A sensitive non-radioactive assay for pyrimidine nucleoside phosphorylase using reversed-phase high performance liquid chromatography

A new sensitive assay for pyrimidine nucleoside phosphorylase using non-radioactive substrates is described. With the natural substrate uridine (UR) and the analog, 5'-deoxy-5-fluorouridine (5'dFUR) conditions have been optimized to measure the product formation with reversed-phase high-performance liquid chromatography. Using automated injection large series of samples may be analyzed. The assay for UR phosphorylase appeared to be comparable to existing methods with radiolabeled UR as substrate regarding sensitivity and linearity. The assay has been used to measure kinetic parameters for 5'dFUR and UR in two cell lines from intestinal origin.     

Transvaginal sonography and rectal endoscopic sonography for the assessment of pelvic endometriosis: a preliminary comparison

BACKGROUND: Endometriosis and possible rectal involvement are difficult to assess by physical examination. Previous studies have shown the diagnostic value of magnetic resonance imaging and rectal endoscopic sonography (RES) in this setting, but not that of transvaginal sonography (TVS). The aims of this study were to compare the accuracy of TVS and RES for the diagnosis of pelvic endometriosis, and to compare the results with histological findings. PATIENTS AND METHODS: In a prospective study, 30 consecutive patients referred with clinical signs of endometriosis underwent TVS and RES; the images were interpreted blindly with regard to physical findings. RESULTS: Endometriosis was confirmed histologically in 28 (93%) of the 30 patients. Endometriomas were also present in 67% of cases. For the diagnosis of uterosacral endometriosis, the sensitivity, specificity, and positive and negative predictive values of TVS and RES were 75 and 75%, 83 and 67, 95 and 90%, and 45 and 40% respectively. For the diagnosis of rectosigmoid endometriosis, the sensitivity, specificity, and positive and negative predictive values of TVS and RES were 95 and 82%, 100 and 88%, 100 and 95%, and 89 and 64% respectively. CONCLUSION: Despite the large proportion of our patients who had intestinal endometriosis, representing a possible source of bias, our results suggest that TVS is as efficient as RES for detecting posterior pelvic endometriosis and should therefore be used as the first-line examination.     

Effect of Pyrimidine Nucleosides on Body Temperatures of Man and Rabbit in Relation to Pharmacokinetic Data

The effect of high-dose uridine on body temperatures of rabbits and man has been studied in relation to plasma concentrations of uridine and its catabolite uracil. Uridine induced fever in both rabbits and man. High-dose cytidine had no influence on body temperature in rabbits. Plasma concentrations of uridine were between 1 and 1.5 mM at 30 min after an iv bolus injection of 400 mg uridine/kg in rabbits and reached peak levels of 2 mM after a 1-hr infusion of 12 g uridine/m² in man. The plasma concentration of cytidine in rabbits was about 0.5 mM and that of uridine was 0.30 mM at 30 min after an iv bolus injection of 400 mg cytidine/kg. The mean residence time for uridine in patients and rabbits varied between 80 and 195 min. The area under the plasma concentration–time curve (AUC) for uridine in rabbits was 2.0 mmol · hr/liter, and that for cytidine was 0.6 mmol · hr/liter. A large AUC for uridine indicates a prolonged exposure of tissues to uridine, which might lead to extensive formation of degradation products. The administration of some of these catabolites, dihydrouracil (at 20–40 mg/kg), carbamyl--alanine (at 60 mg/kg), and -alanine (at 300–400 mg/kg), resulted in a significant increase in body temperature. It is concluded that the change in body temperature associated with uridine administration was not due to bacterial pyrogens but that one of the degradation products might be involved in thermoregulation.     

18F-2-fluoro-2-deoxy-d-glucose positron emission tomography in staging of locally advanced breast cancer.

PURPOSE: To prospectively evaluate the effect of adding whole-body (18)F-2-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) to conventional screening for distant metastases in patients with locally advanced breast cancer (LABC). PATIENTS AND METHODS: All women with LABC referred for participation in the LABC Spinoza trial were considered eligible for this study. Patients were included if chest x-ray, bone scan, liver ultrasound, or computed tomography scan performed by the referring physician failed to reveal distant metastases. They underwent whole-body FDG PET scanning before therapy. Patients with subsequently proven distant metastases were switched to alternative forms of chemotherapy, hormonal therapy, or both. RESULTS: Among the 48 patients evaluated with PET, 14 had abnormal FDG uptake, and metastases were suspected in 12. After simple clinical evaluation (plain x-ray, history), 10 sites that were suggestive of abnormality remained. Further work-up revealed that four sites were metastases. Proven false positivity occurred in one patient with sarcoidosis. In the other five patients, the reason for abnormal FDG uptake (liver, lung, bone) remained unclear, and patients were treated as planned. Eleven months later, distant metastases were found in one patient at sites unrelated to the previous FDG uptake. CONCLUSION: The addition of FDG PET to the standard work-up of patients with LABC may lead to the detection of unexpected distant metastases. This may contribute to a more realistic stratification between patients with true stage III breast cancer and those who are in fact suffering from stage IV disease. Abnormal PET findings should be confirmed to prevent patients from being denied appropriate treatment.     

Hepatocyte growth factor and c-Met in cervical intraepithelial neoplasia: overexpression of proteins associated with oncogenic human papillomavirus and human immunodeficiency virus.

PURPOSE: High prevalence of squamous cervical intraepithelial neoplasia (CIN) linked to oncogenic human papillomavirus (HPV) exits in HIV-infected women. Hepatocyte growth factor (HGF) and its receptor, c-Met, promote cell proliferation and are involved in tumor progression. Nothing is yet known about their expression in low- and high-grade CIN. Therefore, the expression, localization, and behavior of HGF and c-Met in normal and dysplastic cervical epithelium were investigated. EXPERIMENTAL DESIGN: We studied normal cervical mucosa from 10 healthy women, and low- and high-grade cervical lesions, uninfected (condyloma acuminata) or infected with oncogenic HPVs, from 40 HIV-negative and 48 HIV-positive women, using in situ molecular techniques, immunocytochemistry and morphoquantitative methods. RESULTS: In 154 oncogenic HPV-infected CIN encountered in biopsy samples, the total number of epithelial cell layers increased significantly during lesion progression. This number was significantly higher in HIV-positive than in HIV-negative women for CIN1 and CIN2 (P < 0.025 to P < 0.01). In HIV-negative women, the number and percentage of HGF and c-Met immunostained cell layers, and the intensity of immunostaining were enhanced in oncogenic HPV-infected lesions as compared with normal mucosa and condyloma acuminata. The latter parameters were significantly higher in tissues of HIV-positive women (oncogenic HPV-infected CIN1 and CIN2, normal-appearing mucosa contiguous to CIN, condyloma acuminata) than in the corresponding tissues of HIV-negative women (P < 0.025 to P < 0.0001). CONCLUSIONS: Overexpression of HGF/c-Met complex strongly correlates with oncogenic HPV and HIV infection. This overexpressed complex may stimulate cell proliferation in condyloma acuminata and participate in tumor progression in oncogenic HPV-infected lesions.     

Regionalization of perinatal care in Europe.

This review describes European health policies related to the place of birth of very preterm babies, and the organizational context in which these policies were enacted using data from two European studies. It also compiles available information on the place of birth of very preterm babies from the published literature. In Europe, there is significant diversity in approaches to the provision of intensive care services for the small proportion of pregnant women and babies that need it, both in terms of health policies and the supply and characteristics of maternity and neonatal units. These diverse models in countries with similar levels of development and medical technology could offer an opportunity to understand how different organizational characteristics affect access to care, health outcomes and resource use.     

Transvaginal hydrolaparoscopy: practices in French teaching hospitals

STUDY OBJECTIVE: To examine transvaginal hydrolaparoscopy (THL) practices in French tertiary care centers. DESIGN: Prospective longitudinal study (Canadian Task Force classification III). SETTING: University hospital in France. PARTICIPANTS: Gynecology and obstetrics departments of all 48 French teaching hospitals. INTERVENTIONS: Practice of THL using a 8-item questionnaire. MEASUREMENTS AND MAIN RESULTS: Main outcome measure was practice, indications, and complications of THL in French tertiary care centers. Between October 2005 and March 2006, the departments were sent an 8-item questionnaire on the use of diagnostic and operative THL. In all, 38 (79%) hospitals completed the questionnaire. THL was or is still used in 20 (53%) departments. The main reason given by the 18 departments that never used THL was that it was "less informative than laparoscopy." Only 8 (40%) of 20 departments with experience of THL continued to use the procedure routinely. The main reason given for abandoning THL was its limited operative potential. Among the 8 departments that continued to use THL, 6 used operative THL (mainly for ovarian drilling). Among the 30 departments that answered the item on the likely future place of THL, only 6 (20%) considered that THL would continue to be performed. CONCLUSION: Few French teaching hospitals routinely use THL. Further data on THL, and especially its cost effectiveness, are needed to clarify its place to evaluate female fertility.     

Spontaneous uterine artery rupture during pregnancy in a woman with sickle cell disease: a case report

BACKGROUND: Spontaneous rupture of uterine vessels during pregnancy is rare and usually involves uteroovarian veins. Presenting symptoms include acute-onset abdominal pain and maternal hypovolemic collapse due to hemoperitoneum. An atypical case of subacute uterine artery rupture at 27 weeks of gestation occurred in a woman with sickle cell disease. CASE: A 28-year-old, nulliparous woman with sickle cell disease was admitted at 27 weeks of gestation for sharp abdominal pain radiating to the right flank. The first diagnosis included acute renal colic and a sickling vasoocclusive crisis. One week after admission the patient experienced paroxysmal, diffuse abdominal pain associated with acute fetal distress requiring an emergency cesarean section. Laparotomy revealed an 800-mL hemoperitoneum. Active bleeding from a ruptured uterine artery was observed and successfully treated by selective suture. CONCLUSION: Spontaneous rupture of the uterine artery during pregnancy may present as a 2-step process.