Disordered regulation of coagulation and platelet activation in xenotransplantation

Rejection of xenografts is associated with vascular-based inflammation, thrombocytopenia and the consumption of coagulation factors that may evolve into disseminated intravascular coagulation (DIC). Similarly, bone marrow-derived cellular xenotransplantation procedures are associated with endothelial cell activation and thrombotic microangiopathic injury. These complications generally develop despite the best available measures for depletion of xenoreactive natural antibody, inhibition of complement activation and suppression of T- and B-cell mediated immune responses. The mechanisms underlying the DIC and thrombotic microangiopathy associated with xenotransplantation are unclear. A proposed primary biological dysfunction of xenografts with respect to regulation of clotting could amplify vascular injury, promote immunological responses and independently contribute to graft failure. Disordered thromboregulation could have deleterious effects, comparable to unregulated complement activation, in the pathogenesis of xenograft rejection and may therefore represent a substantive barrier to xenotransplantation.     

Should every unit have a 24-hour transvaginal ultrasound available?

The purpose of this debate is to argue the merits of whether the availability of 24-hour transvaginal ultrasound service in every unit will help predict and, subsequently, prevent preterm birth. Any new test introduced will need to fulfil certain criteria. It must be acceptable in terms of risk, cost and patient convenience. It must be an improvement over existing alternatives, and it must aid clinicians to improve care. While the 24-hour availability of transvaginal ultrasound to every maternity unit may be useful to research and teaching, there is, as yet, little evidence that a 24-hour transvaginal ultrasound service improves perinatal and maternal morbidity and mortality. Results from our own centre suggest that experienced clinicians can make an acceptable diagnosis of spontaneous preterm labour (PTL) using only history and digital examination. Based on these findings, the availability of 24-hour vaginal ultrasound in every unit cannot be justified for the diagnosis of spontaneous PTL.     

Distinct hepatitis B virus integration patterns in hepatocellular carcinoma and adjacent normal liver tissue

Infection by the hepatitis B virus (HBV) is one of the main etiologies of hepatocellular carcinoma (HCC). During chronic infection, HBV DNA can integrate into the human genome, and this has been postulated as a possible mechanism of HBV‐induced HCC. In this study we used 2199 HBV integration sites from Dr.VIS v2.0 and mapped them to the human genome (hg19) to obtain viral integration sites (VIS) related to protein‐coding and non‐protein‐coding genes. In total, we found 1,377 and 767 VIS within close proximity to protein coding genes and noncoding genes, respectively. Genes affected more than two times included 23.1% of protein‐coding genes and 24.7% of long noncoding RNAs (lncRNA). Only 4.8% of VIS were shared between HCC and non‐tumor tissues. HBV integrations were more common in chromosomes 5, 8, 10, and 19 in HCC tissue and chromosomes 1 and 2 in non‐tumorous tissue. The number of integration sites on each chromosome correlated with the number of fragile sites in non‐tumorous tissue but not in HCC tissue. Functional enrichment analysis of the protein‐coding genes containing or in close proximity to HBV integration sites in HCC tissue showed an enrichment of cancer related gene ontology terms. Additionally, the most frequently associated lncRNA genes were related to telomere maintenance, protein modification processes, and chromosome localization. Thus, HBV may have preferred integration sites in the human genome that serve a critical role in HCC development. These results show that HCC treatment may benefit from the development of next generation anti‐viral therapies.     

Why has the acceptance of laparoscopic hysterectomy been slow? Results of an anonymous survey of Australian gynecologists

STUDY OBJECTIVE: To determine whether Australian gynecologists would like to increase the proportion of hysterectomies they perform laparoscopically and the factors that might limit their acceptance of laparoscopic hysterectomy (LH). DESIGN: Anonymous postal survey (Canadian Task Force classification III). SETTING: Department of obstetrics and gynecology of a major Australian medical school. PARTICIPANTS: Seven hundred ninety-six certified obstetrician/gynecologists in practice in Australia. MAIN RESULTS: Of 796 respondents, 654 (82%) reported that hysterectomy was part of their normal clinical practice. Of those, 206 (31%) did not perform LH. Respondents who reported performing the highest proportion of LH were those in urban, private hospital settings. Of those who performed hysterectomy, 62% (403/654) reported they did not wish to increase the proportion of LH they undertook. However, of those, 49% (197/403) already performed LH, with 20% (39/197) of that group performing 80% or more of all hysterectomies as LH. Overall, 38% (251/654) of respondents indicated a desire to perform an increased proportion of LH. The commonest factors cited as limited acceptance of LH were insufficient experience and training, lack of hospital equipment, and lack of support from colleagues. CONCLUSION: Many Australian gynecologists report a desire to increase their rate of LH, but those intentions are compromised by problems with training, equipment, and support.     

The Effect of Nutrient Intake on Bone Mineral Status in Young Adults: The Northern Ireland Young Hearts Project

Optimizing peak bone mass in early life may reduce osteoporosis risk in later life. Such optimization may be partly dependent upon diet. In the present study, nutrient intakes and selected lifestyle parameters were assessed in adolescent subjects (238 males, 205 females; aged 15 y) and again, in the same subjects, on one occasion in young adulthood (aged between 20 and 25 y). The extent of the relationships between these parameters and bone mineral density (BMD), dual energy X-ray absorptiometry (DXA), lumbar spine (L2-L4), and femoral neck measured concurrently with diet in young adulthood only, was assessed. Adjusted linear regression models were constructed. Variables included a measure of pubertal status (at age 15 y), age (at young adulthood), height, weight, physical activity, smoking, and mean daily intakes of energy, calcium, protein, vitamin D, phosphorus, total fat, and alcohol. In both sexes, body weight at adolescence and young adulthood was the only factor consistently positively associated with BMD at both measurement sites. Effects of nutrient intake on BMD were inconsistent. Vitamin D and calcium intakes reported by female adolescents showed significant positive relationships with BMD measured in young adulthood (vitamin D measured at the lumbar spine; calcium measured at the femoral neck). The positive relationship between vitamin D and BMD remained significant at young adulthood, but at the femoral neck rather than at the lumbar spine. Also in females, intakes of phosphorus and the calcium:phosphorus ratio (Ca:P) at adolescence were strongly negatively related to femoral neck BMD measured at young adulthood. In males, however, Ca:P reported at young adulthood had a significant positive relationship with lumbar spine BMD, whereas Ca:protein was negatively associated with BMD at the lumbar spine. Intakes of Ca reported by adolescent males also had a strong negative effect on lumbar spine BMD measured at young adulthood.     

Betaine supplementation decreases post-methionine hyperhomocysteinemia in chronic renal failure

BACKGROUND: Fasting and post-methionine load hyperhomocysteinemia are independent risk factors for vascular disease that are common in chronic renal failure. Folate decreases but seldom normalizes fasting total homocysteine (tHcy) concentrations in such patients. Glycine betaine (GB) is known to decrease tHcy in other clinical settings, but whether it is beneficial in chronic renal failure has not been established. METHODS: We conducted a crossover-controlled trial in 36 patients with chronic renal failure to determine if oral GB decreased fasting or post-methionine tHcy concentrations. All subjects received, in randomized sequence, 5-mg folic acid and 50-mg pyridoxine daily, with or without GB 4-g daily, for three months each. Fasting plasma tHcy, GB, folate, B vitamins, serum lipids and creatinine were measured at one and three months, and methionine load tests were performed at the end of each three-month treatment phase. RESULTS: GB and N,N-dimethylglycine (DMG) levels in plasma and urine increased markedly during GB treatment. Fasting tHcy decreased from baseline with both treatments but did not differ between treatments. Post-methionine tHcy decreased with both treatments and was 18% lower on GB than on folate and pyridoxine alone (P < 0.001). There were small increases in lipids during treatment with GB but the ratio of total: HDL cholesterol was unchanged. CONCLUSIONS: GB supplementation had no effect on fasting tHcy in patients with chronic renal failure who were folate and pyridoxine replete, but it significantly decreased tHcy concentrations after methionine loading.