Use of spleen organ cultures to monitor hemopoietic progenitor cell regeneration following irradiation and marrow transplantation

After lethal irradiation of C57BL mice followed by the injection of 10(7) marrow cells, total cellularity and progenitor cell levels exceeded pretreatment levels within 12 days in the spleen, but regeneration remained incomplete in the marrow. The exceptional regenerative capacity of progenitor populations in the spleen was observed in organ cultures of spleen slices prepared 24 hr after irradiation and transplantation, excluding continuous repopulation from the marrow as a significant factor in splenic regeneration.     

Myocardial electrophysiological properties in the presence of an AT1 angiotensin II receptor antagonist

Introduction Blockade of the AT₁ angiotensin II (Ang II) receptor has been shown to provide antihypertensive effects. However, whether AT₁ Ang II receptor antagonists influence myocardial electrophysiological properties remains unclear.Methods and results Accordingly, atrial and ventricular myocardial electrophysiological properties were examined in adult rat (n=13) and guinea pig (n=9) myocardial preparations in the presence of the specific AT₁ Ang II receptor antagonist, valsartan (CGP 48933; 0.5, 5, or 500 mol/L). These concentrations reflect up to 100 fold higher drug concentrations than those observed in clinical trials. Transmembrane potential data were recorded using standard microelectrode techniques at baseline and following superfusion with valsartan. The lower concentrations of valsartan (0.5 and 5 mol/L) had minimal effects on myocardial electrophysiology. In the presence of 500 mol/L of valsartan, resting membrane potential increased from baseline in both rat (–82.3±4.1 vs –76.8±5.8 mV, p<0.05) and guinea pig (–81.6±2.9 vs –76.9±2.0 mV, p<0.05) atrial myocardium. Action potential duration at 90% repolarization was increased in guinea pig atrial (91.7±1.4 vs 80.0±5.6 ms, p<0.05) and ventricular (131.1±8.1 vs 118.7±8.3 ms, p<0.05) myocardium following exposure to 500 mol/L of valsartan. In a separate series of experiments Ang II (1.0 mol/L) had no effect on atrial or ventricular action potential characteristics in either species.Conclusion Thus, the effects of valsartan, which were observed only at concentrations 100 fold higher than those reported in clinical trials, may be due to non-specific drug interactions with the myocyte sarcolemma.     

In vivo real-time analysis of intraperitoneal radiolabeled tumor cell movement during laparoscopy

PURPOSE: A porcine model has been developed to allow the real-time imaging of radiolabeled tumor cell movement throughout the peritoneal cavity, both at rest and during carbon dioxide insufflation. METHODS: Fifteen 30-kg domestic white female pigs were used. Under anesthesia, 15 to 20 million radiolabeled human colorectal tumor cells (LIM1215) were introduced into the peritoneal cavity under laparoscopic vision into the pelvis. Radiolabeled tumor cell movement was examined by using a 25-cm-diameter, low-energy mobile gamma camera with high resolution collimator. Tumor cell movement and distribution during two hours without insufflation was examined in four pigs. Then tumor cell movement and distribution during two hours with CO₂ insufflation was examined in four pigs. In a further four pigs, tumor cells were then mixed with blood and injected into the peritoneal cavity and the effect of no insufflationvs. insufflation was noted. A further three pigs were examined with manipulation of the intra-abdominal contents after injection of LIM1215 cells into the peritoneal cavity. Venting insufflating CO₂ was filtered for tumor cells. RESULTS: Widespread intraperitoneal distribution of tumor cells from the pelvis was identified both with CO₂ insufflation of the peritoneal cavity and without insufflation. Tumor cells dispersed throughout the peritoneal cavity at a slower rate without carbon dioxide insufflation. There was a differential rate of tumor cell movement to the left upper quadrant and right upper quadrant with insufflation and without insufflation. Blood within the peritoneal cavity and an extended contact of the laparoscopic trocars with the peritoneal cavity in this setting increased contamination of the trocars and trocar sites with tumor cells. Tumor cells were identified on laparoscopic instruments in all experiments. No evidence of aerosolization of tumor cells was found. CONCLUSION: Tumor cells move throughout the peritoneal cavity both at rest and during CO₂ insufflation. The pattern of tumor cell dispersion differs with CO₂ insufflation. The presence of blood and extended contact of trocars with peritoneal contents are a major factor in trocar and trocar site tumor cell contamination.This work was performed at The Queen Elizabeth Hospital and the Institute of Medical and Veterinary Sciences, South Australia.Supported by the National Health and Medical Research Council of Australia and the Alfred and Ferrers Scammel Scholarship, Faculty of Medicine, University of Adelaide.Material supplies provided by Johnson and Johnson Australia.Read at the meeting of The American Society of Colon and Rectal Surgeons, San Antonio, Texas, May 2 to 7, 1998.     

Acceptability of the nestorone®/ethinyl estradiol contraceptive vaginal ring: development of a model; implications for introduction

Objectives

Develop and test a theoretical acceptability model for the Nestorone®/ethinyl estradiol contraceptive vaginal ring (CVR); explore whether domains of use within the model predict satisfaction, method adherence and CVR continuation.

Study Design

Four domains of use were considered relative to outcome markers of acceptability, that is, method satisfaction, adherence and continuation. A questionnaire to evaluate subjects' experiences relative to the domains, their satisfaction (Likert scale) and adherence to instructions for use was developed and administered to 1036 women enrolled in a 13-cycle Phase 3 trial. Method continuation was documented from the trial database. Stepwise logistic regression (LR) analysis was conducted and odds ratios (ORs) calculated to assess associations of satisfaction with questions from the four domains. Fisher's Exact Test was used to determine the association of satisfaction with outcome measures.

Results

A final acceptability model was developed based on the following determinants of CVR satisfaction: ease of use, side effects, expulsions/feeling the CVR and sexual activity including physical effects during intercourse. Satisfaction was high (89%) and related to higher method adherence [OR, 2.6 (1.3, 5.2)] and continuation [OR, 5.5 (3.5, 8.4)]. According to the LR analysis, attributes of CVR use representing items from the four domains — finding it easy to remove, not complaining of side effects, not feeling the CVR while wearing it and experiencing no change or an increase in sexual pleasure and/or frequency — were associated with higher odds of satisfaction.

Conclusion

Hypothesized domains of CVR use were related to satisfaction, which was associated with adherence and continuation. Results provide a scientific basis for introduction and future research.

Implications Statement

Acceptability research is important when introducing a new method of contraception and determining whether it can be a successful option in meeting the reproductive health needs of women and men. This study was designed to test a conceptual model of acceptability and identify factors associated with successful use of a new contraceptive delivery modality. Original research was conducted for this publication.     

TIMELINE OF GAINS IN QUADRICEPS STRENGTH SYMMETRY AND PATIENT-REPORTED FUNCTION EARLY AFTER ACL RECONSTRUCTION

Background:Quadriceps weakness is a predictor of long-term knee function and strength recovery can vary from months to years after anterior cruciate ligament reconstruction (ACLR). However, few studies evaluate quadriceps strength and self-reported function within the first several weeks after ACLR.Hypothesis/Purpose:To examine changes over time in quadriceps strength symmetry, quadriceps peak torque, and self-reported knee function prior to and at six, 12, and 24 weeks post-ACLR. The hypotheses were 1) quadriceps strength symmetry, bilateral quadriceps peak torque, and patient-reported function would improve over time from pre-ACLR to 24 weeks post-ACLR and 2) significant improvements in patient-reported function, but not strength symmetry, would occur between time points.Study Design:Prospective, cohort studyMethods:Thirty participants completed four testing sessions: pre-surgery and six, 12, and 24 weeks post-ACLR. Isometric quadriceps strength testing was performed at six weeks and isokinetic quadriceps strength was measured at all other testing points. Quadriceps index was calculated to evaluate between limb quadriceps strength symmetry. The Knee injury and Osteoarthritis Outcome Score (KOOS) and International Knee Documentation Committee Subjective Knee Evaluation Form (IKDC) were administered at each time point. A repeated-measures analysis of variance evaluated changes over time, with post-hoc comparisons to determine at which time-point significant changes occurred.Results:Quadriceps strength symmetry, involved limb quadriceps peak torque and all patient-reported outcome scores increased over time (p<0.02). Post-hoc tests showed that neither self-reported outcomes, nor quadriceps index improved between pre-surgery and six-weeks post-ACLR. From six to 12 weeks post-ACLR, scores on IKDC and KOOS Pain, Symptoms, Quality of Life, and Sport subscales improved (p≤0.003). From 12 to 24 weeks post-ACLR, quadriceps strength symmetry, involved limb quadriceps peak torque, KOOS-Symptoms, Quality of Life, and Sport subscales and the IKDC improved (p≤0.01). Uninvolved limb quadriceps peak torque did not change across any time point (p≥0.18).Conclusion:Patient-reported knee function increased between six and 24 weeks post-ACLR, while increases in involved limb quadriceps strength and quadriceps strength symmetry were not noted until 12-24 weeks post-ACLR.Level of Evidence:2b, individual cohort study     

Multivariate outcome research in arthritis implications for sample sizes

Planning appropriate sample sizes prior to data collection is critical to the overall success of a research project. However, the investigator often encounters practical limitations regarding the number of subjects available. While the literature discusses the various options of analysis of clinical trial data, there is little discussion as to the sample size implications of the statistical method chosen. Since the analysis technique employed affects the required sample size, the investigator should select the analysis that is most appropriate for the data and has the most efficient sample size requirement. This paper addresses the sample size implications of three commonly used methods for comparing two populations when there are two or more outcome measures (multivariate outcome). The concepts and methods are illustrated using a Pain Management Study that was conducted using people with rheumatoid arthritis as subjects.