Associations between vitamin D metabolites, antiretroviral therapy and bone mineral density in people with HIV.

RATIONALE: To see if vitamin D and antiretroviral therapy are associated with bone mineral density (BMD) in people with HIV. RESULT: Lower hip BMD was associated with tenofovir (an antiretroviral medicine) in those with 25(OH)D ≥50 nmol/L. SIGNIFICANCE: The relationship between antiretroviral therapy and hip BMD differs depending on vitamin D status. INTRODUCTION: People with HIV have an increased risk of low BMD and fractures. Antiretroviral therapy contributes to this increased risk. The aim of this study was to evaluate associations between vitamin D metabolites and antiretroviral therapy on BMD. METHODS: The simplification of antiretroviral therapy with tenofovir-emtricitabine or abacavir-lamivudine trial (STEAL) was an open-label, prospective randomised non-inferiority study that compared simplification of current nucleoside reverse transcriptase inhibitors (NRTIs) to fixed-dose combination tenofovir-emtricitabine (TDF-FTC) or abacavir-lamivudine. Serum 25(OH)D and 1,25(OH)2D were measured in 160 individuals (90 receiving TDF-FTC, 70 receiving other NRTIs) at baseline from this study. Multivariable linear regression models were constructed to evaluate the covariates of 1,25(OH)2D and BMD. RESULTS: Protease inhibitor use (p = 0.02) and higher body mass index (BMI) (p = 0.002) were associated with lower 1,25(OH)2D levels in those with 25(OH)D <50 nmol/L. However, TDF-FTC use (p = 0.01) was associated with higher 1,25(OH)2D levels, but only in those with 25(OH)D ≥50 nmol/L. White ethnicity (p = 0.02) and lower BMI (p < 0.001) in those with 25(OH)D <50 nmol/L and with TDF-FTC use (p = 0.008) in those with 25(OH)D ≥50 nmol/L were associated with lower hip BMD. TDF-FTC use, higher serum calcium and serum ßCTX, winter, and lower bone-specific alkaline phosphatase (BALP) and BMI were associated with lower lumbar spine BMD. CONCLUSION: TDF-FTC use (versus non-TDF-FTC use) was associated with lower hip BMD, and this difference was more pronounced in those with 25(OH)D ≥50 nmol/L. Serum 25(OH)D <50 nmol/L was associated with lower hip BMD in all participants. Therefore, the associations between antiretroviral therapy and hip BMD differ depending on vitamin D status.

Nonpenetrating trauma to the thoracic aorta.

Twenty-seven patients underwent surgical repair for nonpenetrating injuries of the thoracic aorta. Emergency operation was performed in 19 patients with acute aortic injury and there were 12 survivors. Left heart bypass (LHB), external shunts, and simple aortic cross-clamping were methods employed during repair. All operative deaths occurred in the left heart bypass group. Morbidity, hospital stay, operative time, and blood loss all were markedly less in patients repaired with an external shunt or simple cross-clamping. Systemic heparinization related adversely to mortality and morbidity. Eight patients had repair of chronic post-traumatic descending aortic aneurysms. One of these had previous repair elsewhere with paraplegia and subsequent mycotic aneurysm at the graft repair site. He presented to us with massive hemoptysis. Surgical correction in the chronic group was performed using either left heart bypass, external shunt, or simple aortic cross-clamp with graft interposition. The only death occurred in a patient repaired on left heart bypass.

Constitutive biosynthesis of plasminogen activator inhibitor type-1 (PAI-1) by cultured human aortic endothelial cells independent of insulin.

BACKGROUND: Both tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1) are synthesized by vascular endothelium, whereas hepatocytes synthesize PAI-1 but not t-PA. Non-insulin-dependent diabetes mellitus (NIDDM) is associated with decreased fibrinolytic activity in blood secondary to increased PAI-1 activity, and the increase in PAI-1 activity is correlated with the magnitude of elevation of plasma immunoreactive insulin. To determine whether the increased PAI-1, known to be associated with accelerated coronary artery disease in non-diabetic subjects, is a consequence of direct effects of insulin on endothelial cells, we performed the present study with primary cultures of human aortic endothelial cells. METHODS: Endothelial cells isolated from human aortas from donor hearts for transplantation were grown to confluence and exposed to selected concentrations of agonists. Accumulation of t-PA and PAI-1 in conditioned media was quantified, as was PAI-1 activity. RESULTS: Insulin at pharmacologic concentrations did not alter either PAI-1 or t-PA production by the human aortic endothelial cells, although insulin stimulated PAI-1 synthesis in human hepatoma (Hep G2) cells as expected. Transforming growth factor-beta (TGF-beta) stimulated endothelial cell PAI-1 production markedly, indicating that the cells could respond positively to stimulation in vitro. PAI-1 activity in the conditioned media was zero under all conditions, which was indicative of the rapid inactivation and degradation of PAI-1 known to occur in media devoid of vitronectin. CONCLUSIONS: The decreased fibrinolytic activity in blood seen in patients with NIDDM appears to reflect direct effects of insulin or its precursor on hepatocytes rather than on endothelial cells.

Dietary intakes of HIV-infected adults in urban UK.

Maintaining a good nutritional status is important for immune health and for managing metabolic comorbidities in adults with HIV infection. Little is known about the dietary habits of adults living with HIV infection in the United Kingdom. The aims of this study were to characterise their dietary intakes, and to identify subgroups of patients who may require nutritional counselling and/or food support services. An observational study of adults attending a London HIV out-patient clinic who completed a demographics questionnaire and a structured 24 h diet recall interview was conducted. In all, 196 (162 men, 34 women) adults participated. Forty-three percent (n=66) of men and thirty-six percent (n=11) of women did not consume enough energy to meet their basal metabolic requirements and activity factor. The majority of both men (64%) and women (56%) consumed more than the recommended amount of saturated fat. Self-report of lipodystrophy (B coefficient -2.27 (95% CI -3.92 to -0.61), P=0.008) was associated with lower dietary fibre intake/1000 kcal per day, and a more recent diagnosis of HIV (B coefficient -0.11 (95% CI -0.20 to -0.02), P=0.013) was associated with a higher dietary fibre/1000 kcal intake per day. Recreational drug use was associated with a higher overall calorie (P=0.003) and protein (P=0.001) intake than non-usage after adjusting for basal metabolic requirements and weight, respectively. Our data describe the dietary intakes of a diverse group of adults with HIV infection in the United Kingdom. These dietary habits may have an impact on their overall health and development of other metabolic comorbidities common in people with HIV.

Trophodynamics and distribution of silver in a Patagonia mountain lake.

Silver (Ag) ions are among the most toxic metallic ions to aquatic biota. In southern Argentina, fish from Patagonian lakes have liver Ag concentrations [Ag] among the highest ever reported globally. Silver concentration in phytoplankton from Lake Moreno (1.82±3.00µgg(-1) dry weight, DW) was found to be significantly higher than [Ag] in zooplankton (0.25±0.13µgg(-1)). Values in snails and decapods (0.60±0.28µgg(-1) and 0.47±0.03µgg(-1) respectively), were higher than in insect larvae (0.28±0.39µgg(-1) for Trichoptera). We examined trophic transfer of Ag in the biota using stable nitrogen and carbon isotopes ratios (δ(15)N and δ(13)C respectively). Silver concentrations in the biota of Lake Moreno were not associated with any particular C source, as assessed by δ(13)C. Hepatic [Ag] significantly increased with trophic position, as measured by δ(15)N, within the brook trout sample set. Biodilution of Ag was observed between primary producers and small forage fish when whole body [Ag] was analyzed. Nevertheless, when considering whole food web biomagnification and hepatic [Ag] of top predator fish, a significant positive regression was found between [Ag] and trophic position, as measured by δ(15)N. The importance of species-specific and tissue-specific considerations to obtain more information on Ag trophodynamics than that usually presented in the literature is shown. To the best of our knowledge, this is the first study in assessing Ag trophodynamics and tissue-specific biomagnification in a whole freshwater food web.

Complications of continuous epidural infusions for postoperative analgesia in children.

To determine the incidences of side effects and complications associated with the use of epidural analgesia for infants and children at the Alberta Children's Hospital, we reviewed our experience over a two-year period. A database was established for recording management, side effects and complications of each epidural, and this is a retrospective review of that database. Problems were identified as complications if there was a need for medical intervention related to the patient complaint, and if the intervention was documented in the patient record. Continuous epidural analgesia with bupivacaine 0.125% or bupivacaine 0.1% with epinephrine was used for managing postoperative pain in 190 children with mean age 5.6 yr (range 1 mo to 18 yr) and the mean weight 22 kg (range 4-88 kg). Mean duration of the epidural infusions was 4.7 days (range 1-16 d). In 127 patients, 203 complications were recorded. Complications, in order of frequency, were nausea and vomiting (23% of patients), motor blockade (15.8% of patients), over-sedation (6.3% of patients), and pruritus (5.2% of patients). Four patients had complications which were potentially related to toxic effects of, or resistance to, bupivacaine, and serum levels of bupivacaine were measured at 3.86, 5.5, 2.1 and 2.34 micrograms.ml(-1). Early discontinuation of the epidural occurred in 41 cases, technical problems with the epidural catheter being the commonest reason (21 cases). Although three potentially serious complications were identified (one catheter site infection, one seizure, one respiratory depression) none was associated with lasting consequences. The majority of complications associated with the use of epidurals were minor and easily remedied.(ABSTRACT TRUNCATED AT 250 WORDS)

Augmentation of synthesis of plasminogen activator inhibitor type-1 in arterial endothelial cells by glucose and its implications for local fibrinolysis.

Because of the frequent occurrence of premature cardiovascular disease in patients with non-insulin-dependent, type II diabetes mellitus (NIDDM), the attenuated fibrinolytic activity of plasma from type II diabetic patients with increased concentrations of plasminogen activator inhibitor type-1 (PAI-1), and the fact that insulin stimulates synthesis of PAI-1 by human hepatic cells in vitro, we and others have hypothesized that accelerated vascular disease in type II diabetes may result in part from impaired fibrinolysis secondary to excessive elaboration of PAI-1 stimulated by insulin. Alternatively, the hyperglycemia associated with type II diabetes could influence the synthesis and secretion of PAI-1 directly. The present study was performed to determine whether PAI-1 secretion is or is not sensitive to the prevailing concentration of glucose in the conditioned medium of endothelial and liver cells, which are thought to be the major sources of circulating PAI-1 in vivo. Confluent cells were exposed to 0, 2.8, 5.6, 11.1, or 22.2 mmol/L (0, 50, 100, 200, or 400 mg/dL) glucose in medium without serum and subsequently to media with or without insulin (7.3 nmol/L). Secretion of PAI-1 by highly differentiated human hepatoma (Hep G2) cells did not increase as a function of increasing concentrations of glucose, whether or not insulin was present. In contrast, with pig aortic endothelial cells, the secretion of PAI-1 increased significantly with extracellular glucose with or without insulin. The increases in PAI-1 were specific (as shown by metabolic labeling experiments) and not attributable to osmotic effects (as shown by replacement of glucose by sorbitol).(ABSTRACT TRUNCATED AT 250 WORDS)