Mixed acid-base disorders, hydroelectrolyte imbalance and lactate production in hypercapnic respiratory failure: the role of noninvasive ventilation

Background

Hypercapnic Chronic Obstructive Pulmonary Disease (COPD) exacerbation in patients with comorbidities and multidrug therapy is complicated by mixed acid-base, hydro-electrolyte and lactate disorders. Aim of this study was to determine the relationships of these disorders with the requirement for and duration of noninvasive ventilation (NIV) when treating hypercapnic respiratory failure.

Methods

Sixty-seven consecutive patients who were hospitalized for hypercapnic COPD exacerbation had their clinical condition, respiratory function, blood chemistry, arterial blood gases, blood lactate and volemic state assessed. Heart and respiratory rates, pH, PaO₂ and PaCO₂ and blood lactate were checked at the 1st, 2nd, 6th and 24th hours after starting NIV.

Results

Nine patients were transferred to the intensive care unit. NIV was performed in 11/17 (64.7%) mixed respiratory acidosis–metabolic alkalosis, 10/36 (27.8%) respiratory acidosis and 3/5 (60%) mixed respiratory-metabolic acidosis patients (p = 0.026), with durations of 45.1±9.8, 36.2±8.9 and 53.3±4.1 hours, respectively (p = 0.016). The duration of ventilation was associated with higher blood lactate (p<0.001), lower pH (p = 0.016), lower serum sodium (p = 0.014) and lower chloride (p = 0.038). Hyponatremia without hypervolemic hypochloremia occurred in 11 respiratory acidosis patients. Hypovolemic hyponatremia with hypochloremia and hypokalemia occurred in 10 mixed respiratory acidosis–metabolic alkalosis patients, and euvolemic hypochloremia occurred in the other 7 patients with this mixed acid-base disorder.

Conclusions

Mixed acid-base and lactate disorders during hypercapnic COPD exacerbations predict the need for and longer duration of NIV. The combination of mixed acid-base disorders and hydro-electrolyte disturbances should be further investigated.     

Bronchial responsiveness is related to increased exhaled NO (FE(NO)) in non-smokers and decreased FE(NO) in smokers

Rationale

Both atopy and smoking are known to be associated with increased bronchial responsiveness. Fraction of nitric oxide (NO) in the exhaled air (FE_NO), a marker of airways inflammation, is decreased by smoking and increased by atopy. NO has also a physiological bronchodilating and bronchoprotective role.

Objectives

To investigate how the relation between FE_NO and bronchial responsiveness is modulated by atopy and smoking habits.

Methods

Exhaled NO measurements and methacholine challenge were performed in 468 subjects from the random sample of three European Community Respiratory Health Survey II centers: Turin (Italy), Gothenburg and Uppsala (both Sweden). Atopy status was defined by using specific IgE measurements while smoking status was questionnaire-assessed.

Main Results

Increased bronchial responsiveness was associated with increased FE_NO levels in non-smokers (p = 0.02) and decreased FE_NO levels in current smokers (p = 0.03). The negative association between bronchial responsiveness and FE_NO was seen only in the group smoking less <10 cigarettes/day (p = 0.008). Increased bronchial responsiveness was associated with increased FE_NO in atopic subjects (p = 0.04) while no significant association was found in non-atopic participants. The reported interaction between FE_NO and smoking and atopy, respectively were maintained after adjusting for possible confounders (p-values<0.05).

Conclusions

The present study highlights the interactions of the relationship between FE_NO and bronchial responsiveness with smoking and atopy, suggesting different mechanisms behind atopy- and smoking-related increases of bronchial responsiveness.     

Impaired Chemosensitivity of Mouse Dorsal Raphe Serotonergic Neurons Overexpressing Serotonin 1A (Htr1a) Receptors

Background

Serotonergic system participates in a wide range of physiological processes and behaviors, but its role is generally considered as modulatory and noncrucial, especially concerning life-sustaining functions. We recently created a transgenic mouse line in which a functional deficit in serotonin homeostasis due to excessive serotonin autoinhibition was produced by inducing serotonin 1A receptor (Htr1a) overexpression selectively in serotonergic neurons (Htr1a raphe-overexpressing or Htr1a^RO mice). Htr1a^RO mice exhibit episodes of autonomic dysregulation, cardiovascular crises and death, resembling those of sudden infant death syndrome (SIDS) and revealing a life-supporting role of serotonergic system in autonomic control. Since midbrain serotonergic neurons are chemosensitive and are implicated in arousal we hypothesized that their chemosensitivity might be impaired in Htr1a^RO mice.

Principal findings

Loose-seal cell-attached recordings in brainstem slices revealed that serotonergic neurons in dorsal raphe nucleus of Htr1a^RO mice have dramatically reduced responses to hypercapnic challenge as compared with control littermates. In control mice, application of 9% CO₂ produced an increase in firing rate of serotonergic neurons (0.260±0.041 Hz, n = 20, p = 0.0001) and application of 3% CO₂ decreased their firing rate (−0.142±0.025 Hz, n = 17, p = 0.0008). In contrast, in Htr1a^RO mice, firing rate of serotonergic neurons was not significantly changed by 9% CO₂ (0.021±0.034 Hz, n = 16, p = 0.49) and by 3% CO₂ (0.012±0.046 Hz, n = 12, p = 0.97).

Conclusions

Our findings support the hypothesis that chemosensitivity of midbrain serotonergic neurons provides a physiological mechanism for arousal responses to life-threatening episodes of hypercapnia and that functional impairment, such as excessive autoinhibition, of midbrain serotonergic neuron responses to hypercapnia may contribute to sudden death.     

Nitrosative and oxidative stresses contribute to post-ischemic liver injury following severe hemorrhagic shock: the role of hypoxemic resuscitation

Purpose

Hemorrhagic shock and resuscitation is frequently associated with liver ischemia-reperfusion injury. The aim of the study was to investigate whether hypoxemic resuscitation attenuates liver injury.

Methods

Anesthetized, mechanically ventilated New Zealand white rabbits were exsanguinated to a mean arterial pressure of 30 mmHg for 60 minutes. Resuscitation under normoxemia (Normox-Res group, n = 16, PaO₂ = 95–105 mmHg) or hypoxemia (Hypox-Res group, n = 15, PaO₂ = 35–40 mmHg) followed, modifying the FiO₂. Animals not subjected to shock constituted the sham group (n = 11, PaO₂ = 95–105 mmHg). Indices of the inflammatory, oxidative and nitrosative response were measured and histopathological and immunohistochemical studies of the liver were performed.

Results

Normox-Res group animals exhibited increased serum alanine aminotransferase, tumor necrosis factor - alpha, interleukin (IL) -1β and IL-6 levels compared with Hypox-Res and sham groups. Reactive oxygen species generation, malondialdehyde formation and myeloperoxidase activity were all elevated in Normox-Res rabbits compared with Hypox-Res and sham groups. Similarly, endothelial NO synthase and inducible NO synthase mRNA expression was up-regulated and nitrotyrosine immunostaining increased in animals resuscitated normoxemically, indicating a more intense nitrosative stress. Hypox-Res animals demonstrated a less prominent histopathologic injury which was similar to sham animals.

Conclusions

Hypoxemic resuscitation prevents liver reperfusion injury through attenuation of the inflammatory response and oxidative and nitrosative stresses.     

Mouse allergen, lung function, and atopy in Puerto Rican children

Objective

To examine the relation between mouse allergen exposure and asthma in Puerto Rican children.

Methods

Mus m 1, Der p 1, Bla g 2, and Fel d 1 allergens were measured in dust samples from homes of Puerto Rican children with (cases) and without (controls) asthma in Hartford, CT (n = 449) and San Juan (SJ), Puerto Rico (n = 678). Linear or logistic regression was used for the multivariate analysis of mouse allergen (Mus m 1) and lung function (FEV₁ and FEV₁/FVC) and allergy (total IgE and skin test reactivity (STR) to ≥1 allergen) measures.

Results

Homes in SJ had lower mouse allergen levels than those in Hartford. In multivariate analyses, mouse allergen was associated with higher FEV₁ in cases in Hartford (+70.6 ml, 95% confidence interval (CI) = 8.6–132.7 ml, P = 0.03) and SJ (+45.1 ml, 95% CI =  −0.5 to 90.6 ml, P = 0.05). In multivariate analyses of controls, mouse allergen was inversely associated with STR to ≥1 allergen in non-sensitized children (odds ratio [OR] for each log-unit increment in Mus m 1 = 0.7, 95% CI = 0.5–0.9, P<0.01). In a multivariate analysis including all children at both study sites, each log-increment in mouse allergen was positively associated with FEV₁ (+28.3 ml, 95% CI = 1.4–55.2 ml, P = 0.04) and inversely associated with STR to ≥1 allergen (OR for each log-unit increment in Mus m 1 = 0.8, 95% CI = 0.6–0.9, P<0.01).

Conclusions

Mouse allergen is associated with a higher FEV₁ and lower odds of STR to ≥1 allergen in Puerto Rican children. This may be explained by the allergen itself or correlated microbial exposures.     

Lung function is associated with arterial stiffness in children

Background

In older adults, an independent association exists between impaired lung function and cardiovascular disease. This interaction might be related to the effects of aging and/or smoking. In order to explore possible childhood antecedents to this association, we hypothesized that decreased lung function and vascular stiffness might be related, in early life.

Objective

To determine the relationship between lung function and carotid augmentation index (AIx), a measure of vascular stiffness, in 8-year old children.

Methods

Data on brachial blood pressure, lung function (FEV₁, FVC, FEV₁/FVC, obtained by spirometry) and carotid AIx75 (AIx standardised to an arbitrary heart rate of 75 beats per minute, obtained by applanation tonometry) was available in 249 community-based 8-year old children. These healthy children had been subjects in a randomised controlled trial of two interventions (omega-3 fatty acid supplementation and house-dust mite avoidance) to prevent asthma. Smoking in pregnancy and childhood environmental tobacco smoke (ETS) exposure was prospectively collected by questionnaire. The association between lung function and carotid AIx75 was assessed in multivariate models that included sex, height, smoking status during pregnancy, ETS exposure and randomisation groups (house dust mite avoidance and dietary intervention) as covariates.

Results

In the fully adjusted models, Carotid AIx75 was independently associated with FEV1 (standardised β = −0.17,b = −6.72, partial R² = .02, p = 0.03), FVC (standardised β = −0.29, b = −9.31, partial R² = 0.04, p<0.001) and FEV1/FVC (standardised β = .13, b = 18.4, partial R² = 0.02, p = 0.04).

Conclusion

Lower lung volumes are associated with increased vascular stiffness at an early age. The interaction between lung function and vascular stiffness may thus represent more than just age-related alterations in both the pulmonary and vascular systems.     

Unique environmental effects on physical activity participation: a twin study

Background

The health benefits of regular physical activity are well established. However, the relative contribution of heritable and environmental factors to physical activity participation remains controversial. Using a cut-point of 60 minutes of total activity per week, data from the GenomEUtwin project revealed consistent genetic influence on physical activity participation in 37,051 twin pairs from seven countries. We hypothesized that the heritability of physical activity participation would be attenuated using the CDC/ACSM recommended minimum threshold of 150 minutes of moderate intensity activity per week.

Methods

Data were obtained from 1,389 twin pairs from the community-based University of Washington Twin Registry. Twin similarity in physical activity participation using both cut-points was analyzed using tetrachoric correlations and structural equation modeling in all same-sex pairs.

Results

Correlations were higher in monozygotic (r_MZ = 0.43, 95% CI = 0.33–0.54) than dizygotic pairs (r_DZ = 0.30, 95% CI = 0.12–0.47) using the 60 minute cut-point. However, differences were attenuated using the 150 minute standard (r_MZ = 0.30, 95% CI = 0.20–0.40; r_DZ = 0.25, 95% CI = 0.07–0.42). Using the lower cut-point, the best fitting model of twin resemblance only included additive genetics and unique environment, with a heritability of 45%. In contrast, using the higher threshold, the best fitting model included the common and unique environment, with the unique environment contributing 72% of the variance.

Conclusion

Unique environment factors provide the strongest influence on physical activity participation at levels recommended for health benefits.     

The effectiveness of online cognitive behavioral treatment in routine clinical practice

Context

Randomized controlled trails have identified online cognitive behavioral therapy as an efficacious intervention in the management of common mental health disorders.

Objective

To assess the effectiveness of online CBT for different mental disorders in routine clinical practice.

Design

An uncontrolled before-after study, with measurements at baseline, posttest, 6-week follow-up, and 1-year follow-up.

Participants & Setting

1500 adult patients (female: 67%; mean age: 40 years) with a GP referral for psychotherapy were treated at a Dutch online mental health clinic for symptoms of depression (n = 413), panic disorder (n = 139), posttraumatic stress (n = 478), or burnout (n = 470).

Interventions

Manualized, web-based, therapist-assisted CBT, of which the efficacy was previously demonstrated in a series of controlled trials. Standardized duration of treatment varied from 5 weeks (online CBT for Posttraumatic stress) to 16 weeks (online CBT for Depression).

Main Outcome Measures

Validated self-report questionnaires of specific and general psychopathology, including the Beck Depression Inventory, the Impact of Event Scale, the Panic Disorder Severity Scale-Self Report, the Oldenburg Burnout Inventory, and the Depression Anxiety Stress Scales.

Results

Treatment adherence was 71% (n = 1071). Study attrition was 21% at posttest, 33% at 6-week FU and 65% at 1-year FU. Mixed-model repeated measures regression identified large short-term reductions in all measures of primary symptoms (d = 1.9±0.2 to d = 1.2±0.2; P<.001), which sustained up to one year after treatment. At posttest, rates of reliable improvement and recovery were 71% and 52% in the completer sample (full sample: 55%/40%). Patient satisfaction was high.

Conclusions

Results suggest that online therapist-assisted CBT may be as effective in routine practice as it is in clinical trials. Although pre-treatment withdrawal and long-term outcomes require further study, results warrant continued implementation of online CBT.     

Allergic asthmatics show divergent lipid mediator profiles from healthy controls both at baseline and following birch pollen provocation

Background

Asthma is a respiratory tract disorder characterized by airway hyper-reactivity and chronic inflammation. Allergic asthma is associated with the production of allergen-specific IgE and expansion of allergen-specific T-cell populations. Progression of allergic inflammation is driven by T-helper type 2 (Th2) mediators and is associated with alterations in the levels of lipid mediators.

Objectives

Responses of the respiratory system to birch allergen provocation in allergic asthmatics were investigated. Eicosanoids and other oxylipins were quantified in the bronchoalveolar lumen to provide a measure of shifts in lipid mediators associated with allergen challenge in allergic asthmatics.

Methods

Eighty-seven lipid mediators representing the cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 (CYP) metabolic pathways were screened via LC-MS/MS following off-line extraction of bronchoalveolar lavage fluid (BALF). Multivariate statistics using OPLS were employed to interrogate acquired oxylipin data in combination with immunological markers.

Results

Thirty-two oxylipins were quantified, with baseline asthmatics possessing a different oxylipin profile relative to healthy individuals that became more distinct following allergen provocation. The most prominent differences included 15-LOX-derived ω-3 and ω-6 oxylipins. Shared-and-Unique-Structures (SUS)-plot modeling showed a correlation (R² = 0.7) between OPLS models for baseline asthmatics (R²Y[cum] = 0.87, Q²[cum] = 0.51) and allergen-provoked asthmatics (R²Y[cum] = 0.95, Q²[cum] = 0.73), with the majority of quantified lipid mediators and cytokines contributing equally to both groups. Unique structures for allergen provocation included leukotrienes (LTB₄ and 6-trans-LTB₄), CYP-derivatives of linoleic acid (epoxides/diols), and IL-10.

Conclusions

Differences in asthmatic relative to healthy profiles suggest a role for 15-LOX products of both ω-6 and ω-3 origin in allergic inflammation. Prominent differences at baseline levels indicate that non-symptomatic asthmatics are subject to an underlying inflammatory condition not observed with other traditional mediators. Results suggest that oxylipin profiling may provide a sensitive means of characterizing low-level inflammation and that even individuals with mild disease display distinct phenotypic profiles, which may have clinical ramifications for disease.     

Elevated peripheral visfatin levels in narcoleptic patients

Objective

Narcolepsy is a severe sleep disorder that is characterized by excessive daytime sleepiness, cataplexies and a tendency towards obesity. Recent discoveries indicate that the major pathophysiology is a loss of hypocretin (orexin) producing neurons due to immunologically mediated degeneration. Visfatin is a recently described proinflammatory adipokine. It is identical to the immune modulating pre-B-cell colony enhancing factor (PBEF). Our study examines the hypothesis that visfatin levels are altered in narcoleptic patients.

Methods

For the analysis, a total of n = 54 patients (n = 18 males and n = 36 females) with the diagnosis of narcolepsy according to DSM-IV and the International Classification of Sleep Disorders were examined (BMI mean 30.3±5.5, age mean 52.5±16.1 years). As a control group 39 unrelated (n = 12 males and n = 27 females) healthy volunteers with no sleep disorder according to DSM-IV were included (BMI mean 28.5±4.6, age mean 51.1±13.6 years). Peripheral visfatin levels were measured using a commercial enzyme immunoassay kit with a measurement range from 0.1–1000 ng/ml. Narcolepsy symptoms, severity and frequency of symptoms as well as the total duration of various aspects of the symptomatology were assessed by unstructured and structured clinical interviews in including the Stanford Center for Narcolepsy Sleep Inventory.

Results

Circulating visfatin was found to be significantly increased in HLA DR2 positive narcoleptic patients compared to controls.

Conclusion

Taken together, our results add to the evidence of disturbed immunological regulation in patients with narcolepsy.     

Resting and post bronchial challenge testing carbon dioxide partial pressure in individuals with and without asthma

Objective

There is conflicting evidence about resting carbon dioxide levels in asthmatic individuals. We wanted to determine if transcutaneously measured carbon dioxide levels prior and during bronchial provocation testing differ according to asthma status reflecting dysfunctional breathing.

Methods

We investigated active firefighters and policemen by means of a validated questionnaire on respiratory symptoms, spirometry, bronchial challenge testing with methacholine (MCT) and measurement of transcutaneous blood carbon dioxide partial pressure (PtcCO₂) at rest prior performing spirometry, one minute and five minutes after termination of MCT. A respiratory physician blinded to the PtcCO₂ results assigned a diagnosis of asthma after reviewing the available study data and the files of the workers medical screening program.

Results

The study sample consisted of 128 male and 10 female individuals. Fifteen individuals (11%) had physician-diagnosed asthma. There was no clinically important difference in median PtcCO₂ at rest, one and five minutes after recovery from MCT in asthmatics compared to non-asthmatics (35.6 vs 35.7 mmHg, p = 0.466; 34.7 vs 33.4 mmHg, p = 0.245 and 37.4 vs 36.4 mmHg, p = 0.732). The median drop in PtcCO₂ during MCT and the increase after MCT was lower in asthmatics compared to non-asthmatics (0.1 vs 3.2 mmHg, p = 0.014 and 1.9 vs 2.9 mmHg, p = 0.025).

Conclusions

PtcCO₂ levels at rest prior and during recovery after MCT do not differ in individuals with or without physician diagnosed asthma. The fall and subsequent increase in PtcCO₂ levels are higher in non-asthmatics than in asthmatics and seems to be related with increased number of respiratory maneuvers during MCT.     

Neighborhood socioeconomic deprivation and mortality: NIH-AARP diet and health study

Purpose

Residing in deprived areas may increase risk of mortality beyond that explained by a person''s own SES-related factors and lifestyle. The aim of this study was to examine the relation between neighborhood socioeconomic deprivation and all-cause, cancer- and cardiovascular disease (CVD)-specific mortality for men and women after accounting for education and other important person-level risk factors.

Methods

In the longitudinal NIH-AARP Study, we analyzed data from healthy participants, ages 50–71 years at study baseline (1995–1996). Deaths (n = 33831) were identified through December 2005. Information on census tracts was obtained from the 2000 US Census. Cox models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for quintiles of neighborhood deprivation.

Results

Participants in the highest quintile of deprivation had elevated risks for overall mortality (HR_men = 1.17, 95% CI: 1.10, 1.24; HR_women = 1.13, 95% CI: 1.05, 1.22) and marginally increased risk for cancer deaths (HR_men = 1.09, 95% CI: 1.00, 1.20; HR_women = 1.09, 95% CI: 0.99, 1.22). CVD mortality associations appeared stronger in men (HR = 1.33, 95% CI: 1.19, 1.49) than women (HR = 1.18, 95% CI: 1.01, 1.38). There was no evidence of an effect modification by education.

Conclusion

Higher neighborhood deprivation was associated with modest increases in all-cause, cancer- and CVD-mortality after accounting for many established risk factors.     

Associations between XPD Asp312Asn polymorphism and risk of head and neck cancer: a meta-analysis based on 7,122 subjects

Background

To investigate the association between XPD Asp312Asn polymorphism and head and neck cancer risk through this meta-analysis.

Methods

We performed a meta-analysis of 9 published case-control studies including 2,670 patients with head and neck cancer and 4,452 controls. An odds ratio (OR) with a 95% confidence interval (CI) was applied to assess the association between XPD Asp312Asn polymorphism and head and neck cancer risk.

Results

Overall, no significant association between XPD Asp312Asn polymorphism and head and neck cancer risk was found in this meta-analysis (Asn/Asn vs. Asp/Asp: OR = 0.95, 95%CI = 0.80–1.13, P = 0.550, P _{heterogeneity} = 0.126; Asp/Asn vs. Asp/Asp: OR = 1.11, 95%CI = 0.99–1.24, P = 0.065, P _{heterogeneity} = 0.663; Asn/Asn+Asp/Asn vs. Asp/Asp: OR = 1.07, 95%CI = 0.97–1.19, P = 0.189, P _{heterogeneity} = 0.627; Asn/Asn vs. Asp/Asp+Asp/Asn: OR = 0.87, 95%CI = 0.68–1.10, P = 0.243, P _{heterogeneity} = 0.089). In the subgroup analysis by HWE, ethnicity, and study design, there was still no significant association detected in all genetic models.

Conclusions

This meta-analysis demonstrates that XPD Asp312Asn polymorphism may not be a risk factor for developing head and neck cancer.     

Association of HbA1c values with mortality and cardiovascular events in diabetic dialysis patients. The INVOR study and review of the literature

Background

Improved glycemic control reduces complications in patients with diabetes mellitus (DM). However, it is discussed controversially whether patients with diabetes mellitus and end-stage renal disease benefit from strict glycemic control.

Methods

We followed 78 patients with DM initiating dialysis treatment of the region of Vorarlberg in a prospective cohort study applying a time-dependent Cox regression analysis using all measured laboratory values for up to more than seven years. This resulted in 880 HbA_1c measurements (with one measurement every 3.16 patient months on average) during the entire observation period. Non-linear P-splines were used to allow flexible modeling of the association with mortality and cardiovascular disease (CVD) events.

Results

We observed a decreased mortality risk with increasing HbA_1c values (HR = 0.72 per 1% increase, p = 0.024). Adjustment for age and sex and additional adjustment for other CVD risk factors only slightly attenuated the association (HR = 0.71, p = 0.044). A non-linear P-spline showed that the association did not follow a fully linear pattern with a highly significant non-linear component (p = 0.001) with an increased risk of all-cause mortality for HbA_1c values up to 6–7%. Causes of death were associated with HbA_1c values. The risk for CVD events, however, increased with increasing HbA_1c values (HR = 1.24 per 1% increase, p = 0.048) but vanished after extended adjustments.

Conclusions

This study considered the entire information collected on HbA_1c over a period of more than seven years. Besides the methodological advantages our data indicate a significant inverse association between HbA_1c levels and all-cause mortality. However, for CVD events no significant association could be found.     

Apparent temperature and air pollution vs. elderly population mortality in Metro Vancouver

Background

Meteorological conditions and air pollution in urban environments have been associated with general population and elderly mortality, showing seasonal variation.

Objectives

This study is designed to evaluate the relationship between apparent temperature (AT) and air pollution (PM_2.5) vs. mortality in elderly population of Metro Vancouver.

Methods

Statistical analyses are performed on moving sum daily mortality rates vs. moving average AT and PM_2.5 in 1-, 2-, 3-, 5-, and 7-day models for all seasons, warm temperatures above 15°C, and cold temperatures below 10°C.

Results

Approximately 37% of the variation in all-season mortality from circulatory and respiratory causes can be explained by the variation in 7-day moving average apparent temperature (r² = 0.37, p<0.001). Although the analytical results from air pollution models show increasingly better prediction ability of longer time-intervals (r² = 0.012, p<0.001 in a 7-day model), a very weak negative association between elderly mortality and air pollution is observed.

Conclusions

Apparent temperature is associated with mortality from respiratory and circulatory causes in elderly population of Metro Vancouver. In a changing climate, one may anticipate to observe potential health impacts from the projected high- and particularly from the low-temperature extremes.     

A 3' UTR SNP in COL18A1 is associated with susceptibility to HBV related hepatocellular carcinoma in Chinese: three independent case-control studies

Background

Accumulated evidences indicate that single nucleotide polymorphisms (SNP) in angiogenesis and tumorigenesis related genes are associated with risk of Hepatocellular carcinoma (HCC). COL18A1 encodes the precursor of endostatin, which is a broad-spectrum angiogenesis inhibitor, and we speculate that SNPs in COL18A1 may be associated with susceptibility to HCC.

Methods and Findings

We carried out a 2-stage association study in 3 independent case-control groups in a total of 1067 chronic hepatitis B (CHB) patients and 808 hepatitis B virus (HBV) related HCC patients in Han Chinese. Four SNPs which can represent all potential functional SNPs with MAF>0.1 recorded in HapMap database were genotyped using TaqMan methods. Levels of total COL18A1 mRNA were also examined using quantitative real-time RT-PCR. We found that rs7499 located in 3′-UTR to be strongly associated with HBV related HCC (P_combined = 0.0000005, OR = 0.72, 95%CI = 0.63–0.82). COL18A1 mRNA expression was significantly decreased as the disease progressed (P = 0.000026).

Conclusion

These findings indicate that COL18A1 rs7499 may contribute to the risk of HCC in Han Chinese.     

Airway Hyperresponsiveness and Quality of Life in Western Red Cedar Asthmatics Removed from Exposure

Objectives

Most western red cedar asthmatics (WRCA) continue to have symptoms even after removal from exposure. Consequently, health-related quality of life (HRQL) is often impaired. The objective of this study was to evaluate the relationship between two measures of AHR and HRQL scores in those with WRCA.

Methods

HRQL was determined by the short form 36 (SF-36) in 46 male, non-smoking individuals with WRCA removed from exposure to western red cedar, on average, 15 years earlier. The relationships between the SF-36 total score and its eight domains with 2 indices from methacholine-stimulated airway hyperresponsiveness (the provocative concentration of methacholine causing a 20% fall in FEV₁ [PC₂₀] and bronchial reactivity index [BRI]) were analyzed by the Pearson correlation and multiple linear regression.

Results

PC₂₀ was significantly correlated with the SF-36 total score and its two domains of bodily pain and general health (r = 0.34, 0.40, 0.40, p = 0.023, 0.006, 0.006, respectively). BRI was significantly correlated with bodily pain and general health (r = −0.35, −0.42, p = 0.017, 0.004, respectively); correlations remain significant after adjusting for age, ethnicity, years since diagnosis, years since last exposure and use of inhaled corticosteroid. BRI and other measures of airway responsiveness were not associated with inhaled corticosteroids use.

Conclusions

In Western red cedar asthmatics removed from exposure, measures of airway responsiveness are associated with HRQL.     

Cardiometabolic plasticity in response to a short-term diet and exercise intervention in young Hispanic and nonHispanic white adults

Background

Young adult Mexican Americans (MA) exhibit lower insulin sensitivity (Si) than nonHispanic whites (NHW), even when controlling for fitness and adiposity. It is unclear if MA are as responsive to the same lifestyle intervention as NHW.

Objective

We developed a model to examine cardiometabolic plasticity (i.e., changes in Si and plasma lipids) in MA compared to NHW adults in response to a diet-exercise intervention.

Design

Sedentary subjects (20 NHW: 11F, 9M, 23.0 y, 25.5 kg/m²; 17 MA: 13F, 4M, 22.7 y, 25.4 kg/m²) consumed their habitual diets and remained sedentary for 7 days, after which fasting blood samples were obtained, and a 3-h intravenous glucose tolerance test (IVGTT) was performed with the insulin area under the curve (IAUC) used to estimate Si. Subjects then completed a 7-day diet/exercise intervention (diet: low saturated fat, low added sugar, high fiber; exercise: cycling, six total sessions lasting 40–45 min/session at 65% VO₂ max). Pre-intervention tests were repeated.

Results

Pre intervention IAUC was 28% higher (p<0.05) in MA (IAUC pre  =  2298 µU*180 min/mL) than in NHW (IAUC = 1795 µU*180 min/mL). Following the intervention, there was a significant reduction in IAUC in MA (29%) and NHW (32%), however, the IAUC remained higher (p<0.05) for MA (post  = 1635 µU*180 min/mL) than for NHW (post = 1211 µU*180 min/mL). Pre test plasma lipids were not different in MA compared to NHW. Plasma cholesterol and TG concentrations significantly improved in both groups, but concentrations of low density lipoprotein-cholesterol and small dense LDL particles significantly improved only in the NHW.

Conclusion

With a short-term diet-exercise intervention, the magnitude of improvements in Si and serum cholesterol and TG in Hispanics are similar to those in NHW. However, because at the outset MA were less insulin sensitive compared to NHW, within the short timeframe studied the ethnic gap in insulin sensitivity remained.     

A retrospective analysis of the haemodynamic and metabolic effects of fluid resuscitation in Vietnamese adults with severe falciparum malaria

Background

Optimising the fluid resuscitation of patients with severe malaria is a simple and potentially cost-effective intervention. Current WHO guidelines recommend central venous pressure (CVP) guided, crystalloid based, resuscitation in adults.

Methods

Prospectively collected haemodynamic data from intervention trials in Vietnamese adults with severe malaria were analysed retrospectively to assess the responses to fluid resuscitation.

Results

43 patients were studied of whom 24 received a fluid load. The fluid load resulted in an increase in cardiac index (mean increase: 0.75 L/min/m² (95% Confidence interval (CI): 0.41 to 1.1)), but no significant change in acid-base status post resuscitation (mean increase base deficit 0.6 mmol/L (95% CI: −0.1 to 1.3). The CVP and PAoP (pulmonary artery occlusion pressure) were highly inter-correlated (r_s = 0.7, p<0.0001), but neither were correlated with acid-base status (arterial pH, serum bicarbonate, base deficit) or respiratory status (PaO₂/FiO₂ ratio). There was no correlation between the oxygen delivery (DO₂) and base deficit at the 63 time-points where they were assessed simultaneously (r_s = −0.09, p = 0.46).

Conclusions

In adults with severe falciparum malaria there was no observed improvement in patient outcomes or acid-base status with fluid loading. Neither CVP nor PAoP correlated with markers of end-organ perfusion or respiratory status, suggesting these measures are poor predictors of their fluid resuscitation needs.     

X-ray repair cross-complementing group 1 (XRCC1) genetic polymorphisms and risk of childhood acute lymphoblastic leukemia: a meta-analysis

Background

Recently, there have been a number of studies on the association between XRCC1 polymorphisms and childhood acute lymphoblastic leukemia (ALL) risk. However, the results of previous reports are inconsistent. Thus, we performed a meta-analysis to clarify the effects of XRCC1 variants on childhood ALL risk.

Methods

A meta-analysis was performed to examine the association between XRCC1 polymorphisms (Arg399Gln, Arg194Trp, and Arg280His) and childhood ALL risk. We critically reviewed 7 studies with a total of 880 cases and 1311 controls for Arg399Gln polymorphism, 3 studies with a total of 345 cases and 554 controls for Arg280His polymorphism, and 6 studies with a total of 783 cases and 1180 controls for Arg194Trp polymorphism, respectively. Odds ratio (OR) and its 95% confidence interval (CI) were used.

Results

Significant association between XRCC1 Arg399Gln polymorphism and childhood ALL risk was observed in total population analyses (OR_{additive model} = 1.501, 95% CI 1.112–2.026, P_OR = 0.008; OR_{dominant model} = 1.316, 95% CI = 1.104–1.569, P_OR = 0.002) and Asian subgroup analyses (OR_{additive model} = 2.338, 95%CI = 1.254–4.359, P_OR = 0.008; OR_{dominant model} = 2.108, 95%CI = 1.498–2.967, P_OR = 0.000). No association was detected in Caucasians, Metizo and mixed populations. Ethnicity was considered as a significant source of heterogeneity in the meta-regression model. For the other two XRCC1 polymorphisms, no association with childhood ALL risk was found.

Conclusions

The meta-analysis results suggested that XRCC1 Arg399Gln polymorphism might be associated with elevated childhood ALL risk among Asian population.