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Biomedical subjects

S Brown

Publications and source records attributed to S Brown.

At least 253 records · Page 14Linked to original sources

The so-called "placebo effect" in benign prostatic hyperplasia treatment trials represents partially a conditional regression to the mean induced by censoring.

OBJECTIVES: To study the variability of assessment instruments (symptom questionnaires and flow rate recordings) in healthy volunteers during repeat administration in short intervals. To study the effect of inclusion criteria-based censoring of patients during screening for benign prostatic hyperplasia (BPH) treatment trials on the outcome of subsequent tests. METHODS: One hundred forty-five male volunteers without known prostatic diseases with a mean age of 52 years (range 23 to 83) were given the American Urological Association (AUA) Symptom Index (SI), BPH Impact Index (II). Quality of Life (QOL) score, and a flow rate recording twice 10 to 20 days apart without any healthcare intervention. Data were collected and analyzed after typical BPH trial criteria were applied to the first test, and patients who did not "qualify" were censored. RESULTS: Good correlation exists between two closely spaced administrations of the AUA SI, BPH II, QOL score, and flow rate recordings in healthy male volunteers with correlation coefficients between 0.73 and 0.89. Censoring patients and excluding them from the analysis of the second test based on typical BPH trial criteria induces a regression to the mean phenomenon, which results in an artificial improvement in these outcome parameters. The magnitude of the improvement increases as the selection and censoring criteria tighten. The mean differences between the first and second test range from 1.4 to 1.7 mL/s for the peak flow rate, from -1.0 to -1.4 for the AUA SI, and from -0.4 to -0.8 for the BPH II. All these differences induced solely by censoring with resulting regression to the mean are statistically significant. CONCLUSIONS: Censoring of patients based on inclusion and exclusion criteria is typical for BPH treatment trials. One of the under-recognized effects of censoring is a regression to the mean, which leads to an apparent improvement in the outcome parameters assessed. In both placebo or sham-controlled trials, as well as in clinical series without controls, one must keep this effect and its relative magnitude in mind, and interpret the data from such trials with appropriate caution.

Adult↗

Incidence of latex sensitization among latex glove users.

BACKGROUND: Although there are several reports of the prevalence of latex sensitization among health care workers, the incidence of sensitization is unknown. OBJECTIVE: The objective of this study was to estimate the incidence of sensitization among latex glove users at a hospital in Hamilton, Ontario, Canada. METHODS: Workers with negative results to the skin test at baseline were followed prospectively over 1 year, some wearing powdered gloves and others using powder-free gloves. They were reevaluated in 1995 with a questionnaire and skin prick test (SPT) sensitivity to latex reagents, three common inhalants, and six foods. A conversion was defined as a (new) latex SPT with wheal diameter at least 4 mm greater than saline control. Glove extracts were assayed for antigenic protein, and air samples were obtained to estimate exposure to airborne latex protein. RESULTS: During powdered glove use, personal exposures ranged from 5 to 616 ng/m3, whereas during powder-free glove use, all but two results for air samples were below the limit of detection (about 0.1 ng/m3). During the study period, the protein concentration in the powdered gloves, initially mean 557 microg/gm of sample, declined at a rate of 295 microg/gm per year (p < 0.0001). Of the 1075 SPT-negative participants at baseline, 479 were working in eligible wards, and of these, 435 (91%) participated in follow-up, 227 using powder-free gloves and 208 using powdered gloves. We identified four conversions, two (1.0%) in the powdered glove group and two (0.9%) in the powder-free group. The two participants using powdered gloves were the only converters who were symptomatic. The significance of skin test conversions identified in the powder-free group, both asymptomatic patients, is unclear. The limitations of the study are discussed, including the limited power, the declines in latex protein concentrations, and the possibility of information (observer) bias. CONCLUSION: To our knowledge, this represents the first reported estimate (about 1%) of incidence of sensitization in hospital personnel using latex gloves.

Cross-Sectional Studies↗

Current use of the TORCH screen in the diagnosis of congenital infection.

The aim of the study was to determine the number of congenital infections detected in Dublin with the current use of the TORCH screen. A review of all laboratory results was undertaken with subsequent review of relevant medical charts. A total of nine cases were documented in a 5-year period from January 1991 to December 1995. Six of these had already been suspected. There was a failure to follow up 47% of positive screens. TORCH screening in Ireland has an unacceptably low yield, and in the opinion of the authors should be abolished.

Animals↗

Immunohistochemical distribution of cannabinoid CB1 receptors in the rat central nervous system.

Immunohistochemical distribution of cannabinoid receptors in the adult rat brain was studied using specific purified antibodies against the amino-terminus of the CB1 receptor. Our results generally agree well with the previous studies using CB1 receptor autoradiography and messenger RNA in situ hybridization. However, because of its greater resolution, immunohistochemistry allowed identification of particular neuronal cells and fibers that possess cannabinoid receptors. CB1-like immunoreactivity was found in axons, cell bodies and dendrites, where it appeared as puncta in somata and processes. Both intensely and moderately or lightly stained neurons were observed. The intensely stained neurons were dispersed and only occur in cortical structures including hippocampal formation and olfactory bulb. Moderately or lightly stained neurons were found in caudate-putamen and amygdala. In the hippocampal formation only intensely stained neurons were observed. The cell bodies of pyramidal neurons in CA1 and CA3 fields appeared to be unstained but surrounded by a dense plexus of immunoreactive fibers. The granule cells in the dentate area were also immunonegative. Many intensely stained neurons were located at the base of the granule cell layer. CB1-like immunoreactive neurons and fibers were also found in the somatosensory, cingulate, perirhinal, entorhinal and piriform cortices, in claustrum, amygdaloid nuclei, nucleus accumbens and septum. Beaded immunoreactive fibers were detected in periaqueductal gray, nucleus tractus solitarius, spinal trigeminal tract and nucleus, dorsal horn and lamina X of the spinal cord. A triangular cap-like mass of immunoreactivity was found to surround the basal part of the Purkinje cell body in the cerebellum. Only small, lightly stained cells were found in the molecular layer in the cerebellum close to the Purkinje cell layer. The CB1 receptor is widely distributed in the forebrain and has a more restricted distribution in the hindbrain and the spinal cord. It appears to be expressed on cell bodies, dendrites and axons. According to the location and morphology, many, but not all, CB1-like immunoreactive neurons appear to be GABAergic. Therefore, cannabinoids and cannabinoid receptors may play a role in modulating GABAergic neurons.

Animals↗

Solid-state 13C NMR investigations of the glycosidic linkage in alpha-alpha' trehalose.

The sugar trehalose is known to play a central role in the desiccation tolerance of many organisms. Essential to trehalose's role are its glass forming abilities and ability to directly interact with lipid molecules. Detailed information on the structure and dynamics of glassy trehalose and its interactions with lipids, however, have been elusive. We have used solid-state NMR and ab initio quantum mechanical methods (Gaussian 94) in order to characterize the possible molecular conformations of trehalose. Using a simplified structure (2-(tetrahydropyran-2-yloxy) tetrahydropyran) as a model we have calculated the energy and 13C magnetic shielding parameters as a function of the two glycosidic torsion angles. Combining ab initio derived maps and using the 13C lineshape as constraints we were able to construct the torsion angle distribution map for alpha-alpha' trehalose. We believe measurements of 13C isotropic chemical shift and other solid-state NMR tensor parameter distributions in combination with ab initio methods can prove useful in identifying sources of structural disorder in glassy trehalose. By monitoring these structural distributions new information about the membrane surface associative properties of trehalose and other sugars should be accessible.

Carbohydrate Conformation↗

Epilepsy needs revisited: a revised epilepsy needs document for the UK.

We revisit epilepsy needs in the United Kingdom, and update our previous publication to take into account new epidemiological data, changes in investigation and treatment and trends in the organization of health and other caring agencies. This document attempts to define and quantify the scope, content and standards of services required, from primary care settings to specialized centres. Reference is also made to the role of other agencies.

Adult↗

Glutamine and vitamin E in the treatment of hepatic veno-occlusive disease following high-dose chemotherapy.

Hepatic veno-occlusive disease (VOD) of the liver is a common complication following high-dose cytotoxic therapy for bone marrow transplantation (BMT). Liver injury is believed to occur following free radical damage to endothelial cells of the sinusoids and small hepatic veins. Glutathione the main antioxidant of the cytosol becomes depleted following chemotherapy. Animal studies have shown that glutamine infusions can maintain glutathione levels and protect against free radical injury. We present two cases of established VOD successfully treated with intravenous glutamine (as dipeptide) and oral vitamin E. Although both cases have possible confounding factors we believe that these give support to the notion that glutamine/vitamin E may have a role in the prophylaxis and treatment of VOD. Further formal trials are indicated.

Adult↗

Phytochrome controls the number of endoreduplication cycles in the Arabidopsis thaliana hypocotyl.

A majority of the cells in the Arabidopsis hypocotyl undergo endoreduplication. The number of endocycles in this organ is partially controlled by light. Up to two cycles occur in light-grown hypocotyls, whereas in the dark about 30% of the cells go through a third cycle. Is the inhibition of the third endocycle in the light an indirect result of the reduced cell size in the light-grown hypocotyl, or is it under independent light control? To address this question, the authors examined the temporal and spacial patterns of endoreduplication in light- or dark-grown plants and report here on the following observations: (i) during germination two endocycles take place prior to any significant cell expansion; (ii) in the dark the third cycle is completed very early during cell growth; and (iii) a mutation that dramatically reduces cell size does not interfere with the third endocycle. The authors then used mutants to study the way light controls the third endocycle and found that the third endocycle is completely suppressed in far red light through the action of phytochrome A and, to a lesser extent, in red light by phytochrome B. Furthermore, no 16C nuclei were observed in dark-grown constitutive photomorphogenic 1 seedlings. And, finally the hypocotyl of the cryptochrome mutant, hy4, grown in blue light was about three times longer than that of the wild-type without a significant difference in ploidy levels. Together, the results support the view that the inhibition of the third endocycle in light-grown hypocotyls is not the consequence of a simple feed-back mechanism coupling the number of cycles to the cell volume, but an integral part of the phytochrome-controlled photomorphogenic program.

Arabidopsis↗

A new approach to visual acuity screening for pre-school children.

The Melbourne Initial Screening Test (MIST) is a vision screening technique which combines the features of an established procedure, the five-letter Sheridan Gardiner Single (SGS) test, with a pass/fail method of assessment. It is a simple screening test for children aged 3.5-4.5 years, which is designed to be easy to use. This paper reports on the preliminary results of a comparison of threshold acuity using the 5-letter single-optotype Sheridan Gardiner (SG) test and the MIST results obtained by orthoptists, and a comparison of MIST results obtained by orthoptists and child health nurses. The orthoptists tested 225 children and the nurses tested 868 children. The MIST results obtained by the orthoptists were similar to the SGS in that there was agreement between the test results in 202 (94%) cases. The MIST has a similar rate of subject compliance (95%) as the SGS test (96%). The rate of compliance for orthoptists' and nurses' use of the MIST was similar, with 97% of children being compliant for the nurses and 96% for the orthoptists. The results suggest that the MIST, using a pass/fail method of assessing visual acuity compared to an assessment of threshold visual acuity, may be useful as part of pre-school vision screening since it is easier than the traditional testing of threshold visual acuity and gives similar results to the SG single-optotype test.

Child, Preschool↗

Modification of a receptor-binding surface of epidermal growth factor (EGF): analogs with enhanced receptor affinity at low pH or at neutrality.

Six mutants of human epidermal growth factor (EGF), which carry single point substitutions within a surface patch proposed to juxtapose the bound receptor, were prepared and characterized for receptor affinity and mitogenicity. Receptor affinities relative to EGF are G12Q > H16D > Y13W > Q43A approximately = H16A approximately = EGF >> L15A. Notably, the reduced receptor affinity of mutant L15A indicates that Leu15 probably contributes substantially to receptor binding whereas unaltered receptor affinities observed for analogs H16A and Q43A indicate that neither His16 nor Gln43 contributes significantly to this interaction. On the other hand, the observed enhanced receptor affinities of analogs G12Q, Y13W and H16D highlight surface loci where additional productive receptor-binding contacts can be introduced. Interestingly, at acidic pH analog H16A reveals substantially greater receptor affinity than that of EGF, a property which may offer enhanced therapeutic utility in acidic environments in vivo.

Amino Acid Sequence↗

Prenatal diagnosis of low level trisomy 15 mosaicism: review of the literature.

Low level chromosome mosaicism found at amniocentesis is problematic for clinicians and patients. We report prenatal diagnosis of a fetus with a rare karyotype of 47,XX, + 15/46,XX. Second trimester amniocentesis was performed for advanced maternal age. Fetal ultrasound revealed a hypoplastic right ventricle and intrauterine growth retardation (IUGR). The rest of the fetal anatomy was within normal limits. A mosaic karyotype of 47,XX, + 15/46,XX was observed. The couple interrupted the pregnancy at 19 weeks by dilation and suction evacuation. Careful evaluation of multiple pieces of fetal parts and placenta revealed one abnormal finding: a single umbilical artery. Cytogenetic metaphase and fluorescent in situ hybridization (FISH) interphase analyses of cells from fetal lung, heart, placenta, and skin revealed the presence of the trisomic line in all tissues. Molecular analysis demonstrated that the origin of the extra chromosome 15 was maternal, the error most likely occurred in meiosis I and the diploid line was of biparental inheritance. This case report discusses the associated findings in this fetus and reviews the literature describing other cases of mosaic trisomy 15.

Amniocentesis↗

Are cuts to health expenditure in Victoria compromising quality of care?

Separate state-wide surveys of women who had recently given birth in Victoria were conducted in 1989 and 1993. The first survey was conducted in conjunction with the Victorian Ministerial Review of Birthing Services. The second survey occurred three years after the release of the Review's final report and three months after the introduction of casemix funding. It coincided with a period of substantial cutbacks to expenditure on Victorian public hospitals. In both studies, surveys were mailed to women 6 to 9 months after the birth. Response rates were 71.4% (n = 790) in 1989 and 62.5% (n = 1336) in 1993. Between the two surveys, the proportion of women giving critical feedback about caregivers, more than doubled. The survey findings suggest that standards of care are being compromised in the current economic and policy environment.

Delivery Rooms↗

Changing childbirth: lessons from an Australian survey of 1336 women.

OBJECTIVE: To investigate the views and experiences of care in labour and birth of a representative sample of women who gave birth in Victoria, Australia in 1993. DESIGN: Cross-sectional survey mailed to women 6-7 months after giving birth. POPULATION: All women who gave birth in a two week period in Victoria, Australia in September 1993, except those who had a stillbirth or neonatal death. RESULTS: After adjusting for parity, the risk status of the pregnancy, and social and obstetric factors, specific aspects of care with the greatest negative impact on the overall rating of intrapartum care were: caregivers perceived as unhelpful (midwives: adjusted OR 12.03 [95% CI 7.8-18.6], doctors: adjusted OR 6.76 [95% CI 4.4-10.3]); and having an active say in decisions only sometimes, rarely or not at all (adjusted OR 8.90 [95% CI 4.9-16.1]). In a separate regression analysis including parity, risk status, obstetric and social factors, but not specific aspects of care, factors associated with dissatisfaction with intrapartum care included: participation in shared antenatal care programme (adjusted OR 1.89 [95% CI 1.2-3.0]) and being of nonEnglish speaking background (adjusted OR 1.70 [95% CI 1.1-2.6]). The following factors lowered the odds of dissatisfaction: attending a birth centre (adjusted OR 0.34 [95% CI 0.1-1.0]) and knowing the midwives before going into labour (adjusted OR 0.68 [95% CI 0.5-0.9]). CONCLUSION: The survey demonstrates the potential for 'new' models of care to have either positive or negative effects on women's experiences of care. Evaluation of innovations in perinatal care taking into account women's views is a prerequisite for improvements in maternity care.

Attitude to Health↗

Maternal health after childbirth: results of an Australian population based survey.

OBJECTIVE: To describe the prevalence of maternal physical and emotional health problems six to seven months after birth. DESIGN: Statewide postal survey, incorporating the Edinburgh Postnatal Depression Scale, distributed to women six to seven months after childbirth. PARTICIPANTS: All women who gave birth in a two-week period in Victoria, Australia in September 1993 except those who had a stillbirth or known neonatal death. RESULTS: The response rate was 62.5% (n = 1336). Respondents were representative of the total sample in terms of mode of delivery, parity and infant birthweight; young women, single women and women of nonEnglish speaking background were under-represented. One or more health problems in the first six postnatal months were reported by 94% of the women; a quarter had not talked to a health professional about their own health since the birth. Of women reporting health problems, 49% would have liked more help or advice. The most common health problems were tiredness (69%), backache (43.5%), sexual problems (26.3%), haemorrhoids (24.6%) and perineal pain (21%); 16.9% of women scored as depressed. Compared with spontaneous vaginal births, women having forceps or ventouse extraction had increased odds for perineal pain (OR 4.69 [95% CI 3.2-6.8]), sexual problems (OR 2.06 [95% CI 1.4-3.0]), and urinary incontinence (OR 1.81 [95% CI 1.1-2.9]). These differences remained significant after adjusting for infant birthweight, length of labour and degree of perineal trauma. CONCLUSION: Physical and emotional health problems are common after childbirth, and are frequently not reported to health professionals despite the fact that many women would like more advice and assistance in dealing with them.

Delivery, Obstetric↗