Venous thromboembolism and obstruction after pacemaker implantation. - A Prospective Study of 150 Consecutive Cardiac Pacing Device Implantations

Background: Pacemaker implantation (PMI) may predispose to venous thromboembolism (VTE) and obstruction (VO). This prospective study aimed at quantifying changes in venous calibers, and at determining the incidence of symptomatic and asymptomatic VTE/VO after PMI. Further goals included an assessment of the role of transesophageal echocardiography (TEE) in the diagnosis of lead-related central venous thrombi (CVT), and determination of predictors for VTE/VO. Methods: 150 (mean age 67; 61% male) consecutive patients with first PMI were enrolled and followed for 6 months. Contrast venography was performed at baseline and 6 months after PMI to measure venous diameters, and to detect stenosis, total occlusions and thrombi. TEE was conducted in 66 patients. Based on clinical suspicion, work-up for pulmonary embolism (PE) or acute deep vein thrombosis (DVT) were performed as needed. A total of 50 cases underwent longer-term (mean 2.4 years) follow-up venography. All cases with VTE/VO during the initial 6 months, and their matched controls, were selected for a case-control study focused on possible predictive role of laboratory and patient-related factors for the development of VTE/VO. Results: 10 (7 %) patients were found to have baseline venous abnormalities (e.g. 8 obstructions). Mean venous diameters diminished significantly during the first 6 months, but no further reduction occurred in late follow-up. New VO was discovered in 19 patients (14 %; 14 stenosis, 5 total occlusions; all asymptomatic). Small non-obstructive thrombi were found in 20/140 (14 %) 6-month venograms. TEE at 6 months disclosed CVT in 6 (9 %) patients. One (0.7 %) patient had acute symptomatic upper-extremity DVT, and PE was discovered in 5/150 (3.3 %) patients during the first 6 months with no further cases thereafter. At 6 months, the total number of cases with VTE/VO amounted to 47 (31.3 %). Additionally, the later 2-year venograms (n=50) disclosed 4 (8 %) total occlusions and 1 (2 %) stenosis. In the case-control study, no parameter was predictive of venous end-points as a single variable, but there appeared to be significant clustering of traditional VTE risk-factors among the cases. Laboratory parameters showed a definite acute hypercoagulative state induced by PMI, but its degree did not predict subsequent development of VTE/VO. Conclusions: This study shows that VTE/VO is relatively common after PMI with an overall incidence of at least 30 %. Although the majority of the lesions are asymptomatic and clinically benign, cases of PE were also encountered, and totally occluded veins may hamper future upgrading or replacement of pacing system. Venous complications seem difficult to prognosticate as firm predictors were not identified from a wide range of parameters analyzed in this study, although clustering of classic VTE risk factors may be a predisposing factor. Parameters related to implantation procedure or pacing systems and the severity of implantation-induced trauma did not emerge as predictors.

Influenza in children – Diagnosis, treatment and prevention

Background: The burden of influenza on children is substantial. Although mortality rates are low, the incidence of influenza is highest in children, among whom also complications are frequent. A more accurate recognition of influenza in children could enable the rational use of antiviral drugs and help to avoid unnecessary courses of antibiotics. Limited data exists on the efficacy of oseltamivir treatment and the trivalent inactivated influenza vaccine (TIV) in children. Aims and methods: We sought for signs and symptoms that could help clinicians to diagnose influenza on clinical grounds in a case-control study in children <13 years of age. We further assessed the feasibility of different diagnostics methods during the early stage of the illness in children aged 1-3 years. The efficacy of early oseltamivir treatment (started <24h from the onset of symptoms) was evaluated in a randomized controlled trial (RCT) conducted in children 1-3 years of age, and the effectiveness of TIV to prevent laboratory-confirmed influenza was determined in a prospective, observational cohort study conducted among children aged 9 months to 3 years of age. Results: Fever was the only symptom predicting influenza in children. The sensitivity of conventionally used laboratory methods to detect influenza during the first 24h of illness was 92%. The sensitivity of the influenza rapid test in the same setting was 90% for influenza A and 25% for influenza B. Early oseltamivir treatment shortened the duration of the illness in children with influenza A by 3.5-4.0 days, but no efficacy was observed against influenza B. The effectiveness of TIV was 84% against the wellmatched influenza A, while no effectiveness against the mismatched influenza B was observed. Conclusions: Laboratory diagnostics are needed for a reliable diagnosis of influenza in children and were found sensitive already during the early stage of the illness. Early oseltamivir treatment was highly effective against influenza A, but no efficacy was seen against influenza B. TIV is effective also in young children if a good match between the vaccine and circulating strain is achieved.

Genetic polymorphisms in the Cytochrome P450 family and squamous cell carcinoma of the oral cavity, pharynx and larynx

Objective:To analyze the genetic polymorphisms of the cytochrome P450 family and their relationship with squamous cell carcinoma of the oral cavity, pharynx and larynx.Methods: We present a narrative literature review, conducted in Pubmed, Lilacs and Cochrane Databases of articles published in the last five years correlating genetic polymorphisms of the cytochrome P450 family and cancer risk in different populations worldwide.Results: We initially found 65 articles and, after selection criteria, 20 case-control studies with various populations worldwide were eligible. The most studied polymorphisms were those of CYP2E1 and CYP1A1 subfamilies. There is little about the other subfamilies. The association found between polymorphisms and cancer risk amounted to a countless number of variables, amongst them: population, selection methods, racial factors and different modes of exposure to carcinogens, genotyping methods, and nomenclature of the polymorphisms.Conclusion: so far, there is no proven link between genetic polymorphisms of cytochrome P450 family and squamous cell carcinoma of the oral cavity, pharynx and larynx relationship.

Risk factors for mortality in blunt abdominal trauma with surgical approach

ABSTRACTObjective:identify risk factors for mortality in patients who underwent laparotomy after blunt abdominal trauma.Methods:retrospective study, case-control, which were reviewed medical records of blunt trauma victims patients undergoing laparotomy, from March 2013 to January 2015, and compared the result of the deaths group with the group healed.Results:of 86 patients, 63% were healed, 36% died, and one patient was excluded from the study. Both groups had similar epidemiology and trauma mechanism, predominantly young adults males, automobilistic accident. Most cases that evolved to death had hemodynamic instability as laparotomy indication - 61% against 38% in the other group (p=0.02). The presence of solid organ injury was larger in the group of deaths - 80% versus 48% (p=0.001) and 61% of them had other associated abdominal injury compared to 25% in the other group (p=0.01). Of the patients who died 96% had other serious injuries associated (p=0.0003). Patients requiring damage control surgery had a higher mortality rate (p=0.0099). Only one of 18 patients with isolated hollow organ lesion evolved to death (p=0.0001). The mean injury score of TRISS of cured (91.70%) was significantly higher than that of deaths (46.3%) (p=0.002).Conclusion:the risk factors for mortality were hemodynamic instability as an indication for laparotomy, presence of solid organ injury, multiple intra-abdominal injuries, need for damage control surgery, serious injury association and low index of trauma score.

Polymorphism in the lymphotoxin-alpha gene, position +252 (rs909253), is not associated with preeclampsia development in Brazilian women

PURPOSE: To investigate the frequencies of polymorphic allele and genotypes for the LT-α gene, position +252 (rs909253), in Brazilian women with preeclampsia.METHODS: This is a case-control study, in which 30 women with preeclampsia, classified according to the criteria of the National High Blood Pressure Education Program, and 115 women in the control group, with at least two healthy pregnancies, were selected. Peripheral blood was collected, and DNA was extracted, followed by genotyping, using specific primers and restriction analysis. The genotypes obtained were AA, AG and GG. Statistical analysis was performed using the χ2association test. The Hardy-Weinberg Equilibrium was tested using the Haploview Program.RESULTS: The results showed no association between genotypes and preeclampsia development (χ2=2.0; p=0.4). When the AG and GG genotypes were grouped according to allele G presence or absence (genotype AA), the data showed that the presence of allele G was not significantly different between cases (women with preeclampsia) and controls (χ2=0.0; p=1.0). The LT-α gene polymorphism, position +252 (rs909253), seems not to be an important candidate for the development of preeclampsia. Other inflammatory genes should be researched, and studies involving gene-environment interactions should be performed, in order to reach a better understanding of the etiology of the preeclampsia.

Detection of Pathologic Changes Following Traumatic Brain Injury Using Magnetic Resonance Imaging

Background: Approximately two percent of Finns have sequels after traumatic brain injury (TBI), and many TBI patients are young or middle-aged. The high rate of unemployment after TBI has major economic consequences for society, and traumatic brain injury often has remarkable personal consequences, as well. Structural imaging is often needed to support the clinical TBI diagnosis. Accurate early diagnosis is essential for successful rehabilition and, thus, may also influence the patient’s outcome. Traumatic axonal injury and cortical contusions constitute the majority of traumatic brain lesions. Several studies have shown magnetic resonance imaging (MRI) to be superior to computed tomography (CT) in the detection of these lesions. However, traumatic brain injury often leads to persistent symptoms even in cases with few or no findings in conventional MRI. Aims and methods: The aim of this prospective study was to clarify the role of conventional MRI in the imaging of traumatic brain injury, and to investigate how to improve the radiologic diagnostics of TBI by using more modern diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) techniques. We estimated, in a longitudinal study, the visibility of the contusions and other intraparenchymal lesions in conventional MRI at one week and one year after TBI. We used DWI-based measurements to look for changes in the diffusivity of the normal-appearing brain in a case-control study. DTI-based tractography was used in a case-control study to evaluate changes in the volume, diffusivity, and anisotropy of the long association tracts in symptomatic TBI patients with no visible signs of intracranial or intraparenchymal abnormalities on routine MRI. We further studied the reproducibility of different tools to identify and measure white-matter tracts by using a DTI sequence suitable for clinical protocols. Results: Both the number and extent of visible traumatic lesions on conventional MRI diminished significantly with time. Slightly increased diffusion in the normal-appearing brain was a common finding at one week after TBI, but it was not significantly associated with the injury severity. Fractional anisotropy values, that represent the integrity of the white-matter tracts, were significantly diminished in several tracts in TBI patients compared to the control subjects. Compared to the cross-sectional ROI method, the tract-based analyses had better reproducibility to identify and measure white-matter tracts of interest by means of DTI tractography. Conclusions: As conventional MRI is still applied in clinical practice, it should be carried out soon after the injury, at least in symptomatic patients with negative CT scan. DWI-related brain diffusivity measurements may be used to improve the documenting of TBI. DTI tractography can be used to improve radiologic diagnostics in a symptomatic TBI sub-population with no findings on conventional MRI. Reproducibility of different tools to quantify fibre tracts vary considerably, which should be taken into consideration in the clinical DTI applications.

Aspergillus fumigatus from normal and condemned carcasses with airsacculitis in commercial poultry

Carcass inspection is important for the detection of certain diseases and for monitoring their prevalence in slaughterhouses. The objective of this study was to assess the occurrence of aspergillosis caused by Aspergillus fumigatus in commercial poultry, through mycological and histopathological diagnosis, and to verify the causal association between the aspergillosis diagnosis criteria and condemnation due to airsacculitis in broilers through a case-control study. The study was carried out with 380 samples. Lungs were collected from broilers that were condemned (95) or not condemned (285) due to airsacculitis directly from the slaughter line. Forty-six (12%) lung samples were positive for A. fumigatus in mycological culture. Among all samples, 177 (46.6%) presented histopathological alterations, with necrotic, fibrinous, heterophilic pneumonia; heterophilic pneumonia and lymphoid hyperplasia being the most frequent. Out of the 380 lungs analyzed, 65.2% (30) showed histopathological alterations and isolation of fungi. The statistical analysis (McNemar's chi-square test) indicated a significant association between the presence of histopathological lesions and the isolation of A. fumigatus. Mycological cultivation and histopathological diagnosis increase the probability of detecting pulmonary alterations in birds condemned by the Final Inspection System, which suggests that such diagnostic criteria can improve the assessment and condemnation of birds affected by airsacculitis.

Factors associated with the development of renal complications of diabetes mellitus in São Paulo city

The incidence of diabetic end-stage renal failure (ESRF) varies worldwide and risk factors have been demonstrated in several populations. The objective of the present study was to identify possible factors associated with the risk of development of ESRF in patients with diabetes mellitus (DM). Two groups of diabetic subjects were included in a case-control study: 1) one group was submitted to renal replacement therapies, attending dialysis centers in São Paulo city and 2) the same number of controls without clinical nephropathy (two negative dipstick tests for urine protein), matched for duration of DM, were obtained from an outpatient clinic. A standardized questionnaire was used by a single investigator and additional data were obtained from the medical records of the patients. A total of 290 diabetic patients from 33 dialysis centers were identified, and 266 questionnaires were considered to contain reliable information. Male/female ratios were 1.13 for ESRF and 0.49 for the control group. A higher frequency of men was observed in the ESRF group when compared with controls (53 vs 33%, P<0.00001), although logistic regression analysis did not confirm an association of gender and diabetic nephropathy (DN). Similar proportions of non-white individuals were found for both groups. Patients with insulin-dependent diabetes mellitus (IDDM) were less common than patients with non-insulin-dependent diabetes mellitus (NIDDM), particularly in the control group (3.4 vs 26.3%, P<0.00001, for controls and ESRF patients, respectively); this type of DM was associated with a higher risk of ESRF than NIDDM, as determined by univariate analysis or logistic regression (OR = 4.1). Hypertension by the time of the DM diagnosis conferred a 1.4-fold higher risk of ESRF (P = 0.04), but no difference was observed concerning the presence of a family history. Association between smoking and alcohol habits and increased risk was observed (OR = 4.5 and 5.9, respectively, P<0.001). A 2.4-fold higher risk of ESRF was demonstrated in patients with multiple hospitalizations due to DM decompensation, which suggested poor metabolic control. Photocoagulation and neuropathy were found to be strongly associated with ESRF but not with macrovascular disease. Data collected in our country reinforce the higher risk attributable to IDDM and the association between hypertension and the progression of DN. Indirect evidence for an association with metabolic control is also suggested

Clinical assessment of the effect of digital filtering on the detection of ventricular late potentials

Ventricular late potentials are low-amplitude signals originating from damaged myocardium and detected on the body surface by ECG filtering and averaging. Digital filters present in commercial equipment may interfere with the ability of arrhythmia stratification. We compared 40-Hz BiSpec (BI) and classical 40- to 250-Hz band-pass Butterworth bidirectional (BD) filters in terms of impact on time domain variables and diagnostic properties. In a transverse retrospective age-adjusted case-control study, 221 subjects with sinus rhythm without bundle branch block were divided into three groups after signal-averaged ECG acquisition: GI (N = 40), clinically normal controls, GII (N = 158), subjects with coronary heart disease without sustained monomorphic ventricular tachycardia (SMVT), and GIII (N = 23), subjects with heart disease and documented SMVT. Conventional variables analyzed from vector magnitude data after averaging to 0.3 µV final noise were obtained by application of each filter to the averaged signal, and evaluated in pairs by numerical comparison and by diagnostic agreement assessment, using conventional and optimized thresholds of normality. Significant differences were found between BI and BD variables in all groups, with diagnostic results showing significant disagreement between both filters [kappa value of 0.61 (P<0.05) for GII and 0.31 for GIII (P = NS)]. Sensitivity for SMVT was lower with BI than with BD (65.2 vs 91.3%, respectively, P<0.05). Filters provided significantly different numerical and diagnostic results and the BI filter showed only limited clinical application to risk stratification of ventricular arrhythmia.

Prenatal and perinatal risk factors for bipolar disorder

Bipolar disorder (BPD) is a severe mental disorder associated with considerable morbidity and mortality. Prenatal insults have been shown to be associated with later development of mental disorders and there is a growing interest in the potential role of prenatal and perinatal risk factors in the development of BPD. The aims of this thesis were to describe the overall study design of the Finnish Prenatal Study of Bipolar Disorders (FIPS-B) and demographic characteristics of the sample. Furthermore, it was aimed to examine the association of parental age, parental age difference, perinatal complications and maternal smoking during pregnancy with BPD. This thesis is based on FIPS-B, a nested case-control study using several nationwide registers. The cases included all people born in Finland between January 1st 1983 and December 31st 1998 and diagnosed with BPD according to the Finnish Hospital Discharge Register (FHDR) before December 31st 2008. Controls for this study were people who were without BPD, schizophrenia or diagnoses related to these disorders, identified from the Population Register Centre (PRC), and matched two-fold to the cases on sex, date of birth (+/- 30 days), and residence in Finland on the first day of diagnosis of the matched case. Conditional logistic regression models were used to examine the association between risk factors and BPD. This study included 1887 BPD cases and 3774 matched controls. The mean age at diagnosis was 19.3 years and females accounted for 68% of the cases. Mothers with the lowest educational level had the highest odds of having BPD in offspring. Being born in Eastern and Southern region of Finland increased the odds of having BPD later in life. A U-shaped distribution of odds ratio was observed between paternal age and BPD in the unadjusted analysis. Maternal age and parental age difference was not associated with BPD. Birth by planned caesarean section was associated with increased odd of BPD. Smoking during pregnancy was not associated with BPD in the adjusted analyses. Region of birth and maternal educational level were associated with BPD. Both young and old father’s age was associated with BPD. Most perinatal complications and maternal smoking during pregnancy were not associated with BPD. The findings of this thesis, considered together with previous literature, suggest that the pre- and perinatal risk factor profile varies among different psychiatric disorders.

Association of the 894G>T polymorphism of the endothelial constitutive nitric oxide synthase gene with unstable angina

The 894G>T polymorphism of the endothelial constitutive nitric oxide synthase gene consists of the substitution of a guanine base by a thymine at the 894th nucleotide of the gene. An association of this polymorphism with acute coronary syndromes has been described, only when in combination with other polymorphisms of this gene. The aim of the present study was to search for an association between this polymorphism and unstable angina in a southern Brazilian population. In a case-control study, 156 patients (group 1 (N = 83): unstable angina, group 2 (N = 73): stable angina) were genotyped by PCR and digestion of the product. Univariate analysis demonstrated that the minimal luminal diameter and the degree of stenosis of the culprit lesion differed between groups (P = 0.006 and 0.005, respectively). In addition, the frequencies of the T allele and of the T allele carriers (combined TT and TG genotypes) were significantly higher in the group with unstable angina (41.6 vs 28.8%; P = 0.025, Pearson chi-square test, and 73.5 vs 45.2%; P = 0.001, Pearson chi-square test, respectively). Multivariate logistic regression showed that the frequency of the T allele carriers was the only variable with a predictive value for unstable angina, when controlled for the other variables (6.1 (95% CI = 2.55-14.43); P < 0.001). Thus, in a homogenous group of patients, the endothelial constitutive nitric oxide synthase 894G>T polymorphism was associated with unstable angina. We suggest that this polymorphism may be a genetic risk factor for unstable angina.

Polymorphisms in genes MTHFR, MTR and MTRR are not risk factors for cleft lip/palate in South Brazil

Non-syndromic cleft lip and palate (CL/P) occurs due to interaction between genetic and environmental factors. Abnormalities in homocysteine metabolism may play a role in its etiology due to polymorphisms in genes involved in this pathway. Because of the involvement of MTHFR, MTR and MTRR genes with folate metabolism and the evidence that maternal use of folic acid in early pregnancy reduces the risk for CL/P, we evaluated the influence of their polymorphisms on the etiology of CL/P through a case-control study. The analyses involved 114 non-syndromic phenotypically white children with clefts (case) and 110 mothers, and 100 non-affected (control) children and their mothers. The polymorphisms 677C>T of MTHFR, 2756A>G of MTR, and 66A>G of MTRR genes were analyzed by PCR-RFLP. Allelic frequencies did not differ from other studies conducted on white populations for MTHFR 677T allele (0.35) and for MTR 2756G allele (0.17), but MTRR 66G allele frequency (0.35) was lower than observed elsewhere. The genotypic distribution of the 677C>T polymorphisms under study did not show significant differences between CL/P patients, their mothers and controls. These results suggest that the alterations of folate metabolism related to these polymorphisms are not involved in clefting in the population under study.

Is there an association between T102C polymorphism of the serotonin receptor 2A gene and urinary incontinence?

The regulation of bladder function is influenced by central serotonergic modulation. Several genetic polymorphisms related to serotonin control have been described in the literature. T102C polymorphism of the serotonin receptor 2A gene (5-HT2A) has been shown to be associated with certain diseases such as non-fatal acute myocardial infarction, essential hypertension, and alcoholism. In the present study, we examined the association between 5-HT2A gene polymorphism and urinary incontinence in the elderly. A case-control study was performed in 298 elderly community dwellers enrolled in the Gravataí-GENESIS Project, Brazil, which studies gene-environmental interactions in aging and age-related diseases. Clinical, physical, biochemical, and molecular analyses were performed on volunteers. 5-HT2A genotyping was determined by PCR-RFLP techniques using the HpaII restriction enzyme. The subjects had a mean age of 68.05 ± 6.35 years (60-100 years), with 16.9% males and 83.1% females. The C allele frequency was 0.494 and the T allele frequency was 0.506. The CC genotype frequency was 21.78%, the CT genotype frequency was 55.24% and the TT genotype frequency was 22.98%. We found an independent significant association between the TT genotype (35.7%) and urinary incontinence (OR = 2.06, 95%CI = 1.16-3.65). Additionally, urinary incontinence was associated with functional dependence and systolic hypertension. The results suggest a possible genetic influence on urinary incontinence involving the serotonergic pathway. Further investigations including urodynamic evaluation will be performed to better explain our findings.

Anxiety and depression symptoms in recurrent painful renal lithiasis colic

Several studies have reported that symptoms of anxiety and depression are significantly associated with diseases characterized by painful crises. However, there is little information about the psychological aspects of recurrent painful episodes of renal stone disease. Our objective was to evaluate the association of symptoms of anxiety, depression and recurrent painful renal colic in a case-control study involving 64 subjects (32 cases/32 controls) matched for age and sex. Cases were outpatients with a confirmed diagnosis of nephrolithiasis as per their case history, physical examination, image examination and other laboratory exams. Patients had a history of at least two episodes within a 3-year period, and were currently in an intercrisis interval. The control group consisted of subjects seen at the Ophthalmology Outpatient Clinic of this University Hospital with only eye refraction symptoms, and no other associated disease. Symptoms of anxiety were evaluated by the State-Trait Anxiety Inventory and symptoms of depression by the Beck Depression Inventory. Statistically significant differences were observed between patients with nephrolithiasis and controls for anxiety state (P = 0.001), anxiety trait (P = 0.005) and symptoms of depression (odds ratio = 3.74; 95%CI = 1.31-10.62). The Beck Depression Inventory showed 34.5% of respondents with moderate and 6% with severe levels of depression. There was a significant linear correlation between symptoms of anxiety (P = 0.002) and depression (P < 0.001) and the number of recurrent colic episodes (anxiety-state: P = 0.016 and anxiety-trait: P < 0.001). These data suggest an association between recurrent renal colic and symptoms of both anxiety and depression.

Association of polymorphisms at the ADIPOR1 regulatory region with type 2 diabetes and body mass index in a Brazilian population with European or African ancestry

Association studies between ADIPOR1 genetic variants and predisposition to type 2 diabetes (DM2) have provided contradictory results. We determined if two single nucleotide polymorphisms (SNP c.-8503G>A and SNP c.10225C>G) in regulatory regions of ADIPOR1 in 567 Brazilian individuals of European (EA; N = 443) or African (AfA; N = 124) ancestry from rural (quilombo remnants; N = 439) and urban (N = 567) areas. We detected a significant effect of ethnicity on the distribution of the allelic frequencies of both SNPs in these populations (EA: -8503A = 0.27; AfA: -8503A = 0.16; P = 0.001 and EA: 10225G = 0.35; AfA: 10225G = 0.51; P < 0.001). Neither of the polymorphisms were associated with DM2 in the case-control study in EA (SNP c.-8503G>A: DM2 group -8503A = 0.26; control group -8503A = 0.30; P = 0.14/SNP 10225C>G: DM2 group 10225G = 0.37; control group 10225G = 0.32; P = 0.40) and AfA populations (SNP c.-8503G>A: DM2 group -8503A = 0.16; control group -8503A = 0.15; P = 0.34/SNP 10225C>G: DM2 group 10225G = 0.51; control group 10225G = 0.52; P = 0.50). Similarly, none of the polymorphisms were associated with metabolic/anthropometric risk factors for DM2 in any of the three populations, except for HDL cholesterol, which was significantly higher in AfA heterozygotes (GC = 53.75 ± 17.26 mg/dL) than in homozygotes. We conclude that ADIPOR1 polymorphisms are unlikely to be major risk factors for DM2 or for metabolic/anthropometric measurements that represent risk factors for DM2 in populations of European and African ancestries.