N-Phenylethyl Amitriptyline in Rat Sciatic Nerve Blockade

Background: The antidepressant amitriptyline is commonly used orally for the treatment of chronic pain, particularly neuropathic pain, which is thought to be caused by high-frequency ectopic discharge. Among its many properties, amitriptyline is a potent Na+ channel blocker in vitro, has local anesthetic properties in vivo, and confers additional blockade at high stimulus-discharge rates (use-dependent blockade). As with other drug modifications, adding a phenylethyl group to obtain a permanently charged quaternary ammonium derivative may improve these advantageous properties.

Methods: The electrophysiologic properties of N-phenylethyl amitriptyline were assessed in cultured neuronal GH3 cells with the whole cell mode of the patch clamp technique, and the therapeutic range and toxicity were evaluated in the rat sciatic nerve model.

Results: In vitro, N-phenylethyl amitriptyline at 10 [mu]m elicits a greater block of Na+ channels than amitriptyline (resting block of approximately 90%vs. approximately 15%). This derivative also retains the attribute of amitriptyline in evoking high-degree use-dependent blockade during repetitive pulses. In vivo, duration to full recovery of nociception in the sciatic nerve model was 1,932 +/- 72 min for N-phenylethyl amitriptyline at 2.5 mm (n = 7) versus 72 +/- 3 min for lidocaine at 37 mm (n = 4; mean +/- SEM). However, there was evidence of neurotoxicity at 5 mm.     

Why is the age-standardized incidence of low-trauma fractures rising in many elderly populations?

Low-trauma fractures of elderly people are a major public health burden worldwide, and as the number and mean age of older adults in the population continue to increase, the number of fractures is also likely to increase. Epidemiologically, however, an additional concern is that, for unknown reasons, the age-standardized incidence (average individual risk) of fracture has also risen in many populations during the recent decades. Possible reasons for this rise include a birth cohort effect, deterioration in the average bone strength by time, and increased average risk of (serious) falls. Literature provides evidence that the rise is not due to a birth cohort effect, whereas no study shows whether bone fragility has increased during this relatively short period of time. This osteoporosis hypothesis could, however, be tested if researchers would now repeat the population measurements of bone mass and density that were made in the late 1980s and the 1990s. If such studies proved that women's and men's age-standardized mean values of bone mass and density have declined over time, the osteoporosis hypothesis would receive scientific support. The third explanation is based on the hypothesis that the number and/or severity of falls has risen in elderly populations during the recent decades. Although no study has directly tested this hypothesis, a great deal of indirect epidemiologic evidence supports this contention. For example, the age-standardized incidence of fall-induced severe head injuries, bruises and contusions, and joint distortions and dislocations has increased among elderly people similarly to the low-trauma fractures. The fall hypothesis could also be tested in the coming years because the 1990s saw many research teams reporting age- and sex-specific incidences of falling for elderly populations, and the same could be done now to provide data comparing the current incidence rates of falls with the earlier ones.     

A double blind comparison of diclofenac and indomethacin in the treatment of ankylosing spondylitis

During almost 12 years of development and clinical trials, diclofenac sodium has been shown to be both effective and safe as a new nonsteroidal antiinflammatory drug (NSAID) for the treatment of rheumatic diseases including ankylosing spondylitis (AS). We compared the safety and efficacy of 75, 100, or 125 mg/day of diclofenac with the same doses of indomethacin in a multicenter, randomized, parallel group trial in patients with AS. A single blind placebo washout period of 2 days to 2 weeks preceded the 13-week double blind treatment period. Both diclofenac and indomethacin produced significant (p less than 0.001) improvement from baseline for all 14 efficacy variables analyzed. There were no significant between treatment differences. Differences favored diclofenac in the frequency and the severity of adverse experiences reported and in the frequency of complaints affecting the central nervous system.     

Follow up of patients with colorectal polyps: are the BSG guidelines being adhered to?

OBJECTIVE: The publication of the BSG guidelines in 2002 provided a framework for the follow up of patients with colorectal polyps. The aim of the present study was to determine whether they had, or were being correctly adhered to in a moderately sized District General Hospital. METHOD: A total of 598 patients were on the waiting list for colonoscopy at Airedale General Hospital (AGH) in February 2005. Of these, 203 were being followed up as a result of the previous finding of a polyp. RESULTS: Only 14.8% of patients had been or were being followed up according to the BSG guidelines. The majority of the 85.2% of patients who did not comply with follow up did so as a result of over investigation. Seventy-eight per cent of the low-risk group and 55% of the intermediate-risk group had been colonoscoped, or were waiting to have colonoscopy, too soon or too frequently according to the BSG guidelines. Twenty-four patients with hyperplastic polyps were being followed up incorrectly, as were 17 patients discovered to have a polyp pathology on flexible sigmoidoscopy. It was established that 131 extra colonoscopies had been, or were planned to be performed unnecessarily. CONCLUSION: These data have major implications with regard to patient safety, service provision and cost to the NHS.     

Intraoperative somatosensory evoked potential monitoring during anterior cervical discectomy and fusion in nonmyelopathic patients--a review of 1,039 cases.

BACKGROUND CONTEXT: Intraoperative somatosensory evoked potential (SSEP) monitoring has been shown to reduce the incidence of new postoperative neurological deficits in scoliosis surgery. However, its usefulness during cervical spine surgery remains a subject of debate. PURPOSE: To determine the utility of intraoperative SSEP monitoring in a specific patient population (those with cervical radiculopathy in the absence of myelopathy) who underwent anterior cervical discectomy and fusion (ACDF) surgery. STUDY DESIGN: Retrospective review. PATIENT SAMPLE: A total of 1,039 nonmyelopathic patients who underwent single or multilevel ACDF surgery. The control group (462 patients) did not have intraoperative SSEP monitoring, whereas the monitored group (577 patients) had continuous intraoperative SSEP monitoring performed. OUTCOME MEASURE: A new postoperative neurological deficit. METHODS: SSEP tracings were reviewed for all 577 patients in the monitored group and all significant signal changes were noted. Medical records were reviewed for all 1,039 patients to determine if any new neurological deficits developed in the immediate postoperative period. RESULTS: None of the patients in the control group had any new postoperative neurological deficits. In the monitored group there were six instances of transient SSEP changes (1 due to suspected carotid artery compression; 5 thought to be due to transient hypotension) which resolved with the appropriate intraoperative intervention (repositioning of retractors; raising the arterial blood pressure). Upon waking up from anesthesia, one patient in the monitored group had a new neurological deficit (partial central cord syndrome) despite normal intraoperative SSEP signals. CONCLUSIONS: ACDF appears to be a safe surgical procedure with a low incidence of iatrogenic neurological injury. Transient SSEP signal changes, which improved with intraoperative interventions, were not associated with new postoperative neurological deficits. An intraoperative neurological deficit is possible despite normal SSEP signals.     

Electron inelastic mean free path formula and CSDA-range calculation in biological compounds for low and intermediate energies.

In this study, for low atomic number targets and biological compounds, an inelastic mean free path (IMFP) formula and energy straggling parameter formula are presented, being valid for low and high electron energies. In addition, calculation of the continuous slowing down approximation-range (CSDA-range) from the stopping power is also made. The IMFP and the energy straggling parameter formulae are evaluated using the generalized oscillator strength (GOS) model and the exchange correction to the inelastic differential cross section (IDCS) given by Inokuti, M., [1978. Inelastic collisions of fast charged particles with atoms and molecules--the Bethe theory revisited. Rev. Mod. Phys. 50, 23-35]. The IMFP and CSDA-range for the biological compounds C5H5N5 (adenine), C5H5N5O (guanine), C4H5N3O (cytosine), C5H6N2O2 (thymine), C20H27N7O13P2 (cytosine-guanine) and C19H26N8O13P2 (thymine-adenine) have been introduced for incident electrons in the energy range 20 eV-1 MeV. The calculated results are compared with semi-empirical results and other theoretical results, good agreement being found with experimental data and Monte Carlo (PENELOPE code) predictions. All the IMFP versus energy curves exhibit minima around 80 eV.     

Serpentine aneurysm of the posterior circulation: report of two cases

Giant serpentine aneurysms form a subgroup of giant intracranial aneurysms with specific radiological and surgical features. Previous reports have stressed the predilection of these lesions for the carotid circulation, particularly the middle cerebral artery. Two cases of serpentine aneurysm affecting the posterior circulation are reported and the problems of diagnosis and treatment of this lesion are discussed.     

Validity of the 'Ten Questions' for screening serious childhood disability: results from urban Bangladesh

A survey of 2576 children aged two to nine years was carried out in Dhaka, Bangladesh, as part of a collaborative study to test the validity of a questionnaire (the Ten Questions) for screening severe childhood disabilities in community settings. Approximately 7% of the children were positive on the screen and this rate was slightly higher in boys than girls. The sensitivity, specificity and negative predictive value of the Ten Questions were perfect or nearly perfect for severe and moderate (serious) disabilities. The positive predictive value was only 22% for serious disabilities, but 70% of children classified as false positives were found to have mild disabilities or other conditions (such as ear infections) for which early detection and treatment could be beneficial. No major age or gender differences in the validity of the questionnaire were apparent, but this finding needs additional study and confirmation with studies based on larger samples. In general, the results indicate that the Ten Questions is a valid tool for screening serious disabilities in children and can potentially improve the efficiency of health services by reducing the number of children requiring attention from professionals. Future studies using the Ten Questions should foster greater attention to the dimensions of childhood disability as a public health problem in the less developed world.