Percutaneous nephropexy

OBJECTIVE: The authors present a 12-year (1986-98) study of a new procedure called percutaneous nephropexy (PCNP). This procedure was performed on 51 renal ptosis patients at two urological departments (in Pakistan and Hungary) with satisfactory results. The idea for PCNP was adapted from the observation that after drain insertion following nephrostomy a scar is quite sufficient to hold the kidney in place. That idea was used to fix the kidney at the required level. MATERIAL AND METHODS: Thirteen patients complained of a palpable mobile mass in the abdomen while others suffered from pain in their affected flank with recurrent attacks of urinary tract infection. On ultrasonic examination the kidney was found to be lower than the normal position. This observation was confirmed by a standing intravenous urography (IVU) examination that also showed a tortuous ureter. Nine patients also had a stone in the affected kidney. The operation involved puncture and dilatation of a channel through the lower calyx. RESULTS: Control IVU examination was performed after wound healing and was repeated 2 months after the operation, followed by consecutive ultrasonic examinations. Standing X-ray films obtained after contrast material injection showed the kidney to be at a higher level with a straight ureter. Forty-five patients (88.2%) recovered completely. CONCLUSION: In the authors' opinion PCNP is a good alternative to open nephropexy operations in renal ptosis cases, particularly when laparoscopic surgery facilities are not available. Although PCNP was developed in circumstances in which the availability of equipment was restricted, in terms of benefits it is comparable with laparoscopic nephropexy.     

Human carcinogenic risk evaluation, Part III: Assessing cancer hazard and risk in human drug development.

Assessing cancer risk for human pharmaceuticals is important because drugs are taken at pharmacologically active doses and often on a chronic basis. Epidemiologic studies on patient populations have limited value because of the long latency period for most cancers and because these studies lack sensitivity. The Center for Drug Evaluation and Research (CDER) of the U.S. Food and Drug Administration relies on short-term surrogate assays (genetic toxicology studies) to assess risk to patients involved in clinical trials and on rodent carcinogenicity studies to assess cancer risk for drug approval. Unlike some other agencies that typically perform quantitative risk assessments on chemical pollutants or pesticide products, CDER does not perform such quantitative extrapolations. Rather, the evaluation of risk is the result of an integrated assessment of what is known about the drug, and risk is considered in the context of the clinical benefit. Mode of action of carcinogenesis and thresholds for effects are important considerations. The results of carcinogenicity studies of approved products are published in the drug labeling and individual clinicians balance risk and benefit in making prescribing decisions.     

Measurement of urinary catecholamines in small samples for mice

IntroductionAnalysis of catecholamines in small samples of urine is difficult and sensitive to stress. Current techniques require pooling of samples or expensive separation by double mass spectrometry. A method for extraction of unconjugated catecholamines in 20 μL urine samples has been developed using alumina extraction prior to separation by high performance liquid chromatography (HPLC) and electrochemical detection (ECD).MethodsThree murine experiments tested the application of the procedure. In the first, collection occurred in the morning and evening prior to handling, and in the morning after three days of handling. In the second, passively obtained urine was compared to stressfully obtained urine in the same mice. Finally, basal collections were compared to urinary catecholamine levels 15 and 30 min into novel cage stress. Urine was extracted alongside 2,3-dihydroxybenzoic acid (DHBA) internal standard via alumina and brought to pH 8.5 with tris buffer. The mixture underwent two wash steps for depuration and eluted with perchloric acid for analysis on HPLC with ECD.ResultsThis novel extraction method using low amounts of urine yielded 48% recovery in the samples and 60% recovery in the standard extraction on average. With a signal to noise ratio of 3:1, the limit of detection (LOD) of a standard is 1.2 pg/mL, which allows for the detection of 3.6 pg/mL in urine or 72 fg in a 20 μL sample. Thus resting catecholamine levels are 216 times higher than the LOD. Unconjugated norepinephrine and epinephrine levels were significantly increased 15 min after novel cage stress and epinephrine remained elevated after 30 min, but did not show significant differences when comparing collection time, handling exposure, or specific collection technique.DiscussionThe technique is an effective measure for sympathetic activity in micro samples, with a limit of detection in the attomole range for 20 μL samples.     

Quantifying cellular forces: Practical considerations of traction force microscopy for dermal fibroblasts

Traction force microscopy (TFM) is a well‐established technique traditionally used by biophysicists to quantify the forces adherent biological cells exert on their microenvironment. As image processing software becomes increasingly user‐friendly, TFM is being adopted by broader audiences to quantify contractility of (myo)fibroblasts. While many technical reviews of TFM’s computational mechanics are available, this review focuses on practical experimental considerations for dermatology researchers new to cell mechanics and TFM who may wish to implement a higher throughput and less expensive alternative to collagen compaction assays. Here, we describe implementation of experimental methods, analysis using open‐source software and troubleshooting of common issues to enable researchers to leverage TFM for their investigations into skin fibroblasts.     

More data,less information? Potential for nonmonotonic information growth using GEE

Statistical intuition suggests that increasing the total number of observations available for analysis should increase the precision with which parameters can be estimated. Such monotonic growth of statistical information is of particular importance when data are analyzed sequentially, such as in confirmatory clinical trials. However, monotonic information growth is not always guaranteed, even when using a valid, but inefficient estimator. In this article, we demonstrate the theoretical possibility of nonmonotonic information growth when using generalized estimating equations (GEE) to estimate a slope and provide intuition for why this possibility exists. We use theoretical and simulation-based results to characterize situations that may result in nonmonotonic information growth. Nonmonotonic information growth is most likely to occur when (1) accrual is fast relative to follow-up on each individual, (2) correlation among measurements from the same individual is high, and (3) measurements are becoming more variable further from randomization. In situations that may lead to nonmonotonic information growth, study designers should plan interim analyses to avoid situations most likely to result in nonmonotonic information growth.