[Active surveillance for early-stage prostate cancer]. / La surveillance active dans la prise en charge du cancer de la prostate précoce.

Diagnostic and treatment management of prostate cancer at its initial stage continues to raise important debates within the involved medical community. To establish a protocol for active surveillance, a validated option in specific conditions of localised prostate cancer management for eight years, is a unique opportunity to gather different specialists in this field. This paper presents this concept.

Structure elucidation and 3D solution conformation of the antibiotic enduracidin determined by NMR spectroscopy and molecular dynamics.

Enduracidin and ramoplanin belong to the large family of cyclodepsipeptide antibiotics, highly effective against Gram-positive bacteria. The primary and 3D solution structure of ramoplanin is already well known, and the primary structure of enduracidin has been determined by a combination of chemical and NMR spectroscopic methods. Both antibiotics share a similar peptide core of 17 amino acids and differ mainly in the length of the acyl chain and the presence of two D-mannose moieties in ramoplanin. Based on the high sequence homology with ramoplanin, the structure in solution of enduracidin is modeled as a cyclic peptide. The tertiary structure thus obtained was refined through molecular dynamics (MD) simulation, in which the interatomic NOE-derived distance restraints were imposed. MD simulations yielded a family of representative 3D structures (RMSD = 0.89), which highlighted a backbone geometry similar to that of ramoplanin in its beta-hairpin arrangement. In contrast, enduracidin displays a different arrangement of the side-chain and of the residues forming the hydrophobic core.

Uses and limitations of two molecular cytogenetic techniques for the study of arrested embryos obtained through assisted reproduction technology

We studied chromosomal abnormalities in arrested embryos produced by assisted reproductive technology with fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH) in order to determine the best technique for evaluating chromosomal aneusomies to be implemented in different situations. We examined individual blastomeres from arrested embryos by FISH and arrested whole embryos by CGH. All of the 10 FISH-analyzed embryos gave results, while only 7 of the 30 embryos analyzed by CGH were usable. Fifteen of the 17 embryos were chromosomally abnormal. CGH provided more accurate data for arrested embryos; however, FISH is the technique of choice for screening in preimplantation genetic diagnosis, because the results can be obtained within a day, while the embryos are still in culture.

Antioxidant liposoluble vitamins and carotenoids in chronic hepatitis.

Background: It is known that antioxidant liposoluble vitamins and carotenoids are reduced in liver cirrhosis, but little is known about chronic viral hepatitis, where oxidative damage has to be taken into account. Methods: Fifty-five patients with chronic hepatitis, mainly C virus-related, were matched with 16 patients with biliary stones and 20 healthy controls. Plasma and liver analyses were carried out using a well-tried HPLC technique that affords an accurate quantification of retinol, tocopherol, alpha- and beta-carotene, cryptoxanthin, and lycopene. Results: Plasma concentration of retinol, tocopherol, beta-carotene, and lycopene was significantly decreased in both patient groups, particularly in those with chronic hepatitis. In contrast, liver concentration of both esterified and free retinol, tocopherol, and some carotenoids was better preserved in the hepatitis group than in the cholelithiasis group. A strict correspondence between aminotransferases and the amount of liver-stored retinol was documented. Conclusions: Plasma vitamin and carotenoid depletion co-existing with preserved liver storage may indicate a functional defect in liver pool mobilization or even a real depletion of the antioxidant defenses, which play a key role in averting cellular damage. The implications for nutrition and therapy need to be taken into account.

Biosynthesis of the thiazolylpeptide antibiotic GE2270.

The biosynthesis of the antibiotic GE2270 in the producing microorganism Planobispora rosea was investigated by adding labelled amino acid precursors. Efficient incorporation of glycine and serine was observed, leading to specific enrichments of selected positions of the thiazole, oxazoline and pyridine rings. Furthermore, efficient enrichment of the C-, N- and O-methyl groups was detected. These results indicate that GE2270 is made through a biosynthetic route similar to that determined for other thiazolylpeptides. At the same time, the result point to an efficient route for the conversion of glycine into serine and methyl equivalents in Planobispora rosea.

Tratamiento combinado con metotrexate sistémico y resección histeroscópica en un caso de embarazo ectópico cervical / Combined treatment with sistemic methotrexate and hysteroscopic resection in a case of cervical ectopic pregnancy

El embarazo ectópico cervical es un cuadro de muy baja frecuencia y sumamente peligroso por la posibilidad de penetración de la pared por el trofoblasto hacia las arterias uterinas con compromiso de la vida de la paciente por hemorragia incontrolable y de su fertilidad futura cuando el único recurso terapéutico es la histerectomía. En la actualidad y gracias a la disponibilidad de recursos que permiten un diagnóstico precoz, son las técnicas no quirúrgicas las que constituyen la primera línea terapéutica. Se presenta el caso de una paciente de 30 años con diagnóstico de esterilidad primaria que ingresa al programa de ART, se realiza un ICSI por factor masculino que resulta en un embarazo bioquímico. Dos ciclos más tarde y durante la evaluación previa al comienzo de un nuevo ciclo luego de tratamiento con acetato de noretisterona por spotting se realiza el diagnóstico ecográfico de embarazo ectópico cervical. Fue tratada con metotrexate sistémico y al presentar sangrado se procedió a su resección por vía histeroscópica con éxito (AU)

Tratamiento combinado con metotrexate sistémico y resección histeroscópica en un caso de embarazo ectópico cervical / Combined treatment with sistemic methotrexate and hysteroscopic resection in a case of cervical ectopic pregnancy

El embarazo ectópico cervical es un cuadro de muy baja frecuencia y sumamente peligroso por la posibilidad de penetración de la pared por el trofoblasto hacia las arterias uterinas con compromiso de la vida de la paciente por hemorragia incontrolable y de su fertilidad futura cuando el único recurso terapéutico es la histerectomía. En la actualidad y gracias a la disponibilidad de recursos que permiten un diagnóstico precoz, son las técnicas no quirúrgicas las que constituyen la primera línea terapéutica. Se presenta el caso de una paciente de 30 años con diagnóstico de esterilidad primaria que ingresa al programa de ART, se realiza un ICSI por factor masculino que resulta en un embarazo bioquímico. Dos ciclos más tarde y durante la evaluación previa al comienzo de un nuevo ciclo luego de tratamiento con acetato de noretisterona por spotting se realiza el diagnóstico ecográfico de embarazo ectópico cervical. Fue tratada con metotrexate sistémico y al presentar sangrado se procedió a su resección por vía histeroscópica con éxito

Low-dose aspirin treatment improves ovarian responsiveness, uterine and ovarian blood flow velocity, implantation, and pregnancy rates in patients undergoing in vitro fertilization: a prospective, randomized, double-blind placebo-controlled assay.

OBJECTIVE: To determine the effects of low-dose aspirin on ovarian response, uterine and ovarian blood flow velocity, and implantation and pregnancy rates in patients undergoing IVF. DESIGN: Prospective, randomized, double-blind placebo-controlled assay. SETTING: Department of Reproductive Medicine, CER Medical Institute, Buenos Aires, Argentina. PATIENT(S): Two hundred ninety-eight infertile patients (mean [+/- SDI age, 35.6+/-4.09 years) undergoing IVF cycles. INTERVENTION(S): In the treatment group, 149 patients underwent controlled ovarian hyperstimulation and received a daily dose of 100 mg of aspirin. In the control group, 149 patients underwent controlled ovarian hyperstimulation in association with placebo. MAIN OUTCOME MEASURE(S): Number of follicles, number of oocytes retrieved, serum E2 levels, uterine and ovarian pulsatility index, cancellation rate, number of embryos transferred, and implantation and pregnancy rates. RESULT(S): There were statistically significant differences between the treatment group and the control group, respectively, in the number of follicles (19.8+/-7.2 versus 10.2+/-5.3), number of oocytes retrieved (16.2+/-6.7 versus 8.6+/-4.6), serum E2 levels (2,923.8+/-1,023.4 versus 1,614.3+/-791.7 pg/mL), uterine pulsatility index (1.22+/-0.34 versus 1.96+/-0.58), ovarian pulsatility index (1.18+/-0.31 versus 1.99+/-0.56), pregnancy rate (45% versus 28%), and implantation rate (17.8% versus 9.2%). CONCLUSION(S): Low-dose aspirin treatment significantly improves ovarian responsiveness, uterine and ovarian blood flow velocity, and implantation and pregnancy rates in IVF patients.

Age at death and rectangularisation of the survival curve: trends in Switzerland, 1969-1994.

OBJECTIVE: To check if signs of rectangularisation of the survival curve appeared during recent decades in Switzerland--that is, if life expectancy is approaching a maximum with a clustering of age at death around an average value (the so called "compression of mortality"). METHODS: Descriptive analysis of age of death and its trends over 26 years, as characterised by the modal value, median, and various percentiles beyond the median. POPULATION: All deaths occurring after the 50th birthday in Switzerland between 1969 and 1994 (n = 1,390,362). MAIN RESULTS: Age at death is increasing at a sustained rate at all percentiles equal or greater than 50, without any slow down in the trend during this period. The increase is more marked among women. Rates of increase are diminishing as the percentiles of age at death are higher, suggesting some clustering of deaths beyond the median value. However, the maximum age at death, if any, seems to be far from the current median values, even for women who enjoy a relatively high median age at death.

Fitting the distributions of length of stay by parametric models.

OBJECTIVES: The purpose of this study was to assess the adequacy of three widely used models--Lognormal, Weibull, and Gamma--for describing the distribution of length of stay. This is a fundamental step in the development of outliers resistant (robust) methods for the statistical analysis of this kind of data, where the main objective is to determine measures of average and total resource consumption of groups of patients. Current practice uses several types of trimming rules, many of which are based on the Lognormal model, although theoretical and experimental bases are still insufficient. METHODS: The three models were adjusted using robust procedures based on M-estimators to approximately 5 million stays grouped by Diagnosis-Related Groups (DRGs). The resulting 3,279 samples were collected in five European countries during 3 years. RESULTS: Most of the distributions observed could be fitted with one of these models. The descriptions provided by the Gamma and the Weibull models were similar, and the Gamma model could be omitted. The casemix description provided by the Log-normal-Weibull family was, for certain countries, significantly better than the one provided by the single Lognormal model. Often, for a given DRG and a given country, length of stay distributions could be described with the same model during several years. A given DRG, however, usually had to be described by means of different models for different countries. CONCLUSIONS: Practical and conceptual consequences of the results are discussed. They can be extended to the analyses of other consumption variables used in health services. Statistical procedures for casemix description, including current rules of trimming, should be improved by means of more flexible families of models.

Pregnancy after human donor oocyte cryopreservation and thawing in association with intracytoplasmic sperm injection in a patient with ovarian failure.

OBJECTIVE: To describe a pregnancy after human donor oocyte cryopreservation in association with intracytoplasmic sperm injection in a patient with ovarian failure. SETTING: Department of Reproductive Medicine, CER Medical Institute, Buenos Aires, Argentina. PATIENT: A 48-year-old patient with ovarian failure. RESULTS: Ten donated oocytes were cryopreserved. Survival after thawing was 30%. Three oocytes were microinjected, and two embryos were obtained. The fertilization rate was 66%, and embryo development was 100%. Both embryos were transferred to a patient who had received hormonal replacement therapy. The attempt was successful, and a pregnancy was achieved after the transfer. CONCLUSION: In association with intracytoplasmic sperm injection, an adequate technique of freezing and thawing of human oocytes might achieve encouraging results in ART programs.

Synthesis and biological evaluation of new fragments from kirromycin antibiotic.

New N-acyl derivatives of 1-N-desmethyl goldinamine were obtained from degradation of kirromycin. Periodate-oxidation of these derivatives provided new aldehydic fragments that were further elaborated. Both N-phenyl ureido and N-phthalimido derivatives of 1-N-desmethyl goldinamine are able to inhibit bacterial protein synthesis in cell-free assay and are active against whole microorganisms, although with lower potency than kirromycin. The derivatives from the aldehydic fragments are totally inactive.

Exploring models for the length of stay distribution.

Diagnosis Related Groups (DRG) are frequently used to standardize the comparison of consumption variables, such as length of stay (LOS). In order to be reliable, this comparison must control for the presence of outliers, i.e. values far removed from the pattern set by the majority of the data. Indeed, outliers can distort the usual statistical summaries, such as means and variances. A common practice is to trim LOS values according to various empirical rules, but there is little theoretical support for choosing between alternative procedures. This pilot study explores the possibility of describing LOS distributions with parametric models which provide the necessary framework for the use of robust methods.

Adenocarcinoma renal: experiencia clínica y tratamiento / Renal adenocarcinoma: clinical experience and treatment

Revisamos 118 adenocarcinomas renales operados en un período de 20 años, con un seguimiento entre 1 y 20 años. La edad, sexo, sitio anatómico, diámetro tumoral y tiempo sintomático no influyeron en la sobrevida. Esta fue mejor a menor estadio tumoral, existiendo dfiferencias significativas en la sobrevida a 10 años, entre el estadio IIIa (58 por ciento) y IIIb (0 por ciento). Similares diferencias mostró el grado de Skinner (56,3 por ciento el grado bajo y 24,5 por ciento el grado alto) y el grado de Broders (54,5 por ciento el grado bajo y 13,7 por ciento el grado alto), corvirtiéndose ambos en exelentes factores pronósticos. No hubo diferencias estadísticas en la sobrevida según tipo histológico y arquitectura tumoral. El principal tratamiento fue la nefrectomía radical (70 por ciento), no encontándose diferencias según vía de abordaje

Evaluation of the consistency of Acute Physiology and Chronic Health Evaluation (APACHE II) scoring in a surgical intensive care unit.

OBJECTIVES: To determine the applicability of the Acute Physiology and Chronic Health Evaluation (APACHE II) scoring system in a Swiss ICU, and to evaluate its utility in evaluating data from 2 yrs of consecutive admissions to show that the predictability of outcome is similar to that predictability observed by Knaus et al. in 1985 (in 5,815 patients), with the provision that large numbers of patients are studied. DESIGN: Prospective clinical trial over 2 yrs, with statistical analysis of the Swiss patients, and between the Swiss patients and the patients studied by Knaus et al. Receiver operating characteristic curves were calculated. SETTING: Surgical ICU in a Swiss university hospital. PATIENTS: A total of 2,061 consecutive patients admitted to the surgical ICU who were classified as postoperative (elective or emergency) and nonoperative. Hospital mortality rate was considered. RESULTS: Patients were 53 +/- 16 yrs of age. Mean APACHE II score was 10.5 +/- 7.0. The mean APACHE II score was significantly (p < .001) lower in the 1,813 survivors (9.0 +/- 5.2) than in the 248 nonsurvivors (21.5 +/- 8.5). The mortality rate was higher among the Swiss patients when compared with the patients studied by Knaus et al. who had postoperative scores of 20 to 29 and nonoperative scores of > 24. The distribution of the scores and mortality rates were stable during the two study periods, as were the differences in mortality rates between the Swiss population and that population studied by Knaus et al. Sensitivity and specificity of the scores were highest in the emergency surgery group (87% and 78%), and lowest in the elective surgery group (76% and 73%). The APACHE equation underestimated the risk of death. CONCLUSIONS: The APACHE II score, because of its consistency over time and the stability of the mortality rates, can be used in our surgical ICU without modification. The calculated risk of death gives no additional information.