Opportunistic screening for genital Chlamydia trachomatis infection and partner follow-up in family planning clinics in three Scottish cities

Three large urban family planning clinics (FPCs) in Scotland participated in a study to examine the implications of opportunistically offering urine testing for genital Chlamydia trachomatis infection and FPC follow-up of positive women and of their male partners. Ninety-eight percent (3029) of women accepted the test. The prevalence of infection was 5.2% and this decreased significantly with age. There was no significant difference in prevalence between centres. Ninety-one percent of positive women intended to inform at least one partner about their infection status. Pretest counselling took about 10 minutes per woman while management (excluding full screening for sexually transmitted infections) of positive women took an additional 10 minutes. Screening in the FPC is acceptable to many women and to some of their male partners. Training and resources for administration and staffing are required if opportunistic screening is to be implemented.     

Phase I and pharmacokinetic study of the farnesyltransferase inhibitor R115777 in combination with irinotecan in patients with advanced cancer

Purpose R115777 is a selective, nonpeptidomimetic inhibitor of farnesyltransferase (FTase), an enzyme responsible for the post-translational modification of several proteins, including Ras. Given the high frequency of K-Ras mutations in malignancies commonly treated with irinotecan, the broad preclinical antiproliferative activity of R115777 and its largely non-overlapping toxicity profile with irinotecan, this phase I study of the combination of R115777 and irinotecan in patients with advanced cancer was undertaken.Patients and methods Enrolled onto the study were 14 patients (eight male, six female; median age 63 years, range 48–72 years). Five patients had an ECOG performance status (PS) of 0, eight patients PS 1, and one patient PS 2. The patients were treated with R115777 orally twice daily for 28 days and irinotecan 100 mg/m² as an intravenous infusion on days 1, 8, 15, and 22 of each 42-day cycle. Seven patients received R115777 100 mg twice daily and seven received R115777 200 mg twice daily.Results Dose-limiting toxicity (DLT) was experienced by one of seven patients treated with R115777 100 mg (grade 3 fatigue), and two of seven patients treated with R115777 200 mg (grade 3 diarrhea, grade 4 neutropenia lasting >5 days). The maximum tolerated dose (MTD) was R115777 100 mg twice daily and irinotecan 100 mg/m² weekly. Non-DLTs were primarily rash, fatigue, diarrhea, and neutropenia. R115777 demonstrated linear pharmacokinetics without interaction with irinotecan and achieved serum levels required for antitumor activity in vitro.Conclusions Serum levels of R115777 exceeded those necessary for FTase inhibition in vitro without evidence of interaction with irinotecan. However, the MTD of R115777 in this study was lower than that obtained with an alternate schedule. Thus, further development of this schedule is not recommended.This work was supported by a grant from Johnson and Johnson Pharmaceutical Research and Development and NCI K12 CA01728.     

Adjuvant therapy in pancreatic cancer: Phase I trial of radiation dose escalation with concurrent full-dose gemcitabine

PURPOSE: To evaluate the clinical significance of the interval between surgery and postoperative radiotherapy (RT) for patients with soft tissue sarcoma. METHODS AND MATERIALS: The records of 799 patients who underwent postoperative RT for soft tissue sarcoma between 1960 and 2000 were retrospectively reviewed. Univariate and multivariate analyses were used to evaluate the potential impact of the timing of postoperative RT on the rate of local control (LC). RESULTS: The actuarial overall LC rate was 79% at 10 years and 78% at 15 years. Univariate analysis indicated that the factors associated with an inferior 10-year LC rate were positive resection margins (p <0.0001); treatment for recurrent disease (p <0.0001); primary location in the head and neck or deep trunk (p <0.0001); age >64 years (p <0.0001); histopathologic subtype of malignant fibrous histiocytoma, neurogenic sarcoma, or epithelioid sarcoma (p = 0.01); tumor size >10 cm (p = 0.02); postoperative radiation dose <64 Gy (p = 0.03); and high histologic grade (p = 0.05). On multivariate analysis, all these factors remained statistically significant, except for high histologic grade and large size. A delay between surgery and the start of RT of >30 days was associated with a decreased 10-year LC rate, but this association was not statistically significant (76% vs. 83%, p = 0.07). The potential association between RT delay and inferior LC could be explained by an imbalance in the distribution of other prognostic factors. CONCLUSION: The interval between surgery and RT did not significantly impact the 10-year LC rate. These findings indicate that an RT delay should not be viewed as an independent adverse factor for LC and that treatment intensification may not be necessary for patients in whom a treatment delay has already occurred.     

The role of industry in improving quality of life for persons with an ostomy: a Canadian consensus

Financial and clinical resources (which include 260 enterostomal therapy nurses nationwide) to provide clinical and rehabilitative expertise to the estimated 50,000 to 60,000 Canadians living with an ostomy are limited. Hence, many persons with an ostomy fall through the cracks in the early pre- and postoperative period or are lost to follow-up afterdischarge. Problems and issues related to ostomy management continue to surface throughout their lives. As a result,the time required for rehabilitation is often lengthy, affecting the person's quality of life. The First Canadian Enterostomal Therapy Nurses' Advisory Council consisting of 10 Canadian enterostomal therapy nurses met in February 2004 to identify key issues and concerns for Canadians living the ostomy experience and to identify gaps in information and services available before surgery, during the immediate postoperative period, and as the time from surgery lengthened and patients moved through age-related life issues. The two most important gaps identified were the development of quality, pertinent resources and the dissemination of those resources. The Council also identified potential strategies to bridge these gaps, including utilizing the resources of manufacturer Customer Service departments to follow a communications protocol to provide information to patients, retailers, and providers. Finally, a process map from which individual ostomy manufacturers can build programs and processes for improving patient/provider/manufacturer communication was developed.     

Astrocytic proliferation in the piriform cortex of amygdala-kindled subjects: a quantitative study in partial versus fully kindled brains

Complex partial epilepsy is a seizure disorder in which attacks frequently arise from foci located in the temporal lobes. The amygdala-kindling model is a widely used model of complex partial epilepsy with secondary generalization. The present study was designed to quantitatively assess astrocytic changes in the rat piriform cortex in the amygdala-kindling model of epilepsy. Bromodeoxyuridine-injected subjects were sacrificed 24 h after the first stage 1 or fifth stage 5 seizure. Brain sections were prepared and examined quantitatively. A significantly higher number of dividing astrocytes (identified by co-labeling with antibodies to bromodeoxyuridine and to one of the astrocytic intermediate filament proteins glial fibrillary acidic protein or vimentin) was found in both partially kindled (stage 1) and fully kindled (stage 5) brains. The partially kindled brains had a significantly higher number of double-labeled cells on the side ipsilateral to stimulation. The opposite trend was observed in the fully kindled brains. Differences between the ipsilateral and contralateral sides of the kindled brain may suggest different role(s) for astrocytes in the development and progression of the seizure-prone state.