and LSBMD increased from lactation to postweaning (P < 0.01). TBBMD and LSBMD were, respectively, 3.6% and 9.7% lower than predicted at lactation and 0.3% and 4.8% lower than predicted in the postweaning period. The increase in age-matched TBBMD adequacy was correlated with the time after resumption of menses (r = 0.86, P < 0.01). Calcium accretion from lactation to postweaning correlated negatively with estradiol (r = -0.86) and prolactin (r = -0.69) and positively with intact parathyroid hormone (r = 0.72) and NTx (r = 0.84) measured at lactation (P < 0.05). CONCLUSIONS: It appears that adolescent mothers with habitually low calcium intakes recover from lactation-associated bone loss after weaning. The rate of bone accretion, however, may not be sufficient to attain peak bone mass at maturity. Hormones regulating bone turnover during lactation may influence bone recovery in adolescent mothers.     

Prevalence of <Emphasis Type="Italic">Chlamydia trachomatis</Emphasis>infection among women in a Middle Eastern community

Background  

Common vaginal infections that manifest in women are usually easily diagnosed. However, Chlamydia infection is often asymptomatic, leading to infertility before it is detected. If it occurs in pregnancy, it could lead to significant neonatal morbidity. It may also play a role with other viral infections for e.g. Human Papilloma Virus in the development of cervical cancer. The objective of this study was to determine the prevalence of Chlamydia infection in women undergoing screening for cervical abnormalities as a part of a research project in primary and secondary care institutions in the United Arab Emirates.     

Outcome of consecutive trabeculectomy

Purpose: To establish a criterion for success of primary phakic trabeculectomy in the second eye of the same patient, using the first operated eye as a predictor for the surgical outcome. Methods: The outcome of primary phakic trabeculectomy was retrospectively compared in both eyes of 23 patients. Sixteen patients were treated with antimetabolites and seven were not. Postoperative intraocular pressure and number of glaucoma medications in paired eyes of the same patients were compared. Surgical success was defined as postoperative IOP of <20 mmHg without medication. Bleb morphology and the number of glaucoma medications were also compared in both eyes. Results: There was a positive correlation between the two eyes of a patient in the IOP values at each postoperative time point in both groups (with and without antimeta­bolites) (P > 0.05). At the last follow‐up visit after trabeculectomy, the number of glaucoma medications used in paired eyes were not significantly different (P > 0.83). Surgical failure occurred more often in paired eyes than in single eyes. Bilateral failure occurred in 60% (3/5) of the failed trabeculectomies with antimetabolites and in 100% (3/3) of the failed trabeculectomies without antimetabolites. Conclusion: Trabeculectomy outcome in paired eyes of patients was similar in both antimetabolites treated and untreated eyes. Thus, trabeculectomy outcome in the first operated eye can predict the surgical result in the second eye of the same patient.     

Primula obconica– is contact allergy on the decline?

Primula obconica, a member of the Primulaceae family, was introduced to Britain from China in 1880. P. obconica cultivars, which are reputed to contain less primin, have been developed over the past number of years in an attempt to reduce the incidence of allergic contact dermatitis. Primin (2-methoxy-6-pentyl-1,4-benzoquinone) is the main sensitizer, although other allergens have been postulated. We believe the incidence of primula allergic contact dermatitis has fallen since the introduction of primin-free P. obconica into the European market and thus the aims of this study were twofold. First, to determine whether the incidence of primula allergic contact dermatitis was truly on the decline and, second, to confirm the presence of primin-free P. obconica in the UK. We surveyed the incidence of primula allergic contact dermatitis in the UK and compared the incidence in the period between 1995 and 2000 with a subsequent follow-up study looking at the incidence for 2002. The results showed a significant fall in primin-positive patch tests from 1995 to 2000. The follow-up results for 2002 showed a further reduction in the number of primin-positive patch tests. The yearly incidence of contact allergy to primin has fallen from 0.785% in 1995/1996 to 0.429% in 2002. This downward trend was statistically significant (P = 0.001). A telephone survey of UK seed suppliers and selected plant retailers was also undertaken to clarify what types of P. obconica were available for sale and to assess suppliers' and retailers' knowledge of the primin-free varieties. This survey showed that 50% of suppliers were selling primin-free varieties but that the majority of surveyed retailers were not currently selling any variety of P. obconica. Our study suggests that although the yearly incidence of contact allergy to primin has fallen significantly over the past 8 years, it is still an important allergen, and thus its inclusion in the standard series remains justified for the foreseeable future.