6-Thioguanine for Crohn's disease during pregnancy: thiopurine metabolite measurements in both mother and child

6-Thioguanine is used as an escape thiopurine for treating inflammatory bowel disease patients intolerant or refractory to azathioprine, 6-mercaptopurine or methotrexate. Case reports show conflicting data on the use of 6-thioguanine throughout pregnancy. The administration of the standard thiopurines is believed to be relatively safe. We describe two patients with Crohn's disease treated with low-dose 6-thioguanine during all trimesters of their pregnancies. The pregnancies resulted in two healthy infants: without congenital abnormalities, laboratory signs of myelosuppression or hepatocellular injury. Thiopurine metabolites were measured in mother and infant. Significantly lower levels of 6-thioguaninenucleotides were found in the erythrocytes of the infant compared to the mother ( ratio 1: 12). Further studies are needed to determine the clinical importance of thiopurine metabolite measurements during pregnancy in mother and chil

PCR based high risk HPV testing is superior to neural network based screening for predicting incident CIN III in women with normal cytology and borderline changes

(*) Professor J M M Walboomers died recently Background/Aims—To improve the accuracy of conventional cytology in cervical cancer screening, high risk human papillomavirus (HPV) testing and neural network based screening have been developed. This study assessed the power of both techniques to detect women at risk of developing incident CIN III; that is, CIN III detected during the follow up of women with normal cytology and borderline nuclear changes. Methods—A cohort of 2250 women, 34–54 years of age, who attended population based cervical cancer screening from 1988 to 1991 and had normal smears or borderline nuclear changes was followed. All smears were tested for high risk HPV and the smears were rescreened using neural network based screening. The value of neural network based screening for predicting incident CIN III during a mean follow up period of 6.4 years was compared with that of high risk HPV testing. In addition, morphological markers presumed to be related to HPV were correlated with HPV status. Results—Thirteen (0.6%) women had incident CIN III. Both high risk HPV positivity and abnormal cytology were associated with an increased risk for incident CIN III (odds ratio, 240 and 22, respectively) and high risk HPV positivity was associated with abnormal cytology. The sensitivity of high risk HPV testing for predicting incident CIN III was much higher than that of neural network based screening (92% and 46%, respectively). None of the morphological markers assessed, including koilocytosis, was correlated with high risk HPV status. Conclusion—High risk HPV testing is superior to neural network based screening in identifying women at risk of developing CIN III. For women with normal cytology and borderline changes and a negative high risk HPV test, the screening interval can be considerably prolonged. Key Words: neural network based screening • high risk human papillomavirus testing • CIN II

Molecular events in uterine cervical cancer

OBJECTIVE: To review the literature regarding the molecular events which occur in the development of uterine cervical cancer, with particular reference to human papillomavirus (HPV) infection. METHODOLOGY: Bibliographic searches of Medline and the ISI citation databases using appropriate keywords, including the following: papillomavirus, cervix, pathology, cyclin, chromosome, heterozygosity, telomerase, smoking, hormones, HLA, immune response, HIV, HSV, EBV. CONCLUSIONS: It has become clear that most cervical neoplasia, whether intraepithelial or invasive, is attributable in part to HPV infection. However, HPV infection alone is not sufficient, and, in a small proportion of cases, may not be necessary for malignant transformation. There is increasing evidence that HPV gene products interfere with cell cycle control leading to secondary accumulation of small and large scale genetic abnormalities. This may explain the association of viral persistence with lesion progression but, in many patients, secondary factors, such as smoking and immune response, are clearly important. However, the mechanisms involved in the interaction between HPV and host factors are poorly understood.