BODY COMPOSITION CHANGES IN MEN WITH HIV/HCV COINFECTION, HIV MONOINFECTION, AND HCV MONOINFECTION.

Context: Both human immunodeficiency virus (HIV) infection and hepatitis C virus (HCV) infection represent systemic diseases that may develop metabolic complications, thus HIV/HCV coinfection metabolic changes need to be depicted. Objective: We aimed to evaluate the body composition changes in patients with either HIV and HCV monoinfections or HIV/HCV coinfection. Methods: 123 young men divided into three groups: 41 with HIV/HCV coinfection, 42 with HIV-monoinfection, and 40 with HCV-monoinfection were evaluated for total and regional bone and soft tissue body composition assessments using a Dual-energy X-ray absorptiometry (DXA) and were compared with 40 healthy men with age and body mass index similar to the study groups. To detect sarcopenia, we calculated the appendicular limbs' lean mass index (ALMI), for obesity, we used the percent of body fat, and for lipodystrophy, we calculated the trunk/limbs index. Results: HIV/HCV coinfection is associated with a significant higher bone demineralization in all regions of interest compared to HCV or HIV monoinfections and to controls. The prevalence of bone demineralization in HIV/HCV patients was 31.7%, more frequently at lumbar spine. Fat mass and lean mass were significantly lower in HIV/HCV-coinfected patients than in controls. Lipodystrophy was found in similar percentages in all three evaluated groups (80.4% in HIV/HCV, 92.5% in HIV, and 95% in the HCV group). Sarcopenia was higher in HIV/HCV group (43.9%) and important in HCV-monoinfection group (30%). Conclusions: HIV/HCV-coinfected patients had the highest prevalence of bone demineralization, fat mass, and lean mass loss, compared to controls and to HIV and HCV monoinfections.

Linear and nonlinear parameters of heart rate variability in ischemic stroke patients.

INTRODUCTION: Cardiovascular system presents cortical modulation. Post-stroke outcome can be highly influenced by autonomic nervous system disruption. Heart rate variability (HRV) analysis is a simple non-invasive method to assess sympatho-vagal balance. OBJECTIVES: The purpose of this study was to investigate cardiac autonomic activity in ischemic stroke patients and to asses HRV nonlinear parameters beside linear ones. METHODS: We analyzed HRV parameters in 15 right and 15 left middle cerebral artery ischemic stroke patients, in rest condition and during challenge (standing and deep breathing). Data were compared with 15 age- and sex-matched healthy controls. RESULTS: There was an asymmetric response after autonomic stimulation tests depending on the cortical lateralization in ischemic stroke patients. In resting state, left hemisphere stroke patients presented enhanced parasympathetic control of the heart rate (higher values for RMSSD, pNN50 and HF in normalized units). Right hemisphere ischemic stroke patients displayed a reduced cardiac parasympathetic modulation during deep breathing test. Beside time and frequency domain, using short-term ECG monitoring, cardiac parasympathetic modulation can also be assessed by nonlinear parameter SD1, that presented strong positive correlation with time and frequency domain parameters RMSSD, pNN50, HFnu, while DFA α1 index presented negative correlation with the same indices and positive correlation with the LFnu and LF/HF ratio, indicating a positive association with the sympatho-vagal balance. CONCLUSIONS: Cardiac monitoring in clinical routine using HRV analysis in order to identify autonomic imbalance may highlight cardiac dysfunctions, thus helping preventing potential cardiovascular complications, especially in right hemisphere ischemic stroke patients with sympathetic hyperactivation.

Autonomic impairment in patients with migraine.

OBJECTIVE: Heart rate variability analysis of electrocardiogram is becoming an increasingly common method to non-invasively evaluate autonomic nervous function. The aim of the study was to investigate cardiac autonomic function in subjects with and without migraine by using 24-hour ambulatory electrocardiographic recordings. PATIENTS AND METHODS: We investigated 27 subjects with migraine (10 with migraine with aura and 17 without aura) during headache free periods and 10 age-matched healthy control subjects. The migraine was diagnosed using the International Classification of Headache Disorders 2nd Edition criteria. Beck Depression and Beck Anxiety Inventory forms were completed by all subjects. Time and frequency-domain of HRV was analyzed for two periods: diurnal and nocturnal. RESULTS: We found an increased frequency of anxiety and depressive symptoms in migraine patients, especially in migraine with aura group. The heart rate variability parameters SDNN, RMSSD, high frequency were decreased and low frequency was increased in migraine patients during night period compared with normal subjects, most affected were migraine with aura patients. During day period we found modification for SDNN, RMSSD and high frequency parameters only in migraine with aura group. CONCLUSIONS: Reduced parasympathetic activity with sympathetic predominance was found in migraine patients during the night period, most affected being migraine with aura patients.

[Takotsubo cardiomyopathy]. / Cardiomiopatia takotsubo.

Takotsubo cardiomyopathy or "heart broken syndrome" or transient apical ballooning syndrome is an increasingly reported syndrome characterized by the fact that most patients are women aged over 65 years. The most common electrocardiographic changes are ST-segment elevation and negative T waves in precordial leads. Symptoms at onset are similar to those of acute myocardial infarction; the ventricular dysfunction is shaped like a takotsubo (a Japanese pot for fishing octopus), echocardiography and ventriculography show akinesia, hipokinesia or diskinesia (ballooning) of apical segments of left ventricle and hyperkinesia of the basal; the coronary arteries are normal angiographic; the dysfunction improves rapidly within a few weeks. Its origins are unclear, there are several pathophysiological theories, most sustained is a myocardial stunning secondary catecholamine-induced excess of intense physical or mental stress. There is no clear standard of treatment. In cases evolving with hemodynamic instability the use of beta agonist agents must be avoided, aortic balloon counterpulsation is preferable. The patient prognosis is usually good, reaching maximum mortality of 8%. In rare situations were reported complications such as acute pulmonary oedema, cardiogenic shock, acute mitral regurgitation, potentially fatal arrythmias ventricular fibrillation or torsades de pointes. In Cardiology Clinic of Cardiovascular Diseases Institute "Prof. Dr. George I.M. Georgescu" Iasi were hospitalized 4 cases with Takotsubo cardiomyopathy from 2008 to 2011. Their features are presented in this paper. The difference of prognosis and treatment between Takotsubo cardiomyopathy and acute myocardial infarction require an accurate diagnosis, the clinical hypothesis result only after knowledge the clinical and paraclinical peculiarities of this pathological entity.

Association of common genetic variants with colorectal cancer risk in a Romanian sample.

Recently, several genome-wide association studies identified and validated loci at which common genetic variants influence the risk of colorectal cancer. We aimed to test the association between eight SNPs and colorectal cancer in a Romanian case-control sample. We genotyped rs10795668, rs16892766, rs3802842, rs4444235, rs4779584, rs4939827, rs6983267, and rs9929218 and we statistically tested the association with the disease. Five SNPs (rs6983267, rs4939827, rs3802842, rs4444235, rs10795668) showed an association with colon and rectal cancer. Three of them proved to be statistically significant: rs6983267 and rs4939827 risk alleles were significantly associated with rectal cancers (p = 0.031 and p = 0.004 for homozygous, p = 0.002 and p = 0.005 for heterozygous). For rs3802842 we found a greater risk for colon than rectal cancer with an OR of 2.26 (CI = 1.04-5.88, p = 0.040) for the dominant model. The rs4444235 confirmed the risk for both homozygous and heterozygous carriers, with the greatest ORs of 1.49 (CI = 0.61-3.61) for heterozygote. For rs10795668 we found an increased risk for rectum cancer vs. controls with an OR of 1.46 (CI = 0.66-3.21), and for rectum cancer vs. colon cancer (OR = 2.19; CI = 0.87-5.55). This is the first Romanian study that confirms previously-identified associations with colorectal cancer risk for five out of eight SNPs investigated and underlines the necessity of extensive replication using larger samples.

Nitrated and oxidized plasma proteins in smokers and lung cancer patients.

Cigarette smoking is a cause of lung cancer and other respiratory diseases. Oxidants either present in cigarette smoke and/or formed in the lung of smokers may trigger oxidative and nitrative damage to DNA and cellular components, contributing to carcinogenesis. We have used immunodot and Western blot analyses to measure nitrated (nitrotyrosine-containing) and oxidized (carbonyl-containing) proteins in plasma samples collected from 52 lung cancer patients and 43 control subjects (heavy and light smokers, nonsmokers with or without exposure to environmental tobacco smoke). The levels of nitrated proteins were significantly higher in lung cancer patients than in controls (P = 0.003). On the other hand, the levels of oxidized proteins were significantly higher in smokers than in nonsmokers (P < 0.001). Western-blot analyses showed the presence of two to five nitrated proteins and one oxidized protein. Using immunoprecipitation and Western-blot analyses with eight different antibodies against human plasma proteins, we identified fibrinogen, transferrin, plasminogen, and ceruloplasmin as nitrated proteins and fibrinogen as the only oxidized protein present in human plasma of lung cancer patients and smokers. Our results indicate that cigarette smoking increases oxidative stress and that during lung cancer development, formation of reactive nitrogen species results in nitration and oxidation of plasma proteins.

Lung cancer risk in nonsmokers and GSTM1 and GSTT1 genetic polymorphism.

Glutathione S-transferase (GST) polymorphism may contribute to the individual variability in detoxifying lung carcinogens. This effect might be particularly relevant at low-level exposure to environmental carcinogens, such as in nonsmokers exposed to environmental tobacco smoke (ETS). We conducted a case-control study among 122 nonsmoking lung cancer cases and 121 nonsmoking controls from eight countries. Information on environmental exposures was obtained through a personal interview. The presence of GSTM1 and GSTT1 genes was determined using multiplex PCR. GSTM1-positive samples were then analyzed for *1A and *1B polymorphism using an allele-specific amplification-PCR method. GSTM1*2 (null) individuals had an odds ratio (OR) of lung cancer of 1.5 [95% confidence interval (CI), 0.9-2.7]; the risk associated with this genotype was higher for cases with squamous and small cell carcinomas (OR, 2.3; 95% CI, 0.9-6.1) than for cases with adenocarcinomas. It was also elevated in individuals with long-term exposure to indoor wood combustion (OR, 3.1; 95% CI, 0.9-9.9), in subjects who mainly lived in a rural setting (OR, 3.6; 95% CI, 1.0-13), and in cases exposed to occupational carcinogens (OR, 10.7; 96% CI, 0.4-260) but not in subjects exposed to ETS. GSTT1*2 subjects did not show a risk of lung cancer. Our study suggests that the effect of GSTM1 polymorphism in nonsmokers is similar to that found in smokers. It does not seem to interact with ETS exposure, although we cannot exclude that it does in association with exposure to other specific environmental carcinogens.

p53 mutations and exposure to environmental tobacco smoke in a multicenter study on lung cancer.

Biomarker data may provide a way to strengthen the link between environmental tobacco smoke (ETS) exposure and lung cancer shown in epidemiological studies. We conducted a multicenter case-control study to investigate the association between ETS exposure and lung cancer in never-smokers using p53 mutations as a biomarker of tobacco-related carcinogenesis. Paraffin-embedded tissue or fresh tissue samples from 91 never-smokers and 66 smokers with histologically confirmed lung cancer and interview data about smoking habits and ETS exposure were analyzed for mutations in the p53 gene. Statistical analysis was performed using multivariate logistic regression. Among the lifelong nonsmokers, the overall mutation prevalence was 10% (nine cases). Among 48 never-smokers ever exposed to spousal ETS, 13% (six cases) showed mutations. Smokers exhibited 17 (26%) mutations. A 3-fold [odds ratio, 2.9; 95% confidence interval (CI), 1.2-7.2] increased risk of p53 mutation was observed for smokers as compared with all never-smokers combined (i.e., irrespective of ETS exposure). The increase was 4.4-fold (95% CI, 1.2-16.2) when compared with never-smokers without ETS exposure. Among never-smokers, the risk of mutation was doubled (odds ratio, 2.0; 95% CI, 0.5-8.7) for exposure to spousal ETS only, based on 6 exposed cases with mutation and 42 exposed cases without mutation. The risk was 1.5 (95% CI, 0.2-8.8) for those ever exposed to spousal or workplace ETS as compared with those never exposed to spousal or workplace ETS. For smokers, the most common mutation type was G:C to T:A transversion (31%), whereas G:C to A:T transitions were predominant among never smokers (57%). In conclusion, our study indicates a significant 3-4-fold increased risk of p53 mutation in smoking lung cancer cases, and it suggests that mechanisms of lung carcinogenesis in ETS-exposed never-smokers include mutations in the p53 gene, similar to that seen in smokers. However, the mutation patterns observed also suggest a difference between smokers and never-smokers. Clearly, additional investigations of the role of p53 mutation as a biomarker for tobacco-related carcinogenesis, including that related to ETS, are indicated.

Exposure to environmental tobacco smoke and risk of adenocarcinoma of the lung.

We conducted a case-control study of adenocarcinoma of the lung and exposure to environmental tobacco smoke (ETS) in 7 countries. We interviewed 70 cases of adenocarcinoma of the lung and 178 population or hospital controls. All subjects had smoked fewer than 400 cigarettes in their lifetimes. Ever exposure to ETS from the parents during childhood was associated with a decreased risk [odds ratio (OR) 0.6, 95% confidence interval (CI) 0.3-1.2], and there was a suggestion of a decreasing trend in risk with increasing duration of exposure. Ever exposure to ETS from the spouse was not associated with an increased risk (OR 1.0, 95% CI 0.5-1.8), while the OR of ever exposure to ETS at the workplace was 1.5 (95% CI 0.8-3.0). For both exposure sources, an increased risk was observed among the highly exposed, and the OR among those with the highest duration of exposure to ETS from the spouse or at the workplace was 1.8 (95% CI 0.5-6.2). A similar risk was estimated for current exposure to ETS from either source. Our results confirm previous reports of a weak effect of adult ETS exposure on risk of adenocarcinoma of the lung. Bias and confounding cannot be excluded as explanations for the apparent decrease in risk from childhood exposure.

4-Hydroxy-1-(3-pyridyl)-1-butanone-hemoglobin adducts as biomarkers of exposure to tobacco smoke: validation of a method to be used in multicenter studies.

Hemoglobin (Hb) adducts of 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB), a metabolite of two tobacco-specific nitrosamines [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and N'-nitrosonornicotine], were measured as biomarkers of exposure to tobacco smoke as part of a study on genetic alterations and susceptibility to lung cancer among nonsmokers. HPB-Hb adducts were measured after collection of RBCs by Ficoll gradient in six collaborating centers, release of HPB by alkaline hydrolysis from Hb, clean-up by solid-phase extraction, and analysis of an electron-capturing derivative by gas chromatography-electron capture mass spectrometry. Prior to analysis of samples from study subjects, the reproducibility of this approach was validated in blood from donors. The coefficient of variation of reproducibility of paired aliquots from five samples ranged from 7 to 25%; the within-sample reproducibilities of four and eight aliquots were 4 and 16%, respectively. The study subjects consisted of 18 smokers and 52 never-smokers. HPB-Hb adduct levels were significantly higher (P = 0.02) in smokers (26 +/- 13 fmol HPB/g Hb) than in never-smokers (20 +/- 8 fmol HPB/g Hb). There was no difference between sexes. These results suggest that the level of HPB-Hb adducts, measured using a method modified to facilitate use in multicenter studies, can be a useful biomarker of exposure to tobacco smoke.

Revealing the distinction between perception and cognition through intra-individual variability of visual evoked responses.

Searching for a method to objectively detect the cognitive activity of the brain, the variability of visual evoked responses (ER) was analysed in 75 human subjects and 10 animals. The individual ERs of a normal subject were found typically very scattered in the first approx. 120 ms after stimulation, converging at 160-220 ms and then diverging again progressively. This variability pattern (VP) is event-related and is not attributable to background noise. On the other hand, statistically significant correlation showed that in most patients, with anatomically intact visual structures but with pronounced mental troubles, the VP is absent and the ERs are randomly scattered. Based on these results we consider that the event-related variability reflects the cognition function of the subjects and that it is instrumental in evidencing the distinction between cognitive and perceptive processes. The results are further consistent with the idea that cognition implies the chaotic activity of certain neural populations and that the VP reflects this chaotic, non-repetitive, non-linear and impredictable but effective neural activity.

Comparative study of the variations of the phagocytic capacity of polymorphonuclear leukocytes and of total plasma antioxidants in patients with pneumoconioses and lung cancer.

A comparative, preliminary study of the phagocytic capacity of polymorphonuclear leukocytes, and of the total plasma antioxidants was carried out in a group of workers professionally exposed to mineral dusts and in a group of patients with lung cancer. Both groups exhibited advanced respiratory failure stages II and III. The phagocytic capacity of polymorphonuclear leukocytes was found significantly increased in workers with pneumoconioses and moderately increased in patients with lung cancer. On the other hand, the peroxides and total plasma antioxidants exhibited great individual variations. Thus in lung cancer it was observed that peroxides had a tendency to decrease and antioxidants to increase. The individual study of the variations of these three parameters might be able to differentiate the reversible from the irreversible stages of the respiratory changes.