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Biomedical subjects

J C Stevens

Publications and source records attributed to J C Stevens.

At least 37 records · Page 2Linked to original sources

Temperature sensitivity of the body surface over the life span.

Detection thresholds to warming and cooling were measured in 13 regions of the body in 60 adults aged between 18 and 88 years. From these thresholds were constructed maps of thermal sensitivity homologous to body maps of spatial acuity (in the older literature two-point discrimination), long known to the somatosensory scientist. Maps of cold and warm sensitivity for young, middle-aged and elderly adults, show how sensitivity changes with age in the various body regions. Three characteristics emerge, irrespective of age: (1) sensitivity varies approximately 100-fold over the body surface. The face, especially near the mouth, is exquisitely sensitive, the extremities, by comparison, poor, other regions, intermediate. (2) All body regions are more sensitive to cold than to warm. (3) The better a region is at detecting cold, the better it is at detecting warm. With age, thermal sensitivity declines. The greatest changes take place in the extremities, especially the foot, where thresholds often become too large to measure. Central regions give up their sensitivity with age more slowly, and even (as in the lips) inconsequentially. Similar age-related changes have also previously been shown to characterize spatial acuity.

Adolescent↗

A multimodal assessment of sensory thresholds in aging.

Young and elderly subjects yielded forced-choice detection thresholds in each of seven sensory tasks: (1) taste of sodium chloride, (2) smell of butanol, (3) cooling, (4) low-frequency vibrotaction, (5) high-frequency vibrotaction, (6) low-frequency hearing, and (7) high-frequency hearing. Average scores across these tasks nearly perfectly separated the 22 elderly from the 15 young subjects. For individual modalities, however, separation between the groups varied from complete (high-frequency touch) to negligible (low-frequency hearing). Scores on the Boston Picture Naming Test and especially the Wechsler Logical Memory Test correlated strongly with average threshold score (Pearson r = .80) and moderately with scores on individual modalities. This sensory-cognitive link is not caused, as might be supposed, by diminishing age-related capacity to handle the detection task, because the very same task resulted in negligible age effect (low-frequency hearing) and large effect (high-frequency hearing) in the same subjects.

Adolescent↗

Pancreatic enzyme supplementation in cystic fibrosis patients before and after fibrosing colonopathy.

BACKGROUND: In 1994 we cared for nine cystic fibrosis patients with fibrosing colonopathy. To evaluate the relationship between fibrosing colonopathy and supplemental pancreatic enzymes we reviewed our dosing of enzymes prior to fibrosing colonopathy development and then evaluated the subsequent effect of drastically reducing pancreatic enzyme dose. METHODS: We retrospectively reviewed pancreatic enzyme dosing for 267 cystic fibrosis patients with pancreatic insufficiency. The supplemental enzyme history of nine patients with fibrosing colonopathy was contrasted with the history of 258 nonaffected patients. The pancreatic enzyme doses of 75 patients taking at least 6,000 U lipase/kg/meal were systematically reduced to approximately 2,000 lipase units/kg/meal. We evaluated the effect of this dose reduction on change in height and weight z scores one year after achievement of stable enzyme dose. RESULTS: In the year prior to diagnosis patients with fibrosing colonopathy took a significantly larger pancreatic enzyme dose, whether assessed by highest dose or cumulative dose, than did nonaffected patients. Similar results were observed after controlling for sex and age. All 75 patients on at least 6,000 U lipase/kg/meal were able to tolerate a significant reduction in dose while achieving clinically acceptable nutrient absorption, with no change over one year in height and weight z scores. CONCLUSIONS: Our data demonstrate a strong relationship between very high doses of pancreatic enzyme supplementation and formation of fibrosing colonopathy. These very high doses do not appear to be needed for adequate nutrient absorption and growth.

Adolescent↗

The costs of early hearing screening in England and Wales.

A survey was carried out in 10 centres in England and Wales to determine the costs of hearing screening in the first year of life. The screens that were studied were targeted neonatal, universal neonatal, and the health visitor distraction test (HVDT) or alternative surveillance. Valid data were available from five centres for targeted neonatal screening (TNS), three for universal neonatal screening (UNS), and nine for the HVDT, although only five of the HVDT screens had valid data for follow up costs. The neonatal costs were consistent across the centres surveyed, whereas those for the HVDT screen varied considerably. The mean service costs for TNS, UNS, and the HVDT at 1994 prices were 5052 Pounds, 13,881 Pounds, and 24,519 Pounds for a standardised district of 1000 live births. Three conclusions seem justified. Firstly, UNS need not be prohibitively expensive as it costs considerably less than HVDT screening. Secondly, TNS appears to be a relatively inexpensive way of improving the age of identification of a proportion of the congenitally hearing impaired. Thirdly, given the published yields for UNS and the HVDT, the results indicate that UNS offers the most cost effective overall approach with alternative systems in place to identify late onset permanent hearing losses.

England↗

Use of transient evoked otoacoustic emissions to detect and monitor cochlear damage caused by platinum-containing drugs.

Transient evoked otoacoustic emissions (TEOAE) have been evaluated as a means of monitoring cochlear function in patients receiving the chemotherapeutic agents cisplatin and carboplatin (-cis-diammine, 1,1-cyclobutane dicarboxylate (2) -0,0-platinum). Patients receiving these drugs were monitored prospectively with pure tone audiometry (PTA), tympanometry and TEOAE. Data was collected on 22 subjects receiving cisplatin and nine subjects receiving carboplatin. Significant deterioration in both PTA thresholds and TEOAE energy levels (with no change in tympanometry) were detected in the cisplatin group. No significant deterioration in audiological parameters occurred in the carboplatin group. It is indicated that cisplatin has a significant ototoxic effect in the majority of patients, whereas any ototoxic effect of carboplatin was undetectable. Our findings were different from previous studies in that the measurable changes in TEOAE occurred later than changes in the pure tone audiogram for the cisplatin group.

Acoustic Stimulation↗

AAEM minimonograph #26: the electrodiagnosis of carpal tunnel syndrome. American Association of Electrodiagnostic Medicine.

The electrodiagnosis of carpal tunnel syndrome (CTS) is reviewed, including discussions of old and new techniques of motor and sensory nerve conduction, anomalous innervation, and needle electrode examination. A variety of sensitive nerve conduction studies (NCSs) are available for the evaluation of a patient with suspected CTS. For any particular patient, the NCS method chosen by the clinical neurophysiologist may vary for a number of reasons, including the severity of the deficit and the presence of superimposed conditions.

Carpal Tunnel Syndrome↗

Detection of very complex taste mixtures: generous integration across constituent compounds.

Mixtures of compounds can often be tasted even when all of their components are too weak to be tasted separately. Such mixtures are said to be integrative. Integration was demonstrated by mixing compounds in concentrations proportional to their separate detection thresholds and then measuring the detection threshold of the mixture as a whole by forced choice with plain water. Mixtures of 3, 6, 12, and 24 compounds were thus evaluated. With earlier data on two-, three-, and four-component mixtures (Stevens, J. C. Detection of taste in mixture with other tastes: Issues of masking and aging. Chem. Senses 21:211-221; 1996.), the results show that the concentration of any constituent compound goes down in approximate proportion to the number of compounds with which it is in mixture. This nearly complete integration seems to describe mixtures of like-quality compounds, of unlike-quality compounds, and of both like- and unlike-quality compounds. Integrative mixtures of the sort studied here provide a model for the detection of the ultracomplex stimuli of everyday life, such as foods and drinking waters. Although the degree of integration may trail off slightly with mixtures of high complexity, the present result proffers no limit on the number of compounds that can be at least partially integrated. In principle, integration permits the detection of natural substances whose myriad components could all be far below threshold. The mechanism of taste integration is speculative, but the facts are congenial to the hypothesis of multiple parallel channels for the processing of intensity and quality.

Adolescent↗

The effect of RPR 102341 on theophylline metabolism and phenacetin O-deethylase activity in human liver microsomes.

PURPOSE: RPR 102341 is structurally similar to the fluoroquinolone class of antibiotics. Because some fluoroquinolones have been shown to inhibit theophylline metabolism, concomitant administration may increase plasma levels of theophylline resulting in serious adverse effects. The purpose of this study was to determine if RPR 102341 affects theophylline metabolism in vitro and, thus, predict whether a clinically significant drug interaction is likely to occur. In addition, the effect of RPR 102341 on phenacetin O-deethylase activity was determined to address the enzymatic basis of a potential drug interaction. METHODS: The in vitro theophylline metabolism assay was conducted according to a modification of a published procedure. The phenacetin O-deethylase assay was conducted according to a modification of a published procedure. RESULTS: The rate of conversion of theophylline to 3-methylxanthine in human liver microsomes in the presence of 100 microM and 500 microM RPR 102341 was 93.6 and 106 percent of the control reactions, respectively. The formation of 1-methylxanthine was 97.6 and 100 percent of the control, and 1.3-dimethyluric acid formation was 88.9 and 95.2 percent of control at 100 microM and 500 microM RPR 102341, respectively. In agreement, RPR 102341 caused no inhibition of human liver CYP1A2-catalyzed phenacetin O-deethylase activity. Finally, no inhibition was observed when RPR 102341 was incubated with human liver microsomes and an NADPH regenerating system prior to the addition of theophylline. CONCLUSIONS: Based on these studies, RPR 102341 is not expected to cause significant drug interactions with theophylline.

Cytochrome P-450 CYP1A2↗

Detection of a target taste in a complex masker.

Detection thresholds for sodium chloride were compared in aqueous solution, in mixture with a sucrose masker, in mixture with a citric acid masker, and in mixture with both of these maskers together. Separately the two maskers raised the threshold of sodium chloride by three to four times, and together by over nine times, a result consistent with independence (additivity) of the two masking effects. To achieve comparable masking with either sucrose alone or with citric acid alone would require increasing their masking concentrations by about ten times. Hence multiple masking can be a far more efficient means of concealing a taste, whether an unpleasant one (e.g. the bitter taste of medicine) or a pleasant one (e.g. a salty or sweet condiment). Multiple masking has dietary and culinary significance, especially for middle aged and elderly persons concerned about salt intake, because their thresholds for NaCl, whether with or without maskers, are typically two or three times higher than those of youthful persons.

Adult↗

Sequential ciprofloxacin therapy in pediatric cystic fibrosis: comparative study vs. ceftazidime/tobramycin in the treatment of acute pulmonary exacerbations. The Cystic Fibrosis Study Group.

BACKGROUND: Cystic fibrosis patients have chronic bacterial infections of the respiratory tract, most commonly Pseudomonas aeruginosa. Although controversial, administration of antibiotic therapy during acute pulmonary exacerbations is standard practice. Fluoroquinolones are currently not indicated for use in young children because of the observation of arthropathy and damage to growing cartilage in beagle puppies. Because of its activity against P. aeruginosa and excellent oral bioavailability, ciprofloxacin offers a unique therapeutic alternative for this patient population. OBJECTIVE: This prospective, randomized, double blind study compared the efficacy and safety of sequential intravenous/oral ciprofloxacin vs. ceftazidime/tobramycin in hospitalized pediatric cystic fibrosis patients with an acute pulmonary exacerbation associated with P. aeruginosa infection. METHODS: One hundred thirty patients (ages 5 to 17 years) were randomized to receive either i.v. ciprofloxacin 10 mg/kg every 8 h for 7 days followed by oral ciprofloxacin 20 mg/kg every 12 h for a minimum of 3 days or i.v. ceftazidime 50 mg/kg every 8 h plus i.v. tobramycin 3 mg/kg every 8 h for a minimum of 10 days. Clinical, bacteriologic and safety responses were assessed throughout the study. RESULTS: All 84 patients (median age, 11 years; range, 5 to 17 years) valid for efficacy in both treatment groups demonstrated clinical improvement. Five patients experienced clinical relapses (3 ciprofloxacin, 2 ceftazidime/tobramycin) by the 2- to 4-week follow-up. Intent-to-treat analysis demonstrated similar clinical findings between the two treatment groups at both the end of therapy and follow-up. Clinical improvement correlated with improvement in pulmonary function studies and the acute clinical scoring system but not with bacteriologic eradication of Pseudomonas. DNA profiles demonstrated that irrespective of colony morphology, usually one clonal strain was associated with each patient's pulmonary exacerbation. Treatment-associated musculoskeletal events occurred with equal frequency (22% vs. 21%) in both study drug groups (n = 129), and arthralgias were within the range of rates for cystic fibrosis arthropathy. None of these events required study drug discontinuation. CONCLUSION: Sequential i.v./oral ciprofloxacin monotherapy offers a safe and efficacious alternative to standard parenteral therapy for acute pulmonary exacerbations in pediatric cystic fibrosis patients.

Acute Disease↗

Orphenadrine and methimazole inhibit multiple cytochrome P450 enzymes in human liver microsomes.

The specificities of orphenadrine and methimazole on eight human liver P450 enzyme activities were evaluated by studying the extent of inhibition at different concentrations in two protocols: competitive inhibition and preincubation. In the competitive inhibition protocol, orphenadrine decreased CYP2B6 marker activity up to 45-57% in human liver microsomes and up to 80-97% in cell microsomes containing cDNA-expressed CYP2B6. Orphenadrine strongly decreased CYP2D6 marker activity by 80-90%. Orphenadrine also partially decreased the CYP1A2, CYP2A6, CYP3A4, and CYP2C19 marker activities. In the preincubation protocol, orphenadrine decreased the CYP2B6 activity in cDNA-expressed cell microsomes to completion. In human liver microsomes, orphenadrine strongly decreased the marker activities of CYP2B6, CYP2D6, as well as CYP2C9; and partially decreased the marker activities of CYP1A2, CYP2A6, CYP3A4, and CYP2C19. In the competitive inhibition protocol, methimazole had no effect on the marker activities of CYP2E1 and CYP2A6; slightly decreased CYP2D6 marker activity; partially decreased the marker activities of CYP2C19, CYP2C9, and CYP2B6; and dramatically decreased CYP3A4 marker activity. Methimazole decreased CYP1A2 marker activity at lower concentrations, but not at the highest concentration studied (1 mM). In the preincubation protocol, methimazole was shown to be a potent and nonspecific inhibitor of all the enzyme activities. Marker activities of CYP2C9, CYP2C19, and CYP3A4 were completely inhibited at relatively low concentrations. This study indicates orphenadrine cannot be used as a selective inhibitor of CYP2B6 in human liver microsomes and that methimazole is not a selective inhibitor of the flavin-containing monooxygenase in human liver microsomes.

Antiparkinson Agents↗

Human liver CYP2B6-catalyzed hydroxylation of RP 73401.

RP 73401 is a potent inhibitor of cyclic nucleotide phosphodiesterase type IV. RP 73401 is metabolized by human liver microsomes almost exclusively by transhydroxylation of the cyclopentyl group to RPR 113406. Liquid chromatography/mass spectrometry/mass spectrometry analysis of plasma from patients given RP 73401 also revealed a molecular ion and fragmentation consistent with RPR 113406. Thus, the objective was to determine the oxidative enzyme(s) responsible for RP 73401 hydroxylation. Kinetic constants of RP 113406 formation ranged from 8 to 26 MM and 0.83 to 5.99 nmol/min/mg protein for K(m) and V(max), respectively (n = 3). Enzyme activity varied 23-fold among 15 human liver microsome samples and correlated with CYP2A6-catalyzed coumarin hydroxylase (r2 = 0.85, P < .01) and CYP2B6-catalyzed 7-ethoxytrifluoromethylcoumarin O-deethylase (r2 = 0.82, P < .01) activities. Chemical inhibition studies showed a 63% decrease in RP 73401 hydroxylation by 500 microM orphenadrine. Coumarin (10 microM), however, did not inhibit RP 73401 hydroxylation. Also, anti-CYP2B1 IgG produced 85% inhibition of RP 73401 hydroxylation, but only a negligible decline in coumarin hydroxylase activity. Of the 10 expressed P450 forms studied, only CYP2B6 catalyzed RP 73401 hydroxylation. Finally, expressed CYP2B6 showed a high affinity (K(m) = 22.5 microM) for RP 73401 hydroxylation, similar to the human liver microsome studies.

Aryl Hydrocarbon Hydroxylases↗

American Association of Electrodiagnostic Medicine guidelines for outcome studies in electrodiagnostic medicine.

Based on a review of the literature and the clinical research experience of the authors and reviewers, the AAEM proposes 17 criteria which should be used to construct and evaluate diagnostic and/or therapeutic outcome studies for patients with symptoms and signs of neuromuscular diseases. Neuromuscular diseases are defined as diseases that cause pathology and/or dysfunction of the sensory, motor, and/or autonomic nerve offers and/or muscles.

Association↗

Neuropathy and vasculopathy in colonic strictures from children with cystic fibrosis.

Colonic strictures are rare in patients who have cystic fibrosis, but recently have developed in those who have been treated with delayed-release high-dose pancreatic enzyme supplements. Colonic strictures from eight such pediatric patients showed neural abnormalities consisting of ganglion cell hyperplasia and ectopia, and intermyenteric plexus hyperplasia. Cholinergic and adrenergic stains of mucosal nerve fibers were more prominent in histological sections of the cystic fibrosis strictures than in sections from colons of children without cystic fibrosis. The mean grade of staining with acetylcholinesterase in the lamina propria of the strictured cystic fibrosis colons was 2.38 +/- 1.25, compared with .93 +/- .93 (P < .055) in bowels from children without cystic fibrosis. The mean grade for tyrosine hydroxylase staining in the lamina propria was 2 +/- .97 in the strictures and was .79 +/- .81 (P < .05) in the bowels of children who did not have cystic fibrosis. Vasoactive intestinal peptide staining in bowels from children with cystic fibrosis with and without stricture did not differ significantly from that of children without cystic fibrosis. Vasculopathy consisting of fibrointimal hyperplasia in submucosal veins and mesenteric arteries was found only in colonic strictures owing to cystic fibrosis. Colonic strictures in patients with cystic fibrosis who received high-dose pancreatic enzyme supplements contain ganglion cell abnormalities, and mucosal cholinergic and adrenergic activity may be increased in these strictures. The stricture vasculopathy may be drug-related and/or related to increased catecholamine activity.

Acetylcholinesterase↗

Detection of tastes in mixture with other tastes: issues of masking and aging.

When one taste (masker) is strong enough, it can completely mask another task (target) of different quality. How strong the masker must be to do this depends on how strong the target is. As the target concentration is increased, the masking concentration must be increased, too, but in ever-increasing proportion. To quantify the conditions for such complete masking, the target's detection threshold was measured as a function of the masker's concentration, from zero to strong. This was done for 12 binary combinations of sucrose, sodium chloride, citric acid and quinine hydrochloride. The 12 functions generated show that some tastants mask each other much more efficiently than others. Masking gives new insight into the role of aging in taste: older (66-90 years) subjects' thresholds, regardless of masking concentration, always measured a constant factor higher than younger (18-29 years) subjects' thresholds (about two to seven times higher, depending on target tastant). Thus, with increasing level of the masker, the thresholds of young and elderly go up in parallel. Thresholds of tastants in water alone are false predictors of elderly persons' ability to perceive ingredients like salt and sugar condiments in foods, where, because of masking, their thresholds can be several times higher than in water. Age manifested itself relatively mildly in sucrose and citric acid, moderately in sodium chloride, and strongly in quinine hydrochloride.

Adolescent↗

Long-term results of trimming of the inferior turbinates.

The long-term benefit of trimming of the inferior turbinates for nasal obstruction is unclear and our aim was to assess this. Fourteen patients who had had pre-operative nasal symptom scores and anterior rhinomanometry prior to inferior turbinate resection were reassessed at least 7 years post-operatively. Both nasal symptom scores for obstruction and nasal resistance had increased significantly in the intervening time period. Nasal crusting and hypertrophy of the cut inferior turbinate are considered to be responsible for this. Patients should be warned some degree of nasal obstruction may recur postoperatively.

Adult↗

Coding of acoustic features for a single-channel tactile aid.

Measurements have been made on the discrimination of speech contrasts on the basis of single-channel vibrotactile presentation of a variety of speech-derived signals, coded as amplitude- and frequency-modulated pulse trains. Stimulation was at the index fingertip. The signals chosen for tactile presentation were the speech amplitude envelope, the voice fundamental frequency FO and the zero-crossing frequency in the 1.3-6.6 kHz band. "Two-feature' codings, which present two of these signals simultaneously (one coded as stimulus frequency and one coded as stimulus amplitude), were found to be no more effective than "single feature' codings which present only one signal (coded as both amplitude and frequency). Scores for consonant discrimination were highest for the single-feature coding of zero-crossing frequency, although differences between the codings were not, in general, significant. Scores for emphatic-stress discrimination were highest for the single-feature coding of F0, and this coding produced best results overall. A practical wrist-worn device, whose design is influenced by these experimental results is briefly described.

Adult↗