An electrophysiological investigation of the properties of a murine recombinant 5-HT3 receptor stably expressed in HEK 293 cells.

1. The pharmacological and biophysical properties of a recombinant 5-HT3 receptor have been studied by use of patch-clamp techniques applied to HEK 293 cells stably transfected with the murine 5-HT3 R-A cDNA. 2. At a holding potential of -60 mV, 77% of cells investigated responded to ionophoretically applied 5-HT with an inward current. Such currents were unaffected by methysergide (1 microM), or ketanserin (1 microM), but were antagonized in a concentration-dependent and reversible manner by the selective 5-HT3 receptor antagonist, ondansetron (IC50 = 440 pM) and the non-selective antagonists (+)-tubocurarine (IC50 = 1.8 nM) and metoclopramide (IC50 50 nM). 3. The 5-HT-induced current reversed in sign (E5-HT) at approximately -2mV and exhibited inward rectification. The influence of extra- and intracellular ion substitutions upon E5-HT indicates the 5-HT-evoked current to be mainly mediated by a mixed monovalent cation conductance. 4. Calcium and magnesium (0.1-10 nM) produced a concentration-dependent, voltage-independent, inhibition of the 5-HT-induced response. Zinc (0.3-300 microM) exerted a biphasic effect with low concentrations enhancing, and high concentrations depressing, the 5-HT-evoked current. 5. Fluctuation analysis of inward currents evoked by a low (1 microM) concentration of 5-HT suggests the current to be mediated by the opening of channels with a conductance of 420 fS. 6. The pharmacological and biophysical properties of the 5-HT3 R-A are similar to those previously described for 5-HT3 receptors native to murine neuroblastoma cell lines, with the exception that the function of the recombinant receptor was enhanced by low concentrations of zinc. This observation suggests that the properties of the native receptor are not completely represented by the 5-HT3 R-A subunit alone.     

Preliminary assessment of the Dex Frame for assisting children with specific learning difficulties

A device called the Dex Frame has recently been marketed as an aid for children with specific learning difficulties. Using a test of reading speed and a test of reading accuracy we have attempted to evaluate the device. Two groups of children with learning difficulties were used, one having sole use of the device and being allowed to carry it with them and a second group who only used the device when attending for remedial tuition and assessment. The results show that no significant improvement occurred in reading performance of the groups with learning difficulties using the Dex Frame as compared with a control group. The teachers of the groups did, however, feel that on an individual basis some children (< 10%) expressed that they felt more comfortable using the device.     

Prospective assessment of biofeedback for the treatment of paradoxical puborectalis contraction

Eighteen patients with chronic constipation were diagnosed as having paradoxical puborectalis contraction (PPC) as the cause for their constipation. The diagnosis of PPC was made after office evaluation, colonic transit study, manometry, cinedefecography, and electromyography (EMG). These 18 patients had a mean duration of symptoms of 26.9 years; none of these patients had unassisted bowel movements. Fourteen patients had a mean of 4.6 laxative-induced bowel evacuations per week, and 11 patients had a mean of 4.4 enema-induced bowel evacuations per week. Patients underwent a mean of 8.9 one-hour EMG-based biofeedback sessions. At a mean follow-up of 9.1 (range, 0.5–12) months, these 18 patients had a mean of 7.3 unassisted bowel actions per week ( P <0.0001). In addition, persistent laxative use was reported by only two patients, and, in both cases, this was once a week or less ( P <0.001). Similarly, enema use was reported by only three patients, one once weekly and the other two thrice weekly ( P <0.002). No biofeedback-related complications were identified. EMG-based biofeedback is a valuable technique associated with an 89 percent success rate in the treatment of PPC.Read at the meeting of The American Society of Colon and Rectal Surgeons, Boston, Massachusetts, May 12 to 17, 1991.     

Changes in the human vocal tract due to aging and the acoustic correlates of speech production: a pilot study.

This investigation used a derivation of acoustic reflection (AR) technology to make cross-sectional measurements of changes due to aging in the oral and pharyngeal lumina of male and female speakers. The purpose of the study was to establish preliminary normative data for such changes and to obtain acoustic measurements of changes due to aging in the formant frequencies of selected spoken vowels and their long-term average spectra (LTAS) analysis. Thirty-eight young men and women and 38 elderly men and women were involved in the study. The oral and pharyngeal lumina of the participants were measured with AR technology, and their formant frequencies were analyzed using the Kay Elemetrics Computerized Speech Lab. The findings have delineated specific and similar patterns of aging changes in human vocal tract configurations in speakers of both genders. Namely, the oral cavity length and volume of elderly speakers increased significantly compared to their young cohorts. The total vocal tract volume of elderly speakers also showed a significant increment, whereas the total vocal tract length of elderly speakers did not differ significantly from their young cohorts. Elderly speakers of both genders also showed similar patterns of acoustic changes of speech production, that is, consistent lowering of formant frequencies (especially F1) across selected vowel productions. Although new research models are still needed to succinctly account for the speech acoustic changes of the elderly, especially for their specific patterns of human vocal tract dimensional changes, this study has innovatively applied the noninvasive and cost-effective AR technology to monitor age-related human oral and pharyngeal lumina changes that have direct consequences for speech production.     

Single dose ciprofloxacin for the eradication of pharyngeal carriage of Neisseria meningitidis

Single dose oral ciprofloxacin was given to all personnel in a naval training establishment as part of the management of an outbreak of meningococcal meningitis. Two thousand one hundred personnel received the drug and Neisseria meningitidis was eradicated from the pharynx of 97% of 570 who were swabbed two to four days later. In a cohort of 277 personnel who were followed for up to nine weeks, pharyngeal carriage was eliminated from 93% of 104 carriers. The overall prevalence of carriage fell from 19% to less than 1.5% as a result of the use of ciprofloxacin. Few side effects were encountered, compliance was good and meningococci resistant to the antibiotic were not found after therapy. A single oral dose of ciprofloxacin 500 mg eliminates pharyngeal carriage of N. meningitidis effectively and has few adverse reactions.