Clustering of metabolic syndrome risk factors and arterial stiffness in young adults: the Northern Ireland Young Hearts Project

OBJECTIVES: This study aimed to investigate whether the clustering of the risk factors of the metabolic syndrome (MetS) is associated with stiffness of central and peripheral arterial segments; whether these associations are similar in men and women; and whether insulin resistance and low-grade inflammation mediate any such associations. BACKGROUND: Increased arterial stiffness may explain, at least in part, the increased cardiovascular and diabetes risk associated with the MetS. However, the mechanisms linking the MetS to an increased arterial stiffness are incompletely understood, and gender differences may exist. METHODS: Cross-sectional analyses of data on 313 young men and women (mean age 23 years) from the Northern Ireland Young Hearts Project. Subjects were categorized according to the number of traits of the MetS; in addition a continuous MetS score was calculated. Arterial stiffness was assessed by measuring pulse wave velocity (PWV) in three arterial segments using a non-invasive optical method. RESULTS: The prevalence of the MetS was similar for men (10.6%) and women (10.5%). After adjustment for potential confounders and other cardiovascular risk factors, PWV of the three arterial segments investigated increased with increasing traits of the MetS in women only. Women with the MetS, as compared to those without risk factors of the syndrome, had greater PWV of the aorto-iliac (+14.0%, P = 0.016), the aorto-radial (+13.2%, P = 0.010) and aorto-dorsalis pedis (+11.8%, P = 0.011) segments. A great deal (up to 75%) of the association between the MetS and aortic-iliac PWV was mediated by heart rate, inflammation markers [C-reactive protein (CRP) and fibrinogen] and insulin resistance [homeostatic model assessment-insulin resistance (HOMA-IR)], whereas these variables did not explain much of the association between the MetS and PWV of the peripheral segments. CONCLUSIONS: Young women with the MetS show increased stiffness of peripheral and central arteries, a mechanism that may explain their increased cardiovascular risk. Low-grade inflammation, insulin resistance and sympathetic activation explain much of the adverse impact of the MetS on central, but not peripheral, arterial stiffness.     

Cdc7 is required throughout the yeast S phase to activate replication origins

The long-standing conclusion that the Cdc7 kinase of Saccharomyces cerevisiae is required only to trigger S phase has been challenged by recent data that suggests it acts directly on individual replication origins. We tested the possibility that early- and late-activated origins have different requirements for Cdc7 activity. Cells carrying a cdc7^ts allele were first arrested in G₁ at the cdc7 block by incubation at 37°C, and then were allowed to enter S phase by brief incubation at 23°C. During the S phase, after return to 37°C, early-firing replication origins were activated, but late origins failed to fire. Similarly, a plasmid with a late-activated origin was defective in replication. As a consequence of the origin activation defect, duplication of chromosomal sequences that are normally replicated from late origins was greatly delayed. Early-replicating regions of the genome duplicated at approximately their normal time. The requirements of early and late origins for Cdc7 appear to be temporally rather than quantitatively different, as reducing overall levels of Cdc7 by growth at semi-permissive temperature reduced activation at early and late origins approximately equally. Our results show that Cdc7 activates early and late origins separately, with late origins requiring the activity later in S phase to permit replication initiation.     

Purification of Hageman factor (factor XII) on columns of popcorn- agarose

Purification of Hageman factor (HF, factor XII) from human plasma is a tedious procedure and the product is not always in the precursor form. Hojima has described a protein derived from corn kernels that inhibits the enzymatic properties of HF. This inhibitor binds to the precursor form of HF. Rapid purification of HF was achieved by using as the major purification step adsorption of this clotting factor to popcorn inhibitor bound to agarose. The product had a specific activity of 50.0 to 67.1 coagulant units of HF per milligram protein, and the yield was 33% to 40% of the HF content of the starting plasma. The purified protein displayed a single band upon unreduced or reduced sodium dodecyl sulfate polyacrylamide gel electrophoresis and less than 0.1% was in an activated form, as measured in coagulant assays. The technique described is more rapid and reliable than methods described earlier.     

The Role of One-Stage Exchange for Prosthetic Joint Infection

Purpose of Review

In an era of increasing numbers of hip and knee replacements, strategies to manage prosthetic joint infection (PJI) that are effective at infection control with good patient-reported outcomes and cost containment for health systems are needed. Interest in single-stage exchange for PJI is rising and we assess evidence from the last 5 years related to this treatment strategy.

Recent Findings

Only five series for total knee replacement and ten series for total hip replacement have been reported in the last five years. More review articles and opinion pieces have been written. Reinfection rates in these recent studies range from 0 to 65%, but a meta-analysis and systematic review of all studies showed a reinfection rate of 7.6% (95% CI 3.4–13.1) and 8.8% (95% CI 7.2–10.6) for single-stage and two-stage revisions respectively. There is emerging evidence to support single-stage revision in the setting of significant bony deficiency and atypical PJIs such as fungal infections.

Summary

Prospective randomised studies are recruiting and are necessary to guide the direction of single-stage revision selection criteria. The onus of surgical excellence in mechanical removal of implants, necrotic tissue, and biofilms lies with the arthroplasty surgeon and must remain the cornerstone of treatment. Single-stage revision may be considered the first-line treatment for all PJIs unless the organism is unknown, the patient is systemically septic, or there is a poor tissue envelope.

     

The use of sustained low efficiency dialysis (SLED) in massive paracetamol overdose

Context: Massive paracetamol ingestion causing mitochondrial dysfunction is uncommon. Use of sustained low-efficiency dialysis (SLED) to improve acidaemia and enhance paracetamol elimination has not been previously described.

Case details: A 44-year-old male presented to the emergency department 2.5?hours post overdose of 200?g (2.5?g/kg) of paracetamol. Examination revealed a BP 85/60?mmHg, pulse 112 bpm, temperature 33.9?°C and blood glucose of 13.9?mmol/l. Venous blood gas 5.5-hours post-ingestion showed a pH 6.9, pCO₂ 58?mmHg, HCO₃ 13?mmol/l and lactate 14?mmol/l. Fifty-grams of nasogastric activated charcoal and double-strength intravenous acetylcysteine were administered. Paracetamol concentration peaked at 4207 µmol/l six hours post-ingestion. SLED was commenced nine-hours post ingestion and acetylcysteine dose was doubled again during dialysis. Paracetamol extraction ratio was 47–52%. Plasma paracetamol clearance was steady throughout SLED (53–58?ml/min). Hepatotoxicity did not develop and the patient recovered.

Discussions: Intermittent hemodialysis (IHD) is more efficient than SLED or continuous renal replacement therapy for enhancing paracetamol elimination and clearance. IHD plasma clearance is reported to range from 36 to 215?ml/min compared with endogenous clearance of 224?ml/70?kg/min.

Conclusions: SLED improved acidaemia with only moderate overall increase in paracetamol plasma clearance. Lack of development of hepatotoxicity was likely the result of early administration of acetylcysteine rather than any effect of SLED on paracetamol elimination.     

The effectiveness of pharmaceutical interventions for obesity: weight loss with orlistat and sibutramine in a United Kingdom population-based cohort

Aims

Drug treatments for obesity have proven efficacy from randomized trials, but their effectiveness in routine clinical practice is unknown. We assessed the effects on weight and body mass index (BMI) of orlistat and sibutramine when delivered in routine primary care.

Methods

We used United Kingdom data from the Clinical Practice Research Datalink to estimate the effects of orlistat or sibutramine on weight and BMI over 3 years following treatment initiation. For comparison, we matched each patient with up to five obese patients receiving neither drug. Mixed effects linear regression with splines was used to model change in weight and BMI. Mean change with 95% confidence intervals (CI) was estimated.

Results

We identified 100 701 patients receiving orlistat, 15 355 receiving sibutramine and 508 140 non-intervention patients, with body mass index of 37.2, 36.6 and 33.2 kg m⁻², respectively. Patients receiving orlistat lost, on average, 0.94 kg month⁻¹ (0.93 to 0.95) over the first 4 months. Weight gain then occurred, although weight remained slightly below baseline at 3 years. Patients receiving sibutramine lost, 1.28 kg month⁻¹ (1.26 to 1.30) over the first 4 months, but by 3 years had exceeded baseline weight. Non-intervention patients had slight increases in weight throughout the 3 year period, with gains ranging between 0.01 and 0.06 kg month⁻¹.

Conclusions

Orlistat and sibutramine had early effects on weight loss, not sustained over 3 years. As new treatments for obesity are approved, their effectiveness should be measured in routine clinical practice, as effectiveness may be considerably less than seen in randomized trials.     

Predictors of HIV Among 1 Million Clients in High-Risk Male Populations in Tanzania

AIDS and Behavior - The World Health Organization identified men as an essential group to target with HIV testing and treatment strategies;: men who have sex with men (MSM) and male clients of...