Cytological screening and management of abnormalities in prevention of cervical cancer: an overview with stochastic modelling.

AIMS--To develop a mathematical model of the histological changes of precancer and the development of invasive cancer and how these are related to cytological findings. To use this to investigate the effects on incidence of cervical cancer, number of smear tests and colposcopies, of different schedules for cervical screening, and the clinical management policies for dyskaryosis. METHODS--A stochastic model was developed relating the available data on tissue progression to the cytological findings. Two strategies, A and B, were compared: under A, women with any abnormal smear receive immediate colposcopy and treatment; under B, women with mild or borderline dyskaryosis have repeated smears at six monthly intervals with colposcopy only for persistent abnormalities. RESULTS--The model predicted an incidence of invasive cervical cancer in an unscreened population of women aged over 18 years of 5.9 per 10,000 per year. With 70% coverage and three yearly screening under strategy A, the incidence fell to 2.00 and under B to 2.10. The number of smears required was similar but A required two to three times as many colposcopies as B. Raising the coverage to 90% reduced the incidence to around 1 per 10,000 per year but changing the screening interval, the specificity or sensitivity of cytology had much less effect. CONCLUSION--The model has been tested under a wide range of possible variations in natural history, specificity and sensitivity of cytology. For low grade smear abnormalities, open colposcopic referral is predicted to reduce invasive cancer only slightly more than repeat cytology, at the expense of much additional colposcopy. Improving cytological coverage is suggested as more effective in reducing invasive cancer than increased use of colposcopy or more frequent screening.     

Thio TEPA pharmacokinetics during intravesical chemotherapy and the influence of Tween 80

Summary A pharmacokinetic study of randomised crossover design was carried out in which eight patients with recurrent stage pTa or pT1 transitional cell carcinoma of the bladder were given thio TEPA (30 mg) in distilled water or in 10% (v/v) Tween 80 (30 ml) intravesically for 2 h, followed 3 months later by the alternative treatment. Thio TEPA and its primary metabolite, TEPA, were measured in plasma and urine using a sensitive and specific chromatographic assay. Large differences between patients were observed in the proportion of thio TEPA absorbed, ranging from 20%–78%. Peak plasma levels of thio TEPA were observed within 1 h of intravesical administration. By 2 h after administration the plasma levels of TEPA were similar to those of thio TEPA and, in contrast to those of the parent compound, remained at a similar level over the next 4 h. The rate of absorption of thio TEPA was not influenced by Tween 80, but it did cause statistically significant increases in mean peak plasma levels (from 101 to 154 ng/ml) and mean AUC values (from 0.376 to 0.496 g h per ml) and a decrease in the mean half-life (from 1.83 to 1.25 h). To obtain plasma levels similar to those achieved after instillation with thio TEPA alone, the dose should be reduced with Tween 80.     

First transmission electron micrograph of continuous mitotic spindle fibers between polar area and chromosome ends

Congenital and/or nevoid skin disorders following the lines of Blaschko may have a delayed onset after birth. They have to be differentiated from acquired dermatoses exhibiting the same linear pattern. In common dermatoses, such as psoriasis or lichen planus, lesions in a blaschkolinear distribution most often occur together with scattered lesions, but occasionally they may be isolated. Less common self-limited dermatoses such as lichen striatus and adult blaschkitis always present in a blaschkolinear fashion. In these diseases, or some other conditions occasionally distributed along these lines (chronic graft versus host reaction, fixed drug eruption, lupus erythematosus, atopic dermatitis, etc.), the cause of the disease may lead to the unmasking of tolerance to an abnormal keratinocyte clone that remained hidden in these lines. In addition to epithelial cells, other cells may be involved in the occurrence of acquired blaschkolinear dermatoses. In linear atrophoderma and linear fibromatosis, the histogenesis seems to involve hypothetic dermal clones. The extension of an acquired dermatosis on a preexisting linear nevoid disorder is an argument in favor of an early embryonic somatic mutation of a skin cell line.     

Magnetic resonance spectroscopy in toxic encephalopathy and neurodegeneration

Magnetic resonance spectroscopy allows neurochemistry to be probed noninvasively in vivo. Recent advances in our understanding of the biochemical significance of the various neurochemicals that are observable allow a variety of pathologic states of relevance to encephalopathies and neurodegenerative disorders to be observed. Measurements of brain glutamate and glutamine allow observation of neuronal/glial substrate cycling and ammonia detoxification. Myo-inositol allows changes in cerebral osmolarity and gliosis to be observed. N-acetylaspartate is a marker of neuronal health and number. Lactate allows nonoxidative glycolysis to be observed. These molecules are now being used to ask etiologic questions that are of relevance to encephalopathies and neurodegeneration, as well to probe longitudinally both natural history and therapeutic interventions in these conditions. Combined with recent advances in anatomic magnetic resonance imaging as well as perfusion magnetic resonance imaging, magnetic resonance spectroscopy has the potential to aid greatly in our understanding of neuronal dysfunction in a wide variety of neurologic pathologies, even in single patients.     

Distal splenorenal shunt: role, indications, and utility in the era of liver transplantation

HYPOTHESIS: The distal splenorenal shunt (DSRS) continues to play an important role in the management of recurrent variceal bleeding with minimal negative impact on subsequent orthotopic liver transplantation (OLT). DESIGN: Case-control study. SETTING: Hepatobiliary surgery and liver transplantation unit in a tertiary referral medical center. PATIENTS: From August 1, 1985, through October 31, 1997, a single team of surgeons performed 81 DSRS procedures for recurrent variceal hemorrhage. Eleven patients undergoing OLT subsequent to DSRS were compared with a group of 274 patients undergoing OLT without any previous shunt during the same period. MAIN OUTCOME MEASURES: Operative time, use of blood products, length of hospital stay, perioperative complications, and survival rates. RESULTS: Operative (30-day) mortality for DSRS was 6% (n = 5). From follow-up information available for 74 patients, the 1- and 5-year survival rates were 86.4% (n = 64) and 74.3% (n = 55), respectively. Recurrent variceal bleeding and hepatic encephalopathy occurred in 5 (6.8%) and 11 patients (14.9%), respectively, after DSRS. In 9 patients, DSRS was used as salvage for failed transjugular intrahepatic portosystemic shunt. CONCLUSIONS: Distal splenorenal shunt is a safe, durable, and effective treatment for controlling recurrent variceal hemorrhage in patients with acceptable operative risk and good liver function. It does not compromise future liver transplantation and can considerably delay the time until transplantation is required. Given the early occlusion rate and need for constant surveillance, transjugular intrahepatic portosystemic shunting should be reserved for patients with Child C classification cirrhosis with chronic hemorrhage or intractable ascites or as an emergency procedure for patients with uncontrollable bleeding using endoscopic therapy.