Complete Clinical Response After Neoadjuvant Chemoradiation Therapy for Distal Rectal Cancer: Characterization of Clinical and Endoscopic Findings for Standardization

BACKGROUND: Complete tumor regression may develop after neoadjuvant chemoradiation therapy for distal rectal cancer. Studies have suggested that selected patients with complete clinical response may avoid radical surgery and close surveillance may provide good outcomes with no oncologic compromise. However, definition of complete clinical response is often imprecise and may vary between different studies. The aim of this study is to provide a clear definition for a complete clinical response after neoadjuvant chemoradiation therapy in patients with distal rectal cancer in addition to actual endoscopic videos from patients managed nonoperatively. METHODS: Patients with nonmetastatic distal rectal cancer treated by neoadjuvant chemoradiation therapy, including 50.4 Gy and concomitant 5-fluorouracil and leucovorin, were assessed for tumor response at least 8 weeks after chemoradiation therapy completion. Complete and incomplete clinical responses were defined based on clinical and endoscopic findings. Patients with complete clinical response were not immediately operated on and were closely followed. Early and late endoscopic findings were recorded. RESULTS: Definition of a complete clinical response should be based on very strict clinical and endoscopic criteria. The finding of any residual superficial ulceration, irregularity, or nodule should prompt surgical attention, including transanal full-thickness excision or even a radical resection with total mesorectal excision. Standard or incisional biopsies should be avoided in this setting. Complete clinical responders should harbor no more than whitening of the mucosa, teleangiectasia with mucosal integrity to be considered for a nonoperative approach. In the presence of these findings, regularly scheduled reassessments may provide a safe alternative to these patients with early detection of recurrent disease. CONCLUSION: Strict definition of the clinical and endoscopic findings of patients experiencing complete clinical response after neoadjuvant chemoradiation therapy may provide a useful tool for the understanding of outcomes of patients managed with no immediate surgery allowing standardization of classifications and comparison between the experiences of different institutions.

Assessment of Occupational Genotoxic Risk among Brazilian Hairdressers

Objectives: To evaluate the genotoxic risk to hairdressers exposed daily to chemical substances such as hair dyes, waving and straightening preparations and manicurists` products by the Comet assay test (single-cell gel electrophoresis). Methods: The Comet assay was performed on blood samples from 69 female hairdressers (36.4 +/- 10.7 years old) currently employed in 21 different beauty institutes in Sao Paulo, Brazil, and on 55 female control blood donors (32.6 +/- 10.0 years old) from the Sao Paulo University Clinical Hospital blood bank. All the control subjects had occupations other than hairdresser. Comet assays were performed by evaluating 100 blood lymphocytes per individual and graded by visual score according to comet tail length. Results: The hairdressers showed a higher frequency of DNA damage revealed by Comet Score (159.8 +/- 71) when compared to the control group (125.4 +/- 64.1), and the difference was statistically significant by the Student`s t-test (P = 0.005). Multiple regression analysis showed that in addition to the hairdressers` profession, tobacco use contributed to the higher frequency of cells with comets (P < 0.05). Conclusions: The observed DNA damage could be associated with the hairdressers` occupational environment, where different chemicals are chronically manipulated and inhaled. Considering that this profession in many countries, including Brazil, is not officially regulated, more attention should focus on these professionals not only by legislative bodies but also by multidisciplinary teams able to develop and implement risk prevention and control strategies for chemical, physical and biological agents to which hairdressers are exposed.

Early motor and electrophysiological changes in transgenic mouse model of amyotrophic lateral sclerosis and gender differences on clinical outcome

Amyotrophic lateral sclerosis (ALS) is a progressive degenerative disorder affecting motoneurons and the SOD1(G93A) transgenic mice are widely employed to study disease physiopathology and therapeutic strategies. Despite the cellular and biochemical evidences of an early motor system dysfunction, the conventional behavioral tests do not detect early motor impairments in SOD1 mouse model. We evaluated early changes in motor behavior of ALS mice by doing the analyses of tail elevation, footprint, automatic recording of motor activities by means of an infrared motion sensor activity system and electrophysiological measurements in male and female wild-type (WT) and SOD1(G93A) mice from postnatal day (P) 20 up to endpoint. The classical evaluations of mortality, weight loss, tremor, rotometer, hanging wire and inclined plane were also employed. There was a late onset (after P90) of the impairments of classical parameters and the outcome varied between genders of ALS mice, being tremor, cumulative survival, weight loss and neurological score about 10 days earlier in male than female ALS mice and also about 20 days earlier in ALS males regarding rotarod and hanging wire performances. While diminution of hindpaw base was 10 days earlier in ALS males (P110) compared to females, the steep length decreased 40 days earlier in ALS females (P60) than ALS males. The automatic analysis of motor impairments showed substantial late changes (after P90) of motility and locomotion in the ALS females, but not in the ALS males. It was surprising that the scores of tail elevation were already decreased in ALS males and females by P40, reaching the minimal values at the endpoint. The electrophysiological analyses showed early changes of measures in the ALS mouse sciatic nerve, i.e., decreased values of amplitude (P40) and nerve conduction velocity (P20), and also an increased latency (P20) reaching maximal level of impairments at the late disease phase. The early changes were not accompanied by reductions of neuronal protein markers of neurofilament 200 and ChAT in the ventral part of the lumbar spinal cord of P20 and P60 ALS mice by means of Western blot technique, despite remarkable decreases of those protein levels in P120 ALS mice. In conclusion, early changes of motor behavior and electrophysiological parameters in ALS mouse model must be taken into attention in the analyses of disease mechanisms and therapeutic effects. (C) 2011 Published by Elsevier B.V.

Cancellation task in very low educated people

Cancellation tasks have been largely used to evaluate visuospatial function and attention. Cognitive evaluation of low literacy subjects remains a challenge in developing countries, when it becomes necessary to distinguish between what is pathological and what is biased by low education. Performance of river bank dwellers of the Amazon region was studied, in a structured nonverbal cancellation task, verifying their searching strategies (randomized/organized), time of completion, number of correct cancelled targets and number of false-positive targets. A difference was observed in performance and searching strategies between illiterates and literates with only a few years of schooling (mean= 0.8, S.D.=1.6 years of education) across all measures. There was a significant difference between literate groups in the searching strategy, as well as between illiterates who had never attended school and those who had, showing that a minimal contact with graphic presentations and organization of writing was able to modify this cognitive function. (C) 2007 National Academy of Neuropsychology. Published by Elsevier Ltd. All rights reserved.

From lateral to mesial: The quest for a surgical cure for temporal lobe epilepsy

Purpose: A gap of more than a hundred years occurred between the first accounts of mesial temporal sclerosis and recognition of its role in the pathogenesis of psychomotor seizures. This paper reviews how the understanding and surgical treatment of temporal lobe epilepsy developed, particularly from the work of Penfield, Jasper, and their associates at the Montreal Neurological Institute (MNI). Methods: Publications on EEG and surgery for temporal lobe seizures from 1935 to 1953 were reviewed and charts of selected patients operated on at the MNI in the same period were examined. Attention was focused on the evolution of surgical techniques for temporal lobe epilepsy. Results: In the late 1930s, some EEG findings suggested deep-lying disturbances originating in the temporal lobe. However, it took another two decades before the correlation of clinical, neurophysiological, and anatomical findings provided evidence for the involvement of the mesial structures in psychomotor or temporal lobe seizures. From 1949 and onward, Penfield and his associates applied this evidence to extend the surgical resections to include the uncus and the hippocampus. Conclusion: The collaborative work of a team led by Penfield and Jasper at the MNI helped to define the role of neurophysiological studies in epilepsy surgery. As a result, the importance of removing the mesial structures in order to obtain better seizure control in patients with temporal lobe epilepsy became firmly established.

RESTORATION OF THE ROTATION CENTER IN MINIMALLY-INVASIVE TOTAL HIP REPLACEMENT

Objective: Our aim was to evaluate the challenges in obtaining a successful restoration of the rotation center as well as a good positioning of the acetabular component when using the minimally-invasive posterior approach for uncemented total hip replacement. Methods: In a comparative non-random prospective study, 64 adult patients underwent elective total hip arthroplasty using the minimally-invasive posterior approach performed by one single surgeon, All patients included in this study had a superior and lateral migration of the rotation center of the hip in comparison to the normal contralateral hip. Patients were excluded from the study if they presented the following: diagnosis of femoral neck fracture, displasic hip types 2, 3 and 4 (Crowe`s classification), osteoarthritis of the contralateral hip. Of the 64 patients in the study, 39 had a radiographic pre-op acetabular size planning equal or less than 50 mm and 25 patients had a radiographic pre-op acetabular size planning equal or more than 52 mm. We considered a good result the following goals: acetabular bend between 35 and 50 degrees, acetabular size according to the pre-op estimative with full contact in the three zones of DeLee-Charnley, a lower medial and vertical positioning of the rotation center in comparison with the pre-op values and a final limb discrepancy lower than 10 mm. Results: A better restoration of the rotation center, as well as, excellent acetabular positioning was found in patients with smaller acetabular size (equal or less than 50), p=0, 04. We must draw attention to two risks when using the minimally-invasive posterior approach: a vertical acetabular position and a lateral position of the acetabular component increasing the risk of a poor contact in the zone 1 due to an insufficient reaming of the medial acetabular host bone. Conclusion: We propose standard surgical approaches in patients with larger anatomical measurements (acetabular planning size more than 50).

BIOMECHANICAL EVALUATION OF ORTHOPAEDIC CEMENT COMBINED WITH ANTIBIOTIC AND METHYLENE BLUE

Objective: Acrylic cement has been used for years on orthopaedic surgeries, especially on knee arthroplasties, deserving special attention when added to antibiotics (for treatment of deep bone infections) or stains (to facilitate its removal). The present study was conducted in order to evaluate potential mechanical differences between the orthopaedic cement itself and when this is added to antibiotic and/or stains. Methods: Surgical bone cement Simplex@P Stryker, vancomycin and methylene blue were used, and the mixtures were submitted to physical and mechanical tests according the ABNT NBR ISO 5833 rule. The parameters studied here were: time for mass formation, intrusion capability, resistance to compression, resistance to flexion and maximum temperature reached by the mixtures. Results: The evaluated mixtures were approved as to mass formation, maximum temperature, intrusion capability and resistance to compression. Only the one containing pure cement was approved on the flexion essay. Conclusion: The addition of vancomycin and/or methylene blue to Surgical Simplex@P Stryker bone cement reduces its resistance to flexion, being unacceptable by the ABNT NBR ISO 5833 rule.

Health technology diffusion in developing countries: a case study of CT scanners in Brazil

Background The development of products and services for health care systems is one of the most important phenomena to have occurred in the field of health care over the last 50 years. It generates significant commercial, medical and social results. Although much has been done to understand how health technologies are adopted and regulated in developed countries, little attention has been paid to the situation in low- and middle-income countries (LMICs). Here we examine the institutional environment in which decisions are made regarding the adoption of expensive medical devices into the Brazilian health care system. Methods We used a case study strategy to address our research question. The empirical work relied on in-depth interviews (N = 16) with representatives of a wide range of actors and stakeholders that participate in the process of diffusion of CT (computerized tomography) scanners in Brazil, including manufacturers, health care organizations, medical specialty societies, health insurance companies, regulatory agencies and the Ministry of Health. Results The adoption of CT scanners is not determined by health policy makers or third-party payers of public and private sectors. Instead, decisions are primarily made by administrators of individual hospitals and clinics, strongly influenced by both physicians and sales representatives of the medical industry who act as change agents. Because this process is not properly regulated by public authorities, health care organizations are free to decide whether, when and how they will adopt a particular technology. Conclusions Our study identifies problems in how health care systems in LMICs adopt new, expensive medical technologies, and suggests that a set of innovative approaches and policy instruments are needed in order to balance the institutional and professional desire to practise a modern and expensive medicine in a context of health inequalities and basic health needs.

AIDS in Latin America: assessing the current status of the epidemic and the ongoing response

Background This article provides a summary of the current status of the HIV/AIDS epidemic in Latin America, as well as an outline of the diverse responses to it. Methods A search of international databases (Pubmed and ISI-Web of Science), regional databases (Scielo and Lilacs), regional and national documents and UNAIDS reports. Data are presented according to subregion. Results In Mexico HIV remains concentrated among urban men who have sex with men (MSM), and has been growing among injecting drug users (IDU) and in rural areas in relation to migration. An increasing proportion of women among those affected is observed in all countries in Central America, the most affected region, as well as increasing the impact on other vulnerable groups, such as indigenous populations. The Andean Countries have urban epidemics concentrated among MSM. In Peru, non-traditional vulnerable populations were identified. In the Southern Cone heterosexual transmission became more relevant, probably in connection with IDU epidemics and is increasingly affecting lower income groups. Incidence rates have been declining since 2002 in Brazil, the first country to guarantee free, universal access to antiretrovirals, where one-third of drug-nave patients are still initiating treatment at an advanced stage. Generally, access to treatment has improved as a result of support from the Global Fund and other initiatives, but there are concerns regarding coverage, equity and sustainability. Conclusions HIV is still concentrated among MSM in Latin America. Non-traditional vulnerable groups such as migrants and lower income populations, usually considered part of the general population, deserve attention. Programmes confronting sexual exclusion are still needed. Access to treatment has improved over time, but inequalities persist.

Effects of childhood development on late-life mental disorders

Purpose of review To explore recent findings bridging childhood development and common late-life mental disorders in the elderly. Recent findings We addressed aging as a part of the developmental process in central nervous system, typical and atypical neurodevelopment focusing on genetic and environmental risk factors and their interplay and links between psychopathology from childhood to the elderly, unifying theoretical perspectives and preventive intervention strategies. Summary Current findings suggest that childhood development is strictly connected to psychiatric phenotypes across the lifespan. Although we are far from a comprehensive understanding of mental health trajectories, some initial findings document both heterotypic and homotypic continuities from childhood to adulthood and from adulthood to the elderly. Our review also highlights the urgent need for investigations on preventive interventions in individuals at risk for mental disorders.

ADHD in a representative sample of the Brazilian population: estimated prevalence and comparative adequacy of criteria between adolescents and adults according to the item response theory

Background: Attention deficit hyperactivity disorder (ADHD) is a clinically significant disorder in adulthood, but current diagnostic criteria and instruments do not seem to adequately capture the complexity of the disorder in this developmental phase. Accordingly, there are limited data on the proportion of adults affected by the disorder, specially in developing countries. Method: We assessed a representative household sample of the Brazilian population for ADHD with the Adult ADHD Self-report Scale (ASRS) Screener, and evaluated the instrument according to the Rasch model of item response theory. Results: The sample was comprised by 3007 individuals, and the overal prevalence of positive screeners for ADHD was 5.8% [95% confidence interval (CI), 4.8-7.0]. Rasch analyses revealed the misfitt of the overall sample to expectations of the model. The evaluation of the sample stratified by age revealed that data for adolescents showed a signficant fittnes to the model expectations, while items completed by adults were not adequated. Conclusions: The lack of fitness to the model for adult respondents challenges the possibility of a linear transformation of the ordinal data into interval measures and the utilization of parametric analyses of data. This result suggests that diagnostic criteria and instruments for adult ADHD must take into account a developmental perspective. Moreover, it calls for further evaluation of currently employed research methods in light of modern theories of psychometrics. Copyright (C) 2010 John Wiley & Sons, Ltd.

Implications of Extending the ADHD Age-of-Onset Criterion to Age 12: Results from a Prospectively Studied Birth Cohort

Objective: To evaluate whether including children with onset of symptoms between ages 7 and 12 years in the ADHD diagnostic category would: (a) increase the prevalence of the disorder at age 12, and (b) change the clinical and cognitive features, impairment profile, and risk factors for ADHD compared with findings in the literature based on the DSM-IV definition of the disorder. Method: A birth cohort of 2,232 British children was prospectively evaluated at ages 7 and 12 years for ADHD using information from mothers and teachers. The prevalence of diagnosed ADHD at age 12 was evaluated with and without the inclusion of individuals who met DSM-IV age-of-onset criterion through mothers` or teachers` reports of symptoms at age 7. Children with onset of ADHD symptoms before versus after age 7 were compared on their clinical and cognitive features, impairment profile, and risk factors for ADHD. Results: Extending the age-of-onset criterion to age 12 resulted in a negligible increase in ADHD prevalence by age 12 years of 0.1%. Children who first manifested ADHD symptoms between ages 7 and 12 did not present correlates or risk factors that were significantly different from children who manifested symptoms before age 7. Conclusions: Results from this prospective birth cohort might suggest that adults who are able to report symptom onset by age 12 also had symptoms by age 7, even if they are not able to report them. The data suggest that the prevalence estimate, correlates and risk factors of ADHD will not be affected if the new diagnostic scheme extends the age-of-onset criterion to age 12. J. Am. Acad. Child Adolesc. Psychiatry, 2010;49(3):210-216.

Lack of Association Between a 3 ` UTR VNTR Polymorphism of Dopamine Transporter Gene (SLC6A3) and ADHD in a Brazilian Sample of Adult Patients

Objective: To investigate a possible association between a 3`UTR VNTR polymorphism of the dopamine transporter gene (SLC6A3) and ADHD in a Brazilian sample of adult patients. Method: Study Case-control with 102 ADHD adult outpatients (DSM-IV criteria) and 479 healthy controls. The primers` sequence used were: 3`UTR-Forward: 5`TGT GGT GAT GGG AAC GGC CTG AG 3` and 3`UTR-Reverse: 5`CTT CCT GGA GGT CAC GGC TCA AGG 3`. Alleles of the 3`UTR were coded according to their number of repeats: 6- repeat 320 bp (allele 6), 8- repeat 400 bp (allele 8), 9-repeat 480 bp (allele 9), 10- repeat 480 bp (allele 10), and 11- repeat 520 bp (allele 11). Results: There were no allelic (chi(2) = 2.67, 5df, p = .75) and genotypic (chi(2) = 7.20, 1df, p = .61) association between adult ADHD and VNTR 3`UTR polymorphism of SLC6A3. Conclusion: Our findings do not support SLC6A3 as marker genetic susceptibility factor in adult ADHD. More comprehensive polymorphism coverage within the SLC6A3 region should be conducted in larger samples, including comparisons in clinical subgroups, and in samples with different ethnic backgrounds. (J. of Att. Dis. 2011; 15(4) 305-309)

Saliva of laboratory-reared Lutzomyia longipalpis exacerbates Leishmania (Leishmania) amazonensis infection more potently than saliva of wild-caught Lutzomyia longipalpis

In order to compare the saliva effect from wild-caught and lab-reared L. longipalpis on the development of experimental cutaneous leishmaniasis, C57BL/6 mice were inoculated subcutaneously into the hind footpads with promastigotes of L (L.) amazonensis Plus salivary gland lysate from wild-caught (SGL-W) and lab-colonized (SGL-C) vectors. Lesion sizes were significantly larger in the mice infected with both saliva compared to mice infected with parasites alone; moreover, the lesions caused by parasite+SGL-C were significantly larger than the lesions caused by parasite+SGL-W. Histopathological morphometric studies regarding the acute phase of infections showed lower numbers of polymorphonuclear cells, greater numbers of mononuclear cells and parasites in SGL-C infected mice compared to SGL-W infected mice. In the chronic phase of infection, the number of mononuclear cells was lower and the number of parasites was greater in SGL-C infected mice than SGL-W infected mice. In vitro studies showed increased infection index of macrophages infected with parasites plus saliva compared to infection with parasites alone, with no difference between the saliva infection indices. SDS-PAGE gel for SGL-C and SGL-W showed differences in the composition and quantity of protein bands, determined by densitometry. These results call attention to the experimental saliva model, which shows exacerbation of infection caused by sandfly saliva. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Assessment of psychosocial adjustment in patients with temporal lobe epilepsy using a standard measure

Despite the growing evidence of poor psychosocial adjustment, at present there is no formal method of assessment of social adjustment in patients with temporal lobe epilepsy (TLE). First, we assessed social adjustment in patients with TLE using a self-report questionnaire and compared the results with those from quality-of-life (QOL) scales. Second, we verified the influence of cognitive performance and clinical variables of epilepsy on social adjustment and QOL We evaluated 35 people with TLE and 38 healthy controls. Patients had worse social adjustment, and it was correlated with worse perception of cognitive function. Attention and verbal memory dysfunctions were negatively correlated with social adjustment. However, there was no significant correlation between cognitive performance and QOL Regarding clinical variables, persons with left TLE showed worse social adjustment and patients with frequent seizures showed worse QOL These findings indicate the relevance of evaluating social adjustment and emphasize the importance of cognitive rehabilitation to improved social adjustment. (c) 2010 Elsevier Inc. All rights reserved.