Assessment of statistic analysis in non-radioisotopic local lymph node assay (non-RI-LLNA) with alpha-hexylcinnamic aldehyde as an example

The murine local lymph node assay (LLNA) is used for the identification of chemicals that have the potential to cause skin sensitization. However, it requires specific facility and handling procedures to accommodate a radioisotopic (RI) endpoint. We have developed non-radioisotopic (non-RI) endpoint of LLNA based on BrdU incorporation to avoid a use of RI. Although this alternative method appears viable in principle, it is somewhat less sensitive than the standard assay. In this study, we report investigations to determine the use of statistical analysis to improve the sensitivity of a non-RI LLNA procedure with alpha-hexylcinnamic aldehyde (HCA) in two separate experiments. Consequently, the alternative non-RI method required HCA concentrations of greater than 25% to elicit a positive response based on the criterion for classification as a skin sensitizer in the standard LLNA. Nevertheless, dose responses to HCA in the alternative method were consistent in both experiments and we examined whether the use of an endpoint based upon the statistical significance of induced changes in LNC turnover, rather than an SI of 3 or greater, might provide for additional sensitivity. The results reported here demonstrate that with HCA at least significant responses were, in each of two experiments, recorded following exposure of mice to 25% of HCA. These data suggest that this approach may be more satisfactory-at least when BrdU incorporation is measured. However, this modification of the LLNA is rather less sensitive than the standard method if employing statistical endpoint. Taken together the data reported here suggest that a modified LLNA in which BrdU is used in place of radioisotope incorporation shows some promise, but that in its present form, even with the use of a statistical endpoint, lacks some of the sensitivity of the standard method. The challenge is to develop strategies for further refinement of this approach.     

Worldwide evaluation of a defibrillation lead with a small geometric electrode surface for high-impedance pacing

Background

Pacing leads with a small electrode surface for high-impedance stimulation have been shown to prolong pacemaker longevity, but no sufficient data is available on the safety and feasibility of a defibrillation lead with this novel design.

Methods

We evaluated the clinical performance of a tined, steroid-eluting defibrillation lead with a small electrode surface area (model 6944) in a prospective multicenter study. A total of 542 patients with conventional indications for an implantable cardioverter defibrillator were randomized 1:1 to receive either the model 6944 or a tined, steroid-eluting defibrillation lead with a conventional sized electrode surface area (model 6942). Device performance and electrical parameters were evaluated at implant and 1, 3, 6, and 12 months thereafter (mean follow-up 11.3 ± 5.6 months).

Results

Baseline characteristics, lead implant success rates, and defibrillation thresholds did not differ significantly between the 2 groups. While pacing thresholds did not differ significantly during follow-up, pacing impedance was approximately twice as high in the model 6944 as in the model 6942 lead (P < .0001). Mean R-wave amplitudes were smaller in patients with a 6944 (9.1 ± 3.1 mV vs 9.8 ± 3.6 mV for model 6942, P < .05), but remained stable within both groups throughout the observation period. The total number of ventricular lead-related adverse events and patient survival did not differ significantly between the 2 groups.

Conclusions

The use of a defibrillation lead with a small electrode surface for high-efficiency pacing is safe and feasible and increases pacing impedance without significantly compromising clinical performance.     

The need for long-term audiologic follow-up of neonatal intensive care unit (NICU) graduates

OBJECTIVE: To evaluate the adequacy of newborn hearing screening in the identification of hearing loss in post-neonatal intensive care unit (NICU) infants. METHODS: Eighty-two post-NICU infants who had initially passed automated auditory brainstem response (AABR) screening were studied prospectively between November 1997 and July 1999. Tympanometry and transient evoked otoacoustic emissions (TEOAE) were used to evaluate middle ear status and screen the hearing of subjects when they were seen routinely in the Mary L. Johnson Infant Development Clinic, where NICU graduates are followed at our institution. TEOAEs were not performed in subjects with abnormal tympanometry, defined as negative pressures greater than 200 daPa or flat tympanograms. RESULTS: Of the 82 subjects, 31 (37%) had abnormal tympanometry in at least one ear, with 24 (29%) exhibiting abnormal values bilaterally. Two subjects were identified with delayed-onset or previously undiagnosed sensorineural hearing loss. One had a history of persistent pulmonary hypertension (PPHN) and extracorporeal membrane oxygenation. The other infant had no risk factors for sensorineural hearing loss. CONCLUSIONS: Our data indicate that newborn hearing screening programs may not provide adequate vigilance for NICU graduates. The high incidence of abnormal middle ear status and the identification of delayed-onset hearing loss in an infant without known risk factors highlights the need for close audiologic and speech/language follow-up in the post-NICU population.     

Pathophysiology of respiratory disease and its significance to anaesthesia

Significant changes occur in the respiratory physiology of healthy patients during anaesthesia. In patients with underlying respiratory pathology, these changes in respiratory physiology may lead to clinical problems during the conduct of anaesthesia and the perioperative period. An understanding of the disease processes that can affect the lungs and pleura allows the anaesthetist to account for the potential complications of these conditions and manage the anaesthetic accordingly.     

Short-term outcomes of five heroin detoxification methods in the Australian NEPOD Project

This study included 380 participants in five heroin detoxification trials whose data were pooled to enable direct comparison of five detoxification methods in the Australian National Evaluation of Pharmacotherapies for Opioid Dependence (NEPOD). Rapid detoxification achieved similar initial abstinence rates with either anaesthesia or sedation (average 59%), which were higher than was achieved by inpatient detoxification using clonidine plus other symptomatic medications (24%), which in turn was higher than outpatient detoxification using either buprenorphine (12%) or clonidine plus other symptomatic medications (4%). Older participants and those using more illicit drugs were more likely to achieve abstinence. Entry rates into ongoing postdetoxification treatment were as follows: buprenorphine outpatient (65%), sedation (63%), anaesthesia (42%), symptomatic outpatient (27%), and symptomatic inpatient (12%). Postdetoxification treatment with buprenorphine or methadone was preferred over naltrexone. Participants with more previous detoxification attempts were more likely to enter postdetoxification treatment. Given that outpatient detoxification was more effective with buprenorphine than with symptomatic medications and that rapid detoxification was more effective than the symptomatic inpatient method, the roles of the symptomatic methods should be reconsidered.