Wheezing in infants: frequency, clinical characteristics and treatment

Objective: To estimate the frequency and describe the clinical characteristics and respective treatments of previous history of wheezing. Methods: Infants aged 6-23 months with upper respiratory tract complaints and reporting previous wheezing were followed-up retrospectively. Data were registered on a validated standardized form. Results: Out of 451 infants, 164 (36.4%; 95%CI: 31.9-41.0) had a report of prior history of wheezing, 148 (32.8%; 95%CI: 28.5-37.4) during the first year of life. The mean age at the first episode of wheezing was 5.3 +/- 3.9 months. Among those who had had their first episode before 12 months of age, 38.5% reported 3 to 6 episodes and 14.2% > 6 episodes. Mean age at first episode was lower for those with a >= 3 episodes in comparison with those with <= 2 episodes (3.2 +/- 2.7 vs. 5.7 +/- 2.5 months, p < 0.001). Conclusion: One third of the infants reported wheezing during the first year of life. The earlier the first episode occurs, the more frequently wheezing recurs.

Different morphology, stage and treatment affect immune cell infiltration and long-term outcome in patients with non-small-cell lung carcinoma

Aims: Development of effective immune-based therapies for patients with non-small-cell lung carcinoma (NSCLC) depends on an accurate characterization of complex interactions that occur between immune cells and the tumour environment. Methods and results: Innate and adaptive immune responses were evaluated in relation to prognosis in 65 patients with surgically excised NSCLC. Immunohistochemistry and morphometry were used to determine the abundance and distribution of immune cells. We found low numbers of immune cells and levels of cytokines in the tumour environment when compared with surrounding parenchyma. Smoking was associated inversely with the adaptive immune response and directly with innate immunity. We observed a prominent adaptive immune response in squamous cell carcinomas (SCC) but greater innate immune responses in adenocarcinomas and large cell carcinomas. Cox model analysis showed a low risk of death for smoking <41 packs/year, N-0 tambour stage, squamous carcinoma, CD4(+) > 16.81% and macrophages/monocytes >4.5%. Collectively, the data indicate that in NSCLC there is not a substantive local immune cell infiltrate within the tumour. Conclusion: Although immune cell infiltration is limited in NSCLC it appears to have an impact on prognosis and this may be of relevance for new immunotherapeutic approaches.

Ameloblastoma demographic, clinical and treatment study - analysis of 40 cases

Dental lesions represent about 1% of oral cavity tumors being ameloblastoma the most common one. It is a tumor of epithelial origin that mainly affects the jaw, and less commonly the maxilla. Its clinical presentation is that of an asymptomatic slow-growing tumor. Despite being a benign tumor, it has an invasive behavior with a high rate of recurrence if not treated properly. Objective: To describe the cases of ameloblastoma in a reference department. Methods: Retrospective analysis of 40 cases. The variables analyzed were: age, gender, ethnicity, tumor location, type of treatment, complications and recurrence. Results: The most affected gender was male - 21 cases (52.5%); with a predominance of Caucasians - 24 cases (60%). The mean age was 35.45 years; the most common location was in.the jaw - 37 cases (92.5%). Facial asymmetry was the most frequent complaint. Of the 40 cases, 33 were submitted to surgery. Of those submitted to surgery, 24 (72.72%) underwent segmental resection, with recurrence in 4 (12.12%) cases. Conclusion: Ameloblastoma may relapse when treatment is not performed with broad surgical resection of the lesion with wide safety margins.

Approach to and Treatment of Goiters

The main causes of simple diffuse goiter (SDG) and multinodular goiter (MNG) are iodine deficiency, increase in serum thyroid-stimulating hormone (TSH) level, natural goitrogens, smoking, chronic malnutrition, and lack of selenium, iron, and zinc. Increasing evidence suggests that heredity is equally important. Treatment of SDG and MNG still focuses on L-thyroxine-suppressive therapy surgery. Radioiodine alone or preceded by recombinant human TSH stimulation is widely used in Europe and other countries. Each of these therapeutic options has advantages and disadvantages, with acute and long-term side effects.

Evidence-based guidelines for interpreting change scores for the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30

Aim: To use published literature and experts' opinion to investigate the clinical meaning and magnitude of changes in the Quality of Life (QOL) of groups of patients measured with the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). Methods: An innovative method combining systematic review of published studies, expert opinions and meta-analysis was used to estimate large, medium, and small mean changes over time for QLQ-C30 scores. Results: Nine hundred and eleven papers were identified, leading to 118 relevant papers. One thousand two hundred and thirty two mean changes in QOL over time were combined in the meta-analysis, with timescales ranging from four days to five years. Guidelines were produced for trivial, small, and medium size classes, for each subscale and for improving and declining scores separately. Estimates for improvements were smaller than respective estimates for declines. Conclusions: These guidelines can be used to aid sample size calculations and interpretation of mean changes over time from groups of patients. Observed mean changes in the QLQ-C30 scores are generally small in most clinical situations, possibly due to response shift. Careful consideration is needed when planning studies where QOL changes over time are of primary interest; the timing of follow up, sample attrition, direction of QOL changes, and subscales of primary interest are key considerations. (C) 2012 Elsevier Ltd. All rights reserved.

Photodiagnosis and treatment of condyloma acuminatum using 5-aminolevulinic acid and homemade devices

Background: The objective of this study was to improve the feasibility of applying topic 5-aminolevulinic acid (ALA) in photodiagnosis (PD) and treatment of condyloma caused by human papillomavirus (HPV) using two homemade handheld devices and to discuss the photodynamic therapy (PDT) as a suitable alternative for each of the cases studied. Both, protoporphyrin IX production and photodegradation were analyzed, and the pain experienced during the illumination was correlated with the light intensities. Methods: A total of 40 women with different grades of lesions caused by HPV were chosen from patients of the School of Medicine of Ribeirao Preto (University of Sao Paulo) and of the Unit of Public Health of Araraquara, Sao Paulo. Results: We did not encounter any unexpected difficulties using our devices during the treatment. The existence of an easily observable reddish fluorescence with large intensity concentrated on the Lesions is the clinical indication of the penetration and the selective concentration of protoporphyrin IX in the clinical and subclinical lesions rather than in the healthy tissue. The aesthetic results were much better than those obtained by conventional techniques as surgery or cryogenics, with no recurrence reported after two years of treatment. Conclusions: Our results are proof for the various advantages using ALA cream for the PD and PDT in many different cases of condyloma by HPV. This study will be continued to investigate the PpIX photobleaching and the irradiance and fluence rate to optimize conducting the clinical trials, to improve the devices and therefore increase the treatment response. (c) 2011 Elsevier B.V. All rights reserved.

CYP3A5 and NAT2 gene polymorphisms: role in childhood acute lymphoblastic leukemia risk and treatment outcome

Susceptibility to acute lymphoblastic leukemia can be highly influenced by genetic polymorphisms in metabolizing enzyme genes of environmental carcinogens. This study aimed to evaluate the impact of the CYP3A5 and NAT2 metabolizing enzyme polymorphisms on the risk of childhood acute lymphoblastic leukemia. The analysis was conducted on 204 ALL patients and in 364 controls from a Brazilian population, using PCR-RFLP. The CYP3A5*3 polymorphic homozygous genotype was more frequent among ALL patients and the *3 allele variant was significantly associated with increased risk of childhood ALL (OR = 0.29; 95% CI, 0.14-0.60). The homozygous polymorphic genotype for the *6 allele variant was extremely rare and found in only two individuals. The heterozygous frequencies were similar for the ALL group and the control group. No significant differences were observed between the groups analyzed regarding NAT2 variant polymorphisms. None of the polymorphisms analyzed was related to treatment outcome. The results suggest that CYP3A5*3 polymorphism may play an important role in the risk of childhood ALL.

Early and One-Year Stroke Case Fatality in Sao Paulo, Brazil: Applying the World Health Organization's Stroke STEPS

Case fatality rate is considered a main determinant of stroke mortality trends. We applied the World Health Organization's Stroke STEPS to identify case fatality rates in a community hospital in Brazil. We evaluated all patients with first-ever stroke seeking acute care at the hospital's emergency ward between April 2006 and December 2008 to verify early and late case fatality according to stroke subtype. We used years of formal education as a surrogate for socioeconomic status. Of 430 first-ever stroke events, 365 (84.9%) were ischemic and 65 (15.1%) were intracerebral hemorrhage. After 1 year, we adjudicated 108 deaths (86 ischemic; 22 hemorrhagic). Age-adjusted case fatality rates for ischemic stroke and intracerebral hemorrhage were 6.0% v 19.8% at 10 days, 10.6% v 22.1% at 28 days, 17.6% v 29.1% at 6 months, and 21.0% v 31.5% at 1 year. Illiteracy or no formal education was a predictor of death at 6 months (odds ratio [OR], 4.31; 95% confidence interval [CI] 1.34-13.91) and 1 year (OR, 4.21; 95% CI, 1.45-12.28) in patients with ischemic stroke, as well as at 6 months (OR, 3.19; 95% CI, 1.17-8.70) and 1 year (OR, 3.30; 95% CI, 1.30-8.45) for all stroke patients. Other variables, including previous cardiovascular risk factors and acute medical care, did not change this association to a statistically significant degree. In conclusion, case fatality, particularly up to 6 months, was higher in hemorrhagic stroke, and lack of formal education was associated with increased stroke mortality.

The Interactive Effect of GHR-Exon 3 and -202 A/C IGFBP3 Polymorphisms on rhGH Responsiveness and Treatment Outcomes in Patients with Turner Syndrome

Context: There is great interindividual variability in the response to recombinant human (rh) GH therapy in patients with Turner syndrome (TS). Ascertaining genetic factors can improve the accuracy of growth response predictions. Objective: The objective of the study was to assess the individual and combined influence of GHR-exon 3 and -202 A/C IGFBP3 polymorphisms on the short-and long-term outcomes of rhGH therapy in patients with TS. Design and Patients: GHR-exon 3 and -202 A/C IGFBP3 genotyping (rs2854744) was correlated with height data of 112 patients with TS who remained prepubertal during the first year of rhGH therapy and 65 patients who reached adult height after 5 +/- 2.5 yr of rhGH treatment. Main Outcome Measures: First-year growth velocity and adult height were measured. Results: Patients carrying at least one GHR-d3 or -202 A-IGFBP3 allele presented higher mean first-year growth velocity and achieved taller adult heights than those homozygous for GHR-fl or -202 C-IGFBP3 alleles, respectively. The combined analysis of GHR-exon 3 and -202 A/C IGFBP3 genotypes showed a clear nonadditive epistatic influence on adult height of patients with TS treated with rhGH (GHR-exon 3 alone, R-2 = 0.27; -202 A/C IGFBP3, R-2 = 0.24; the combined genotypes, R-2 = 0.37 at multiple linear regression). Together with clinical factors, these genotypes accounted for 61% of the variability in adult height of patients with TS after rhGH therapy. Conclusion: Homozygosity for the GHR-exon3 full-length allele and/or the -202C-IGFBP3 allele are associated with less favorable short-and long-term growth outcomes after rhGH treatment in patients with TS. (J Clin Endocrinol Metab 97: E671-E677, 2012)

Early and late neurodegeneration and memory disruption after intracerebroventricular streptozotocin

Glucose metabolism and insulin signaling disruptions in the brain have been proposed as a likely etiology of Alzheimer's disease. The aim of the present study was to investigate the time course of cognitive impairments induced by intracerebroventricular injection of streptozotocin (STZ) in rats and correlate them with the ensuing neurodegenerative process. Early and late effects of STZ were evaluated by using the reference and working memory versions of the Morris' water maze task and the evaluation of neurodegenerative markers by immunoblotting and the Fluoro-jade C histochemistry. The results revealed different types of behavioral and neurodegenerative responses, with distinct time courses. We observed an early disruption on the working memory as early as 3 h after STZ injections, which was followed by degenerative processes in the hippocampus at 1 and 15 days after STZ injections. Memory disruption increases over time and culminates with significant changes in amyloid-beta peptide and hyperphosphorylated Tau protein levels in distinct brain structures. These findings add information on the Alzheimer's disease-like STZ animal model and on the mechanisms underlying neurodegenerative processes. (C) 2012 Elsevier Inc. All rights reserved.

Correlation between insulin resistance and treatment-resistant acne

Physiologically during puberty and adolescence, when juvenile acne usually appears, the response to a glucose load is increased if compared to the one observed in adult and at pre-pubertal age, while insulin sensitivity is reduced. Insulin is a hormone that acts at different levels along the axis which controls the sex hormones. It increases the release of LH and FSH by pituitary gland, stimulates the synthesis of androgens in the gonads and stimulates the synthesis of androgenic precursors in adrenal glands. Finally, it acts in the liver by inhibiting the synthesis of Sex Hormone Binding Globulin (SHBG). Insulin is also able to act directly on the production of sebum and amplify the effects of Iinsulin Growth Factor-1 in the skin, inhibiting the synthesis of its binding protein (IGF Binding Protein-1). In female subjects with acne and Polycystic Ovary Syndrome (PCOS) insulin resistance is a well known pathogenetic factor, while the relationship between acne and insulin resistance has been poorly investigated in males so far. The purpose of this study is to investigate the correlation between insulin resistance and acne in young males who do not respond to common therapies. Clinical and biochemical parameters of glucose, lipid metabolism, androgens and IGF-1 were evaluated. Insulin resistance was estimated by Homeostasis Model assessment (HOMA-IR) and Oral Glucose Tolerance Test was also performed. We found that subjects with acne had higher Sistolic and Diastolic Blood Pressure, Waist/Hip Ratio, Waist Circumference, 120' OGTT serum insulin and serum IGF-1 and lower HDL-cholesterol than subjects of comparable age and gender without acne. The results thus obtained confirmed what other authors have recently reported about a metabolic imbalance in young males with acne. Furthermore, these results support the hypothesis that insulin resistance might play an important role in the pathogenesis of treatment-resistant acne in males.

A model of ischemic isolated acute liver failure in pigs: standardizing monitoring and treatment

Acute liver failure (ALF) models in pigs have been widely used for evaluating newly developed liver support systems. But hardly any guidelines are available for the surgical methods and the clinical management.

Integrating novel agents into multiple myeloma treatment - current status in Switzerland and treatment recommendations

The treatment of multiple myeloma has undergone significant changes in the recent past. The arrival of novel agents, especially thalidomide, bortezomib and lenalidomide, has expanded treatment options and patient outcomes are improving significantly. This article summarises the discussions of an expert meeting which was held to debate current treatment practices for multiple myeloma in Switzerland concerning the role of the novel agents and to provide recommendations for their use in different treatment stages based on currently available clinical data. Novel agent combinations for the treatment of newly diagnosed, as well as relapsed multiple myeloma are examined. In addition, the role of novel agents in patients with cytogenetic abnormalities and renal impairment, as well as the management of the most frequent side effects of the novel agents are discussed. The aim of this article is to assist in treatment decisions in daily clinical practice to achieve the best possible outcome for patients with multiple myeloma.

Changing patterns of cancer incidence in the early- and late-HAART periods: the Swiss HIV Cohort Study

The advent of highly active antiretroviral therapy (HAART) in 1996 led to a decrease in the incidence of Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma (NHL), but not of other cancers, among people with HIV or AIDS (PWHA). It also led to marked increases in their life expectancy.