Noise-induced hearing loss and combined noise and vibration exposure.

BACKGROUND: While there is a wide body of literature addressing noise-induced hearing loss (NIHL) and hand-arm vibration syndrome (HAVS) independently, relatively few studies have considered the combined effects of noise and vibration. These studies have suggested an increased risk of NIHL in workers with vibration white finger (VWF), though the relationship remains poorly understood. AIMS: To determine whether hearing impairment is worse in noise-exposed workers with VWF than in workers with similar noise exposures but without VWF. METHODS: The Quebec National Institute of Public Health audiometric database was used in conjunction with work-related accident and occupational diseases data from the Quebec workers' compensation board to analyse differences in audiometry results between vibration-exposed workers in the mining and forestry industries and the overall source population, and between mining and forestry workers with documented VWF and those without VWF. The International Organization for Standardization (ISO) 7029 standards were used to calculate hearing loss not attributable to age. RESULTS: 15751 vibration-exposed workers were identified in an overall source population of 59339. Workers with VWF (n = 96) had significantly worse hearing at every frequency studied (500, 1000, 2000 4000 Hz) compared with other mining and forestry workers without VWF. CONCLUSIONS: This study confirms previous findings of greater hearing loss at higher frequencies in workers with VWF, but also found a significant difference in hearing loss at low frequencies. It therefore supports the association between combined noise and hand-arm vibration (HAV) exposure and NIHL.

A meta-analysis of the efficacy and safety of unboosted atazanavir compared with ritonavir-boosted protease inhibitor maintenance therapy in HIV-infected adults with established virological suppression after induction.

OBJECTIVES: Treatment simplification involving induction with a ritonavir (RTV)-boosted protease inhibitor (PI) replaced by a nonboosted PI (i.e. atazanavir) has been shown to be a viable option for long-term antiretroviral therapy. To evaluate the clinical evidence for this approach, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating efficacy and safety in patients with established virological suppression. METHODS: Several databases were searched without limits on time or language. Searches of conferences were also conducted. RCTs were included if they compared a PI/RTV regimen to unboosted atazanavir, after induction with PI/RTV. The meta-analysis was conducted using a random effects model for the proportion achieving virological suppression (i.e. HIV RNA < 50 and <400 HIV-1 RNA copies/mL), CD4 cell counts, lipid levels and liver function tests. Dichotomous outcomes were reported as risk ratios (RRs) and continuous outcomes as mean differences (MDs). RESULTS: Five studies (n = 1249) met the inclusion criteria. The meta-analysis demonstrated no statistically significant difference in efficacy (i.e. HIV RNA < 50 copies/mL) between PI/RTV and unboosted atazanavir [RR = 1.04; 95% confidence interval (CI) 0.99 to 1.10], with no heterogeneity. Findings were similar in a subanalysis of studies where atazanavir/RTV was the only PI/RTV used during induction. Additional efficacy results support these findings. A significant reduction in total cholesterol (P < 0.00001), triglycerides (P = 0.0002), low-density lipoprotein (LDL) cholesterol (P = 0.009) and hyperbilirubinaemia (P = 0.02) was observed with unboosted atazanavir vs. PI/RTV. CONCLUSIONS: The meta-analysis demonstrated that switching patients with virological suppression from an RTV-boosted PI to unboosted atazanavir leads to improvements in safety (i.e. blood parameter abnormalities) without sacrificing virological efficacy.

Design and implementation of a randomized crossover study of valproic acid and antiretroviral therapy to reduce the HIV reservoir.

BACKGROUND: HIV reservoirs represent the major obstacles for eradication and are defined as a cell type that allows persistence of replication-competent HIV in patients on optimal long-term antiretroviral therapy (HAART). Several pilot clinical trials have been implemented to assess the value of experimental therapy to reduce reservoir size or eradicate HIV. In order to eradicate HIV, valproic acid was used as a new strategy to increase viral gene expression in the nucleus of infected cells with the expectation of generating a direct cell death or destruction by nearby cytotoxic cells. Previous pilot studies using VPA have showed conflicting results on the ability of VPA to reduce the size of HIV reservoirs. PURPOSE: As the role of VPA on HIV reservoirs remains unclear, we conducted a multicenter clinical trial with a specific study design to obtain optimal information on reservoir changes while exposing the smallest number of individuals to the experimental medication. METHOD: To this aim, a randomized, crossover design with 2 different treatment durations was implemented. By doubling the therapeutic period in one study arm, we were in a position to assess the impact of an extended duration of VPA on the size of the HIV reservoir and to evaluate the duration of treatment effects upon VPA withdrawal in the other arm. However, limitations for this type of study design included the logistical complexity of 2 uneven study arms and longer study duration. CONCLUSION: Despite the absence of demonstrable impact of VPA on reservoir size, such crossover study design should be considered in the early stage testing of novel HIV therapeutics targeted to reduce reservoir size or eradicate HIV.

Valproic acid in association with highly active antiretroviral therapy for reducing systemic HIV-1 reservoirs: results from a multicentre randomized clinical study.

OBJECTIVES: Conflicting results have been reported regarding the ability of valproic acid (VPA) to reduce the size of HIV reservoirs in patients receiving suppressive highly active antiretroviral therapy (HAART). In a randomized multicentre, cross-over study, we assessed whether adding VPA to stable HAART could potentially reduce the size of the latent viral reservoir in CD4 T cells of chronically infected patients. METHODS: A total of 56 virologically suppressed patients were randomly assigned either to receive VPA plus HAART for 16 weeks followed by HAART alone for 32 weeks (arm 1; n = 27) or to receive HAART alone for 16 weeks and then VPA plus HAART for 32 weeks (arm 2; n = 29). VPA was administered at a dose of 500 mg twice a day (bid) and was adjusted to the therapeutic range. A quantitative culture assay was used to assess HIV reservoirs in CD4 T cells at baseline and at weeks 16 and 48. RESULTS: No significant reductions in the frequency of CD4 T cells harbouring replication-competent HIV after 16 and 32 weeks of VPA therapy were observed. In arm 1, median (range) values of IU per log(10) billion (IUPB) cells were 2.55 (range 1.20-4.20), 1.80 (range 1.0-4.70) and 2.70 (range 1.0-3.90; P = 0.87) for baseline, week 16 and week 48, respectively. In arm 2, median values of IUPB were 2.55 (range 1.20-4.65), 1.64 (range 1.0-3.94) and 2.51 (range 1.0-4.48; P = 0.50) for baseline, week 16 and week 48, respectively. CONCLUSIONS: Our study demonstrates that adding VPA to stable HAART does not reduce the latent HIV reservoir in virally suppressed patients.

Treatment durability, effectiveness, and safety with atazanavir/ritonavir-based HAART regimen in treatment-naïve HIV-infected patients.

PURPOSE: To describe the durability of treatment, virological and immunological response, and safety of an atazanavir/ritonavir (ATV/RTV)-based highly active antiretroviral therapy (HAART) regimen in treatment-naïve HIV-infected patients. METHODS: This was a multicentre retrospective study. Medical charts of antiretroviral-na'i've HIV-infected adults who initiated ATV/RTV (300/100 mg) from January 2004 to December 2007 in 10 Canadian clinics were reviewed. Data were collected from time of ATV/RTV treatment initiation until discontinuation of ATV. Durability of treatment and time to virological response were estimated with Kaplan-Meier functions. Change in viral load, CD4 cell counts, and lipid parameters were assessed with linear regression analyses. RESULTS: 176 patients were enrolled, 153 (86.9%) were male, and the majority (52.3%) were 40 to 54 years old. Duration of observation ranged from 1.6 to 56 months. The mean (SE) durability of treatment was 33.5 (0.7) months. There were 37 (21.0%) patients who discontinued ATV/ RTV, among whom 18 (10.2%) discontinued due to toxicity, suboptimal virological response, loss to follow-up, or death. The mean (SE) time to HIV viral load of <50 and <400 copies/mL was 6.6 (0.4) and 4.3 (0.3) months, respectively. At 96 weeks of treatment, least squares mean (LSM) estimated change in log10(HIV copies/mL) was -2.94 (P < .001) and +245 cells/mL (P < .001) for CD4 cell count. A significant LSM increase in HDL-C of 0.24 mmol/L (P = .007 for trend over time) was also observed; total cholesterol, triglycerides, and LDL-C increased over time but their change did not reach statistical significance. The most frequently reported adverse event was increased bilirubin (16.5%). CONCLUSIONS: ATV/RTV-based first-line HAART regimen demonstrated durability and effectiveness and was well tolerated in treatment-naïve HIV-infected patients.

Effect of antiretroviral therapy on HIV-1 genetic evolution during acute infection.

The rapid evolution of HIV-1 is a major obstacle to viral eradication. Early antiretroviral therapy (ART) during primary HIV-1 infection could limit viral diversity. Eighteen patients recently infected with HIV-1 were selected. Nine initiated ART soon after enrolment and nine remained untreated. Replication-competent (RC) viruses were quantified at baseline and after one year of follow-up. Viral diversity in the C2V5 envelope region was evaluated from plasma, peripheral blood mononuclear cells (PBMCs), and cell culture at both time points. The amount of RC virus in the treated group declined (median -5.42 infectious units per million [IUPM]) while it remained stable or increased in the untreated group (median +0.87 IUPM). At one year post infection, we observed a significant increase in diversity for the C2V5 (+0.150%) region, specifically in the hypervariable loops V4 (+0.73%) and V5 (+0.77%), in the untreated group. More importantly, viral diversity did not significantly increase in treated individuals during the first year post infection. Genetic diversity during primary infection remains low through the first year of infection. Early treatment could contribute to a decrease in RC viruses from PBMCs and to limitation of viral diversification in the viral reservoir. These findings may have relevance for the rational design of specific immunotherapeutic strategies.

Long-term efficacy and safety of fosamprenavir plus ritonavir versus lopinavir/ritonavir in combination with abacavir/lamivudine over 144 weeks.

PURPOSE: The KLEAN study extension assessed the long-term efficacy and safety of fosamprenavir-ritonavir (FPV/r) and lopinavir-ritonavir (LPV/r), both administered with abacavir/lamivudine (ABC/3TC) fixed dose combination, over 144 weeks. METHODS: KLEAN was an open-label, noninferiority study that randomised antiretroviral-naïve patients to FPV/r twice daily (bid) or LPV/r bid with ABC/3TC once daily (qd). Patients with a viral load of <400 copies/mL at Week 48 were eligible to participate in the KLEAN study extension (up to 144 weeks) and continued with their previously randomised therapy. RESULTS: The KLEAN study extension (48 to 144 weeks) randomized 199 patients. The proportion of TLOVR responders (HIV-1 RNA <50 copies/mL) at Week 144 was 73% and 60% in the FPV/r and LPV/r arms, respectively. The proportion of TLOVR responders (<50 copies/mL) was the same irrespective of baseline HIV-1 RNA (>100,000 or 100,000 copies/mL). The Week 144 median (interquartile range) change from baseline CD4+ cell count was 300 (236-433) cells/mm3 and 335 (225-444) cells/mm3 in the FPV/r and LPV/r arms, respectively. Diarrhea was the most frequently reported adverse event. A small proportion of patients (FPV/r, 13%; LPV/r, 9%) discontinued study medication due to adverse events. Three patients (FPV/r, 1; LPV/r, 2) experienced virological failure between Week 48 and Week 144. CONCLUSION: The findings of the KLEAN study extension (48 to 144 weeks) support durable viral suppression with both FPV/r and LPV/r treatment regimens when used in combination with ABC/3TC irrespective of viral load at baseline. Both regimens were well tolerated and had similar safety profiles.

A randomized herd-level field study of dietary interactions with monensin on milk fat percentage in dairy cows.

This field trial evaluated the effects of dietary supplementation with 16 mg/kg (based on total dry matter intake) of monensin sodium on bulk tank milk fat percentage (MFP) of commercial dairy herds. Interactions between monensin and nutritional factors on MFP were studied. The trial was conducted in 47 Holstein dairy herds in Québec, Canada, between November 2005 and May 2006. The herd was the unit of interest. Enrolled herds were followed for a 7-mo period. Monensin treatment was randomly allocated in a crossover design where monensin was supplemented to the lactating dairy cow diet for a consecutive 12-wk period. Twenty-four herds were allocated to monensin treatment for the first period of trial, and 23 herds were allocated for the second period. Diet composition and ration physically effective particle level were collected every 8 wk. Milk fat percentage data were retrieved from weekly bulk tank measures. Data were analyzed in linear mixed models using repeated measures within herd where MFP was considered the outcome variable. In addition to the main effect of monensin treatment, the following covariates were forced a priori into all statistical models: treatment period, weekly herd mean parity, and weekly herd mean days in milk. The majority of herds were fed a total mixed ration (n = 29) and were housed in tie-stalls (n = 42). Monensin significantly decreased bulk tank MFP by 0.12 percentage points. The reduction of MFP associated with monensin was larger for herds having a diet high (>39.7%) in nonfiber carbohydrates, having a low level of physically effective particles in ration (>45.0%; >or=8 mm), and not feeding dry hay as first meal in the morning. Significant interactions between monensin and nutritional factors on bulk tank MFP were related to nonfiber carbohydrate and fiber concentrations in the diet.

Longitudinal assessment of changes in HIV-specific effector activity in HIV-infected patients starting highly active antiretroviral therapy in primary infection.

Both the magnitude and breadth of HIV-specific immunity were evaluated longitudinally on samples collected from six subjects starting highly active antiretroviral therapy (HAART) preseroconversion (group 1), 11 recently infected subjects starting HAART postseroconversion (group 2), five subjects starting HAART in the second half of the first year of infection (group 3), and six persons starting treatment in the chronic phase of infection (group 4). HIV-specific immunity was measured by IFN-gamma ELISPOT, detecting the frequency of cells responding to a panel of HLA-restricted HIV-1 peptides. Intracellular cytokine staining was used to detect the frequency of HIV-1 Gag p55-specific CD4(+) and CD8(+) T cells in a subset of participants. The magnitude and breadth of HIV-specific responses persisted in all group 1 subjects and in 5 of 11 (45%) group 2 subjects. Both of these parameters declined in 6 of 11 (55%) group 2 and in all group 3 and 4 individuals. All persons who maintained detectable numbers of HIV-1 Gag p55-specific CD4(+) and CD8(+) T cells after starting HAART preserved the intensity and breadth of their HIV-specific effector response. Our results show that HIV-specific immunity can be preserved even if HAART is initiated beyond the acute phase of infection.

Calciphylaxis: seven new cases.

BACKGROUND: Calciphylaxis is a rare condition occurring most frequently in patients with end-stage renal disease (ESRD). It is characterized by vascular calcifications with a large variety of skin lesions. Even though this entity was first reported almost 50 years ago, the pathogenesis is still not well understood. OBJECTIVE: Having retrieved seven new cases from a single tertiary care hospital, the disease occurs probably more frequently than reported until now. The potential mechanism of action in this disease is discussed, particularly the hypercoagulability state. We also review potential treatments described in the literature. METHODS: Seven patients with calciphylaxis that occurred at the Hôtel-Dieu hospital between 1992 and 1998 were identified and their case histories reviewed and analyzed. CONCLUSION: Although hyperparathyroidism and imbalance of calcium-phosphorus homeostasis are paramount for calciphylaxis to occur, other mechanisms must be involved because the disease manifests itself in only a minority of ESRD patients. As the majority were under anticoagulation therapy and as we found abnormalities of the coagulation pathway in one patient, we suggest emphasizing these phenomena in the future. Along with evaluation of putative risk factors (abnormalities of the calcium:phosphate axis, diabetes), a detailed evaluation of the coagulation system should be done in every patient with calciphylaxis until more data are available.

[A new family intervention method]. / Méthode novatrice d'intervention auprès des familles.

PROBLEM BEING ADDRESSED: Family medicine residents have difficulty developing the complex skills needed to work with families. OBJECTIVE OF PROGRAM: To develop an educational program to teach family medicine residents at Laval University a new type of family intervention technique, based on the systems approach, using a practical and interactive method. MAIN COMPONENTS OF PROGRAM: Using Brien's systematic planning model, the authors developed and tested a series of six interactive workshops on three themes. The first theme aims to motivate residents by showing them why it is important to use a systems approach with their patients. The second theme explores a family situation in an individual interview. The third enables residents to conduct a family interview. The whole program has been tested and evaluated. All of the materials needed to teach these skills are contained in a trainer's guide and a video cassette. CONCLUSION: This educational program's originality lies in its combination of the systems approach and interactive training for residents. The program could easily be presented as a continuing medical education activity.

Longitudinal fracture of the sacrum: case report.

A 51-year-old woman was involved in a motor vehicle crash, sustaining multiple injuries including a longitudinal displaced burst fracture of the sacrum associated with neurologic deficits and fractures of the pelvis. A computed tomographic scan was valuable in properly identifying the extent of the sacral fracture. Because of the neurologic deficits and displacement of the sacral fracture, decompression of the sacral canal and attempted reduction of the sacral fracture and fixation of the pelvic fracture were performed. The patient's neurologic deficits improved, and at last follow-up examination she was ambulating without assistance.

Predictors of chlamydial infection and gonorrhea among patients seen by private practitioners.

OBJECTIVE: To identify the predictors of chlamydial infection and gonorrhea among patients tested by general practitioners. DESIGN: Prospective study. SETTING: General private practice, family planning and abortion clinic, adolescent clinic, sexually transmitted disease (STD) clinic and community health clinic in downtown Montreal. PATIENTS: The 2856 patients were included because of symptoms compatible with an STD, a history of sexual contact with a person known or suspected to have chlamydial infection, a history of a nonexclusive sexual relationship or presentation for an abortion. MEASURES: Patient information was obtained by the attending physician on a standard form. Enzyme immunoassay (EIA) for Chlamydia trachomatis and culture for Neisseria gonorrhoeae were performed on cervical (female) or urethral (male) samples. Stepwise logistic regression was used to identify the predictors of infection. RESULTS: The EIA results were positive in 11.1% of the cases and the culture results in 2.3%. Among the males chlamydial infection was independently associated with low age (odds ratio [OR] = 0.88 per year), heterosexuality (OR = 4.99), urethral discharge (OR = 3.74) and the absence of a history of gonorrhea (OR = 0.51). Gonorrhea was associated with urethral discharge (OR = 24.3) and homosexuality (OR = 3.68). Among the females chlamydial infection was associated with low age (OR = 0.79 per year), a history of sexual contact with a person known to have chlamydial infection (OR = 2.30), multiple sexual partners in the previous 12 months (OR = 1.60) and a reason for the test other than screening purposes (OR = 0.60). Gonorrhea was associated with a reason other than screening (OR = 0.24) and low age (OR = 0.74 per year). Among the patients tested for screening purposes age was the only significant predictor of chlamydial infection (OR = 0.79 per year), and the prevalence of gonorrhea was 0.4%. The actual rate of chlamydial infection was 11.8% among the patients younger than 25 years, 5.7% among those 25 to 34 years and 0.6% among those over 34. CONCLUSIONS: Age alone can be used as a criterion to screen for chlamydial infection among asymptomatic patients without a history of sexual contact with a person known or suspected to have such infection and with a history of a nonexclusive relationship. The prevalence in our population justifies screening people up to 34 years of age.

Suppression of immunoglobulin production by germinal centre HNK-1+ CD3+ cells.

Germinal centre T cells co-expressing HNK-1 antigen have little lytic activity against NK targets (K562 cells). In order to determine whether these cells regulate B cell function, they were purified from human tonsils by panning on anti-HNK-1 antibody coated Petri dishes and co-cultured with autologous and allogeneic tonsillar T and B cells in the presence of pokeweed mitogen. At the end of 7 days of culture, supernatants were assayed for immunoglobulin concentration by ELISA. A dose-dependent suppression of both IgG and IgM production was demonstrated at ratios from 1:125 to 1:16 of HNK-1+ cells to B cells, but enhancement was observed at very low ratios (less than 1:500) or ratios exceeding 1:16 in some tonsil preparations. Similar results were obtained with peripheral blood HNK-1+ cells but without enhancement in some cases at the extremes of HNK-1+ cells to B cell ratios. The suppression was not MHC-restricted. These preliminary experiments indicate that germinal centre HNK-1+ cells may be intrafollicular suppressor cells.

A study of foot disease of dairy cattle in quebec.

A 12 month survey of the different diseases of the digital region of dairy cattle was conducted in the province of Quebec in order to determine the relation between the frequency of the main digital lesions and different factors involved.Sole ulcer, white zone disease and erosion of the bulb represented 88.6% of all the lesions. The majority of the cases were recorded during the pasture season. An initial peak of prevalence was found in two year old heifers but cows were mainly affected between the ages of five to eight years. Sixty-six percent of the lesions appeared during the first three months of lactation.

[Prenatal diagnosis of a cardiac tumor resembling Bourneville's tuberous sclerosis]. / Diagnostic anténatal d'une tumeur cardiaque évocatrice d'une sclérose tubéreuse de Bourneville.

The antenatal diagnosis of a tumour of the heart after 32 weeks of amenorrhoea made us think Bourneville's tuberous sclerosis. This is a familial condition that had not been noted before and which was confirmed after the birth. The diagnosis and prognostic problems that arise when such tumours are discovered in the heart are considered.

A critical review of the biomechanical stress analysis of the human femur.

The objective of this paper is to present a critical review of the mechanical behaviour of the human femur with particular emphasis on the determination of the internal stress distribution under the action of a variety of forces resulting from daily living activities. For attaining such a goal, knowledge of the applied forces in combination with the internal structure and the mechanical properties of the material of the femur is needed. The whole work is divided into four parts. In the first two parts a brief description of the structure and the mechanical properties of the cortical and cancellous bones of the femur determined from the tension, compression, shear, bending, torsion and impact tests takes place. The third part deals with the analysis of the joint and muscle forces acting on the femur. In the fourth part the mathematical and experimental methods for the determination of the stress distribution in the femur are presented in detail. The mathematical methods include use of the beam theory and finite elements, while the experimental methods incorporate the brittle and photoelastic coatings, the strain gauges and the two- and three-dimensional photoelasticity. Finally, an analysis of the strength characteristics of the femur from the point of view of fracture mechanics is undertaken.

[Postparturient hemoglobinuria in a Quebec dairy herd (author's transl)]. / Hémoglobinurie puerpérale dans un troupeau laitier du Québec.

Postparturient hemoglobinuria in a Quebec dairy herdA case of post parturient hemoglobinuria which occurred in a Quebec dairy herd is reported. Anemia and hypophosphoremia were present in many animals without any clinical signs, while others were showing severe signs of hemoglobinuria. History, diagnostic techniques and treatment are discussed.

[Production of colicins V and V2 in vitro and in vivo. Study of their inhibitory action on phagocytosis by peritoneal macrophages]. / Production de colicines V et V2 in vitro et in vivo. étude de leur action inhibitrice sur la phagocytose par des macrophages péritonéaux.

In recent years, a possible relationship between pathogenicity and colicinogeny in some Escherichia coli colicin V-producing strains had been inferred. In our laboratory, we have elaborated a simple in vitro method for the production of colicin V free of large, non dialyzable macromolecules and presumably of bacterial endotoxin. This allows study of the effects of colicin V in vivo without an undesirable added physiological response of the experimental animal to endotoxin. All the Col V+ strains we have studied displayed a greater ability to survive in the peritoneal cavity of mice than the Col V- strains. Also, we have detected colicin V in peritoneal fluids of agonizing mice injected with Col V+ strains. Phagocytosis by peritoneal macrophages seemed to be inhibited in vitro in the presence of colicin V. Colicin V is not toxic in vivo in low concentration, after intraperitoneal or intravenous injection but it may favor the multiplication and the invasiveness of the strains that produce it.