Tobacco use in first-episode psychosis, a multinational EU-GEI study.

BACKGROUND: Tobacco is a highly prevalent substance of abuse in patients with psychosis. Previous studies have reported an association between tobacco use and schizophrenia. The aim of this study was to analyze the relationship between tobacco use and first-episode psychosis (FEP), age at onset of psychosis, and specific diagnosis of psychosis. METHODS: The sample consisted of 1105 FEP patients and 1355 controls from the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. We assessed substance use with the Tobacco and Alcohol Questionnaire and performed a series of regression analyses using case-control status, age of onset of psychosis, and diagnosis as outcomes and tobacco use and frequency of tobacco use as predictors. Analyses were adjusted for sociodemographic characteristics, alcohol, and cannabis use. RESULTS: After controlling for cannabis use, FEP patients were 2.6 times more likely to use tobacco [p ⩽ 0.001; adjusted odds ratio (AOR) 2.6; 95% confidence interval (CI) [2.1-3.2]] and 1.7 times more likely to smoke 20 or more cigarettes a day (p = 0.003; AOR 1.7; 95% CI [1.2-2.4]) than controls. Tobacco use was associated with an earlier age at psychosis onset (ß = -2.3; p ⩽ 0.001; 95% CI [-3.7 to -0.9]) and was 1.3 times more frequent in FEP patients with a diagnosis of schizophrenia than in other diagnoses of psychosis (AOR 1.3; 95% CI [1.0-1.8]); however, these results were no longer significant after controlling for cannabis use. CONCLUSIONS: Tobacco and heavy-tobacco use are associated with increased odds of FEP. These findings further support the relevance of tobacco prevention in young populations.

Lifetime psychopathology in child and adolescent offspring of parents diagnosed with schizophrenia or bipolar disorder: a 2-year follow-up study.

Having one parent diagnosed with a severe mental disorder is considered one of the main risk factors for developing that disorder in adulthood, and it also increases the risk of a wide range of mental disorders in the offspring. The aim of this study is to compare the prevalence of several psychopathological diagnoses, the presence of prodromal symptoms, and global functioning in offspring of parents with schizophrenia or bipolar disorder and in offspring of controls at baseline and 2-year follow-up. This study included 41 offspring of parents with schizophrenia, 90 offspring of parents with bipolar disorder, and 107 offspring of controls (mean age 11.7 ± 3.2 at baseline and 13.9 ± 3.2 at follow-up). The prevalence of psychopathology and comorbidity was higher in offspring of parents with schizophrenia and offspring of parents with bipolar disorder than in offspring of controls at baseline and at 2-year follow-up. Interestingly, mood disorders were more prevalent in offspring of parents with bipolar disorder and disruptive disorders were more prevalent in offspring of parents with schizophrenia. Prodromal symptoms were more frequent in offspring of parents with schizophrenia than in offspring of controls, while the offspring of parents with bipolar disorder showed an intermediate pattern. Finally, global functioning was lower in the offspring of parents with schizophrenia than the offspring of parents with bipolar disorder and the offspring of controls. Screening patients' children is clinically relevant, since, as a group, they have an elevated risk of developing a psychiatric disorder and of experiencing their first symptoms during childhood and adolescence.

Narrative skills in deaf children who use spoken English: Dissociations between macro and microstructural devices.

Previous research has highlighted that deaf children acquiring spoken English have difficulties in narrative development relative to their hearing peers both in terms of macro-structure and with micro-structural devices. The majority of previous research focused on narrative tasks designed for hearing children that depend on good receptive language skills. The current study compared narratives of 6 to 11-year-old deaf children who use spoken English (N=59) with matched for age and non-verbal intelligence hearing peers. To examine the role of general language abilities, single word vocabulary was also assessed. Narratives were elicited by the retelling of a story presented non-verbally in video format. Results showed that deaf and hearing children had equivalent macro-structure skills, but the deaf group showed poorer performance on micro-structural components. Furthermore, the deaf group gave less detailed responses to inferencing probe questions indicating poorer understanding of the story's underlying message. For deaf children, micro-level devices most strongly correlated with the vocabulary measure. These findings suggest that deaf children, despite spoken language delays, are able to convey the main elements of content and structure in narrative but have greater difficulty in using grammatical devices more dependent on finer linguistic and pragmatic skills.

["New" virus and "old" risks. Reflections on H1N1 pandemic in the newspapers in Italy, France and UK]. / "Nuovi" virus e "vecchi" rischi. Riflessioni sul caso del virus H1N1 nelle principali testate giornalistiche di Italia, Francia ed Inghilterra.

AIMS: Social scientist Ulrick Beck links the idea of "risk society" with images of chronic uncertainties. The aim of this paper is to study how health risks are communicated in this social context. MATERIALS AND METHODS: In order to do that we explored a selection of articles published by two of the most popular newspapers in Italy, Corriere della Sera e La Repubblica, the UK, The Times e The Guardian, and France, Le Monde e Le Figaro, during 2009. RESULTS. This study allowed us to identify a transnational interest towards H1N1 pandemic that is characterized by picks of attention followed by periods of general indifference, and an alarmist frame. In alternative to this cross-country representation of H1N1 pandemic, however, we also identified three specific frames, one per each country. According to our analysis these frames can only be understood in close relation to citizens' trust towards the policy of science and the institutions, as well as the local and cultural traditions of science communication. CONCLUSIONS: Having said that, we are convinced that there is no perfect receipt that transcends the local context can be implemented to communicate health risks such as the ones associated H1N1. Nevertheless, our data indicate that there are good examples of health risks communication actually happening in Europe balancing between the risks of generating alarmism and denying the uncertainties of science become that are by now more and more evident.

[The concept of medical professionalism of medical students: basic assessment for a cohort study]. / L'idea di professionalità medica degli studenti di Medicina: rilevazione di base per uno studio di coorte.

AIMS: Education for professionalism is an international challenge. This paper reports the results of the assessment performed on two cohorts of first year students of Medicine, relating to attitudes toward three basic components of the construct of professionalism such as sensitivity to sociocultural differences, empathetic behaviors and professional skills in relationship to self, colleagues, patients and society. These components are analyzed with respect to their importance in the process of healthcare. MATERIALS AND METHODS: The assessment of the three components was performed through the validated Italian versions of three instruments: the Socio-Cultural Attitudes in Medicine Inventory, the Jefferson Scale of Empathy and the Nijmegen Professionalism Scale, administered for two consecutive years to all the students of the C curriculum in Medicine of Sapienza University of Rome (Italy). RESULTS: On a total of 196 students, the responses showed no significant differences related to gender or type of high school for the three examined components. A trend is present toward a familiar influence when one of the parents is a doctor and an idea of professionalism more technical-oriented than addressed to communication and empathy. CONCLUSIONS: The follow up study of these cohorts of students will provide important information for further educational design.

Self-expanding plastic stents for the treatment of post-operative esophago-jejuno anastomosis leak. A case series study

Objetive: Self-expandable plastic stents (SEPS) are increasingly being used for treatment of postoperative esophageal leak. This complication occurs in 4-27% of patients after radical gastrectomy, and has a high mortality rate up to 60%. The aim of this study is to evaluate the efficacy of SEPS (Polyflex®) for treatment of post-operative eshopago-jejuno anastomosis leak after radical gastrectomy for gastric cancer. Material and methods: During one year period patients who underwent a radical gastrectomy in our hospital for gastric cancer and developed a postoperative anastomotic leak were prospectively included in the study after signing a consent form, and treated with SEPS placement under endoscopic and fluoroscopic control for leak occlusion. Results: Four patients were included (3 men/1 woman). The mean interval between operation and SEPS placement was 16 days (range: 4-34). SEPS deployment was easily performed in all patients with complete occlusion of esophageal lumen in three patients. In the fourth patient we needed to deploy a second coaxial stent to achieve a complete occlusion of the fistula. SEPS migration did not happen in our series. One patient had already developed a mediastinitis by the time we placed the SEPS and he died 3 days later. Extraction of the SEPS was easily performed 4-8 weeks after deployment. Conclusion: We achieved a complete healing of the anastomotic fistula after radical gastrectomy in 3 out of 4 patients, without major complications related to SEPS. Placement of SEPS is an appealing minimally invasive alternative to surgical repair for patients with postoperative anastomotic leak(AU)

Pain prevalence in patients with chronic kidney disease.

BACKGROUND: The prevalence of pain in patients with chronic kidney diseases (CKD) is not known. In the current study, we aim to determine the prevalence of pain in CKD patients and its associations with various medical and psychosocial factors. METHODS: Consecutive CKD patients who were presented to the renal clinic at Olive View-UCLA Medical Center, a Los Angeles County tertiary referral center, over a 3-month period were interviewed on their medical and psychosocial histories and a history of pain including duration, severity and source. Chi2-testing for independence and binary logistic regression performed for the presence of pain and CKD stages as well as other medical and psychosocial factors were determined. A separate survey for pain was also done for 100 consecutive non-CKD patients who were presented to our ambulatory medicine clinic for routine care. RESULTS: 54.6% of 130 patients with known CKD interviewed were women. Any type of pain of at least a 2 week duration was reported in 72.9%. The most common source of pain was musculoskeletal. The presence of pain of less than a 2 week duration was associated with worse CKD stages (3 - 5 versus 1 - 2) and non-exercisers. Higher body mass index was associated with having pain lasting longer than a 2 week duration. Among patients who had pain, 33.8% used acetaminophen, 15.4% nonsteroidal anti-inflammatory drugs and 7.8% combination analgesics. In contrast to CKD patients, only 9% of non-CKD patients reported to have any type or duration of pain. CONCLUSIONS: Pain was much more prevalent among our CKD compared with non-CKD patients.

Self-expanding plastic stents for the treatment of post-operative esophago-jejuno anastomosis leak. A case series study.

OBJECTIVE: Self-expandable plastic stents (SEPS) are increasingly being used for treatment of postoperative esophageal leak. This complication occurs in 4-27% of patients after radical gastrectomy, and has a high mortality rate up to 60%.The aim of this study is to evaluate the efficacy of SEPS (Polyflex®) for treatment of post-operative esophago-jejuno anastomosis leak after radical gastrectomy for gastric cancer. MATERIAL AND METHODS: During one year period patients who underwent a radical gastrectomy in our hospital for gastric cancer and developed a postoperative anastomotic leak were prospectively included in the study after signing a consent form, and treated with SEPS placement under endoscopic and fluoroscopic control for leak occlusion. RESULTS: Four patients were included (3 men/1 woman). The mean interval between operation and SEPS placement was 16 days (range: 4-34). SEPS deployment was easily performed in all patients with complete occlusion of esophageal lumen in three patients. In the fourth patient we needed to deploy a second coaxial stent to achieve a complete occlusion of the fistula. SEPS migration did not happen in our series. One patient had already developed a mediastinitis by the time we placed the SEPS and he died 3 days later. Extraction of the SEPS was easily performed 4-8 weeks after deployment. CONCLUSION: We achieved a complete healing of the anastomotic fistula after radical gastrectomy in 3 out of 4 patients, without major complications related to SEPS. Placement of SEPS is an appealing minimally invasive alternative to surgical repair for patients with postoperative anastomotic leak.

A new fibrin sealant from Crotalus durissus terrificus venom: applications in medicine.

Fibrin sealant, a widely available tissue adhesive, has been used since 1940 in a variety of clinical applications. Commercially available fibrin sealant products are synthesized from bovine thrombin and human fibrinogen, which may transmit infectious diseases, and recipients may also develop antibodies against bovine thrombin. Bearing these disadvantages in mind, a new fibrin sealant was developed in 1989 by a group of researchers from the Center for the Study of Venoms and Venomous Animals, in Sao Paulo State, Brazil. The main purpose was to produce an adhesive fibrin without using human blood, to avoid transmitting infectious diseases. The components of this novel sealant were extracted from large animals and a serine proteinase extracted from Crotalus durissus terrificus snake venom. The applicability of this sealant was tested in animals and humans with beneficial results. The new fibrin sealant can be a useful tool clinically due to its flexibility and diversity of applications. This sealant is a biological and biodegradable product that (1) does not produce adverse reactions, (1) contains no human blood, (3) has a good adhesive capacity, (4) gives no transmission of infectious diseases, and (5) may be used as an adjuvant in conventional suture procedures. The effectiveness of this new fibrin sealant is reviewed and its development and employment are described.

Loss-of-function mutations in the Nav1.7 gene underlie congenital indifference to pain in multiple human populations.

Congenital indifference to pain (CIP) is a rare condition in which patients have severely impaired pain perception, but are otherwise essentially normal. We identified and collected DNA from individuals from nine families of seven different nationalities in which the affected individuals meet the diagnostic criteria for CIP. Using homozygosity mapping and haplotype sharing methods, we narrowed the CIP locus to chromosome 2q24-q31, a region known to contain a cluster of voltage-gated sodium channel genes. From these prioritized candidate sodium channels, we identified 10 mutations in the SCN9A gene encoding the sodium channel protein Nav1.7. The mutations completely co-segregated with the disease phenotype, and nine of these SCN9A mutations resulted in truncation and loss-of-function of the Nav1.7 channel. These genetic data further support the evidence that Nav1.7 plays an essential role in mediating pain in humans, and that SCN9A mutations identified in multiple different populations underlie CIP.

Subclinical hypothyroidism and Down's syndrome; studies on myocardial structure and function.

BACKGROUND: The management of subclinical hypothyroidism (SH) is still controversial, as the benefit to risk ratio of prolonged L-thyroxine therapy is not clear cut. Some authors have shown abnormalities of myocardial function and structure in adults with SH, which could be reversed by L-thyroxine therapy. As SH frequently affects children with Down's syndrome (DS), and almost one half of these are affected by congenital heart disease, a concomitant SH related impairment of cardiac function might further compromise their clinical condition. AIMS: To establish whether SH influences myocardial structure and function in children with DS. METHODS: Sixteen children with DS and untreated SH and 25 matched euthyroid controls with DS underwent echocardiographic analysis of left ventricular mechanics and tissue characterisation. RESULTS: None of the 16 patients had myocardial impairment. CONCLUSION: Results suggest that children with DS who have SH are not at risk of cardiac disease. Clinicians should consider these data in the management of SH, as the benefit to risk ratio of prolonged L-thyroxine therapy is not clear cut.

Down syndrome and breastfeeding.

AIM: The aim of the study was to investigate the frequency of breastfeeding among children with Down syndrome. METHODS: The mothers of 560 children with Down syndrome attending four university hospitals in Italy were interviewed and the neonatal clinical records retrieved. Information was collected on the type of infant feeding and on why some mothers had not breastfed their children. Two groups of healthy children whose feeding habits had been previously investigated were recruited as control subjects (1601 and 714, respectively). A paediatrician in each hospital was interviewed about the neonatal admission policy of children with Down syndrome. RESULTS: Among the 560 Down children, 246 (44%) were admitted to the neonatal unit. Compared with the two control groups, children with Down syndrome were significantly more frequently bottle-fed (57% vs 15% and 24%, respectively, odds ratio 7.5, 95% CI 6.0-9.4 and 4.2, 95% CI 3.3-5.4. respectively). Only 30% of infants admitted to the neonatal unit were breastfed. The main reasons reported by the mothers for not having breastfed were infants' illness in infants who had been admitted to the neonatal unit and frustration or depression, perceived milk insufficiency and difficulty with suckling for those babies who had not been admitted to the unit. The paediatricians reported that the admission of a baby with Down syndrome to the neonatal unit could sometimes take place not for medical reasons, but for diagnostic work-up or for a more appropriate diagnosis and to maintain communication with the family. CONCLUSIONS: Down syndrome babies are less frequently breastfed compared with healthy children. Support in breastfeeding should become a relevant point of health supervision for children with Down syndrome.

Congenital insensitivity to pain with anhidrosis (CIPA): novel mutations of the TRKA (NTRK1) gene, a putative uniparental disomy, and a linkage of the mutant TRKA and PKLR genes in a family with CIPA and pyruvate kinase deficiency.

Congenital insensitivity to pain with anhidrosis is an autosomal recessive hereditary disorder characterized by recurrent episodic fever, anhidrosis (inability to sweat), absence of reaction to noxious stimuli, self-mutilating behavior, and mental retardation. The human TRKA gene (NTRK1), located on chromosome 1q21-q22 encodes the receptor tyrosine kinase for nerve growth factor. We reported that TRKA is the gene responsible for CIPA and we developed a comprehensive strategy to screen for TRKA mutations and polymorphisms, as based on the gene's structure and organization. Here we report eight novel mutations detected as either a homozygous or heterozygous state in nine CIPA families from five countries. Mendelian inheritance of the mutations was confirmed in seven families for which samples from either parent were available. However, non-mendelian inheritance seems likely for the family when only samples from the mother and siblings, (but not from the father) were available. A paternal uniparental disomy for chromosome 1 is likely to be the cause of reduction to homozygosity of the TRKA gene mutation in this family. Interestingly, a Hispanic patient from the USA has two autosomal genetic disorders, CIPA and pyruvate kinase deficiency, whose genetic loci are both mapped to a closely linked chromosomal region. A splice mutation and a missense mutation were detected in the TRKA and PKLR genes from the homozygous proband, respectively. Thus, concomitant occurrence of two disorders is ascribed to a combination of two separate mutant genes, not a contiguous gene syndrome. This finding suggests a mechanism responsible for two autosomal genetic disorders in one patient. All these data further support findings that TRKA defects can cause CIPA in various ethnic groups. This will aid in diagnosis and genetic counseling of this painless but severe genetic disorder.

Coincident linkage of fasting plasma insulin and blood pressure to chromosome 7q in hypertensive hispanic families.

BACKGROUND: Insulin resistance (IR) and hyperinsulinemia are phenotypically associated with hypertension. We have previously provided evidence that blood pressure (BP) and IR cosegregate in Hispanic families, suggesting that this association has a genetic component. In the present study, we provide further support for the hypothesis of a genetic basis for the BP-IR relationship from a genetic linkage study. METHODS AND RESULTS: A 10-cM genome scan was conducted in 390 Hispanic family members of 77 hypertensive probands. Detailed measurements of BP, glucose, insulin levels, and insulin sensitivity (euglycemic clamp) were performed in adult offspring of probands. Multipoint variance component linkage analysis was used. A region on chromosome 7q seemed to influence both IR and BP. The greatest evidence for linkage was found for fasting insulin (lod score=3.36 at 128 cM), followed by systolic BP (lod score=2.06 at 120 cM). Fine mapping with greater marker density in this region increased the maximum lod score for fasting insulin to 3.94 at 125 cM (P=0.00002); lod score for systolic BP was 2.51 at 112 cM. Coincident mapping at this locus also included insulin sensitivity measured by the homeostasis assessment model (HOMA) and serum leptin concentrations. Insulin sensitivity by euglycemic clamp did not map to the same locus. CONCLUSIONS: Our results demonstrate that a major gene determining fasting insulin is located on chromosome 7q. Linkage of BP, HOMA, and leptin levels to the same region suggests this locus may broadly influence traits associated with IR and supports a genetic basis for phenotypic associations in IR syndrome.

Cholelithiasis in Down's syndrome.

Cholelithiasis is considered uncommon in infancy, childhood, and adolescence. We performed a prospective, controlled study showing that children with Down's syndrome have a significantly higher prevalence of cholelithiasis (4.7%) compared with controls (0.2%). Clinicians should be aware of the risk of gallstones in children with Down's syndrome.

Evidence for joint genetic control of insulin sensitivity and systolic blood pressure in hispanic families with a hypertensive proband.

BACKGROUND: The clustering of hypertension, insulin resistance, and obesity remains unexplained. We tested for genetic and nongenetic influences on the association among these traits in Hispanic families with hypertension. METHODS AND RESULTS: Blood pressure and body mass index (BMI) were measured in 331 members of 73 Hispanic families in which an index case (proband) had hypertension. Insulin sensitivity (S(I)) was measured by euglycemic clamp in 287 probands and their spouses (parents' generation) or their adult offspring. Correlation analysis examined relationships among traits within and between generations. Path analysis estimated genetic and nongenetic contributions to variability in systolic blood pressure (SBP), S(I), and the correlation between them. In the offspring, there was a significant correlation between individuals for each trait, as well as significant correlations within and between individuals for all possible pairs of traits. Between generations, SBP, S(I), and BMI in parents correlated with the same traits in their offspring; BMI in parents correlated with S(I) and SBP in offspring; and S(I) in parents correlated with SBP in offspring. Path analysis estimated that among offspring, genetic effects unrelated to BMI accounted for 60.8% of the variation in SBP, 36.8% of the variation in S(I), and 31.5% of the correlation between SBP and S(I) after adjustment for age and sex. Heritable effects related to BMI accounted for an additional 14.0% of variation in SBP, 26.8% of variation in S(I), and 56.3% of variation in their correlation. CONCLUSIONS: Clustering of hypertension and insulin resistance in Hispanic Americans is accounted for in part by heritable factors both associated with and independent of BMI.

Multisystem involvement in congenital insensitivity to pain with anhidrosis (CIPA), a nerve growth factor receptor(Trk A)-related disorder.

Congenital insensitivity to pain with anhidrosis (CIPA), a rare autosomal recessive disorder, is characterized by insensitivity to pain, self-mutilating behaviour, anhidrosis and recurrent hyperpyrexia. It is a hereditary sensory and autonomic neuropathy, also classified as HSAN, due to a defect of the receptor for nerve growth factor. CIPA is the first human genetic disorder caused by a defect in the neurotrophin signal transduction system. This is the first clinical report of CIPA patients characterized on molecular grounds. The clinical phenotypes of our patients show that CIPA is characterized by a multisystem involvement besides the nervous system, including bone fracture with slow healing, immunologic abnormalities, such as low response to specific stimuli, chronic inflammatory state ending in systemic amyloidosis. The molecular characterization allows a better understanding of most of the clinical features.