Abstract Hereditary cancer risk assessment is a multidisciplinary and dynamic process, with the purpose of estimating probabilities of germline mutations in cancer susceptibility genes and assessing empiric risks of cancer based on personal and family histories, in order to offer clinical and molecular diagnoses and clinical management based on these risks. Genetic tests are available and most of them are reimbursed by insurance companies, although they are generally not covered by the public health systems of developing countries. More recently, molecular diagnosis of hereditary cancer is feasible through next-generation sequencing (NGS) panels. Here we review the benefits and limitations of NGS technologies in the clinical practice.

OBJECTIVE: Prader-Willi Syndrome is a common etiology of syndromic obesity that is typically caused by either a paternal microdeletion of a region in chromosome 15 (microdeletions) or a maternal uniparental disomy of this chromosome. The purpose of this study was to describe the most significant clinical features of 35 Brazilian patients with molecularly confirmed Prader-Willi syndrome and to determine the effects of growth hormone treatment on clinical outcomes. METHODS: A retrospective study was performed based on the medical records of a cohort of 35 patients diagnosed with Prader-Willi syndrome. The main clinical characteristics were compared between the group of patients presenting with microdeletions and the group presenting with maternal uniparental disomy of chromosome 15. Curves for height/length, weight and body mass index were constructed and compared between Prader-Willi syndrome patients treated with and without growth hormone to determine how growth hormone treatment affected body composition. The curves for these patient groups were also compared with curves for the normal population. RESULTS: No significant differences were identified between patients with microdeletions and patients with maternal uniparental disomy for any of the clinical parameters measured. Growth hormone treatment considerably improved the control of weight gain and body mass index for female patients but had no effect on either parameter in male patients. Growth hormone treatment did not affect height/length in either gender. CONCLUSION: The prevalence rates of several clinical features in this study are in agreement with the rates reported in the literature. Additionally, we found modest benefits of growth hormone treatment but failed to demonstrate differences between patients with microdeletions and those with maternal uniparental disomy. The control of weight gain in patients with Prader-Willi syndrome is complex and does not depend exclusively on growth hormone treatment.

A isquemia seguida de reperfusão intestinal (I/R) é um evento clínico comum que favorece a translocação bacteriana em órgãos à distância, como os pulmões. A antibioticoterapia prévia pode ser uma conduta eficaz para atenuar o desenvolvimento desse processo. Este esudo tem por finalidade reconhecer a concentração dos polimorfonucleares (PMN) nos septos alveolares em ratos, após indução de isquemia seguida de reperfusão intestinal, com e sem antibioticoterapia prévia. Utilizaram-se 48 ratos divididos, aleatoriamente em 6 grupos (A,B,C,D,E,F)com 8 animais cada um. Os grupos A,C e E não receberam antibiótico,e os grupos B, D e F receberam 500mg/Kg de eritromicina por via oral. Os grupos A e B serviram de controle; C e D induziu-se isquemia intestinaL por 30 min; e os grupos E e F seguiu-se à isquemia, reperfusão por 30 min. Em seguida, abriu-se o tórax e ressecaram-se os pulmões, sendo encaminhados para análise histopatológica e histométrica, obtendo-se uma média de PMN nos septos alvéolos. O grupo controle(A) apresentou média de 4,2 PMN campo nos septos; o grupo isquêmico(C), 13,6 e o reperfundido (E), 17,5. A comparação entre as médias dos grupos A e C e A e E tiveram p<0,0001. Entretanto, a comparação entre os grupos C e E não foi significante (p=0,095). A média de PMN por campo foi de 8,6 no grupo B; 9,9 no grupo D e 12,9 no grupo F. A comparação entre os grupos B e D teve p=0,007. A comparação entre os grupos que receberam ou não antibiótico permitiu verificar que o número de PMN do grupo B foi o dobro do grupo A (p=0,004). O grupo C apresentou maior concentração de PMN que o grupo D (p=0,019). No grupo E, houve maior concentração de PMN que no grupo F (p=0,014). Pode-se concluir que: (1) a isquemia intestinal levou a maior concentração de PMN nos septos alveolares; (2) a antibioticoterapia prévia aumentou o infiltrado inflamatório pulmonar nos alvéolos dos ratos com intestino normal; (3) nos septos alveolares dos animais submetidos a I/R, a densidade de PMN foi maior que nos não reperfundidos e (4) a antibioticoterapia prévia diminuiu significantemente a concentração de PMN após I/R.

Ischemia following intestinal reperfusion is a common place event that favors bacterial translocation in remote organs, such as the lungs. Previous antibioticotherapy may be an efficient procedure to lessen the hazards of this process. The purpose of this study was to analyse the concentration of polimorphonuclears (PMN) in the lung alveolar septum of rats, after induced ischemia followed by intestinal reperfusion, with and without previous antibiotictoherapy. Forty-eight rats were used, randomly divided into 6 groups of 8 animals each (A, B, C, D, E, and F). Groups A, C and E did not receive antibiotic and groups B, D and F received 500mg/Kg of erythromycin orally. Groups A and B were the control groups. In the groups C and D intestinal ischemia was induced for 30 min; and in groups E and F reperfusion for 30 min followed the ischemia. A thoracothomy was performed and the lungs were removed and sent for histopathologic and histometric analysis. The number of PMN in the alveolar septum was observed. The control group (A) showed a mean number of 4.2 PMN per field in the septum; in the ichemia group (C) , the mean number of PMN was 13.6 and in the group where the reperfusion followed ischemia (E), the number of PMN was 17,5. The comparison between the mean number of PMN in groups A and C and A and E showed a statistically significant difference (p<0.0001). However, the difference between the groups C and E was not significant (p=0.095). The mean number of PMN per field was of 8.6 in group B; 9.9 in group D and 12.9 in group F. The comparison between the groups B and D demonstrated a p=0.007. The comparison between the groups that received antibiotics or not demonstrated that the number of PMN in group B was twice as much as in group A (p=0.0049) . Group C showed a greater concentration of PMN than did group D (p=0.019). In group E there was a greater concentration of PMN than in group F (p=0.014). It may be concluded that: (1) intestinal ischemia leads to a greater PMN concentration in the alveolar septum; (2) previous antibioticotherapy increased lung inflammatory infiltrate in the alveolus of rats with normal intestines; (3) PMN density was greater in alveolar septum of animals who underwent I/R than those who were not reperfused, and (4) previous antibioticotherapy reduced significantly the PMN concentration after I/R.