Incidence of total knee and hip replacement for osteoarthritis in relation to the metabolic syndrome and its components: A prospective cohort study

Objective

To examine whether components of metabolic syndrome (MetS), either singly or additively, were associated with the incidence of severe knee and hip OA, and whether these associations were independent of obesity assessed by body mass index (BMI).

Methods

Twenty thousand, four hundred and thirty participants who had blood lipids, anthropometric and blood pressure measurements during 2003–2007 were selected from the Melbourne Collaborative Cohort Study. MetS was defined as central obesity assessed by waist circumference and any two of raised triglyceride level, reduced HDL cholesterol level, hypertension or impaired fasting glycaemia. The incidence of total knee and hip replacement was determined by linking cohort records to the Australian Orthopaedic Association National Joint Replacement Registry.

Results

Six hundred and sixty participants had knee OA and 562 had hip OA. After adjustment for age, gender, country of birth, education, physical activity and BMI, central obesity [hazard ratio (HR) 1.59, 95% confidence interval (CI) 1.25–2.01] and hypertension (1.24, 1.05–1.48) were associated with increased risk of knee OA. The accumulation of MetS components was associated with knee OA risk, independent of BMI: one component, 2.12 (1.15–3.91); two components, 2.92 (1.60–5.33) and three or more components, 3.09 (1.68–5.69). No statistically significant associations were observed for hip OA.

Conclusion

Cumulative number of MetS components and central obesity and hypertension were associated with increased risk of severe knee OA, independent of BMI. No associations were observed with severe hip OA. These findings suggest that the pathogenesis of knee and hip OA differ and that targeting the management of MetS may reduce the risk of knee OA.     

Amino acid addition to Vibrio cholerae LPS establishes a link between surface remodeling in gram-positive and gram-negative bacteria

Historically, the O1 El Tor and classical biotypes of Vibrio cholerae have been differentiated by their resistance to the antimicrobial peptide polymyxin B. However, the molecular mechanisms associated with this phenotypic distinction have remained a mystery for 50 y. Both gram-negative and gram-positive bacteria modify their cell wall components with amine-containing substituents to reduce the net negative charge of the bacterial surface, thereby promoting cationic antimicrobial peptide resistance. In the present study, we demonstrate that V. cholerae modify the lipid A anchor of LPS with glycine and diglycine residues. This previously uncharacterized lipid A modification confers polymyxin resistance in V. cholerae El Tor, requiring three V. cholerae proteins: Vc1577 (AlmG), Vc1578 (AlmF), and Vc1579 (AlmE). Interestingly, the protein machinery required for glycine addition is reminiscent of the gram-positive system responsible for D-alanylation of teichoic acids. Such machinery was not thought to be used by gram-negative organisms. V. cholerae O1 El Tor mutants lacking genes involved in transferring glycine to LPS showed a 100-fold increase in sensitivity to polymyxin B. This work reveals a unique lipid A modification and demonstrates a charge-based remodeling strategy shared between gram-positive and gram-negative organisms.     

Tumor radiation response enhancement by acoustical stimulation of the vasculature

We have discovered that ultrasound-mediated microbubble vascular disruption can enhance tumor responses to radiation in vivo. We demonstrate this effect using a human PC3 prostate cancer xenograft model. Results indicate a synergistic effect in vivo with combined single treatments of ultrasound-stimulated microbubble vascular perturbation and radiation inducing an over 10-fold greater cell kill with combined treatments. We further demonstrate with experiments in vivo that induction of ceramide-related endothelial cell apoptosis, leading to vascular disruption, is a causative mechanism. In vivo experiments with ultrasound and bubbles permit radiation doses to be decreased significantly for comparable effect. We envisage this unique combined ultrasound-based vascular perturbation and radiation treatment method being used to enhance the effects of radiation in a tumor, leading to greater tumor eradication.     

Men's experiences of vasectomy: a grounded theory study

This paper presents a theoretical model derived from a grounded theory analysis of interviews with 19 men who had had a vasectomy three years previously. The aim was to track men's experience of vasectomy through decision making, surgery and adjustment and to develop a model to shed light on the process. Early studies of vasectomy had suggested that men adopt more stereotypically masculine behaviours after vasectomy and their authors had conjectured that these were compensatory for a diminished sense of masculinity. Interesting findings from the present study suggest that, for these participants at least, vasectomy often enhanced their sense of masculinity. Surgery was sometimes construed as a “bloodbath” heroically endured and part of the construction of a valued identity of a “family man”. Peer pressure, particularly in the workplace, appeared to be a powerful motivator when making the decision to be sterilized and the authors suggest that vasectomy can be a passport to membership of a socially valued group.     

Treatment and surveillance of polypoid lesions of the gallbladder in the United Kingdom

Objectives

The increase in the routine use of abdominal imaging has led to a parallel surge in the identification of polypoid lesions in the gallbladder. True gallbladder polyps (GBP) have malignant potential and surgery can prevent or treat early gallbladder cancer. In an era of constraint on health care resources, it is important to ensure that surgery is offered only to patients who have appropriate indications. The aim of this study was to assess treatment and surveillance policies for GBP among hepatobiliary and upper gastrointestinal tract surgeons in the UK in the light of published evidence.

Methods

A questionnaire on the management of GBP was devised and sent to consultant surgeon members of the Association of Upper Gastrointestinal Surgeons (AUGIS) of Great Britain and Ireland with the approval of the AUGIS Committee. It included eight questions on indications for laparoscopic cholecystectomy and surveillance based on GBP (size, number, growth rate) and patient (age, comorbidities, ethnicity) characteristics.

Results

A total of 79 completed questionnaires were returned. The vast majority of surgeons (>75%) stated that they would perform surgery when a single GBP reached 10 mm in size. However, there was a lack of uniformity in the management of multiple polyps and polyp growth rate, with different surveillance protocols for patients treated conservatively.

Conclusions

Gallbladder polyps are a relatively common finding on abdominal ultrasound scans. The survey showed considerable heterogeneity among surgeons regarding treatment and surveillance protocols. Although no randomized controlled trials exist, national guidelines would facilitate standardization, the formulation of an appropriate algorithm and appropriate use of resources.     

The BILAG2004-Pregnancy index is reliable for assessment of disease activity in pregnant SLE patients

Objective. To assess the inter-rater reliability of the BILAG2004-Pregnancy index for assessment of SLE disease activity in pregnancy. Methods. Pregnant SLE patients were recruited from four centres and assessed separately by two raters/physicians in routine clinical practice. Disease activity was determined using the BILAG2004-Pregnancy index. Reliability was assessed using level of agreement, κ-statistics and analysis of disagreement. Major disagreement was defined as a score difference of A and C/D/E or B and D/E between the two raters, and minor disagreement was a score difference of A and B or B and C between raters. Results. A total of 30 patients (63.3% Caucasian, 13.3% Afro-Caribbean, 16.7% South Asian) were recruited. The majority of patients had low-level disease activity according to the local rater's assessment, and there was no grade A activity, with grade B activity present in the following systems: mucocutaneous (nine patients), musculoskeletal (two patients), cardiorespiratory (one patient) and renal (one patient). The distribution of disease activity was similar to the external rater's assessment. Good levels of agreement (>70%) were achieved in all systems. κ-statistics were not appropriate for use in the gastrointestinal, ophthalmic, constitutional and neuropsychiatric systems, as there was minimal variation between patients but good levels of agreement otherwise. There were three major disagreements (0.1 per patient, all differences between B and D/E) and five minor disagreements (0.17 per patient). Conclusion. The BILAG2004-Pregnancy index is reliable for assessment of disease activity in pregnant SLE patients.     

Impaired vasodilation in the pathogenesis of hypertension: focus on nitric oxide, endothelial-derived hyperpolarizing factors, and prostaglandins

Under resting conditions the arterial vasculature exists in a vasoconstricted state referred to as vascular tone. Physiological dilatation in response to increased flow, a function of normal endothelium is necessary to maintain normal blood pressure. Endothelial dysfunction in vascular smooth muscle cells thus results in loss of normal vasorelaxant function and the inability of arteries to appropriately dilate in response to increased blood flow in either a systemic or regional vascular bed, resulting in increased blood pressure, a sequence that may represent a common pathway to hypertension. Normal vasorelaxation is mediated by a number of endothelial systems including nitric oxide (NO), prostaglandins (PGI2 and PGE2), and a family of endothelial-derived hyperpolarizing factors (EDHF). In response to hemodynamic shear stress, endothelium continuously releases NO, EDHF, and PGI2 to provide vasodilatation. EDHF, not a single molecule but rather a group of molecules that includes epoxyeicosatrienoic acids, hydrogen peroxide, carbon monoxide, hydrogen sulfide, C-natriuretic peptide, and K+ itself, causes vasodilatation by activation of vascular smooth muscle cell K+ channels, resulting in hyperpolarization and thus vasorelaxation. The understanding and effective management of blood pressure requires an understanding of both physiologic and pathophysiologic regulation of vascular tone. This review describes molecular mechanisms underlying normal endothelial regulation and pathological states, such as increased oxidative stress, which cause loss of vasorelaxation. Possible pharmacological interventions to restore normal function are suggested.