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Biomedical subjects

P Smith

Publications and source records attributed to P Smith.

At least 127 records · Page 7Linked to original sources

Evidence of association and linkage disequilibrium between a novel polymorphism in the transforming growth factor beta 1 gene and hip bone mineral density: a study of female twins.

OBJECTIVE: Bone mineral density (BMD) in later life is a major determinant of osteoporotic fracture risk and has been shown to be under strong genetic influence. Transforming growth factor beta 1 (TGF-beta 1) is an important regulatory cytokine, is found in high concentrations in the bone matrix, and is a plausible candidate for the genetic regulation of BMD. METHODS: This study investigated whether a novel polymorphism within the TGF-beta 1 gene is associated with BMD in a large normal female population of 1706 dizygotic (DZ) twins (age range 18-76 yr). RESULTS: A C--->T [corrected] polymorphism was identified in intron 5, the T [corrected] allele having a frequency of 0.25. Subjects homozygous for the presence of the TGF-beta 1 T [corrected] allele had a 4% reduction in femoral neck BMD compared with the other two genotype groups (P<0.025). No effect was seen at the lumbar spine or ultradistal radius, or with calcaneal ultrasound measurements. Results were unaffected after adjustment for potential confounders. These findings were predominantly seen in pre-menopausal subjects, suggesting that this locus has an effect on the attainment of peak BMD. In pre-menopausal women, subjects who were homozygous for the T [corrected] allele had a 5-fold excess risk of having osteoporosis at the femoral neck compared with the other genotype groups. A within-pair analysis using the sibling transmission disequilibrium test confirmed these findings in pre-menopausal women and supported the candidacy of the TGF-beta 1 locus in the genetic regulation of hip BMD. CONCLUSIONS: These results indicate that allelic variation at the TGF-beta 1 gene contributes to the development of osteoporosis at the hip. The study also highlights the power of candidate gene analysis in twins, in whom loci having modest effects on disease risk can be identified.

Adolescent↗

A comparison of the prevalence of respiratory illness and non-specific health symptoms in two Victorian cities.

OBJECTIVE: To compare the prevalence of respiratory illness and non-specific health symptoms among adults and children aged 4-15 years living in Portland and Warrnambool, Victoria. METHODS: A postal survey of 3,903 adults in Portland and Warrnambool systematically selected from the electoral roll was undertaken. Both an adults and children's questionnaire were enclosed in the mailing to each adult. If there were children aged 4-15 years in the household, an adult was asked to complete a questionnaire for the child who would next celebrate a birthday. Questionnaires were returned by 2,111 adults (54%) and for 585 children. RESULTS: No significant differences in the prevalence of self-reported asthma or wheeze were observed among adults or children residing in Portland and Warrnambool. The likelihood of itchy eyes, skin rash and stuffy nose was significantly higher in Portland adults and children compared with those in Warrnambool. Dry cough at night was increased among Portland children, but not significantly so. CONCLUSIONS: Higher rates of non-specific symptoms were observed in Portland but from a cross-sectional survey such as this, it is not possible to identify the cause of these higher rates. They may be related to environmental factors such as pollens or emissions from aluminium production, fertiliser production or bulk handling activities on the wharf, or they may be attributable to other factors such as response or recall bias.

Adolescent↗

Initial experience with a low profile, high energy excimer laser catheter for heavily calcified coronary lesion debulking: parameters and results of first seven human case experiences.

BACKGROUND: Excimer laser coronary angioplasty (ELCA) has not been used in the setting of highly calcified, tight stenoses because the energies required to use existing catheters would lead to excessive heat damage and dissection. There are, however, cases that frequently benefit from debulking prior to percutaneous intervention. A new, small laser catheter capable of high energies and repetition was previously examined in vitro. This study describes the first in vivo use. PURPOSE: To determine the safety and feasibility of a new, low profile, high energy laser catheter for creating a pilot hole to facilitate coronary angioplasty and stenting in patients with heavily calcified and occluded coronary arteries where a balloon has either failed to pass or was predicted to perform poorly. These patients represent the first patients treated with this new catheter. METHODS: At a high volume center, seven consecutive patients with anatomy as summarized above were treated and studied with QCA and then followed for 30 days postprocedure for complications and Canadian Cardiovascular Society (CCS) angina class. RESULTS: The laser catheter crossed five out of seven lesions and partially penetrated the remaining lesions. The mean maximum luminal diameter (MLD) postlasing was 1.0 mm with Thrombolysis in Myocardial Infarction (TIMI) 3 flow. It was possible to easily balloon and stent after the pilot hole creation in all but one patient. TIMI 3 was achieved for the final result after adjunct therapy in all patients. All patients except one, who died at 3 months postprocedure of stroke, were improved by an average of two angina classes. No late procedural-related complications developed. CONCLUSIONS: The new, low profile laser catheter is easy to use and achieved good results in cases where a balloon either failed to pass or was predicted to give poor results. Further trials are warranted for this niche technology.

Aged↗

MtDNA mutations in maternally inherited diabetes: presence of the 3397 ND1 mutation previously associated with Alzheimer's and Parkinson's disease.

Mutations in the mitochondrial tRNA(leu) (UUR) gene have been associated with diabetes mellitus and deafness. We screened for the presence of mtDNA mutations in the tRNA(leu) (UUR) gene and adjacent ND1 sequences in 12 diabetes mellitus pedigrees with a possible maternal inheritance of the disease. One patient carried a G to A substitution at nt 3243 (tRNA(leu) (UUR) gene) in heteroplasmic state. In a second pedigree a patient had an A to G substitution at nt 3397 in the ND1 gene. All maternal relatives of the proband had the 3397 substitution in homoplasmic state. This substitution was not present in 246 nonsymptomatic Caucasian controls. The 3397 substitution changes a highly conserved methionine to a valine at aa 31 and has previously been found in Alzheimer's (AD) and Parkinson's (PD) disease patients. Substitutions in the mitochondrial ND1 gene at aa 30 and 31 have associated with a number of different diseases (e.g. AD/PD, MELAS, cardiomyopathy and diabetes mellitus, LHON, Wolfram-syndrome and maternal inherited diabetes) suggesting that changes at these two codons may be associated with very diverse pathogenic processes. In a further attempt to search for mtDNA mutations outside the tRNAleu gene associated with diabetes, the whole mtDNA genome sequence was determined for two patients with maternally inherited diabetes and deafness. Except for substitutions previously reported as polymorphisms, none of the two patients showed any non-synonymous substitutions either in homoplasmic or heteroplasmic state. These results imply that the maternal inherited diabetes and deafness in these patients must result from alterations of nuclear genes and/or environmental factors.

Alzheimer Disease↗

Effect of osmolarity and presence of serum on the efficiency of cell transfection using immunoporation.

Immunoporation is a novel method of cell transfection based upon the use of a new type of beads, Immunofect beads, that can be targeted to make holes in different types of cells depending on the type of bead used. It is known that the efficiency of transfection of cells by some techniques can be affected by the presence of serum and another important factor that appears to affect transfection efficiency and cell viability is the osmolarity of the transfection medium. This report presents studies on the effects of serum and varying osmolarity on the efficiency of transfection using immunoporation. The results clearly indicate that in hypertonic media the presence of serum decreases the efficiency of transfection. In the case of osmolarity, increasing the osmolarity of the immunoporation medium increases the efficiency of transfection but above about 650 mOsm this increasing efficiency is offset by the much lower viability of the cells.

Blood↗

Osteoprotegerin inhibits prostate cancer-induced osteoclastogenesis and prevents prostate tumor growth in the bone.

Prostate cancer (CaP) forms osteoblastic skeletal metastases with an underlying osteoclastic component. However, the importance of osteoclastogenesis in the development of CaP skeletal lesions is unknown. In the present study, we demonstrate that CaP cells directly induce osteoclastogenesis from osteoclast precursors in the absence of underlying stroma in vitro. CaP cells produced a soluble form of receptor activator of NF-kappaB ligand (RANKL), which accounted for the CaP-mediated osteoclastogenesis. To evaluate for the importance of osteoclastogenesis on CaP tumor development in vivo, CaP cells were injected both intratibially and subcutaneously in the same mice, followed by administration of the decoy receptor for RANKL, osteoprotegerin (OPG). OPG completely prevented the establishment of mixed osteolytic/osteoblastic tibial tumors, as were observed in vehicle-treated animals, but it had no effect on subcutaneous tumor growth. Consistent with the role of osteoclasts in tumor development, osteoclast numbers were elevated at the bone/tumor interface in the vehicle-treated mice compared with the normal values in the OPG-treated mice. Furthermore, OPG had no effect on CaP cell viability, proliferation, or basal apoptotic rate in vitro. These results emphasize the important role that osteoclast activity plays in the establishment of CaP skeletal metastases, including those with an osteoblastic component.

Animals↗

Sex- and age-related differences in primary and secondary dentin formation.

Clinical studies carried out on dentin thickness in adults, as well as experimental studies carried out on ovariectomized animals, indicate that odontoblast activity, like that of osteoblastic cells, differs in the two sexes. To examine the evidence for differences in odontoblast activity before puberty, we have measured dentin thickness and other crown dimensions from bitewing radiographs of the lower first molars in 240 children aged 4-16 years. The radiographs were obtained from pedodontic clinics throughout Israel. Only teeth without caries or fillings were used, and the study population had minimal attrition. The results showed that dentin thickness, measured on the roof of the pulp chamber, was significantly greater in boys than in girls at all ages, and that the differences increased during puberty. The differences remained highly significant even when standardized for crown size. They demonstrate that dimorphism in dentin thickness is present even in the earliest stages of odontogenesis and increase with puberty.

Adolescent↗

Geriatric services offered by hospitals: predicting services by internal and external community characteristics.

This article explores the role of hospitals in providing geriatric services and identifies associated community and hospital characteristics. The sample is 4571 community hospitals responding to the 1995 American Hospital Association (AHA) Annual Survey. Most hospitals offer some geriatric services; the mean is 3.3. The dependent variable is an index of 13 geriatric services created from the AHA data. Independent variables are taken from the AHA survey, Area Resource File, and census data. Regression analysis explains fifteen percent of the variance. Hospital characteristics predicting provision of geriatric services are non-profit tax status, hospital bed size and system membership. Community characteristics predicting provision of geriatric services included higher population density, high percentage of county aged, and county nursing facility beds. Hospital characteristics yielded slightly higher predictive ability than did community characteristics. The findings suggest policies to increase hospital leadership in providing access to senior services require a multi-dimensional approach.

Aged↗

Inquiry cantos: poetics of developmental disability.

Postmodern thought is increasingly critical of foundations central to modern, positivist research into the lives of people labeled as having so-called developmental disabilities and mental retardation. This approach has brought about changes in how developmental disability is both understood and, ultimately, created. Responding to what has been called the postmodern turn, some disability studies scholars are choosing to represent their work in alternative textual formats, including poetry and fiction. These texts, representing multiple subjectivities, offer ways to explicate, problematize, and reconstruct new ways of understanding so-called developmental disability that are complex and plural. Examples of alternative research texts are provided from a recent qualitative research project with self-advocates and their construction of choice, control, and power.

Child↗

On-line sample preparation for high throughput reversed-phase LC/MS analysis of combinatorial chemistry libraries.

An on-line sample preparation method utilizing a time-programmed autosampler is described for high throughput liquid chromatography/mass spectrometry (LC/MS). This approach is particularly helpful for the LC/MS analysis of samples which require solvents incompatible with HPLC in the sample preparation process. The on-line sample preparation approach minimizes a bottleneck in throughput and improves sample recovery under some circumstances.

Chromatography, High Pressure Liquid↗

Evaluation of the fluorescence polarization assay and comparison to other serological assays for detection of brucellosis in cervids.

The complement fixation test (CFT), competitive enzyme immunoassay (CELISA), indirect enzyme immunoassay (IELISA) and fluorescence polarization assay (FPA) were evaluated for the detection of antibodies to Brucella abortus and Brucella suis biotype 4 in caribou (Rangifer tarandus caribou), elk (Cervus elapus), red deer (Cervus elapus), and reindeer (Rangifer tarandus tarandus). When combining the data the FPA and the CELISA were determined to be the most suitable tests for serodiagnosis of Cervidae. The overall actual sensitivity of the CFT and the IELISA was 100%. The overall actual sensitivity for the CELISA and FPA was 99%. The overall relative specificity of the CFT (including treatment of anti-complementary data as positive or negative for analysis), the CELISA, the IELISA and the FPA were 65%, 93%, 99%, 99%, and 99%, respectively. The specificities of the buffered plate agglutination test (BPAT), the CFT, the CELISA, the FPA and the IELISA for 55 elk vaccinated with B. abortus strain 19 and tested 4 mo post vaccination were 14%, 31%, 51%, 84%, and 2%, respectively. The FPA is the diagnostic test of choice because it has sensitivity and specificity values comparable to the CELISA; it has the capability to distinguish vaccinal antibody and antibody resulting from exposure to cross-reacting organisms such as Yersinia enterocolitica 0:9 from antibody to Brucella spp. in most cases; it is technically simple to do; it is adaptable to field use and it is relatively inexpensive.

Animal Diseases↗

The effect of brief halothane anesthesia during daily gavage on complications and body weight in rats.

We examined retrospectively the effects of brief halothane anesthesia during daily gavage administration of vehicle on gavage-related complications and body weight in ovariectomized female Wistar rats. The number of gavage-related deaths or animals requiring euthanasia due to gavage problems was dramatically reduced, but the occurrence of incomplete vehicle retention during gavage was increased appreciably in halothane-anesthetized animals. Halothane-anesthetized rats maintained daily body weight for a longer period than did awake animals. Our observations suggest that the use of brief inhalational anesthesia reduces gavage-associated death and euthanasia due to esophageal trauma and minimizes stress-related weight loss.

Anesthesia↗

War exposure and maternal reactions in the psychological adjustment of children from Bosnia-Hercegovina.

As part of a UNICEF-sponsored Psychosocial Programme in Bosnia, data were collected from a representative sample of 339 children aged 9-14 years, their mothers, and their teachers in order to investigate risk and moderating factors in children's psychological reactions to war. Self-report data from children revealed high levels of post-traumatic stress symptoms and grief reactions, but normal levels of depression and anxiety. Mothers' self-reports also indicated high levels of post-traumatic stress reactions, but normal levels of depression and anxiety. Child distress was related to both their level of exposure and to maternal reactions. Structural equation modeling was used to quantify the relationships between these risk factors and child distress, and to examine putative pathways to account for the association between child and maternal health. Children's adjustment was associated significantly with both exposure (phi = .37) and maternal mental health (phi = .37). Modeling also revealed a significant distorting effect of mother's own mental health on behavioural ratings of her child (psi = .59). Although evidence exists for an association between maternal mental health and mother rating errors, there is also a substantive association between maternal mental health and children's adjustment following war.

Adaptation, Psychological↗

Making decisions about cancer screening when the guidelines are unclear or conflicting.

OBJECTIVE: Our purpose was to determine the factors involved in the cancer screening decisions of family physicians in situations where the clinical practice guidelines are unclear or conflicting as opposed to when they are clear and uncontroversial. STUDY DESIGN: We analyzed discussions with focus groups using a constant comparative approach. POPULATION: A total of 73 family physicians in active practice participated in 10 focus groups (1 urban group and 1 rural group in each of 5 Canadian provinces). OUTCOME MEASURES: Our main outcome measures were participants' perceptions regarding cancer screening when the guidelines were unclear or conflicting. RESULTS: We propose a model of the determinants of cancer screening decision making with regard to unclear and conflicting guidelines. This model is rooted in the physician-patient relationship, and is an interactive process influenced by patient factors (anxiety, expectations, and family history) and physician factors (perception of guidelines, clinical practice experience, influence of colleagues, distinction between the screening styles of specialists and family physicians, and the amount of time and financial costs involved in performing the maneuver). CONCLUSIONS: Our model is unique, because it is embedded in the physician-patient relationship. Ultimately, a modified model could be used to design interventions to assist with the implementation of preventive services guidelines.

Adult↗

High prevalence of HIV risk-behavior and the identification of predictors for sharing injecting materials among young drug users in Prague, Czech Republic.

This study is one of the first studies in the Czech Republic evaluating the extent of the HIV epidemic among drug users. Interview data on demographics, drug use, sexual practices, and HIV knowledge and risk perception were obtained from study participants and a saliva sample was obtained for an HIV antibody test. Although the HIV infection rate is low (0.2%), the prevalence of high risk behaviors, such as sharing injecting equipment and unsafe sexual practices, indicate a potential for rapid HIV spread in this high risk population. Preventive measures need to be targeted toward drug users, especially those of younger age and women.

AIDS Serodiagnosis↗