Long-term safety and efficacy of lentiviral hematopoietic stem/progenitor cell gene therapy for Wiskott-Aldrich syndrome.

Patients with Wiskott-Aldrich syndrome (WAS) lacking a human leukocyte antigen-matched donor may benefit from gene therapy through the provision of gene-corrected, autologous hematopoietic stem/progenitor cells. Here, we present comprehensive, long-term follow-up results (median follow-up, 7.6 years) (phase I/II trial no. NCT02333760 ) for eight patients with WAS having undergone phase I/II lentiviral vector-based gene therapy trials (nos. NCT01347346 and NCT01347242 ), with a focus on thrombocytopenia and autoimmunity. Primary outcomes of the long-term study were to establish clinical and biological safety, efficacy and tolerability by evaluating the incidence and type of serious adverse events and clinical status and biological parameters including lentiviral genomic integration sites in different cell subpopulations from 3 years to 15 years after gene therapy. Secondary outcomes included monitoring the need for additional treatment and T cell repertoire diversity. An interim analysis shows that the study meets the primary outcome criteria tested given that the gene-corrected cells engrafted stably, and no serious treatment-associated adverse events occurred. Overall, severe infections and eczema resolved. Autoimmune disorders and bleeding episodes were significantly less frequent, despite only partial correction of the platelet compartment. The results suggest that lentiviral gene therapy provides sustained clinical benefits for patients with WAS.

A novel approach for the treatment of Morgagni hernias: robotic transabdominal preperitoneal diaphragmatic hernia repair.

PURPOSE: We introduce a novel approach to the surgical repair of Morgagni hernias (MHs) utilizing the robotic transabdominal preperitoneal repair (rTAPP) approach. Borrowed from our previous and robust experience with rTAPP repairs for hernias of the anterior abdominal wall, this technique boasts the benefits of hernia sac reduction, the use of an uncoated mesh in an extraperitoneal plane, and minimal fixation leading to lower postoperative pain relative to other approaches. METHODS: To evaluate the effectiveness of this novel approach, five consecutive symptomatic Morgagni hernias (MHs) were repaired with the rTAPP approach. The size of the defect, mesh size, length of stay, follow-up imaging, and follow-up complications were documented for comparison. RESULTS: The size of the MH defects ranged from 4 × 6 cm to 5 × 10 cm. LOS was an average of 1.2 days. Two out of the five patients underwent concomitant repair of a lower abdominal hernias (one Spigelian hernia, and one indirect inguinal hernia). Outpatient follow-up from surgery ranged anywhere from 6 months to 4 years, with most patients receiving follow-up after 1 year. Four out of the five patients received follow-up CT scans to confirm the absence of hernia recurrence. One patient experienced an incisional hernia from the midline 12-mm port site which was repaired 1 year after. CONCLUSION: We propose a new technique for a minimally invasive strategy to treat these complex hernias utilizing an rTAPP technique resulting in minimal length of stay and a durable result in long-term follow-up. The benefits of repair, which include minimal postoperative pain, minimal length of stay, and cost-effective prosthetic mesh hidden from the visceral contents, are consistent with the author's experience for rTAPP repairs for hernias of the anterior abdominal wall.

Chronic hepatitis in the English springer spaniel: clinical presentation, histological description and outcome.

Medical records and liver histology of 68 English springer spaniels (ESS) with a histological diagnosis of CH were reviewed retrospectively. PCR was performed on liver tissue for canine adenovirus-1 (CAV-1), canine parvovirus, canine herpesvirus and pathogenic Leptospira species. Follow-up information was obtained to calculate survival times. Median age at presentation was three years seven months (range, seven months to eight years five months) and there were 48 female and 20 male dogs. Clinical signs were non-specific and five dogs were asymptomatic. All dogs had an increase in serum activity of one or more hepatobiliary enzymes. Histopathology demonstrated hepatocyte necrosis and apoptosis with varying amounts of fibrosis. A predominantly lymphoplasmacytic infiltrate throughout the hepatic parenchyma was found in all 68 dogs, but 45 of these dogs also had a neutrophilic component to the inflammatory infiltrate. There was no significant copper accumulation and no aetiological agent was identified by PCR. The median survival time was 189 days (range, 1 to 1211 days), 38 dogs died within three months and 12 dogs survived more than a year following diagnosis.

Effects of the addition of methyltestosterone to combined hormone therapy with estrogens and progestogens on sexual energy and on orgasm in postmenopausal women.

OBJECTIVE: To evaluate the effect of the addition of methyltestosterone to estrogen and progestogen therapy on postmenopausal sexual energy and orgasm. METHODS: Sixty postmenopausal women in a stable relationship with a partner capable of intercourse, and presenting sexual complaints that appeared after menopause, were randomly divided into two groups: EP (n = 29) received one tablet of equine estrogens (CEE) 0.625 mg plus medroxyprogesterone acetate (MPA) 2.5 mg and one capsule of placebo; EP + A (n = 31) received one tablet of CEE 0.625 mg plus MPA 2.5 mg and one capsule of methyltestosterone 2.0 mg; The treatment period was 12 months. The effects of treatment on sexual energy were assessed using the Sexual Energy Change Scale. The ability to reach orgasm in sexual relations with the partner was verified through monthly calendars and by calculating the ratio between monthly frequency of orgasms in sexual relations and monthly sexual frequency. RESULTS: There was a significant relationship between improvement in level of sexual energy and the addition of methyltestosterone to CEE/MPA treatment (p = 0.021). No significant effect on orgasmic capacity was noted after the treatment period. CONCLUSION: Addition of methyltestosterone to CEE/MPA therapy may increase sexual energy, but might not affect the ability to obtain orgasm in sexual relations.

Perfil sexual da populaçäo brasileira: resultado do Estudo do Comportamento Sexual (ECOS) do Brasileiro / Sexual profile of brazilian population: results from Brazilian Study of Sexual Behavior(BSSB)

Objetivo: Apresentar os principais hábitos e disfunçöes sexuais da polpulaçäo brasileira. Materiais e métodos: Amostrta de 2.835 indivíduos (47 porcento homens e 53 porcento mulheres), maiores de 18 anos, foi pesquisada no ano de 2000. testes de qui-quadrado foram realizados. Resultados: Para homens, as principais disfunçöes foram: disfunçäo erétil (DE)- 46,2 porcento, ejaculaçäo precoce (EP)- 15,8 porcento, falta de desejo sexual (FDS)- 12,3 porcento e disfunçäo orgásmica (DO)- 10 porcento. Para mulheres: disfunçäo orgásmica (DO)- 29,3 porcento, dor à relaçäo sexual (DRS)- 21,1 porcento e falta de desejo sexual - 34,6 porcento. $,9 porcento dos homens e 16,4 porcento das mulheres näo têm vida sexual ativa.Mulheres iniciam vida sexual 5,6 anos mais cedo que há 40 anos. O número médio de relaçöes sexuais por semana foi de 3,1 para homens e 2,8 para mulheres. A maioria dos homens (72,4 porcento) e das mulheres (57,7 porcento) se disseram à vontade para falar de sexo, sendo os indivíduos mais velhos os mais insatisfeitos com a vida sexual. Afeto e carinho foram os elementos considerados mais importantes num relacionamento sexual, para homens (63,3 porcento) e para mulheres (71,3 porcento). O maior medo masculino numa relaçäo sexual foi näo satisfazer a parceira (62,6 porcento) e em segundo lugar contaminar-se com DST (58,3 porcento). Para mulheres, oresultado foi inverso: contaminar-se com DST (54,1 porcento) e näo satisfazer o parceiro (45 porcento). Conclusöes: DE é a disfunçäo mais referida entre os homens. DO e FDS säo muito mais comum em mulheres. Para homens, o maior medo é de mau desempenho sexual e para mulheres, contaminaçäo com DST. Insatisfaçäo sexual aumenta com a idade, para ambos os sexos. Nas últimas quatro décadas, o onício da vida sexual tem ocorrido mais cedo para mulheres, enquanto para homens näo se observou muita diferença.(au)

Pedofilia: uma Proposta Terapeutica / Pedophilia: a therapeutic purpose

Os autores fazem uma revisao bibliografica sobre pedofilia, um transtorno da preferncia sexual que ocorre principalmente em homens e que acarreta varios problemas sociais, legais e pessoais, dando enfase aos aspectos terapeuticos. Apresentam como ilustracao o relato de um paciente de 35 anos de idade com diagnostico de pedofilia, que realiza tratamento psicoterapico e medicamentoso

Diagnóstico em psiquiatria e relaçäo médico-paciente / Psychiatric diagnosis and physician-patient relationship

A autora salienta a importância do diagnóstico, como procedimento médico. Em seguida, apresenta um breve histórico do desenvolvimento da Psiquiatria e do diagnóstico psiquiátrico para, entao, caracterizá-lo como pluridimensional e comentar sua sistematizaçao, privilegiando a sistemática de Leme Lopes. Chama a atençao para a atual tendência de sistemas classificatórios ateóricos em relaçao à etiologia. E, paradoxalmente, de recursos cada vez mais sofisticados, no campo do diagnóstico causal. Alerta para o reconhecimento das tensoes geradas pelo curso médico, as quais podem contribuir para a complexidade dos procedimentos diagnósticos, com prejuízo do aperfeiçoamento da relaçao médico-paciente e da finalidade terapêutica da Medicina e da Psiquiatria.