Contraceptive efficacy of the Copper T380A and the Multiload Cu250 IUD in three developing countries

The clinical performance of the Copper T380A (TCu380A) and the Multiload 250 (MLCu250) intrauterine devices (IUDs) were evaluated for 12 months in a group of women who had one of the two IUDs inserted. Results are from a randomized clinical trial conducted at four collaborating research sites located in three developing countries.The gross cumulative life-table pregnancy rate of the TCu380A IUD was significantly lower than the rate with the MLCu250 IUD at 12 months (0.5 and 1.2, respectively,p<0.01). No statistically significant differences between the two study IUDs were found with regard to IUD expulsion or IUD removal due to bleeding/pain, personal reasons, medical reasons, or planned pregnancy. TCu380A IUD users were more likely to report experiencing increased dysmenorrhea (p<0.01) or intermenstrual pelvic pain (p<0.01) than were MLCu250 IUD users. However, few of these users discontinued use of their assigned IUD because of having experienced menstrual bleeding disturbances or intermenstrual pelvic pain.These data indicate that the TCu380A IUD may be a better option than the MLCu250 IUD for women wishing to practice highly effective long-term birth control without having to resort to hormonal methods.

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Resumen El resultado clínico de los dispositivos intrauterinos (DIU) Copper T380A y Multiload 250 (MLCu250) se evaluó durante 12 meses en un grupo de mujeres a quienes se había colocado uno de los dos DIU. Los resultados corresponden a un ensayo clínico aleatorizado efectuado en cuatro emplazamientos de investigaciones en colaboración situados en tres países en desarrollo.La tasa bruta acumulativa de embarazo de las tablas de vida del DIU TCu380A fue significativamente inferior a la tasa correspondiente al DIU MLCu250 a los 12 meses (0,5 y 1,2, respectivamente,p<0,01)). No hubo diferencias estadísticamente significativas entre los dos DIU del estudio con respecto a su expulsión o retiro debido a microrragia/dolor, razones personales, razones médicas o embarazo planificado. Era más probable que las usuarias del DIU TCu380A notificaran mayor dismenorrea (p<0,01) o dolor pélvico intermenstrual (p<0,01) que las usuarias del DIU MLCu250. Sin embargo, un número menor de este grupo de usuarias dejó de utilizar el DIU que le había sido asignado por haber experimentado trastornos menstruales de microrragia o dolor pélvico intermenstrual.Estos datos indican que el DIU TCu380A podría ser una mejor opción que el DIU MLCu250 para las mujeres que desean praticar un control de la natalidad a largo plaza altamente eficaz sin tener que recurrir a métodos hormonales.

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Resumé Les résultats cliniques des dispositifs intra-utériens (DIU) Copper T38OA (TCu380A) et Multiload 250 (MLCu250) ont été évalués pendant 12 mois chez un groupe de femmes qui portaient l'un ou l'autre de ces dispositifs. Les résultats proviennent d'un essai clinique randomisé, effectué en collaboration par quatre établissements de recherche dans trois pays en développement.Au terme de 12 mois, le taux brut cumulé de grossesses des tables de survie pour le dispositif TCu380A était significativement inférieur au taux correspondant pour le dispositif MLCu250 (0,5 et 1,2 respectivement,p<0,01). Aucune différence statistiquement significative entre les deux dispositifs étudiés n'a été constatée du point de vue de l'expulsion du DIU ou de son retrait pour cause de microrragie/douleurs, pour des raisons personnelles ou médicales ou pour une grossesse planifiée. Les utilisatrices du TCu380A ont plus fréquemment signalé une dysménorrhée (p<0,01) ou des douleurs pelviennes intermenstruelles (p<0,01) que les utilisatrices du MLCu250. Peu nombreuses était cependant cells qui avaient, en raison de perturbations du flux menstruel ou de douleurs pelviennes intermenstruelles, abandonné l'usage du dispositif qui leur avait été assigné.Ces résultats indiquent que le dispositif TCu380A représente peut-être une meilleure solution que le dispositif MLCu250 pour les femmes recherchant à long terme une méthode hautement efficace de régulation des naissances, sans avoir recours aux méthodes hormonales.

     

Short-Ti inversion-recovery pulse sequence: analysis and initial experience in cancer imaging

Inversion recovery (IR), commonly considered a pulse sequence capable of producing T1-weighted images with excellent display of normal anatomy, is versatile: The null point and peak time provide a useful, succinct summary of the properties of IR and its capacity for producing both T1- and T2-weighted images. Shortening of the inversion time (TI) and creation of a short-TI inversion-recovery (STIR) pulse sequence increases sensitivity to malignancy and other abnormalities by making the effects of prolonged T1 and T2 on signal intensity additive and by nulling the signal from fat. The authors examined over 300 patients with various malignancies and compared STIR images with T1- and T2-weighted images obtained at 0.5 T. In 43 cases, signal-difference-to-noise ratios (SD/Ns) were calculated between tumor, fat, and muscle. In general, STIR images demonstrated tumor as a conspicuously high-intensity area in a background of muted, discernible anatomic detail. The good contrast achieved with STIR sequences between tumor and fat (SD/N = 18.1) and tumor and muscle (SD/N = 12.9) consolidated into a single image the information contained separately on T1- and T2-weighted images, which facilitates efficient detection and localization of malignancy.     

The effects of antioxidant supplementation during Percoll preparation on human sperm DNA integrity

The integrity of sperm DNA is crucial for the maintenance of genetic health. A major source of damage is reactive oxygen species (ROS) generation; therefore, antioxidants may afford protection to sperm DNA. The objectives of the study were, first, to measure the effects of antioxidant supplementation in vitro on endogenous DNA damage in spermatozoa using the single cell gel electrophoresis (comet) assay and, second, to assess the effect of antioxidant supplementation given prior to X-ray irradiation on induced DNA damage. Spermatozoa from 150 patients were prepared by Percoll centrifugation in the presence of ascorbic acid (300, 600 microM), alpha tocopherol (30, 60 microM), urate (200, 400 microM), or acetyl cysteine (5, 10 microM). DNA damage was induced by 30 Gy X-irradiation. DNA strand breakage was measured using the comet assay. Sperm DNA was protected from DNA damage by ascorbic acid (600 microM), alpha tocopherol (30 and 60 microM) and urate (400 microM). These antioxidants provided protection from subsequent DNA damage by X-ray irradiation. In contrast, acetyl cysteine or ascorbate and alpha tocopherol together induced further DNA damage. Supplementation in vitro with the antioxidants ascorbate, urate and alpha tocopherol separately has beneficial effects for sperm DNA integrity.      

How to use Chlamydia antibody testing in subfertility patients

Screening for tubal factor subfertility by means of Chlamydia antibody testing (CAT) was introduced into the initial work-up of subfertile couples several years ago. The results reported, however, are heterogeneous, and no uniformity exists in cut-off levels of titres, or in definitions of tubal factor subfertility. We performed a prospective cohort study to evaluate the implications of varying the definitions of tubal pathology and of modifying the cut-off levels on the clinical impact of CAT in predicting tubal factor subfertility. In 227 consecutive patients who attended our fertility clinic, the Chlamydia IgG antibody titre was determined and related to tuboperitoneal abnormalities at laparoscopy as a reference standard. According to received operating characteristic (ROC) curve analysis, a titre of 16 is the optimum cut-off level. Increasing the cut-off level improves specificity and positive likelihood ratio (LR+), at the expense of sensitivity and negative LR (LR-). Changing the definition of tubal factor subfertility from unspecified tuboperitoneal abnormalities into extensive adhesions and/or bilateral distal tubal occlusion improves LR+, LR- and kappa significantly. We conclude that CAT is more accurate in predicting severe distal tubal pathology than unspecified tuboperitoneal abnormalities. Although from a statistical point of view a titre of 16 is the optimum cut-off level, from a clinical point of view 32 or 64 may be preferable, depending on the aim of screening and the inception cohort.      

Inactivation of the p16 gene by hypermethylation and loss of heterozygosity in adenocarcinoma of the lung

We investigated the aberrant promoter hypermethylation of p16, p15 and p14 genes and loss of heterozygosity (LOH) at 9p21-22 in 48 cases of adenocarcinoma of the lung. The frequencies of hypermethylation of genes were as follows: p16, 25.0%; p15, 22.9%; and p14, 18.8%. The frequency of LOH at chromosome 9p21-22 was 60.9%. The frequency of two-hit inactivation of the p16 gene by hypermethylation and LOH was 21.7%. Two-hit inactivation of the p16 gene showed loss of protein expression and was significantly correlated with tumor size, tumor grade and the Ki-67 labeling index. Hypermethylation of the p16 gene was not significantly correlated with hypermethylation of the p15 and p14 genes, both of which are close to the p16 gene locus, suggesting that hypermethylation of these genes occurs selectivity. In conclusion, biallelic inactivation of the p16 gene by hypermethylation and LOH might cause loss of p16 expression and play an important role in the development of adenocarcinoma of the lung. Therefore, controlling and monitoring for hypermethylation of the p16 gene may be partially useful for treatment and early diagnosis of adenocarcinoma of the lung.     

Toremifene in the treatment of breast cancer

Although more widespread screening and routine adjuvant therapy has improved the outcome for breast cancer patients in recent years, there remains considerable scope for improving the efficacy, safety and tolerability of adjuvant therapy in the early stage disease and the treatment of advanced disease. Toremifene is a selective estrogen receptor modifier (SERM) that has been widely used for decades in hormone receptor positive breast cancer both in early and late stage disease. Its efficacy has been well established in nine prospective randomized phase III trials compared to tamoxifen involving more than 5500 patients, as well as in several large uncontrolled and non-randomized studies. Although most studies show therapeutic equivalence between the two SERMs, some show an advantage for toremifene. Several meta-analyses have also confirmed that the efficacy of toremifene is at least as good as that of tamoxifen. In terms of safety and tolerability toremifene is broadly similar to tamoxifen although there is some evidence that toremifene is less likely to cause uterine neoplasms, serious vascular events and it has a more positive effect on serum lipids than does tamoxifen. Toremifene is therefore effective and safe in the treatment of breast cancer. It provides not only a useful therapeutic alternative to tamoxifen, but may bring specific benefits.     

von Willebrand factor released from Weibel-Palade bodies binds more avidly to extracellular matrix than that secreted constitutively

Large multimers of von Willebrand factor (vWf) are released from the Weibel-Palade bodies of cultured endothelial cells following treatment with a secretagogue (Sporn et al, Cell 46:185, 1986). These multimers were shown by immunofluorescent staining to bind more extensively to the extracellular matrix of human foreskin fibroblasts than constitutively secreted vWf, which is composed predominantly of dimeric molecules. Increased binding of A23187-released vWf was not due to another component present in the releasate, since releasate from which vWf was adsorbed, when added together with constitutively secreted vWf, did not promote binding. When iodinated plasma vWf was overlaid onto the fibroblasts, the large forms bound preferentially to the matrix. These results indicated that the enhanced binding of the vWf released from the Weibel-Palade bodies was likely due to its large multimeric size. It appears that multivalency is an important component of vWf interaction with the extracellular matrix, just as has been shown for vWf interaction with platelets. The pool of vWf contained within the Weibel-Palade bodies, therefore, is not only especially suited for platelet binding, but also for interaction with the extracellular matrix.     

Detection of circulating crosslinked fibrin derivatives by a heat extraction-SDS gradient gel electrophoretic technique

A technique has been developed to identify and quantitate unique plasmic degradation products of crosslinked fibrin in plasma. In this method, fibrin derivatives are extracted by heat precipitation and dissolved with disulfide bond reduction, after which the crosslinked gamma-gamma chain remnants are identified by SDS-polyacrylamide gradient gel electrophoresis and quantitated by densitometric analysis. A heterogenous group of gamma-gamma chains with molecular weights between 100,000 and 76,000 daltons was identified in lysates of crosslinked fibrin during plasmic degradation in vitro. Three stages of crosslinked fibrin degradation have been arbitrarily defined based primarily on the extent of degradation of these gamma-gamma polypeptide chains. As little as 20 microgram of crosslinked fibrin digests added to 1 ml of normal plasma could be detected by the heat-extraction--gel- electrophoresis technique, identifying the gamma-gamma derivatives with molecular weights of 96,000, 86,000, 82,000, and 76,000 daltons. Plasmic derivatives of gamma-gamma chains were not found in normal plasma, but they were identified in the plasma of patients with disseminated intravascular coagulation and deep-vein thrombosis, both before and in increased quantity during successful thrombolytic therapy.