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.

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)

Age-adjusted recipient pretransplantation telomere length and treatment-related mortality after hematopoietic stem cell transplantation

Telomere attrition induces cell senescence and apoptosis. We hypothesized that age-adjusted pretransplantation telomere length might predict treatment-related mortality (TRM) after hematopoietic stem cell transplantation (HSCT). Between 2000 and 2005, 178 consecutive patients underwent HSCT from HLA-identical sibling donors after myeloablative conditioning regimens, mainly for hematologic malignancies (n = 153). Blood lymphocytes' telomere length was measured by real-time quantitative PCR before HSCT. Age-adjusted pretransplantation telomere lengths were analyzed for correlation with clinical outcomes. After age adjustment, patients' telomere-length distribution was similar among all 4 quartiles except for disease stage. There was no correlation between telomere length and engraftment, GVHD, or relapse. The overall survival was 62% at 5 years (95% confidence interval [CI], 54-70). After a median follow-up of 51 months (range, 1-121 months), 43 patients died because of TRM. The TRM rate inversely correlated with telomere length. TRM in patients in the first (lowest telomere length) quartile was significantly higher than in patients with longer telomeres (P = .017). In multivariate analysis, recipients' age (hazard ratio, 1.1; 95% CI, .0-1.1; P = .0001) and age-adjusted telomere length (hazard ratio, 0.4; 95% CI; 0.2-0.8; P = .01) were independently associated with TRM. In conclusion, age-adjusted recipients' telomere length is an independent biologic marker of TRM after HSCT. (Blood. 2012;120(16):3353-3359)

Diagnosis and treatment of coronary artery disease in hemodialysis patients evaluated for transplant

We present a review of current strategies for the diagnosis and treatment of coronary artery disease (CAD) in patients with advanced chronic kidney disease who are on the waiting list for transplants, based on data from the literature and originated from a single-center cohort of 1,250 patients with maximum follow-up of 12 years. We discuss the best way to select patients to be tested for CAD, how to choose the more adequate screening test for CAD and cardiovascular disease, how to select patients for invasive treatment studies and how to treat patients with significant CAD. We also suggest new research avenues to be explored to resolve some problems in this area.

Molecular basis for the diagnosis and treatment of acute promyelocytic leukemia

Acute promyelocytic leukemia is characterized by gene rearrangements that always involve the retinoic acid receptor alpha on chromosome 15. In the majority of patients t(15;17) is detected, which generates the promyelocytic leukemia gene/retinoic acid receptor alpha rearrangement. This rearrangement interacts with several proteins, including the native promyelocytic leukemia gene, thus causing its delocalization from the nuclear bodies, impairing its function. The immunofluorescence staining technique using the anti-PML antibody may be used to provide a rapid diagnosis and to immediately start therapy using all-trans retinoic acid. The experience of the International Consortium on Acute Promyelocytic Leukemia has demonstrated that early mortality was significantly reduced by adopting the immunofluorescence technique. All-trans retinoic acid combined with chemotherapy is the standard therapy; this promotes complete remission rates greater than 90% and cure rates of nearly 80%. However, early mortality is still an important limitation and hematologists must be aware of the importance of treating newly diagnosed acute promyelocytic leukemia as a medical emergency.

Impact of the rapid antigen detection test in diagnosis and treatment of acute pharyngotonsillitis in a Pediatric emergency room

OBJECTIVE: To evaluate the impact of the routine use of rapid antigen detection test in the diagnosis and treatment of acute pharyngotonsillitis in children. METHODS: This is a prospective and observational study, with a protocol compliance design established at the Emergency Unit of the University Hospital of Universidade de São Paulo for the care of children and adolescents diagnosed with acute pharyngitis. RESULTS: 650 children and adolescents were enrolled. Based on clinical findings, antibiotics would be prescribed for 389 patients (59.8%); using the rapid antigen detection test, they were prescribed for 286 patients (44.0%). Among the 261 children who would not have received antibiotics based on the clinical evaluation, 111 (42.5%) had positive rapid antigen detection test. The diagnosis based only on clinical evaluation showed 61.1% sensitivity, 47.7% specificity, 44.9% positive predictive value, and 57.5% negative predictive value. CONCLUSIONS: The clinical diagnosis of streptococcal pharyngotonsillitis had low sensitivity and specificity. The routine use of rapid antigen detection test led to the reduction of antibiotic use and the identification of a risk group for complications of streptococcal infection, since 42.5% positive rapid antigen detection test patients would not have received antibiotics based only on clinical diagnosis.

Treatment times of Class II malocclusion: four premolar and non-extraction protocols

The purpose of this study was to retrospectively compare the treatment times of Class II division 1 malocclusion subjects treated with four first premolar extractions or a non- extraction protocol and fixed edgewise appliances. Eighty- four patients were selected and divided into two groups. Group 1, treated with four first premolar extractions, consisted of 48 patients (27 males and 21 females) with a mean age of 13.03 years and group 2, treated without extractions, consisted of 36 patients (18 males and 18 females) with a mean age of 13.13 years. Group 2 was subdivided into two subgroups, 2A consisting of 16 patients treated in one phase and 2B consisting of 20 patients treated in two phases. The initial and final Treatment Priority Index (TPI), initial ages, initial mandibular crowding, and treatment times of groups 1 and 2 were compared with t- tests. These variables were also compared between group 1 and the subgroups with analysis of variance followed by Tukey's tests. The treatment times for groups 1 and 2 and subgroups 2A and 2B were 2.36, 2.47, 2.25, and 2.64 years, respectively, which were not significantly different. Treatment times with non-extraction and four premolar extraction protocols are similar.

Treatment-resistant depression increases health costs and resource utilization

Objective: Major Depressive Disorder (MDD) is a debilitating condition with a marked social impact. The impact of MDD and Treatment-Resistant Depression (TRD+) within the Brazilian health system is largely unknown. The goal of this study was to compare resource utilization and costs of care for treatment-resistant MDD relative to non-treatment-resistant depression (TRD-). Methods: We retrospectively analyzed the records of 212 patients who had been diagnosed with MDD according to the ICD-10 criteria. Specific criteria were used to identify patients with TRD+. Resource utilization was estimated, and the consumption of medication was annualized. We obtained information on medical visits, procedures, hospitalizations, emergency department visits and medication use related or not to MDD. Results: The sample consisted of 90 TRD+ and 122 TRD-patients. TRD+ patients used significantly more resources from the psychiatric service, but not from non-psychiatric clinics, compared to TRD-patients. Furthermore, TRD+ patients were significantly more likely to require hospitalizations. Overall, TRD+ patients imposed significantly higher (81.5%) annual costs compared to TRD-patients (R$ 5,520.85; US$ 3,075.34 vs. R$ 3,042.14; US$ 1,694.60). These findings demonstrate the burden of MDD, and especially of TRD+ patients, to the tertiary public health system. Our study should raise awareness of the impact of TRD+ and should be considered by policy makers when implementing public mental health initiatives.