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Biomedical subjects

P Smith

Publications and source records attributed to P Smith.

At least 181 records · Page 10Linked to original sources
PubMed2000

Effects of warfarin, aspirin and the two combined, on mortality and thromboembolic morbidity after myocardial infarction. The WARIS-II (Warfarin-Aspirin Reinfarction Study) design.

The efficacy and safety of warfarin, aspirin, and the two combined are compared in a long-term, randomized, open, multicentre study involving 3606 patients after acute myocardial infarction (1202 in each treatment group). In this trial three groups receive either warfarin, aimed at a therapeutic level of the International Normalized Ratio (INR) 2.8-4.2, or 160 mg aspirin daily, or 75 mg aspirin daily combined with warfarin with INR 2.0-2.5. A placebo group is not included. Patients are screened before randomization and are given major examinations at 4 weeks and at the end of the study. In addition, all patients are given a questionnaire every 6 months. Composite endpoints include death, non-fatal reinfarction and cerebral stroke. All analyses are conducted on the intention-to-treat principle and on on-efficacy basis. The analyses control for recruiting centre, use of beta blockade, use of thrombolytic therapy and use of angiotensin converting enzyme (ACE) inhibitors.

Adult↗
PubMed2000

Gene expression in abnormal ovarian structures of ewes homozygous for the inverdale prolificacy gene.

Animals heterozygous (I+) for the Inverdale prolificacy gene (FecX(I)) have an increased ovulation rate whereas those homozygous (II) for FecX(I) are infertile with "streak" ovaries and follicular development arrested at the primary (type 2 follicle) stage. The streak ovaries also contain small oocyte-free nodules with granulosa-like cells and often tumor-like structures. It has been hypothesized that these abnormal structures are of granulosa cell origin, and the aim of this study was to determine whether genes normally expressed in granulosa cells are also expressed in the nodules and tumor-like structures. The mRNAs encoding c-kit and its ligand stem cell factor (SCF), FSH receptor (FSH-R), follistatin, alpha-inhibin subunit, and the beta(A)- and beta(B)-activin/inhibin subunits were localized in ovaries of ewes with 0 (++), 1 (I+), or 2 (II) copies of the FecX(I) gene (n = 4-9 animals per genotype per gene) using in situ hybridization. Ontogeny of expression of all mRNAs examined was similar between ++ and I+ ewes. Expression of c-kit mRNA was observed in the oocyte of all follicular types present in ++, I+, and II ewes. Moreover, granulosa cells of type 2 (II) and type 2 and larger follicles (++, I+) expressed SCF mRNA. The mRNAs encoding FSH-R, follistatin, alpha-inhibin subunit, and beta(B)-activin/inhibin subunit were identified in type 3 and larger follicles of ++ and I+ ewes but not in follicles of II ewes that were only at the type 1, 1a, or 2 stages of development. However, the cells within the oocyte-free nodules of II ewes expressed all of these genes. The mRNAs encoding c-kit and beta(A)-activin/inhibin subunit were not observed in granulosa cells until antrum formation (type 5 follicles) or in the nodules of II ewes. Tumors from 4 ewes were obtained and classified as cystic, semisolid, or solid structures containing granulosa-like cells or as solid structures containing predominately fibroblast- and luteal-like cells. Often, two tumors were present on the same ovary. Tumors containing granulosa-like cells (n = 3-4 per gene) expressed the mRNAs encoding alpha-inhibin subunit, beta(A)-, and beta(B)-activin/inhibin subunits, follistatin, and the FSH-R but did not contain detectable amounts of mRNA for c-kit or SCF. Tumors composed predominately of fibroblast- and luteal-like cells expressed very low levels of SCF mRNA; of the other mRNAs examined, none were detected. Also, none of the genes examined were found to be expressed by the surface epithelium, theca externa, fibroblast, or vascular cells within the ovary of animals of any genotype. These findings are consistent with the hypothesis that the somatic cells in oocyte-free nodules and tumor-like tissue in II ewes originate from the granulosa cells of the small follicles.

Activins↗
PubMed2000

Potential of gene therapy for treating osteogenesis imperfecta.

Osteogenesis imperfecta is a heterogeneous group of genetic disorders that affect connective tissue integrity, with bone fragility being the major clinical feature. Most forms of osteogenesis imperfecta are the result of mutations in the genes that encode the pro alpha1 and pro alpha2 polypeptide chains of Type I collagen. Because osteogenesis imperfecta is an incurable genetic disease, cell therapy and gene therapy are being investigated as potential treatments. Gene therapy for osteogenesis imperfecta however is a major challenge; because most of the mutations in osteogenesis imperfecta are dominant negative, supplying the normal gene without silencing the abnormal gene may not be beneficial. Null mutations in which an allele is not expressed or absent may be amenable to gene therapy or alternatively after silencing a mutant allele, a normal gene could be supplied. In addition, overexpression of the normal collagen gene in cells expressing mutant collagen polypeptide chains potentially could lead to synthesis of a sufficient percentage of normal molecules to normalize clinical status. The authors currently are examining the possibility of developing gene therapy for treating a mouse model of human osteogenesis imperfecta (oim) using bone marrow stromal cells as vehicles for delivering normal collagen genes to bone. In the current study, the potential of gene therapy for treating osteogenesis imperfecta is discussed in the context of the complexity of the mutations in Type I collagen genes that lead to different osteogenesis imperfecta phenotypes.

Animals↗
PubMed2000

Using gene therapy to protect and restore cartilage.

Numerous gene products have the potential to help protect cartilage from degradation and to repair cartilage that has become damaged as a result of disease or injury. The genes that encode these products thus may serve as chondroprotective and chondroregenerative medicines. To bring these agents into clinical use, it is necessary to screen candidate genes for efficacy under in vitro and in vivo conditions, to determine the best cells to target, and to develop appropriate gene transfer technologies. As discussed in the current review, progress has been made in each of these areas. Various viral and nonviral vectors are able to deliver genes to synoviocytes, articular chondrocytes, and mesenchymal stem cells. There also is evidence to suggest that ex vivo and in vivo approaches can be used for gene transfer to articular cartilage, synovium, and meniscus. Moreover various cytokine antagonists and growth factors have been shown to protect cartilage and stimulate chondrogenesis. In vivo methods and strategies that target synovium may be useful in a chondroprotective mode but because they do not increase the number of chondrogenic cells within lesions, they may be ill-equipped to repair large defects. Ex vivo methods however, provide cells and genes. It also is important to distinguish the treatment of isolated lesions occurring as a result of injury from the treatment of lesions resulting from underlying disease processes. Additional development of these approaches should result in clinically useful genetic methods for the protection and regeneration of cartilagenous tissues.

Animals↗
PubMed2000

Integration of nurse executives into executive level administration in Utah hospitals.

Nurse executives (NEs) in Utah acute care hospitals perceive that they are integrated into executive level administration. This perception is shared by NEs' career supporters and hinderers. To integrate NEs, influential colleagues used active methods, especially involvement. NEs add value to the administrative team by combining clinical and managerial expertise. NE integration is manifest in decision making, participation and interaction. Continued integration depends upon commitment from the chief executive officer (CEO), leadership in organizational change, addressing "glass ceiling" issues, and NEs' continuous demonstration of competence.

Career Mobility↗
PubMed2000

Aboriginal deaths in Western Australia: 1985-89 and 1990-94.

OBJECTIVE: To examine death data for Aboriginal and non-Aboriginal persons in Western Australia (WA) in 1985-89 and 1990-94. METHODS: Population estimates were provided by the Health Information Centre of the WA Health Department based on data from the Australian Bureau of Statistics (ABS). Death data came from the WA Registrar-General's Office. Standard methods were used to obtain rates and levels of significance. RESULTS: Main causes of deaths among Aboriginal males in 1990-94 were circulatory conditions, respiratory, injury and poisoning, neoplasms and endocrine diseases; in Aboriginal females they were circulatory, neoplasms, endocrine diseases, respiratory diseases, and injury and poisoning. From 1985-89 to 1990-94, the Aboriginal male all-cause age-standardised death rates fell 3% (ns) while the non-Aboriginal male rate fell 11% (p < 0.05). The Aboriginal female all-cause death rate rose 11% (ns) while the non-Aboriginal rate fell 5% (p < 0.05). The all-cause death rate ratio (Aboriginal:non-Aboriginal) changed from 2.4 to 2.6 (males) and 2.5 to 2.9 (females). There was a major increase in deaths from endocrine diseases among Aborigines and non-Aborigines. This increase was proportionally much greater among Aborigines. In non-Aborigines there was a significant decrease in deaths from circulatory diseases (mainly ischaemic heart disease); this did not occur among Aborigines. CONCLUSIONS: Over the study period, Aboriginal health standards, as reflected by death rates, apparently worsened relative to non-Aboriginal standards. IMPLICATIONS: Better health promotion, disease prevention and disease care are required to help achieve acceptable health standards among Aboriginal peoples.

Adolescent↗
PubMed2000

Consumerism, disorientation and postmodern space: a modest test of an immodest theory.

There has recently been an explosion of theoretical literature on social space. A central claim in this literature is that postmodern spaces are experienced as confusing or disorienting by human subjects. This claim remains untested. The paper reports results from a small-scale survey conducted in one form of postmodern space--the shopping mall. It suggests that unsupported assertions about the disorienting effects of postmodern space and their associated influence on consumerist activities should be treated with scepticism. Through practice humans are able to develop routines which enable them to competently navigate these spaces.

Community Participation↗
PubMed2000

Distribution of oxytetracycline resistance plasmids between aeromonads in hospital and aquaculture environments: implication of Tn1721 in dissemination of the tetracycline resistance determinant tet A.

Oxytetracycline-resistant (OT(r)) mesophilic aeromonads were recovered from untreated hospital effluent (72 isolates) and from fish farm hatchery tanks (91 isolates) at sites within the English Lake District, Cumbria, England. The transfer of OT(r) plasmids from these isolates was investigated. Using Escherichia coli J53-1 as a recipient, 11 isolates from the hospital site and 6 isolates from the fish farm site transferred OT(r) plasmids (designated pFBAOT1 to 17). Original isolates were identified using fatty acid methyl ester and fluorescent amplified fragment length polymorphism comparisons as either Aeromonas hydrophila HG3 (eight isolates), A. veronii b.v. sobria HG8 (six isolates), and A. caviae HGB5 (one isolate). One isolate remained unidentified, and one could not be assigned a taxonomic designation beyond the genus level. Plasmids pFBAOT1 to -17 were screened for the presence of the tetracycline resistance determinants Tet A to E and Tet G. Only determinant Tet A (10 plasmids) was detected in these plasmids, with 7 tet gene determinants remaining unclassified. In all cases, Tet A was located on a 5.5-kb EcoRI restriction fragment. Hybridization with inc-rep probes N, P, Q, W, and U showed pFBAOT3, -4, -5, -6, -7, -9, and -11, from the hospital environment, to be IncU plasmids. Further, restriction fragment length polymorphism (RFLP) analyses and DNA probing demonstrated that pFBAOT plasmids were closely related to IncU OT(r) plasmids pASOT, pASOT2, pASOT3, pRAS1 (originally isolated from A. salmonicida strains from fish farms in Scotland and Norway, respectively), and pIE420 (isolated from a German hospital E. coli strain). In addition, DNA analyses demonstrated that plasmids pRAS1 and pIE420 had identical RFLP profiles and that all fragments hybridized to each other. The presence of tetracycline resistance transposon Tn1721 in its entirety or in a truncated form in these plasmids was demonstrated. These results provided direct evidence that related tetracycline resistance-encoding plasmids have disseminated between different Aeromonas species and E. coli and between the human and aquaculture environments in distinct geographical locations. Collectively, these findings provide evidence to support the hypothesis that the aquaculture and human compartments of the environment behave as a single interactive compartment.

Aeromonas↗
PubMed2000

Expression of interleukin-9 leads to Th2 cytokine-dominated responses and fatal enteropathy in mice with chronic Schistosoma mansoni infections.

Mice infected with Schistosoma mansoni develop Th2 cytokine-mediated granulomatous pathology that is focused on the liver and intestines. In this study, transgenic mice constitutively expressing IL-9 were infected with S. mansoni and the outcome of infection was determined. Eight weeks after infection, transgenic mice with acute infections had a moderate increase in Th2 cytokine production but were overtly normal with respect to parasite infection and pathological responses. Transgenic mice with chronic infections died 10 weeks after infection, with 86% of transgenic mice dead by week 12 of infection, compared to 7% mortality in infected wild-type mice. Stimulation of mesenteric lymph node cells from infected transgenic mice with parasite antigen elicited elevated interleukin-4 (IL-4) and IL-5 production and reduced gamma interferon and tumor necrosis factor alpha production compared to the responses in wild-type mice. Morbid transgenic mice had substantial enlargement of the ileum, which was associated with muscular hypertrophy, mastocytosis, eosinophilia, goblet cell hyperplasia, and increased mucin expression. We also observed that uninfected transgenic mice exhibited alterations in their intestines. Although there was hepatic mastocytosis and eosinophilia in infected transgenic mice, there was no hepatocyte damage. Death of transgenic mice expressing IL-9 during schistosome infection was primarily associated with enteropathy. This study highlights the pleiotropic in vivo activity of IL-9 and demonstrates that an elevated Th2 cytokine phenotype leads to death during murine schistosome infection.

Animals↗
PubMed2000

Chronic alcohol ingestion induces osteoclastogenesis and bone loss through IL-6 in mice.

To investigate the role of IL-6 in alcohol-mediated osteoporosis, we measured a variety of bone remodeling parameters in wild-type (il6(+/+)) or IL-6 gene knockout (il6(-/-)) mice that were fed either control or ethanol liquid diets for 4 months. In the il6(+/+) mice, ethanol ingestion decreased bone mineral density, as determined by dual-energy densitometry; decreased cancellous bone volume and trabecular width and increased trabecular spacing and osteoclast surface, as determined by histomorphometry of the femur; increased urinary deoxypyridinolines, as determined by ELISA; and increased CFU-GM formation and osteoclastogenesis as determined ex vivo in bone marrow cell cultures. In contrast, ethanol ingestion did not alter any of these parameters in the il6(-/-) mice. Ethanol increased receptor activator of NF-kappaB ligand (RANKL) mRNA expression in the bone marrow of il6(+/+) but not il6(-/-) mice. Additionally, ethanol decreased several osteoblastic parameters including osteoblast perimeter and osteoblast culture calcium retention in both il6(+/+) and il6(-/-) mice. These findings demonstrate that ethanol induces bone loss through IL-6. Furthermore, they suggest that IL-6 achieves this effect by inducing RANKL and promoting CFU-GM formation and osteoclastogenesis.

Absorptiometry, Photon↗
PubMed2000

Electroencephalographic indices related to hypnosis and amnesia during propofol anaesthesia for cardioversion.

Most previous studies which have assessed the depth of anaesthesia using the Bispectral Index (BIS) have used multi-agent anaesthetics with relatively slow induction and recovery times. Elevation of electroencephalographic (EEG) Beta/Alpha Ratio has been linked to onset of midazolam amnesia. Propofol anaesthesia for cardioversion in 19 patients enabled us to profile the changes in BIS and Beta/Alpha Ratio during a short, single-agent anaesthetic with a relatively rapid induction and recovery period. BIS values did not alter significantly through onset of amnesia and hypnosis as compared with awake values. Cardioversion occurred over a wide range of BIS values (38 to 94), with recovery at a median BIS value of 79. We observed the BIS to lag about 60 s behind the clinical situation (termed BIS60). The BIS60 more closely tracked the clinical level of consciousness, showing statistically significant differences from the uncorrected BIS. (amnesia (median BIS60 = 82, P = 0.02), hypnosis (median BIS60 = 67, P = 0.01), eye opening (median BIS60 = 90, P = 0.001)). An early EEG Beta/Alpha Ratio peak occurred at a mean of 4.6 s (SD = 16.6) after clinical amnesia onset and a late peak at a mean 58 s (SD = 144) after eye opening. There was no significant EEG response to cardioversion. We conclude that: (1) in rapidly changing conditions, the value of the BIS most accurately reflects the level of consciousness of the patient about 60 s in the past, and (2) the onset and offset of propofol-induced amnesia commonly corresponds to a peak in Beta/Alpha Ratio of the EEG.

Adult↗
PubMed2000

Validation of the fluorescence polarization assay and comparison to other serological assays for the detection of serum antibodies to Brucella abortus in bison.

A number of serological tests were compared for the detection of antibodies to Brucella abortus in bison (Bison bison). The performance of the fluorescence polarization assay (FPA) in both the preliminary evaluation and a subsequent blind validation indicated that this test was the most suitable for serological diagnosis of brucellosis in bison. The sensitivity and specificity in the preliminary evaluation were 92.1% and 99.4%, respectively. The sensitivity and specificity in a subsequent blind study were 96.3% and 97.6%, respectively. In a double blind study conducted on bison vaccinated with B. abortus strain 19, the data suggests that the FPA can differentiate bison infected with B. abortus from bison vaccinated with B. abortus strain 19. Both the indirect immunoassay (IELISA) and the competitive immunoassay (CELISA) performed nearly as well as the FPA. The buffered antigen plate agglutination test (BPAT) and the complement fixation test (CFT) did not perform as well as the FPA, CELISA or the IELISA in both studies. The FPA is a homogeneous assay eliminating the washing steps and reducing incubation to minutes rather than hours saving on time, equipment, materials, reagents and cost. These attributes, together, with its excellent sensitivity and specificity make the FPA an attractive test for the detection of serum antibodies to Brucella abortus in bison.

Agglutination Tests↗
PubMed2000

A randomized British National Lymphoma Investigation trial of CHOP vs. a weekly multi-agent regimen (PACEBOM) in patients with histologically aggressive non-Hodgkin's lymphoma.

BACKGROUND: Between 1987 and 1991, the British National Lymphoma Investigation randomized 459 patients with non-Hodgkin's lymphoma with a large-cell component to either CHOP or the PACEBOM regimen. PATIENTS AND METHODS: Four hundred fifty-nine eligible patients were included in this trial, four hundred one with diffuse large-cell lymphoma and fifty-eight with diffuse mixed-cell lymphoma according to the Working Formulation. Two hundred twenty-six patients were randomized to receive CHOP and two hundred thirty-three to receive PACEBOM. The two arms of the trial were well balanced for all potential prognostic factors. RESULTS: The complete remission rate with PACEBOM was 64% and with CHOP 57% (NS). At eight years, the actuarial cause specific survival (CSS) in the PACEBOM arm is 59% compared to 49% in the CHOP arm (P = 0.09). Patients < 50 years of age fared significantly better in the PACEBOM arm both for CSS and overall survival (P = 0.002) and the CSS was also significantly improved in stage IV disease (P = 0.02). CONCLUSIONS: The mature data from this trial suggest that an etoposide-containing multi-agent weekly regimen can be superior to CHOP.

Adolescent↗
PubMed2000

Are specialist mental health services being targeted on the most needy patients? The effects of setting up special services in general practice.

BACKGROUND: Around 25% of patients with psychoses lose contact with specialist psychiatric services, despite the government's policy to focus the efforts of community teams on this group. AIM: To identify patient and practice factors associated with continuing contact and loss of contact with specialist services. METHOD: Cross-sectional comparison was made of patients in and out of specialist contact, through detailed interviews with 102 patients among 26 south west London practices. Associations were sought between contact with specialist services and patient factors (illness severity, social functioning, quality of life, needs for care, and satisfaction with general practitioner [GP] services) and practice factors (size, location, fundholding status, training status, and the presence of mental health professionals on site). RESULTS: Thirty-one (30%) patients were currently out of specialist contact. No significant differences were found between those in and out of contact on any measures of diagnosis or psychiatric history. Those in contact had significantly more symptoms, poorer social functioning, poorer quality of life, and more needs for care. The proportion out of contact was significantly higher in two practices that had employed their own mental health professionals to provides services on site for severe mental illnesses. Two factors remained significant predictors of contact in a logistic regression model: whether or not the patient's practice offered a special service on site, and greater patient needs for care. CONCLUSIONS: Secondary mental health services are being targeted towards the more needy patients. The provision of special services in practices can shift care further away from secondary care while still meeting patients' needs.

Analysis of Variance↗
PubMed2000

The assessment and treatment of Post-traumatic Stress Disorder in children and adolescents.

Post-traumatic Stress Disorder (PTSD) is a syndrome defined by the intrusive re-experiencing of a trauma, avoidance of traumatic reminders, and persistent physiological arousal. PTSD is associated with high levels of comorbidity and may increase the risk for additional disorders over time. While controversies remain regarding the applicability of the PTSD criteria to very young children, it has proved to be a useful framework for guiding assessment and treatment research with older children and adolescents. This article presents an overview of the literature on the clinical characteristics, assessment, and treatment of PTSD in children and adolescents.

Adaptation, Psychological↗
PubMed2000

Therapeutic and financial outcomes using a pulsating low-air-loss surface for patients surviving severe posterior burns.

Patients with posterior burns require extensive stays in the intensive care unit for recovery. The authors hypothesized that pulsating low-air-loss therapy would decrease the intensive care unit length of stay for burn patients, resulting in a potentially significant reduction in charges to payors. Eighty-one posterior burn patients enrolled in the primary study were randomly assigned to a pulsating low-air-loss surface (study group) or a nonpulsating low-air-loss surface (control group). The 54 survivors in this analysis (the secondary study) were well matched for age, pre-existing conditions, and total body surface area burned. Average intensive care unit length of stay was less for the study patients compared with the control patients--40 days versus 64 days (P < .05). Control patients used specialty surfaces for 49 days and study patients used them for 38 days. Based on a daily intensive care unit charge of $1,000 and the average daily specialty surface rental charge, the study patients averaged potential charges of under $44,000 in comparison to more than $67,000 for control patients. These data suggest that treatment of posterior burns with pulsating low-air-loss therapy may be of great clinical and financial benefit, decreasing the intensive care unit length of stay and potentially contributing to reduced charges to payors.

Adult↗
PubMed2000

Substance abuse and trauma in Cape Town.

OBJECTIVE: To obtain baseline data on the incidence of acute alcohol intoxication, chronic alcoholism and illicit drug usage among a cohort of injured patients. DESIGN: A prospective, descriptive study of 254 injured patients presenting at the trauma unit of Groote Schuur Hospital over an idealized week in 1997. Alcohol consumption was assessed by means of the Lion SD2 alcolmeter. Chronic alcoholism was assessed using the CAGE questionnaire. Each patient's urine was analysed for four drugs (cannabis, morphine, opiates and methaqualone) using conventional 'wet' analysis. Sweat was tested for cannabis using a Drugwipe. MAIN OUTCOME MEASURES: Socio-demographics, cause of injury, injury severity, acute alcohol intoxication, chronic alcohol usage and illicit drug involvement. RESULTS: Patients were predominantly male, coloured and an average of 31.3 years old. The majority had been injured as a result of interpersonal violence. Self-reported alcohol consumption was reliable but this was not so for self-reported drug usage. Sixty per cent of patients had positive alcohol levels on breath analysis. More than one-quarter of all the patients could be classified as chronic alcoholics on the CAGE questionnaire. On urine analysis, 40% of patients were found to have used at least one illicit drug in the recent past. The most commonly abused drugs were cannabis or a combination of cannabis and Mandrax, locally called a 'white pipe'. Use of the white pipe was confined almost exclusively to patients injured as a result of interpersonal violence. CONCLUSIONS: Alcohol remains the most commonly abused substance among trauma patients, but there are growing numbers of patients who simultaneously abuse illicit drugs. This study will be conducted annually to detect trends and identify emerging problems.

Adolescent↗