Female circumcision (female genital mutilation): a problem for brachytherapy in cervical cancer

Female circumcision is a traditional practice common in African countries. It involves partial or total removal of external female genitalia. It has led to many complications, in particular, the scarring of the external genitalia. The consequence is a very narrow introitus making the intracavitary brachytherapy treatment component difficult when these women develop cancer of cervix. We present two such cases from our institution. Our aim is to make the radiation and gynecological oncologists, both in developed and developing countries, aware of this practice and the problems they can encounter in the management of such cases. Intracavitary brachytherapy is an important component in the potentially curative role of radiation therapy for cervical cancer. Every effort should be made to ensure that the sequelae of genital mutilation does not deprive these women of the same standard of care as the general population.     

Effect of tissue inhibitor of metalloproteinases-3 genetics polymorphism on clinicopathological characteristics of uterine cervical cancer patients in Taiwan

Single nucleotide polymorphisms (SNPs) of tissue inhibitor of metalloproteinases-3 (TIMP-3) have been revealed to be related to various cancers. To date, no study explores the relationships between TIMP-3 polymorphisms and uterine cervical cancer. The purposes of this research were to investigate the associations among genetic variants of TIMP-3 and development and clinicopathological factors of uterine cervical cancer, and patient 5 years survival in Taiwanese women. The study included 123 patients with invasive cancer and 97 with precancerous lesions of uterine cervix, and 300 control women. TIMP-3 polymorphisms rs9619311, rs9862 and rs11547635 were checked and their genotypic distributions were determined by real-time polymerase chain reaction. It showed that women with genotypes CT/TT in rs9862 were found to display a higher risk of developing cervical cancer with moderate and poor cell differentiation. Moreover, it revealed that cervical cancer patients carrying genotypes CC in rs9619311 exhibited a poorer 5 years survival, as compared to those with TT/TC in Taiwanese women, using univariate analysis. In addition, pelvic lymph node metastasis was determined to independently predict 5 years survival in cervical cancer patients using multivariate analysis. Conclusively, TIMP-3 SNPs polymorphisms rs9619311 are related to cervical patient survival in Taiwanese women.     

Interleukin-3, GM-CSF, and TPA induce distinct phosphorylation events in an interleukin 3-dependent multipotential cell line

The mechanism of action of the hemopoietic growth factor, murine interleukin-3 (mIL-3), was investigated using an mIL-3-dependent multipotential hematopoietic cell line, B6SUtA1. Murine granulocyte- macrophage colony-stimulating factor (mGM-CSF) was as potent as mIL-3 in stimulating these cells. In addition, sodium orthovanadate, an inhibitor of phosphotyrosine phosphatase, and 12-O-tetradecanoyl- phorbol-13-acetate (TPA), a known activator of protein kinase C, also stimulated DNA synthesis in these cells, suggesting that protein phosphorylation might be involved in the mechanism of action of mIL-3 and mGM-CSF. To assess this possibility, intact B6SUtA1 cells exposed for brief periods to mIL-3, mGM-CSF, and TPA were analyzed for changes in phosphorylation patterns using metabolic 32P-labeling and antibodies to phosphotyrosine. Both mIL-3 and mGM-CSF induced the serine-specific phosphorylation of a 68-Kd cytosolic protein, whereas all three agents stimulated the serine-specific phosphorylation of a 68-Kd membrane protein. Furthermore, mIL-3 stimulated tyrosine phosphorylation of the 68-Kd membrane protein, as well as of 140-, 90-, 55, and 40-Kd proteins. The 90-Kd protein was also tyrosine phosphorylated in response to mGM-CSF. These phosphotyrosine containing proteins were not detected in TPA-treated cells. These results indicate that protein phosphorylations on tyrosine and serine residues occur in B6SUtA1 cells following short-term incubation with mIL-3 or mGM-CSF and that most of these phosphorylation events are mediated by kinases other than protein kinase C (PkC).     

Favourable outcome in sclerotherapy for bleeding oesophageal varices in schistosomiasis: Results in 30 patients

Abstract Thirty consecutive patients with bleeding oesophageal varices secondary to schistosomal liver disease received injection sclerotherapy. These formed a part of a prospective study, to evaluate the role of sclerotherapy in the treatment of bleeding oesophageal varices due to different aetiological factors in patients seen at the Gastroenterology Unit, Riyadh Armed Forces Hospital, Saudi Arabia, between December 1980 and July 1984.
Schistosomiasis is endemic in parts of Saudi Arabia. Sclerotherapy has a special place in schistosomal liver disease as liver function is well preserved in this disease. The new antischistosomal drugs are effective and may halt the progress of the disease. However, in many patients portal hypertension with bleeding oesophageal varices is found at diagnosis. Of the patients with schistosomiasis, 63.3% were Group A Child's Classification. Oesophageal varices have been eradicated in 11 cases during the mean follow-up period of 28 months (range 3-44 months). Four patients were referred for surgery because of bleeding gastric varices, two of whom died following operation. One patient, who was also hepatitis B surface antigen positive, died due to re-bleeding from gastric varices. The remaining 25 patients had no recurrence of bleeding and their liver function remained satisfactory.
Surgical procedures for oesophageal varices in schistosomiasis carry the risk of peri-operative and postoperative morbidity and mortality. In contrast, complications following sclerotherapy are minor compared to surgical procedures and none of our patients had any serious sclerotherapy complications.     

Identification of an oncogenic form of the thrombopoietin receptor MPL using retrovirus-mediated gene transfer

Thrombopoietin and its receptor (MPL) are important regulators of megakaryopoiesis. We have identified an activating mutation of MPL using a combination of a retrovirus-mediated gene transfer and polymerase chain reaction-driven random mutagenesis. This point mutation causes a single amino acid substitution from Ser498 to Asn498 in the transmembrane region and abrogates factor-dependency of all interleukin-3-dependent cell lines tested. Murine interleukin-3- dependent Ba/F3 cells expressing the mutated but not the normal form of MPL were tumorigenic when transduced into syngeneic mice. Analysis of intracellular signaling pathways indicated that the mutant MPL protein constitutively activated two distinct signaling pathways, SHC-Raf-MAPK and JAK2-STAT3/STAT5.     

Outcomes after liver transplantation for combined alcohol and hepatitis C virus infection

Alcohol abuse and chronic hepatitis C virus(HCV)infection are two major causes of chronic liver disease in the United States.About 10%-15%of liver transplants performed in the United States are for patients with cirrhosis due to combined alcohol and HCV infection.Data on outcomes on graft and patient survival,HCV recurrence,and relapse of alcohol use comparing transplants in hepatitis C positive drinkers compared to alcohol abuse or hepatitis C alone are conflicting in the literature.Some studies report a slightly better overall outcome in patients who were transplanted for alcoholic cirrhosis vs those transplanted for HCV alone or for combined HCV and alcohol related cirrhosis.However,some other studies do not support these observations.However,most studies are limited to a retrospective design or small sample size.Larger prospective multicenter studies are needed to better define the outcomes in hepatitis C drinkers.