End-of-study safety, immunogenicity, and efficacy of quadrivalent HPV (types 6, 11, 16, 18) recombinant vaccine in adult women 24-45 years of age.

BACKGROUND: Previous analyses from a randomised trial in women aged 24-45 years have shown the quadrivalent human papillomavirus (qHPV) vaccine to be efficacious in the prevention of infection, cervical intraepithelial neoplasia (CIN), and external genital lesions (EGLs) related to HPV 6/11/16/18. In this report, we present end-of-study efficacy, safety, and immunogenicity data with a median follow-up time of 4.0 years. METHODS: We enrolled 3819 24-45-year-old women with no history of cervical disease or genital warts in the past 5 years. Women received quadrivalent vaccine or placebo at day 1, and at months 2 and 6. Ascertainment of CIN/EGL was accomplished through Pap testing, genital inspection, and cervicovaginal sampling (every 6 months). The main analysis was conducted in a per-protocol efficacy population (that received three doses, was naive to the relevant HPV types at day 1, and remained free of infection through month 7). Efficacy was also estimated in other naive and non-naive populations. RESULTS: Vaccine efficacy against the combined incidence of persistent infection, CIN/EGL related to HPV6/11/16/18 in the per-protocol population was 88.7% (95% CI: 78.1, 94.8). Efficacy for women who were seropositive and DNA negative for the relevant vaccine HPV type at the time of enrolment who received at least 1 dose was 66.9% (95% CI: 4.3, 90.6). At month 48, 91.5, 92.0, 97.4, and 47.9% of vaccinated women were seropositive to HPV 6/11/16/18, respectively. No serious vaccine-related adverse experiences were reported. CONCLUSIONS: The qHPV vaccine demonstrated high efficacy, immunogenicity, and acceptable safety in women aged 24-45 years, regardless of previous exposure to HPV vaccine type.

A flexible stochastic curtailing procedure for the log-rank test.

For safety and ethical reasons, a data monitoring committee of a clinical trial may wish to assess the futility of continuing a trial if the currently available data at an interim look show no beneficial effect due to treatment, especially when accompanied by mounting evidence of treatment emergent adverse effects. Stochastic curtailing whereby conditional power is evaluated given currently observed data is one way of evaluating futility. In clinical trials that look at "time-to-event" as the primary outcome, difference between treatment groups with respect to the primary outcome is commonly evaluated using the log-rank test. Although the unconditional power function for the log-rank test has been described previously, its conditional power has not been widely investigated. We describe a method for evaluating conditional power when the log-rank test is used to assess the difference between the survival distributions of two treatment groups with respect to some failure-time outcome. The method is useful under a wide range of assumptions regarding the underlying survival distribution, patient entry distribution, losses to follow-up, and (if applicable) noncompliance, drop-ins, lag in treatment effect, and stratification. This level of applicability is attained by generalizing a flexible Markov chain approach to unconditional power computation, described previously, to compute conditional power.

A novel and highly efficient synthesis of gem-difluorocyclopropanes

[reaction: see text] A new and highly versatile source of difluorocarbene is reported. Trimethylsilyl fluorosulfonyldifluoroacetate (TFDA) undergoes decomposition in the presence of catalytic fluoride to form difluorocarbene under conditions that allow its addition to relatively electron deficient alkenes in high yield. For example, unprecedented CF2: addition to n-butyl acrylate proceeded in 73% yield.

Skin collagen glycation, glycoxidation, and crosslinking are lower in subjects with long-term intensive versus conventional therapy of type 1 diabetes: relevance of glycated collagen products versus HbA1c as markers of diabetic complications. DCCT Skin Collagen Ancillary Study Group. Diabetes Control and Complications Trial.

The relationships between long-term intensive control of glycemia and indicators of skin collagen glycation (furosine), glycoxidation (pentosidine and N(epsilon)-[carboxymethyl]-lysine [CML]), and crosslinking (acid and pepsin solubility) were examined in 216 patients with type 1 diabetes from the primary prevention and secondary intervention cohorts of the Diabetes Control and Complications Trial. By comparison with conventional treatment, 5 years of intensive treatment was associated with 30-32% lower furosine, 9% lower pentosidine, 9-13% lower CML, 24% higher acid-soluble collagen, and 50% higher pepsin-soluble collagen. All of these differences were statistically significant in the subjects of the primary prevention cohort (P < 0.006-0.001) and also of the secondary intervention cohort (P < 0.015-0.001) with the exception of CML and acid-soluble collagen. Age- and duration-adjusted collagen variables were significantly associated with the HbA1c value nearest the biopsy and with cumulative prior HbA1c values. Multiple logistic regression analyses with six nonredundant collagen parameters as independent variables and various expressions of retinopathy, nephropathy, and neuropathy outcomes as dependent variables showed that the complications were significantly associated with the full set of collagen variables. Surprisingly, the percentage of total variance (R2) in complications explained by the collagen variables ranged from 19 to 36% with the intensive treatment and from 14 to 51% with conventional treatment. These associations generally remained significant even after adjustment for HbA1c, and, most unexpectedly, in conventionally treated subjects, glycated collagen was the parameter most consistently associated with diabetic complications. Continued monitoring of these subjects may determine whether glycation products in the skin, and especially the early Amadori product (furosine), have the potential to be predictors of the future risk of developing complications, and perhaps be even better predictors than glycated hemoglobin (HbA1c).

Illeo biliar. Presentacion de 18 pacientes. / Biliary ileus. Report of 18 patients

Se presentan 18 casos de ileo biliar estudiados en un periodo de 7 anos en el Hospital General del Centro Medico Nacional.Existio predominio del sexo femenino (94, 4%), con edades de 46 a 85 anos. Todos los pacientes presentaron cuadro de obstruccion intestinal, tanto clinica como radiologicamente. El diagnostico preoperatorio de ileo biliar solo se realizo en el 16.7% pero al efectuar un analisis retrospectivo de los estudios radiologicos se llego a la conclusion que debio ser mas elevado. El tipo de fistula biliar interna mas frecuente fue la colecistoduodenal (66,6%).Diez y siete enfermos fueron tratados quirurgicamente y la mortalidad global fue de 5.6%. La operacion con la que se obtuvieron mejores resultados fue la enterotomia y extraccion del calculo, no se recomienda el cierre de la fistula de primera intencion. En los pacientes con ileo biliar debe tratarse de llegar a un diagnostico correcto lo mas pronto posible, para efectuar el tratamiento oportuno y disminuir la morbimortalidad

La endoscopía en el estómago operado. / Endoscopy in operated stomach.

Se analiza la utilidad de la endoscopía del tubo digestivo superior en pacientes con cirugía gástrica por úlcera péptica gastroduodenal. En un período de 15 años se operaron 3,855 enfermos por presentar complicaciones de úlcera gástrica o duodenal. Las intervenciones quirúrgicas realizadas con mayor frecuencia fueron: vagotomía con piloroplastía, vagotomía con gastroyeyunoanastomosis y gastrectomía subtotal con gastroduodenoanastomosis. Posterior al tratamiento quirúrgico 368 pacientes continuaron con síntomas pépticos y ameritaron exámenes radiológicos y endoscópicos. Se analizan los resultados obtenidos con ambos procedimientos y se concluye que la endoscopía es el procedimiento de elección para establecer el diagnóstico de las lesiones secundarias a la cirugía gástrica como: esofagitis, gastritis, úlcera marginal, gástrica y duodenal, bezoar y granulomas. Los estudios baritados son el procedimiento de elección en la obstrucción de la anastomosis, dilatación de asas y asa ciega.

[Study on breast feeding in a suburban area]. / Estudio sobre la lactancia materna en un área suburbana.

Human milk is considered the best nourishment a child can have during his first months of life, providing that it exists in sufficient amount. In a study of the feeding characteristics in suburban areas of Mexico City, it was found that 71 mothers would continue to breast-feed their children up to the twelfth month. Supplemental feeding began during the first four months with: fruit, vegetables, eggs, meat and in final stages, soups and cereals. The great majority of the mothers thought that human milk is the ideal food for their babies. The medical concept about breast-feeding in the suburban areas of Mexico City is mistaken, due to information based on foreign studies contrary to national reality. In spite of the widespread belief that breast-feeding has decreased in frequency, in this study it was found that it is still popular and commonplace. We recommend that through all information sources, the inestimable value of human milk as an ideal nourishment, due to its nutritional, economical, psychological and hygienic properties, should be emphasized.

The ultrastructure of liver cells in women under steroid therapy. II. Contraceptive therapy.

PIP: The fine structures of liver cells biopsies of 14 women using oral contraceptives and 8 women who were not using steroids were studied electron microscopically. In all the women studied, liver function and coagulation tests were normal. Women treated with microdoses of progestogens and with combinations of progestogens and estrogens showed dilation and vesiculation of both the rough and smooth endoplasmic reticulum. Women using sequential OC's showed more marked vesiculation. 5-10% of the mitochondria per cell of women using chlormadione and 20-40% of the mitochondria of women on combined or sequential therapy showed elongation and crystalloid inclusions in the mitochondrial matrices. Fatty degeneration was noted. This was more pronounced in women using combined and sequential OC's. The nucleus, Golgi-complex, bile canaliculi, and glycogen granules were all unmodified.^ieng