A phase I clinical and pharmacokinetic study of the topoisomerase I inhibitor topotecan (SK&F 104864) given as an intravenous bolus every 21 days.

Topotecan (SK&F 104864) is a novel antitumor agent whose mechanism of action is inhibition of the DNA unwinding protein topoisomerase I. An analog of camptothecin, topotecan was designed to be more water soluble in an effort to decrease the severe and sporadic toxicities experienced during phase I/II trials of the parent compound. In this phase I clinical and pharmacological trial, topotecan was given as a bolus intravenous (i.v.) infusion over 30 min every 21 days. A total of 42 patients entered the study, receiving doses ranging from 2.5 to 22.5 mg/m2. The maximum tolerated dose (MTD) of topotecan given in this schedule was 22.5 mg/m2. Myelosuppression, primarily neutropenia, was dose-limiting. The extent of prior therapy did not predict for more severe neutropenia. Non-hematologic toxicities were mild and included low-grade to moderate fever, nausea, vomiting, alopecia, diarrhea and skin rashes. There were no objective partial or complete responses, although there was a suggestion of antitumor activity in three patients. Topotecan undergoes pH-dependent hydrolysis of the lactone ring; only the closed, lactone form is active. The lactone form predominated during infusion, with hydrolysis occurring rapidly following the end of infusion. There were linear relationships between dose administered and peak plasma lactone concentrations as well as AUC lactone to AUC total. The lactone was rapidly cleared from plasma with a total body clearance of 25.7 (+/- 6.7) l/h/m2. The plasma lactone concentration declined rapidly with a harmonic mean terminal half-life of 3.4 (+/- 1.1)h. Lactone hydrolysis and renal excretion were the major routes of elimination.(ABSTRACT TRUNCATED AT 250 WORDS)     

Microsurgical epididymovasostomy by tubule intussusception: a new technique in rat model

This experimental study on 15 adult male rats with bilateral epididymovasostomies evaluates a new technique of tubule intussusception as an improved form of end-to-end anastomosis. This paper describes in detail the steps in this technique and offers physiological, anatomical, and histological follow-up after 3 months. With this technique there is a 97% patency rate and a 23.3% incidence of macroscopic spermatic granuloma. Complications are discussed in detail.     

Successful fetal therapy for cystic adenomatoid malformation associated with second-trimester hydrops

Fetal hydrops secondary to cystic adenomatoid malformation was detected in a second-trimester fetus. In utero thoraco-amniotic shunt placement resulted in resolution of the hydrops. At term, there was no evidence of pulmonary hypoplasia.     

Self-efficacy in weight management

Self-efficacy is an important mediating mechanism in advancing understanding of the treatment of obesity. This study developed and validated the Weight Efficacy Life-Style Questionnaire (WEL), improving on previous studies by the use of clinical populations, cross-validation of the initial factor analysis, exploration of the best fitting theoretical model of self-efficacy, and examination of change in treatment. The resulting 20-item WEL consists of five situational factors: Negative Emotions, Availability, Social Pressure, Physical Discomfort, and Positive Activities. A hierarchical model was found to provide the best fit to the data. Results from two separate clinical treatment studies (total N = 382) show that the WEL is sensitive to changes in global scores as well as to a subset of the five situational factor scores. Treatment programs may be incomplete if they change only a subset of the situational dimensions of self-efficacy. Theoretical and clinical implications are discussed.     

Coronary artery bypass graft surgery in older women and men.

OBJECTIVE: To compare women and men younger than 70 years of age and 70 years or older undergoing coronary artery bypass surgery. DESIGN: Retrospective chart review, case-control series. SETTING: University medical center. PATIENTS: All women (n = 465) having first-time isolated coronary artery bypass surgery between 1983 and 1988, and 465 men matched for age and year of surgery. Predominantly white; 33% were 70 years or older. MEASURES: Medical record data: demographics, preoperative comorbidities, perioperative and postoperative complications, mortality, length of stay. RESULTS: Preoperatively, women 70 years of age or older had a higher incidence of congestive heart failure, renal disease and hypertension, and a lower incidence of smoking history compared with women less than 70 years old. Men 70 years or older had a higher incidence of congestive heart failure and renal disease, and a lower incidence of smoking history compared with men less than 70 years old. There was no difference in mortality between older and younger women, whereas the mortality rate for older men was higher than that for younger men. There were fewer differences between women younger than 70 and those 70 years or older in incidence of postoperative complications than between men of those same age groups. Among patients 70 years or older, incidence of postoperative congestive heart failure was greater in women than in men. There were no other differences between women and men younger than 70 and those 70 years or older in incidence of postoperative complications. Controlling for the influence of postoperative complications, age was related to length of stay for women and men. CONCLUSIONS: Older women were at no greater risk of mortality or the occurrence of postoperative complications compared with younger women or older men. A functional component influencing recovery and length of hospital stay needs to be considered to provide optimal nursing care after surgery.     

Antimicrobial properties of heartwood,bark/sapwood and leaves of Juniperus species

Hexane and methanol extracts of heartwood, bark/sapwood and leaves of twelve taxa of Juniperus from the United States were assayed for antifungal and antibacterial activities. The hexane extract of the heartwood of several junipers appeared comparable in antibacterial activity to streptomycin. Antibacterial activity of the hexane extracts from the bark/sapwood of J. monosperma and J. californica were comparable to streptomycin. No appreciable antibacterial activities were found in the leaf extracts from any species examined. No antifungal activities comparable to amphotericin B were found in either hexane or methanol extracts of the heartwood nor from the bark/sapwood. Antifungal activity against Cryptococcus neoformans comparable to amphotericin B was found in the hexane extract of the leaves of J. occidentalis var. australis. The methanol extracts from the leaves of J. osteosperma and J. californica had antifungal activities comparable to amphotericin B against Trichophyton mentagrophytes.     

Simple color tests based on an alanyl peptidase reaction which differentiate Listeria monocytogenes from other Listeria species.

The hydrolysis of DL-alanine-beta-naphthylamide and D-alanine-p-nitroanilide for identification of Listeria spp. has been studied with 227 cultures. All species of Listeria, except L. monocytogenes, hydrolyzed these substrates. The reactions were detected by simple chromogenic reactions and could substitute for the CAMP test.     

Safety of outpatient tonsillectomy and adenoidectomy

Recent changes in reimbursement for tonsillectomy and adenoidectomy have resulted in a large number of these procedures being done on an outpatient basis. There is still considerable controversy, however, as to the safety of this concept. We reviewed the charts of 1000 consecutive patients who underwent these procedures. Three hundred ninety-six procedures were performed as inpatient surgery and 604 were performed as outpatient surgery. Patients were considered as candidates for outpatient surgery if they met specific criteria, such as good overall medical health, no central apnea, normal bleeding history and profile, and had adequate social considerations. The inpatient group included those patients who did not meet the criteria to be outpatients. We compared the complication rates of these two groups with regard to age, type of procedure performed (tonsillectomy, adenoidectomy, adenotonsillectomy), and indication for surgery in order to determine if there was any increased risk of outpatient surgery, despite strict selection criteria. The two groups were similar in their distribution with regards to age, sex, type of procedure, and indication for surgery. The overall complication rate for the entire group was 7.9%, with an 11.8% complication rate for inpatients and 4.1% complications for outpatients. The higher complication rate among the inpatient group is probably a direct result of the selection process because this group included the higher-risk patients. On the basis of these findings, we believe that surgery of the tonsils and adenoids can be performed safely as an outpatient procedure, regardless of age, indication, or procedure, if the candidates for ambulatory surgery are carefully selected by the surgeon.