Anal incontinence among primiparous women increases over time and is affected by further childbirth. Anal incontinence at 9 months postpartum is an important predictor of persisting symptoms.

Human deoxyribonucleoside kinases are required for the pharmacological activity of several clinically important anticancer and antiviral nucleoside analogs. Human deoxycytidine kinase and thymidine kinase 1 are described as cytosolic enzymes in the literature, whereas human deoxyguanosine kinase and thymidine kinase 2 are believed to be located in the mitochondria. We expressed the four human deoxyribonucleoside kinases as fusion proteins with the green f luorescent protein to study their intracellular locations in vivo. Our data showed that the human deoxycytidine kinase is located in the cell nucleus and the human deoxyguanosine kinase is located in the mitochondria. The fusion proteins between green f luorescent protein and thymidine kinases 1 and 2 were both predominantly located in the cytosol. Sitedirected mutagenesis of a putative nuclear targeting signal, identified in the primary structure of deoxycytidine kinase, completely abolished nuclear import of the protein. Reconstitution of a deoxycytidine kinase-deficient cell line with the wild-type nuclear or the mutant cytosolic enzymes both restored sensitivity toward anticancer nucleoside analogs. This paper reports that a deoxyribonucleoside kinase is located in the cell nucleus and we discuss the implications for deoxyribonucleotide synthesis and phosphorylation of nucleoside analogs.

Persistent anal incontinence 10 years after the first parturition is frequent and sometimes severe, especially if vaginal delivery was complicated by an anal sphincter disruption.

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Abstract.A consecutive series of 118 samples from patients referred to colposcopy assessment and follow-up with cytology and biopsies were analysed with immunocytochemical staining to determinate the expression of p16 INK4a . Accumulation of p16INK4a antigen has been proposed as a biomarker helpful for the identification of dysplastic cervical cells. In our study all benign cases were negative for p16 INK4a , while more than half of the high grade lesions showed moderate or strong reactivity. There was a correlation between CIN grade and p16INK4a expression levels with more advanced lesions showing stronger reactivity. The correlation between p16INK4a immunoreactivity and the severity of cytological abnormality was stronger, when the diagnosis was based on simultaneous routine cytology (p<0.001, χ 2 exact test for trend). There was no or weak reactivity in benign cases, as well as almost all low-grade lesions, while two thirds of high-grade lesions showed moderate or strong staining for p16 INK4a antigen. Thus p16INK4a expression analysis yielded information which is consistent with results from the histopathology and is a simple way of emphasizing the presence of premalignant cell reactive atypias. This staining can be applied to cytological samples, and might be a complement prognostic procedure in order to find women at risk for cervical cancer. IntroductionPreinvasive lesions of the cervix are frequent in young women, with a peak in incidence between the age of 25 and 40 years (1). Cytopathological screening for precancerous cervical lesions has achieved a considerable reduction in cervical cancer incidence and mortality in industrialized nations (2). Nevertheless, it remains the principle female cancer in developing countries, mainly due to lack of screening (3).Human papillomavirus (HPV) of high-risk types have been identified as the causative agent in cervical cancers (4). The presence of HPV has however a low predictive value since most infections are transient and only a small fraction of women positive for oncogenic types of HPV develop cervical cancer (5-7).In Sweden, a combination of organized and opportunistic screening has reduced the incidence of squamous carcinoma substantially during the last decades (1,8). All abnormal samples are followed-up with colposcopy, biopsy and ultimately conization. Both cytological and histopathological assessment rely on defined morphological criteria, but are also associated with intra-and interobserver variation (9-11), and could therefore benefit from complementary, more objective procedures.Various screening strategies have been proposed in which HPV testing is combined with the cytological examination to increase sensitivity. HPV testing has shown satisfying sensitivity, but it lacks specificity to be used as a primary screening tool (12,13). The ideal would be an objective test distinguishing women with non-progressive mild neoplasia from those with oncogenic transformation and at risk of developing invasive cancer, to facilitate decision on therapy and nee...

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