Switch to raltegravir decreases soluble CD14 in virologically suppressed overweight women: the Women, Integrase and Fat Accumulation Trial.

OBJECTIVES: Soluble CD14 (sCD14) is a monocyte activation marker associated with increased mortality in HIV infection. We assessed 48-week changes in sCD14 and other inflammatory biomarkers in virologically suppressed, HIV-infected women switching to raltegravir (RAL) from a protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI). METHODS: HIV-infected women with central adiposity and HIV-1 RNA < 50 HIV-1 RNA copies/mL continued their thymidine-sparing nucleoside reverse transcriptase inhibitor (NRTI) backbone and were randomized to switch to open-label RAL at week 0 (immediate) or 24 (delayed). In an exploratory analysis, inflammatory biomarkers were measured on stored fasting plasma. RESULTS: Of the 37 evaluable subjects, 78% were non-White; the median age was 43 years, the median body mass index (BMI) was 32 kg/m(2) and the median CD4 count was 558 cells/µL. At baseline, biomarker values were similar between groups. After 24 weeks, median sCD14 significantly declined in subjects switching to RAL [-21% (P < 0.001) vs. PI/NNRTI -5% (P = 0.49); between-group P < 0.01]. After 48 weeks, immediate-switch subjects maintained this decline and delayed-switch subjects experienced a similar decline following the switch to RAL (-10%; within-group P < 0.01). Immediate-switch subjects also experienced an initial increase in tumour necrosis factor (TNF)-α that was neither maintained after 48 weeks nor seen in delayed-switch subjects. After adjustment for multiple testing, only declines in sCD14 remained significant. CONCLUSIONS: In this randomized trial of women with central adiposity, a switch to RAL from a PI or NNRTI was associated with a statistically significant decline in sCD14. Further studies are needed to determine whether integrase inhibitors have improved monocyte activation profiles compared with PIs and/or NNRTIs, and whether measured differences between antiretroviral agents translate to demonstrable clinical benefit.

Nutrition and HIV infection: review of weight loss and wasting in the era of highly active antiretroviral therapy from the nutrition for healthy living cohort.

Despite major advances in the treatment and survival of patients infected with human immunodeficiency virus (HIV), weight loss and wasting remain common problems. In the HIV-infected population, weight loss is associated with lower CD4+ cell counts and is an independent predictor of mortality. The etiology of weight loss and wasting is complex and multifactorial. We discuss, on the basis of a large longitudinal cohort that examined nutritional status in HIV infection, data on weight loss and wasting from the present clinical era. The definition, prevalence, and significance of HIV-associated weight loss and wasting are summarized. The etiology of weight loss is discussed for 2 main categories: inadequate nutrient intake and altered metabolism. Finally, studies of interventions to treat HIV-associated weight loss and wasting are discussed. This information is intended to raise awareness among health care providers of HIV-infected patients that weight loss and wasting remain important acquired immunodeficiency syndrome-defining conditions, despite the advent of HAART.

Daptomycin-resistant, methicillin-resistant Staphylococcus aureus bacteremia.

We describe a patient who developed daptomycin-resistant, methicillin-resistant Staphylococcus aureus (MRSA) during an episode of presumed septic thrombophlebitis of the portal vein. Although daptomycin is an alternative agent for treatment of drug-resistant gram-positive bacterial infections, development of resistance during prolonged use may occur with MRSA bacteremia from a persistent focus.

Effects of hemodialytic treatment on uremic polyneuropathy. A clinical and electrophysiological follow-up study.

The involvement of peripheral motor and sensory nerve, at least on a subclinical level, is nearly constant event with chronic renal failure. The study of the motor and sensory propagation velocity indicates that a widespread functional lesion of the axon with a peripheral point of attack and secondary demyelination, may be the basic pathogenetic event of uremic polyneuropathy. Prolonged hemodialytic treatment is substantially unable to influence the evolution of uremic polyneuropathy. The electrophysiological follow-up study of the peripheral nerve does not seem to be an index of adequate dialysis.

Relationship between PCBs in blood and D-glucaric acid in urine.

The polychlorinated biphenyls (PCBs) have been demonstrated to be inducers of hepatic microsomal enzymes and some of their effects such as hormonal imbalance, and alteration of lipid and porphyrin metabolism could be ascribed to this mechanism. For this reason, the urinary excretion of D-glucaric acid (DGA), an indirect indicator of enzymatic induction, was suggested as a biological marker of effect following exposure to PCBs. The aim of the present study was to investigate whether any inductive effects resulting from exposure to these compounds through ingestion of contaminated food could be detected early by measuring urinary DGA (U-DGA). U-DGA was measured in 73 subjects exposed to PCBs due to ingestion of PCB-contaminated food and levels ranged from 1.7 to 12.4 mmol/mol creatinine, with a mean value of 5.96 mmol/mol creatinine. These values were higher than those usually found in the general population. Sex and smoking habits did not affect U-DGA excretion, while age and alcohol intake were significantly correlated with U-DGA excretion, a finding in agreement with the results of other investigations. Neither total PCB blood concentration nor PCB chlorine content was significantly correlated with U-DGA excretion, and only the PCB 138 congener was weakly correlated with U-DGA levels. The results indicate that, for exposure to PCB resulting in blood concentrations up to 394 microg/l, no statistically significant effect of these persistent organochlorine compounds on human enzyme induction could be demonstrated, as measured by DGA urinary excretion.

Assessment of reference values for mercury in urine: the results of an Italian polycentric study.

The results of a polycentric study to assess the reference values of urinary mercury (U-Hg) in four Italian cities are presented. A total of 383 subjects were selected on the basis of standardised criteria by a questionnaire on personal habits, lifestyle, occupational or non-occupational exposure to Hg, medical history, number and area of dental amalgams. U-Hg was determined by hydride generation atomic absorption method (HG-AAS), with a detection limit of 0.5 microg/l and by flow injection (FI) inductively coupled plasma mass spectrometry (ICP-MS), with a detection limit of 0.03 microg/l. The median value of U-Hg, determined by HG-AAS, was 0.78 microg/g creatinine (0.75 for males and 0.83 for females), with 5 degrees and 95 degrees percentiles, respectively, of 0.17 and 3.66 microg/g creatinine. When determined by FI ICP-MS, the median value was 0.79 microg/g creatinine (0.77 for males and 0.79 for females) with 5 degrees and 95 degrees percentiles of, respectively, 0.12 and 5.02 microg/g creatinine. Among the independent variables, city of origin, area of dental amalgams, fish intake and tobacco smoking significantly influenced the U-Hg levels. The U-Hg reference values from this survey are lower than those from other recent investigations, probably due to characteristics and selection of the examined individuals and to the strict control of pre-analytical and analytical factors of variability.

[Alcohol and working]. / Alcol e lavoro.

Due to its negative impact on both health and productivity, alcohol misuse is a serious concern in the workplace. Some occupations (e.g. employees of the catering and hotel trade, seamen, sales representatives, brewers and distillers, journalists, physicians, lawyers) are associated with a high rate of alcohol abuse. Alcohol intake can modify worker's behaviour (impaired judgement and vigilance, dulled reflexes) causing reduced performance, mistakes during operating procedures, accidents and injuries. Moreover it can affect the toxicokinetic and toxicodinamic properties of several substances in the workplace, inducing a more complex evaluation of exposure assessment and diagnostic procedures of occupational diseases. The occupational physician, during health surveillance program, can face several alcohol related issues. These entail diagnostic evaluation of alcoholism, job fitness evaluation, in heavy drinkers, advise of rehabilitation and health promotion program.

Metanalytical assessment of reference values for polychlorinated biphenyl in human blood.

Due to their physico-chemical characteristics, polychlorinated biphenyls (PCBs) are highly persistent in the environment and therefore easily measured in the biological matrices of more and more large groups of general population. For these reasons it would be useful to determine suitable Reference Values (RVs) for these xenobiotics. In this paper, a metanalysis to the published data on PCBs values in human blood is presented. This investigation was carried out in order to reach adequate information on their RVs and to focus some specific topics to be taken into account when producing directly RVs for PCBs. The PCBs RVs resulted between 1.2 e 8.28 microg/L for males and between 2.69 e 5.17 microg/L for females the general range varied from 0.9 to 56 microg/L. The main criticisms in the assessment of RVs for PCBs resulted: the number of examined subjects; the inclusion and stratification criteria; the analytical method adopted and their quality assurance; the type and number of congeners to be determined and their specific quantification; the calculation of blood PCBs concentration (weight/volume or weight/lipids); the statistical analysis and in particular the treatment of not detectable data.

[Reference values of urinary mercury in the Italian population]. / Valori di riferimento del mercurio urinario nella popolazione Italiana.

This paper shows the results of a polycentric study performed to assess the reference values of urinary mercury (U-Hg) in Italian population. 374 subjects from four Italian cities (Bari, Brescia, Genova e Siena) have been examined. A questionnaire on life style, dietary habits, occupational or environmental exposure to Hg and clinical history has been administered to every participant and number and surface of dental amalgams have been verified for all subjects. The determination of U-Hg has been performed on urinary extemporary samples by hydride generation atomic absorption method (HG-AAS); urinary creatinine has been determinated to reduce the intraindividual variability. U-Hg reference values were: 0.21-3.20 micrograms/g creat (5 degrees and 95 degrees percentile) and 0.12-6.04 micrograms/g creat (range). Moreover study results have shown that number and surface of dental amalgams, dietary fish intake and body mass index (BMI) influenced significatively U-Hg excretion. U-Hg reference values from this polycentric study resulted comparable to those assessed in other European countries, whereas the mean U-Hg observed in the referent Italian population was lower.

[Significance of biological indicators of mercury exposure]. / Significato degli indicatori biologici di esposizione a mercurio.

BACKGROUND: It was considered appropriate to update of the significance and use of the different mercury exposure indicators. OBJECTIVE: The aim of the this paper was to correctly select biological media and sampling time and to understand the toxic kinetics of mercury for assessment of accurate biological monitoring. RESULTS: It was confirmed that mercury in blood (B-Hg) is a good indicator of recent exposure, while urinary mercury (U-Hg) indicates current exposure when mercury reaches the renal steady state. B-Hg values are greatly influenced by fish consumption, while the variables influencing U-Hg values are amalgam fillings, commercial gamma-globulin preparations, vaccines, topical remedies, environmental pollution and hobbies, occupational exposure and, partly, fish consumption. The speciation of mercury (Hg0, Hg++, methylmercury and ethylmercury) in biological media, should provide additional and important information in evaluating mercury toxicity. CONCLUSION: It was stressed that the appropriate choice of exposure indicators has to take account of the different variability factors and the characteristics of the toxic kinetics of mercury. The results of biological monitoring must be compared with references values, which are generally in the order of several micrograms/g creatinine, and limit values such as ACGIH BEI (U-Hg 35 micrograms/g creatinine and B-Hg 15 micrograms/l) or the DFG BAT (U-Hg 100 micrograms/l and B-Hg 25 micrograms/l).

[Evaluation of the dose of mercury in exposed and control subjects]. / Valutazione delle dosi di mercurio negli esposti e nei controlli.

OBJECTIVES: The aim of this paper was to analyse the concentrations of HgU and HgB in three different groups: 122 workers exposed, 18 workers formerly exposed and 196 subjects not occupationally or environmentally exposed to mercury. METHODS: All the subjects filled out a questionnaire concerning personal data, lifestyle, occupational or non-occupational exposure to Hg and medical history. The amalgam fillings area was measured by a standardised method. RESULTS: Urinary mercury excretion was significantly greater in the group of the exposed workers respect to the group of subjects not occupationally exposed (Median value of 8.3 micrograms/g creatinine and the 5 degrees and 95 degrees percentile respectively of 2.66 e 23.50 micrograms/g creatinine against Median value of 1.2 micrograms/g creatinine and the 5 degrees and 95 degrees percentile respectively of 0.18 and 5.42 micrograms/g creatinine). U-Hg in formerly exposed workers were comparable to U-Hg in non-occupationally exposed subjects, with a median value of 1.6 micrograms/g creatinine. B-Hg values were similar in the three groups: the median value was 3.1 micrograms/l in the non-occupationally exposed, 4.0 micrograms/l in the exposed workers and 3.9 micrograms/l in the past exposed. These value were not significantly different. Among the considered variables (amalgam fillings, fish consumption, age, sex, alcohol intake, chewing-gum and smoking) dental amalgam and fish consumption were significantly related with the Hg urinary excretion and the B-Hg levels. This is particularly true considering the subjects altogether: for the exposed workers, indeed, the occupational exposure was the most relevant variable. CONCLUSIONS: The results of the present research confirmed that the U-Hg excretion in non-occupationally exposed subjects is influenced by amalgam dental fillings. Furthermore, in our study Hg urinary excretion was significantly related with fish consumption. This fact can be explained, according to several recent experimental human and animal trials, considering that methylmercury contained in fish is partially converted, through breakage of the carbon-Hg bond, into Hg inorganic forms, which accumulate in the kidney and have a urinary excretion pathway.

Rechallenging subjects with occupational asthma due to toluene diisocyanate (TDI), after long-term removal from exposure.

OBJECTIVES: Aims of this study were to define (1) whether toluene diisocyanate (TDI) bronchial hyper-responsiveness persists in subjects with occupational asthma after long-term cessation of exposure; (2) whether evolution of specific bronchial TDI sensitization and symptoms and functional abnormalities of asthma were coincident, and (3) the determinants at the time of diagnosis of patients' outcome. METHODS: Twenty-five nonatopic spray painters with occupational asthma due to TDI were re-examined 58 +/- 7 (46-73) months after removal from exposure. On both examinations, the severity of asthmatic symptoms and the need for antiasthma treatment over the past 12 months were graded and lung function tests, measurement of airway responsiveness to methacholine (PD(20)), circulating total IgE and TDI-HSA specific IgE, skin tests with common inhalant allergens and specific bronchial challenge with TDI were carried out. RESULTS: Seven subjects were still TDI-reactors and 18 lost reactivity to it. All persistent reactors had still asthma and their symptom score, medication score, FEV(1), PD(20) and serum IgE were unchanged between assessments. In the 18 subjects no longer responsive to TDI, 8 had still features of asthma: their symptom and medication score had improved significantly, but FEV(1), PD(20) and serum IgE had not significantly changed; the other ten patients no longer reactors to TDI were also asymptomatic and their PD(20) had become normal. The duration of symptomatic exposure to TDI was the only feature at diagnosis that differentiated patients with persistent TDI airway hyper-responsiveness and asthma from those who were no longer responsive to TDI but still asthmatic and those who were no longer responsive to TDI and no longer asthmatic (4 +/- 1.6; 2.1 +/- 0.8; 0.6 +/- 0.3 years, respectively; p < 0.001). CONCLUSION: our study demonstrates that airway sensitization to TDI and symptoms and functional airway abnormalities of asthma can persist for years after cessation of exposure and may have different outcome. If avoidance of the offending agent takes place within few months after the development of symptoms, remission of asthma and of TDI bronchial hyper-responsiveness can occur, whereas waiting for years makes it too late to cure asthma and, in the end, to reverse specific sensitization.

MDR 1 activation is the predominant resistance mechanism selected by vinblastine in MES-SA cells.

Single-step selection with vinblastine was performed in populations of the human sarcoma cell line MES-SA, to assess cellular mechanisms of resistance to the drug and mutation rates via fluctuation analysis. At a stringent selection with 20 nM vinblastine, resulting in 5-6 logs of cell killing, the mutation rate was 7 x 10(-7)per cell generation. Analysis of variance supported the hypothesis of spontaneous mutations conferring vinblastine resistance, rather than induction of adaptive response elements. Surviving clones displayed a stable multidrug resistance phenotype over a 3-month period. All propagated clones demonstrated high levels of resistance to vinblastine and paclitaxel, and lower cross-resistance to doxorubicin and etoposide. Activation of MDR 1 gene expression and P-glycoprotein function was demonstrable in all clones. No elevation was found in the expression of the mrp gene, the LRP-56 major vault protein and beta-tubulin isotypes (M40, beta4, 5beta, and beta9) in these mutants. We conclude that initial-step resistant mechanism in these vinblastine-selected mutants commonly arises from a stochastic mutation event with activation of the MDR 1 gene.

Hepatobiliary and pancreatic complications of ascariasis in children: a study of seven cases.

OBJECTIVES: This study presents seven cases of severe hepatobiliary and pancreatic complications of ascariasis in children. The authors describe the clinical, laboratory, and imaging findings, as well as the patients' clinical evolution. METHODS: These cases were studied within a period of approximately 1 year and included children younger than 11 years (mean age, 4.4 years). The authors reviewed their medical history and evaluated the results of their main diagnostic examinations. RESULTS: All of the patients had vomiting, abdominal pain, pallor, and abdominal distension at presentation. Passage of Ascaris lumbricoides in stool occurred in five cases, emesis with worms in three, fever in three, and hepatomegaly in two. Five patients had pancreatitis, of which two were necrohemorrhagic and one had pseudocyst of the pancreas. In three patients, A. lumbricoides was present in the pancreatic duct. Two patients had hepatic abscess (28.6%), and one of them also had cholangitis. One of the patients with pancreatitis also had signs of cholecystitis at presentation. CONCLUSIONS: Ultrasonography was the imaging diagnostic method of choice and demonstrated the presence of A. lumbricoides in the biliary and the pancreatic ducts, as well as signs of pancreatitis, cholecystitis, and hepatic abscess. Endoscopic retrograde cholangiopancreatography, used to confirm the diagnosis, was a fundamental procedure in the treatment, allowing the removal of worms from the biliary duct in four of seven patients.