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Biomedical subjects

A Davis

Publications and source records attributed to A Davis.

At least 127 records · Page 7Linked to original sources

Ovarian activity in women taking an oral contraceptive containing 20 microg ethinyl estradiol and 150 microg desogestrel: effects of low estrogen doses during the hormone-free interval.

OBJECTIVE: We assessed the effect of low ethinyl estradiol doses given during the nominally hormone-free interval of the Mircette (brand of desogestrel/ethinyl estradiol and ethinyl estradiol) contraceptive regimen on ovarian activity. STUDY DESIGN: In a randomized, double-blind study, healthy women received 150 microg desogestrel and 20 microg ethinyl estradiol for 21 days followed by either placebo for 7 days (Mircette/placebo; N = 24) or placebo for 2 days and 10 microg ethinyl estradiol for 5 days (Mircette/ethinyl estradiol; N = 23). RESULTS: During cycles 2 and 3, the Mircette/placebo group had a higher incidence of persistent ovarian follicles (eight subjects versus three subjects) and on average a greater maximum follicle diameter than the Mircette/ethinyl estradiol group. One Mircette/placebo subject probably ovulated in cycle 2, and another had a luteinized unruptured follicle; no such activity was seen in the in the Mircette/ethinyl estradiol group. The study medication was well tolerated, and there were no apparent between-group differences in vaginal bleeding patterns. CONCLUSION: The Mircette regimen, which includes low ethinyl estradiol doses during the hormone-free interval, more effectively suppresses ovarian follicular activity with a low monthly estrogen dose.

Adolescent↗

The prevalence of allergic rhinosinusitis: a review.

A review of the literature indicates that there is an increase in the prevalence of self-reported symptoms suggestive of seasonal allergic rhinitis over the last 70 years. The reason for this remains unclear. Epidemiological studies which relate to the effect of pollution suggest that while pollution can exacerbate respiratory tract symptoms, there is no consistent evidence that high levels result in an increase in the prevalence of allergic rhinitis. The increased prevalence of house-dust mite, an alteration in immunity--possibly related to the number of childhood respiratory tract infections, and increased disease awareness, are all factors which may influence the reported prevalence of allergic rhinitis. At present the inconsistencies which exist in the literature mean that it is possible to 'pick' publications which support one view and ignore the rest, so that a variety of views may be held, each with apparently well referenced endorsement. The criteria defined by Bradford Hill (1965) to establish causation and not mere association between any of these factors and allergic rhinitis have, as yet, not been met (see Table V).

Adolescent↗

The prevalence of allergic rhinitis and nasal symptoms in Nottingham.

From 1200 households selected at random, 2114 questionnaires were returned from individuals over 14 years old. They reported that in the previous year the prevalence of 'symptoms of nasal obstruction every day for more than 14 consecutive days' was 16.9%; 19.8% had had a 'runny nose'; 7.1% reported sneezing bouts; and 19.6% had hay fever during the same period. Also, 13.7% had had rhinosinusitis in the previous year using the criterion of 'two out of three symptoms of congestion, rhinorrhoea and sneezing for more than 1 h per day for a period in excess of 2 weeks'. The prevalence of perennial symptoms in individuals who did not have hay fever was 8.6%. Over the previous 2 years 18.2% of all respondents had visited their General Practitioner and 0.2% had visited a hospital as a result of their hay fever. Individuals who responded as having hay fever were significantly more likely to have worked in an environment with a lot of dust in the last 2 years than asymptomatic respondents (chi 2, P = 0.002), although fume exposure was not found to be a significant risk factor (P = 0.0681). Individuals with perennial symptoms were no more likely to have been working in a dusty or smoky environment. In those with either seasonal or perennial symptoms there was no significant effect of either social class or manual/non-manual occupation.

Adolescent↗

The effect of pre-movement delays on pointing accuracy in middle childhood.

In adults, the introduction of a pre-response delay has been shown to affect accuracy in pointing tasks while leaving accuracy in perceptual matching tasks unaffected. Here, we report on the effect of pre-movement delays on pointing accuracy in 6-10-year-old children. Children of this age group are of particular interest as their reliance on visual cues to monitor and correct their reaches appears to change during this period of development. Nineteen children were asked to point to the location of a target light after a delay of 0, 1, 2, or 4 s following target extinction. Performance was measured in two conditions: (i) open-loop, where the child reproduced the target locations in complete darkness, and (ii) with visual feedback, where information about hand position was available. Errors in the direction and in the amplitude of each reaching movement were recorded separately. The results show that temporal delay significantly affects the pointing movements of these children. Accuracy (mean) deteriorated after only 1 s whereas the precision (standard deviation) of the responses deteriorated after 4 s. Errors in amplitude, but not errors in direction, were reduced by the provision of visual feedback. Taken together, the findings suggest that amplitude and directional components of pointing in childhood utilise different sources of information, which differ in the extent to which temporal constraints operate.

Child↗

Field sensitivity of targeted neonatal hearing screening using the Nottingham ABR Screener.

OBJECTIVE: A population of children having bilateral moderate to profound hearing impairment was investigated to find out the number who passed (false negatives) and who failed (true positives) a screening test based on the auditory brain stem response (ABR). DESIGN: This study of the ABR is a parallel report to Lutman, Davis, Fortnum, and Wood (1997), where the transient evoked otoacoustic emission was examined on a similar but not identical population of at-risk neonates. Hearing screening was undertaken in at-risk neonates (targeted screening) at seven hospitals in the UK using the Nottingham ABR Screener. During the period from January 1988 to December 1993, a total of 6983 neonates had been tested. Assessment of audiological records from the participating centers ascertained that 201 children born between January 1988 and December 1993 had hearing threshold levels in both ears of 50 dB or more, averaged over the speech frequencies 0.5, 1, 2, and 4 kHz. Of these, 51 had completed the ABR screening test. Examination of the ABR records, which included both machine and visual scoring, indicated whether they had passed or failed the screening test. RESULTS: Forty-six of the 51 hearing impaired babies failed the neonatal ABR screen either on one or both ears (five false negatives), and 42 failed the test on both ears (nine false negatives). This resulted in field sensitivities of 90% and 82%, respectively. Two cases of suspected progressive hearing loss have been included in the numbers of false negative results. The percentage of babies passing the screen on both ears and subsequently having normal hearing (specificity) is typically 93%. CONCLUSIONS: Neonatal hearing screening in an at-risk population using a highly automated ABR test is a viable and effective tool for identification of hearing impairment. Although the field sensitivity of the test is high, it is unable to identify all babies with a criterion level of hearing loss. There are a number of possible explanations as to the origin of false negative results: configuration of the pure-tone audiogram, a progressive hearing loss, acquired sensorineural or conductive loss, retrocochlear deafness, or an incorrect interpretation of the screening test. Passing a neonatal screening test, therefore, does not exclude the possibility of subsequent hearing impairment and highlights the need for further surveillance.

Auditory Threshold↗

Neurogenic sarcomas: experience at the University of Toronto.

OBJECTIVE: Elucidation of the natural history and optimal management of neurogenic sarcomas is not straightforward, because of diagnostic difficulties and the low incidence of this disease. The majority of neurogenic sarcomas are categorized and treated as soft tissue sarcomas, and only a few centers have sufficient experience to add to our understanding of these malignant tumors. This article proposes an algorithm for the management of these tumors. METHODS: A cohort of 18 cases of neurogenic sarcoma (overall mean follow-up period after oncological diagnosis, 33.7 mo), representing approximately 3% of all soft tissue sarcomas treated at the University of Toronto Musculoskeletal Oncology Unit (Toronto, Canada) between 1989 and 1995, were reviewed. The clinical and pathological criteria used to establish the diagnosis of neurogenic sarcoma, the presenting symptoms, the tumor size and grade, the ability to obtain tumor-free margins during en bloc resection, the time to recurrence, and the overall survival rates were noted. A centralized pathological review of the biopsy was undertaken in all cases. RESULTS: A metastatic survey demonstrated localized disease for 16 of the 18 patients. The overall management strategy for these 16 neurogenic sarcomas with localized disease was to obtain local control by en bloc resection. Tumor size, tumor grade, and, most importantly, the ability to obtain tumor-free margins were all relevant prognostic factors for survival. Tumor-free surgical margins were obtained for 11 of 16 patients, with 9 of these 11 patients remaining disease-free. In contrast, all patients for whom tumor-free margins could not ultimately be achieved died as a result of their disease. CONCLUSION: Based on our experience, we propose an algorithm for the management of these rare tumors, for both optimal patient care and oncological research.

Adolescent↗

Corticobasal ganglionic degeneration and progressive supranuclear palsy presenting with cognitive decline.

Corticobasal ganglionic degeneration (CBGD) and progressive supranuclear palsy (PSP) were originally described in the sixties as predominantly motor syndromes. Over the years, the detailed study of additional cases of CBGD has shown that it is a distinctive histological entity which can often present as dementia or aphasia. Although some pathological features of CBGD overlap with those of other forms of non-Alzheimer non-Lewy body dementia, the distribution and relative number of these abnormalities and the distinctive pattern of tau immunodeposits allows the distinction of CBGD from Pick's disease and fronto-temporal dementia. In contrast, PSP only rarely presents with prominent dementia or behavioral changes. In these unusual PSP cases, care must be taken to exclude the diagnoses of CBGD and familial tangle-only dementia.

Basal Ganglia Diseases↗

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↗

Reduced dendritic spine density on cerebral cortical pyramidal neurons in schizophrenia.

OBJECTIVE: A pilot study of the density of dendritic spines on pyramidal neurons in layer III of human temporal and frontal cerebral neocortex in schizophrenia. METHODS: Postmortem material from a group of eight prospectively diagnosed schizophrenic patients, five archive schizophrenic patients, 11 non-schizophrenic controls, and one patient with schizophrenia-like psychosis, thought to be due to substance misuse, was impregnated with a rapid Golgi method. Spines were counted on the dendrites of pyramidal neurons in temporal and frontal association areas, of which the soma was in layer III (which take part in corticocortical connectivity) and which met strict criteria for impregnation quality. Altogether 25 blocks were studied in the schizophrenic group and 21 in the controls. If more than one block was examined from a single area, the counts for that area were averaged. All measurements were made blind: diagnoses were only disclosed by a third party after measurements were completed. Possible confounding affects of coexisting Alzheimer's disease were taken into account, as were the effects of age at death and postmortem interval. RESULTS: There was a significant (p<0.001) reduction in the numerical density of spines in schizophrenia (276/mm in control temporal cortex and 112/mm in schizophrenic patients, and 299 and 101 respectively in the frontal cortex). An analysis of variance, taking out effects of age at death and postmortem interval, which might have explained the low spine density for some of the schizophrenic patients, did not affect the significance of the results. CONCLUSION: The results support the concept of there being a defect in the fine structure of dendrites of pyramidal neurons, involving loss of spines, in schizophrenia and may help to explain the loss of cortical volume without loss of neurons in this condition, although the effect of neuroleptic drugs cannot be ruled out.

Adult↗

Frontal lobe volume in patients with Huntington's disease.

Neuropathologic and neuroimaging studies have suggested that frontal lobes are affected in Huntington's disease (HD), and that atrophy in this region may be associated with some of the cognitive impairment and clinical decline observed in patients with HD. We measured gray and white matter volumes within the frontal lobes on MRI for 20 patients with HD (10 mildly affected and 10 moderately affected) and 20 age- and sex-matched control subjects. We also correlated frontal lobe measurements with measures of symptom severity and cognitive function. Patients who were mildly affected had frontal lobe volumes (both gray and white matter) essentially identical to those of control subjects, despite clearly abnormal basal ganglia. Patients who were moderately affected demonstrated significant reductions in total frontal lobe volume (17%) and frontal white matter volume (28%). Frontal lobe white matter volume reductions, but not total frontal lobe volume reductions, were disproportionately greater than overall brain volume reductions (17%). Frontal lobe volume correlated with symptom severity and general cognitive function, but these correlations did not remain significant after taking into account total brain volume. We conclude that cognitive impairment and symptom severity are associated with frontal lobe atrophy, but this association is not specific to the frontal lobes. Frontal lobe atrophy (like total brain atrophy) occurs in later stages of increasing HD symptom severity and this atrophy primarily involves white matter.

Adult↗

Attitudes of respiratory care practitioners and students regarding pulmonary prevention.

STUDY OBJECTIVES: (1) To examine attitudes of respiratory care practitioners (RCPs) and RCP students toward pulmonary disease prevention behaviors and their role in promoting them. (2) To compare RCPs' attitudes regarding pulmonary prevention with existing medical student survey data. DESIGN: Cross-sectional survey. SETTING: Three sites (Valhalla, NY; Winston-Salem, NC; Houston, TX). PARTICIPANTS: One hundred ninety RCPs and 164 RCP students compared with 5,744 medical students. MEASUREMENT AND RESULTS: Subjects completed a 35-item RCP Preventive Pulmonary Attitude (PPA) Survey using a five-point scale (1 = strongly disagree to 5 = strongly agree). A higher score indicates a more positive attitude toward prevention. RCP total scores averaged 117.6 (SD, 15.7; range, 52 to 160). RCP student total scores were significantly higher than RCP practitioners. No significant differences were observed by gender or by type of patient served (pediatric vs adult). RCPs with a history of tobacco smoking had significantly lower scores than RCPs who had never smoked. Most, but not all, respondents acknowledged the importance of patients with chronic lung disease receiving a yearly influenza vaccination. Total PPA scores for medical students were significantly lower than scores for both RCPs and RCP students. Significant differences were noted for a number of individual items. CONCLUSIONS: In general, RCPs had positive attitudes regarding the importance of prevention counseling and their role in providing this to patients. This is important given their potential as a resource in pulmonary prevention efforts. More attention to inclusion of training and evaluation of RCP effectiveness in promoting respiratory health is needed.

Adolescent↗

Anomalous screening outcomes from click-evoked otoacoustic emissions and auditory brainstem response tests.

Transiently evoked otoacoustic emissions (TEOAE) and auditory brainstem response (ABR) tests were used in parallel to screen 862 neonates with risk factors for hearing loss. Seven neonates (0.81%) passed on TEOAE screen yet failed on ABR in one ear (six neonates) or both ears (one neonate). This combination of results has been termed 'anomalous'. Examination of audiometric results obtained on follow-up shows that in one ear of one neonate the result was consistent with the later confirmed audiogram shape. The explanation for the anomalous results in the remaining ears is unclear although neural maturation and the effects of hyperbilirubinaemia are possibilities. There were no instances of progressive or retrocochlear hearing loss identified. None of the seven neonates had better ear hearing loss of > or = 40 dB on long term follow-up.

Acoustic Stimulation↗

Effect of propylthiouracil-induced hypothyroidism on the onset of skeletal muscle necrosis in dystrophin-deficient mdx mice.

1. Duchenne and Becker muscular dystrophies are X-linked disorders caused by defects in muscle dystrophin. The mdx mouse is an animal model for Duchenne muscular dystrophy which has a point mutation in the dystrophin gene, resulting in little (<3%) or no expression of dystrophin in muscle. Mdx mice show a characteristic pattern of muscle necrosis and regeneration. Muscles are normal until the third postnatal week when widespread necrosis commences. This is followed by muscle regeneration, with the persistence of centrally nucleated fibres. 2. This work has examined the hypothesis that the onset of this muscle necrosis is associated with postnatal maturation of the thyroid endocrine system and that pharmacological inhibition of thyroid hormone synthesis delays the onset of muscle necrosis. 3. Serum T4 and T3 concentrations of mice were found to rise immediately before the onset of muscle necrosis in the mdx mouse, and induction of hypothyroidism by treatment of animals with propylthiouracil was found to delay the onset of muscle necrosis. 4. The results provide the first demonstration of experimental delay of muscle necrosis by manipulation of the endocrine system in muscle lacking dystrophin, and provide a novel insight into the way in which a lack of dystrophin interacts with postnatal development to precipitate muscle necrosis in the mdx mouse.

Animals↗

A GT-rich sequence binding the transcription factor Sp1 is crucial for high expression of the human type VII collagen gene (COL7A1) in fibroblasts and keratinocytes.

Type VII collagen is the major component of anchoring fibrils, structural elements that stabilize the attachment of the basement membrane to the underlying dermis. In this study, we have dissected the human type VII collagen gene (COL7A1) promoter to characterize the cis-elements responsible for the expression of the gene in cultured fibroblasts and keratinocytes. Using transient cell transfections with various 5' end deletion COL7A1 promoter/chloramphenicol acetyltransferase reporter gene plasmid constructs, we determined that the region between nucleotides -524 and -456, relative to the transcription start site, is critical for high promoter activity in both cell types studied. Gel mobility shift assays using several DNA fragments spanning this region identified a GT-rich sequence between residues -512 and -505, necessary for the binding of nuclear proteins to this region of the promoter. Point mutations abolished the binding of nuclear proteins in gel shift assays and drastically diminished the activity of the promoter in transient cell transfections. Supershift assays with antibodies against various transcription factors including Sp1, Sp3, c-Jun/AP-1, and AP-2, and competition experiments with oligonucleotides containing consensus sequences for Sp1 and AP-1 binding identified Sp1 as the transcription factor binding to this region of the COL7A1 promoter. Indeed, recombinant human Sp1 was shown to bind the COL7A1 promoter GT-rich element but not its mutated form in gel mobility shift assays. In addition, co-transfection of pPacSp1, an expression vector for Sp1, together with the COL7A1 promoter/chloramphenicol acetyltransferase construct into Sp1-deficient Drosophila Schneider SL2 cells unequivocally demonstrated that Sp1 is essential for high expression of the COL7A1 gene. These data represent the first in-depth analysis of the human COL7A1 promoter transcriptional control.

Collagen↗