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Biomedical subjects

J C Stevens

Publications and source records attributed to J C Stevens.

At least 73 records · Page 4Linked to original sources

Conditions associated with carpal tunnel syndrome.

With use of a comprehensive medical records-linkage system, we identified the comorbid conditions and risk factors in the residents of Rochester, Minnesota, who had a diagnosis of carpal tunnel syndrome during 1961 through 1980. In 43.2% of the 1,016 patients, no associated conditions were found on review of the medical records, whereas associated conditions were documented in 56.8%. The most frequent of these conditions were Colles' fracture, rheumatoid arthritis, hormonal agents or oophorectomy (or both), diabetes mellitus, and, among men, occupations that involved excessive use of the hands. Rheumatoid arthritis, diabetes mellitus, and pregnancy were significantly more frequent among the study patients with carpal tunnel syndrome than in the general population of Rochester, Minnesota. The standardized morbidity ratio was 3.6 for rheumatoid arthritis, 2.3 for diabetes mellitus, and 2.5 for pregnancy. The population attributable risk for pregnancy among women 15 to 44 years old was 7.0%. The standardized morbidity ratio for polymyalgia rheumatica was not significantly increased.

Adolescent↗

Characteristics of Groningen tracheo-oesophageal speaking valves prior to insertion and after removal for failure.

The Groningen valve was first used in Sheffield in 1986 in a patient who underwent laryngectomy for malignant disease. Since then it has been the main tracheo-oesophageal prosthesis used on our Unit for speech rehabilitation post-laryngectomy. This biflanged device inserted primarily or as a secondary procedure remains in situ until failure occurs either because of leakage or because increased effort is required to produce satisfactory phonation. This in vitro study we examined the differences between new valves prior to insertion and those removed for failure. The mean forward opening pressures were shown to be similar in the two populations but the mean forward resistances were increased in those valves which were defective (P less than 0.001). In addition the mean reverse opening pressure was found to be significantly lower in the defective valves when compared with their new counterparts (P less than 0.05).

Adult↗

An apparatus to measure pressure, flow and speech parameters in patients producing speech using the Groningen valve prosthesis.

We present a validated method of determining in vivo pressure, flow and voice parameters from patients using tracheo-oesophageal voice prostheses post laryngectomy. This apparatus was constructed simply using equipment which should be available in most large Otolaryngology Departments. There was good agreement between measurements made over two separate sessions of in vivo opening pressure, maximum flow through the device and maximum voice amplitude and these were significant. These measurements may be useful in monitoring patient progress and also in elucidating the mechanics of prosthesis failure.

Airway Resistance↗

Aging and spatial acuity of touch.

Spatial acuity of the skin of the fingertip deteriorates markedly with age, as assessed by 2-point thresholds measured with a forced-choice method in 80 subjects between the ages of 18 and 91 years. This loss of "minimum separable" acuity appears to be pervasive, demonstrably affecting many middle-aged and a great majority of the elderly persons tested. Mean threshold was 1.95 mm for young (18-33 years), 2.68 mm for middle-age (41-63 years), and 5.03 mm for elderly (66-91 years) subjects. Over half of the variance in 2-point threshold was attributable to age (r = .74). Threshold on the arm, measured in subsets of 15 young and 15 elderly, was also age-dependent, but (reckoned as a percentage) the difference is minor compared to the finger. Analysis implies that the perception of tactile patterns, in general, and tactile reading (braille, Optacon) by the sensory handicapped, in particular, could run into age-related difficulty by reason of impairment of spatial acuity at the most basic level.

Adolescent↗

Post-lumbar puncture headaches: experience in 501 consecutive procedures.

To ascertain the frequency and risk factors for post-lumbar puncture headache, we studied all adults who had an ambulatory lumbar puncture (LP) in a 1-year period. Patients filled out a questionnaire detailing their headache experience on the day of, and the 6 days following, LP. Those who did not return the questionnaire were telephoned. We systematically collected and analyzed many items, including the lumbar puncturist's experience, the degree of difficulty of the LP, CSF findings, final diagnosis, and the patient's demographic characteristics. Patients reporting headache before LP were more likely to report post-LP headaches. In addition to this, younger female patients with a lower body mass index have the highest risk of developing post-LP headaches. CSF opening pressure, cells, and protein, patient's position during LP, the duration of recumbency following LP, and the amount of CSF removed at the time of LP did not influence the occurrence of headache.

Adolescent↗

The human hepatic cytochromes P450 involved in drug metabolism.

The cytochromes P450 are a superfamily of hemoproteins that catalyze the metabolism of a large number of xenobiotics and endobiotics. The type and amount (i.e., the animal's phenotype) of the P450s expressed by the animal, primarily in the liver, thus determine the metabolic response of the animal to a chemical challenge. A majority of the characterized P450s involved in hepatic drug metabolism have been identified in experimental animals. However, recently at least 12 human drug-metabolizing P450s have been characterized at the molecular and/or enzyme level. The characterization of these P450s has made it possible to "phenotype" microsomal samples with respect to their relative levels of the various P450s and their metabolic capabilities. The purpose of this review is to compare and contrast the human P450s involved in drug metabolism with their related forms in the rat and other experimental species.

Cytochrome P-450 Enzyme System↗

Molecular basis for a functionally unique cytochrome P450IIB1 variant.

Liver microsomes from phenobarbital-treated rats of four inbred strains expressing distinct allelic variants of cytochrome P450IIB1 were analyzed. The Wistar Munich (WM) strain exhibited 5- to 10-fold lower androstenedione 16 beta-hydroxylase activity (a specific P450IIB1 marker) than the Lewis, Wistar Kyoto, and Wistar Furth strains. The androstenedione 16 beta-hydroxylase in the WM liver microsomes was refractory to inactivation by N-(2-p-nitrophenethyl)chlorofluoroacetamide, a selective P450IIB1 inactivator in the other three strains. Purified P450IIB1-WM was insensitive to the inactivator and exhibited 5-fold lower androstenedione 16 beta-hydroxylase, testosterone 16-hydroxylase, and 7-ethoxycoumarin deethylase activities but the same benzphetamine demethylase activity and slightly higher androstenedione 16 alpha-hydroxylase activity than a P450IIB1 purified from outbred Sprague-Dawley rats, which appears to correspond to the form in Lewis rats. The stereoselectivity of androstenedione 16-hydroxylation catalyzed by P450IIB1-WM (16 beta-OH:16 alpha-OH = 1.4) is thus distinct from that (16 beta-OH:16 alpha-OH = 12-15) of other P450IIB1 preparations described. A cDNA encoding P450IIB1-WM was cloned and sequenced, revealing a single amino acid substitution (Gly-478----Ala) compared with the published sequence (Fujii-Kuriyama, Y., Mizukami, Y., Kawajiri, K., Sogawa, K., and Muramatsu, M. (1982) Proc. Natl. Acad. Sci. U. S. A. 79, 2793-2797). Heterologous expression of P450IIB1 and P450IIB1-WM confirmed the striking difference in androstenedione metabolite profiles, strongly implicating the involvement of Ala-478 in defining the distinctive catalytic properties of P450IIB1-WM.

Alleles↗

Mechanism-based inactivation of bovine adrenal cytochromes P450 C-21 and P450 17 alpha by 17 beta-substituted steroids.

A series of progesterone derivatives has been studied as potential inactivators of the bovine adrenocortical cytochromes P450, P450 17 alpha, and P450 C-21. Replacement of the 21-methyl group of progesterone with a difluoromethyl group resulted in a selective inactivator of P450 C-21 in a reconstituted system. The loss of 21-hydroxylase activity caused by this compound exhibits a number of characteristics of mechanism-based inactivation including NADPH dependence, pseudo-first-order kinetics, saturability, irreversibility, and protection by substrate. In addition to the difluoro compound, 21,21-dichloroprogesterone, the acetylenic compound pregn-4-en-20-yn-3-one, and the olefinic compound pregna-4,20-dien-3-one all inactivate P450 C-21. In contrast, the only compound to inactivate the rabbit adrenal progesterone 21-hydroxylase is 21,21-dichloroprogesterone. In binding studies, the 21,21-dihalo steroids produce a greater maximal type I spectral shift of P450 C-21 than the two 17 beta-unsaturated steroids. The dihalo compounds inactivate P450 C-21 by both heme destruction and protein modification as shown by significant decreases in residual 21-hydroxylase activity and spectrally detectable P450 after incubation with P450 C-21 in a reconstituted system. Liquid chromatographic and mass spectral analyses of the organic extracts from these incubations showed that 21-pregnenoic acid is a major metabolite of the dihalo compounds with a partition ratio of 5 nmol of acid produced/nmol of P450 C-21 inactivated. This supports the hypothesis that inactivation proceeds in part through an acyl halide intermediate. In contrast, the acetylenic compound pregn-4-en-20-yn-3-one inactivates P450 C-21 mainly by protein modification, producing an NADPH-dependent irreversible type I spectral shift. The stoichiometry of inactivation is approximately 1.5 nmol of compound bound/nmol of enzyme inactivated, indicating selective modification of the enzyme at or near the substrate binding site.

Adrenal Glands↗

On the discrimination of missing ingredients: aging and salt flavor.

This study reports on the ability of young, middle-aged, and elderly persons to discriminate the presence-absence of the salt flavoring in a published recipe for a soup. Although all but one young person tested was able to make this discrimination above chance level, more than half of each of the two older groups failed to do so. Both the discrimination score and the absolute threshold for NaCl in water solution correlated significantly with age over a span from 18 to 89 yrs. These results add to previous ones from a similar study of the discrimination of an aromatic spice, marjoram (Cain et al., 1990), in demonstrating that taste and smell weakness revealed in recent psychophysical tests can reveal themselves in the perception of everyday food and beverage preparations. A secondary study compared thresholds for NaCl in water with NaCl thresholds in the presence of tomato, the principal ingredient of the published recipe. These thresholds, presumably because of "mixture suppression" of tastes, were from seven to ten times higher than thresholds in water. Although thresholds for young and old were more alike in the tomato medium than in water, the elderly nevertheless needed over twice as much salt concentration than did the young just barely to appreciate its presence. Computer evaluation of the salt content of a large number of soup recipes revealed that (a) the salt content of the tomato soup we used to study discrimination was reasonably representative of other published recipes for tomato soups and (b) that the salt content of the average of these tomato soup recipes was greater than that of the average of non-tomato soup recipes.

Adult↗

Auditory screening in high risk neonates: selection of a test protocol.

As part of a programme evaluating evoked oto-acoustic emissions (EOAE) as a screen for hearing impairment in graduates of a neonatal intensive care unit (NICU), a detailed study has been carried out on 250 infants to determine the best test protocol. EOAE and air conduction auditory brain-stem response (ABR) tests have been carried out on all infants and bone conduction ABR on air conduction ABR failures. Screen failure rates were not dependent on age when tested but were affected by gestational age if the infant was tested before discharge. Coverage was 98% for infants tested before discharge but was 81% for infants tested as out-patients at a mean age of 47 weeks (post-conception). Consideration of different test protocols and the shorter test time for the EOAE test led to the conclusion that, where large numbers are involved, the most cost-effective method is to screen initially by EOAE. Failures would then be re-tested before discharge by ABR. Where numbers are small then ABR alone would be used. Follow up would be by ABR rather than EOAE as this gave a lower failure rate and threshold can be measured. Bone conduction ABR was found to be a feasible test in routine use allowing differentiation between conductive and sensorineural losses.

Evoked Potentials, Auditory↗

Early cortical tactile-evoked potentials, laterality and schizophrenia.

No significant difference in the lateralisation of tactile-evoked potentials was found when a tactile stimulus was applied to the index finger of 14 schizophrenic patients and 14 age- and sex-matched controls. The early tactile responses, recorded from contralateral and ipsilateral parietal scalp electrodes, were compared. Our results differ from previously reported results.

Adult↗

Evaluation of click-evoked oto-acoustic emissions in the newborn.

Click-evoked oto-acoustic emissions and auditory brainstem responses (ABR) have been recorded in 723 babies taken largely from a neonatal intensive care unit to evaluate the use of oto-acoustic emissions as a method of screening for hearing impairment. Twenty-nine infants failed to pass the initial ABR test and repeat ABR tests carried out up to the age of 3 months. The 'sensitivity' and 'specificity' of the oto-acoustic emission test for the ABR test results up to 3 months of age in surviving infants were 93% and 84% respectively. It is proposed that click-evoked oto-acoustic emissions be considered as the initial method to screen for hearing impairment, test failures being followed up by ABR.

Acoustic Stimulation↗

A device to measure head-turn reflex in the distribution test used for infant hearing assessment.

A device was constructed to measure infant head rotation during orienting reflexes to sound stimuli. An experiment was devised to compare the device output with visual observation of the infant. Four stimulus and four no-stimulus control trials were presented randomly to each of 24 infants. Fourteen scorers examined a hardcopy record of the device output followed by a video of the same tests for the presence of head-turn responses to the sound stimuli. The results of this study have shown that it is possible to construct a device to detect head-turn reflexes from young children. However, the success rate in detecting head-turns was inferior to visual scoring of the video of the child's behavior. This was due to the lack of precision of the device. An improved device may overcome this problem and could provide the basis for a useful addition to distraction testing.

Acoustic Stimulation↗

Optimal filtering of the auditory cortical evoked potential.

The development of a linear filter to optimise the signal-to-noise ratio of the auditory cortical evoked potential is described. The filter characteristics were derived from the frequency spectra of cortical potentials taken from 40 normal and 20 hearing impaired adult ears, at two test frequencies (120 tests). The performance of the filter was compared with a typical filter used in clinical practice (1.5 Hz to 15 Hz second-order Butterworth filter). Results showed that the filter produced an average increase in the signal-to-noise ratio of approximately 38%. Further comparisons were made using 14 different Butterworth filters (all second order) and the best of these, the 5 Hz to 9 Hz filter, produced a 28% improvement in the signal-to-noise ratio. The signal-to-noise ratio was calculated by comparing the absolute integral area of the average post-stimulus data to that of the pre-stimulus data. This improvement in the signal-to-noise ratio enhances signals for objective machine scoring analysis or alternatively, allows for a reduction in the number of sweeps (and hence time) required to record the evoked potential.

Adult↗

The biochemical basis for the species difference in hepatic microsomal 4-vinylcyclohexene epoxidation between female mice and rats.

Mice but not rats are susceptible to 4-vinylcyclohexene (VCH)-induced ovarian toxicity and carcinogenicity. This is due in part to a 4- to 6-fold greater rate of hepatic microsomal bioactivation of VCH to the ovotoxicant VCH-1,2-epoxide. The biochemical basis for this difference was investigated in microsomes using enzyme induction, enzyme inhibition with chloramphenicol or specific inhibitory antibodies, and correlation with marker steroid hydroxylase activities to associate VCH epoxidation with particular cytochrome P450 forms. Testosterone 6 beta- and 15 alpha-hydroxylase activities and VCH epoxidation were decreased in microsomes from chloramphenicol-treated mice, initially suggesting the possible involvement of P450IIIA and P450IIA forms in VCH metabolism. Although both testosterone 6 beta-hydroxylase and VCH epoxidase activities were increased by dexamethasone treatment (P450IIIA inducer), anti-rat P450IIIA IgG inhibited testosterone 6 beta-hydroxylase (68%) but not VCH epoxidase activity. These latter results do not support the involvement of mouse P450IIIA forms in VCH epoxidation. However, results were obtained which indicated that mouse P450IIA forms are involved in VCH epoxidation. In microsomes from untreated female mice VCH epoxidase activity was inhibited 48% by antibodies to mouse P45015 alpha (P450IIA3) at a concentration that inhibited testosterone 15 alpha-hydroxylase activity by 86%. No protein immunochemically related to mouse P45015 alpha was detected in female rat hepatic microsomes. VCH epoxidation by hepatic microsomes was increased in female mice and rats by phenobarbital treatment and was inhibited by approximately one-third by anti-rat-P450IIB1 IgG in microsomes from untreated animals of both species. Furthermore, microsomal VCH epoxidase and testosterone 16 alpha-hydroxylase activities were lower (34%) in female 129/J mice (deficient in constitutive expression of P450IIB forms) than in B6C3F1 mice. These results suggested partial involvement of P450IIB forms in the microsomal epoxidation of VCH. Therefore, P450 forms IIA and IIB account for the majority of VCH bioactivation in female mouse liver, which explains in part the susceptibility of mice to VCH-induced ovarian toxicity and carcinogenicity.

Animals↗

Click evoked otoacoustic emissions in neonatal screening.

Seven hundred and twenty-three neonates under intensive care have been tested by evoked otoacoustic emissions (EOAE) and the auditory brain stem response (ABR) to investigate the use of EOAE as a test for hearing impairment. Three hundred and thirty-one have had follow-up tests to the age of at least 2 years. The EOAE test has been found to be practical and quick to perform. The proportion of NICU infants producing a recordable EOAE is 80%, and the sensitivity and selectivity to the ABR result in the period up to 3 months post due date is 93 and 84%, respectively. These figures are high enough and the reduction in time compared to ABR is sufficient for the EOAE to be considered as the primary screen. The follow-up data show mixed results with both false positives and false negatives present. The incidence of severe hearing impairment is close to that expected from retrospective studies at 2 in 331 (1 bilateral, 1 unilateral). Firm conclusions on the sensitivity of EOAE to long-term hearing impairment await the results from larger numbers of infants and further follow up data.

Audiometry, Evoked Response↗