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Biomedical subjects

P White

Publications and source records attributed to P White.

At least 55 records · Page 3Linked to original sources
PubMed2001

Developmental expression analysis of thyroid hormone receptor isoforms reveals new insights into their essential functions in cardiac and skeletal muscles.

Nuclear thyroid hormone (TH) receptors (TR) play a critical role in mediating the diverse actions of TH in development, differentiation, and metabolism of most tissues, but the role of TR isoforms in muscle development and function is unclear. Therefore, we have undertaken a comprehensive expression analysis of TRalpha 1, TRbeta 1, TRbeta 2 (TH binding), and TRalpha 2 (non-TH binding) in functionally distinct porcine muscles during prenatal and postnatal development. Use of a novel and highly sensitive RNase protection assay revealed striking muscle-specific developmental profiles of all four TR isoform mRNAs in cardiac, longissimus, soleus, rhomboideus, and diaphragm. Distribution of TR isoforms varied markedly between muscles; TRalpha expression was considerably greater than TRbeta and there were significant differences in the ratios TRalpha 1:TRalpha 2, and TRbeta 1:TRbeta 2. Together with immunohistochemistry of myosin heavy chain isoforms and data on myogenesis and maturation of the TH axis, these findings provide new evidence that highlights central roles for 1) TRalpha isoforms in fetal myogenesis, 2) the ratio TRalpha 1:TRalpha 2 in determining cardiac and skeletal muscle phenotype and function; 3) TRbeta in maintaining a basal level of cellular response to TH throughout development and a specific maturational function around birth. These findings suggest that events disrupting normal developmental profiles of TR isoforms may impair optimal function of cardiac and skeletal muscles.

Animals↗
PubMed2001

Redefining reference in an academic health sciences library: planning for change.

Deciding that changes in the pattern of questions at the reference desk required focused consideration, the reference librarians at the Health Sciences Library of the University at Buffalo held a planning retreat. Technology-induced changes in the information-seeking behavior and reference needs of the library's clientele caused a reassessment of how these needs could best be met and what is the best use of librarians' time. The librarians considered current trends in reference in other academic libraries, the specific needs of the clientele of the Health Sciences Library, and the strengths and expertise of the library staff. The results of this structured discussion produced ideas for redefining reference to provide customized services for the clients and environment.

Academic Medical Centers↗
PubMed2001

Diagnosis of enteric pathogens in children with gastroenteritis.

The aim of this study was to determine the isolation trends of common and emerging pathogens in children over a 12-month period. The study group included 412 children under 6 years with diarrhoea who were either hospitalised, or seen in the outpatients department of The Sydney Children's Hospital. Pathogens were detected in 137 (33%) samples, with rotavirus most common (40%), followed by adenovirus (26%), astrovirus (12%), Campylobacter jejuni (12%), Salmonella spp. (10%) and Giardia lamblia (< 1 %). Giardia-specific antigen (GSA) was detected in 11 of 382 (3%) using an enzyme immunoassay (EIA), and this included four samples in which cysts of G. lamblia were detected by microscopy. Using electron microscopy (EM), viruses were detected in 29 of 120 (24%) samples from hospitalised children and 53 of 171 (31%) outpatients (P = 0.23). Amongst this subset, Norwalk-like viruses (NLVs) were detected by RT-PCR in 10 samples including six of 14 with small round viruses, one of seven with small viral-like particles (SVLPs), and three of 126 EM-negative samples. Lactoferrin, detected by EIA, was 59% more likely to be positive in samples infected with salmonella/campylobacter than in samples in which bacterial pathogens were not isolated. As an indicator for infection with these bacterial agents, the assay showed a sensitivity and specificity of 95 and 40.3%, respectively. A routine microbiological analysis of stools from children of this age group should include a screen for foodborne bacterial agents and rotavirus. Tests for adenovirus, astrovirus and NLVs should be secondary. The cost-effectiveness of including the EIAs for lactoferrin and G. lamblia in the routine testing protocol needs to be evaluated.

Animals↗
PubMed2001

Erectile function after anterior urethroplasty.

PURPOSE: We ascertained the impact of anterior urethroplasty on male sexual function. MATERIALS AND METHODS: A validated questionnaire was mailed to 200 men who underwent anterior urethroplasty to evaluate postoperative sexual function. Questions addressed the change in erect penile length and angle, patient satisfaction with erection, preoperative and postoperative coital frequency, and change in erection noted by the sexual partner. Results were stratified by the urethral reconstruction method, namely anastomosis, buccal mucosal graft, penile flap and all others, and compared with those in a similar group of men who underwent circumcision only. RESULTS: Of the 200 men who underwent urethroplasty 152 who were 17 to 83 years old (mean age 45.7) completed the questionnaire. Average followup was 36 months (range 3 to 149). Overall there was a similar incidence of sexual problems after urethroplasty and circumcision. Penile skin flap urethroplasty was associated with a slightly higher incidence of impaired sexual function than other procedures (p >0.05). Men with a longer stricture were most likely to report major changes in erectile function and penile length (p <0.05) but improvement was evident with time in 61.8%. CONCLUSIONS: Overall anterior urethral reconstruction appears no more likely to cause long-term postoperative sexual dysfunction than circumcision. Men with a long stricture may be at increased risk for transient erectile changes.

Adult↗
PubMed2000

Mathematical elements of attack risk analysis for mountain pine beetles.

Three different mathematical approaches are combined to develop a spatial framework in which risk of mountain pine beetle (MPB) attack on individual hosts may be assessed. A density-based partial differential equation model describes the dispersal and focusing behavior of MPB. A local projection onto a system of ordinary differential equations predicts the consequences of the density equations at individual hosts. The bifurcation diagram of these equations provides a natural division into categories of risk for each host. A stem-competition model links host vigor to stand age and demographics. Coupled together, these models illuminate spatial risk structures which may also shed light on the role of climatic variables in population outbreaks. Preliminary results suggest that stand microclimate has much greater influence on risk of attack than host vigor and stand age.

Animals↗
PubMed2000

Mutational analysis of the propensity for amyloid formation by a globular protein.

Acylphosphatase can be converted in vitro, by addition of trifluoroethanol (TFE), into amyloid fibrils of the type observed in a range of human diseases. The propensity to form fibrils has been investigated for a series of mutants of acylphosphatase by monitoring the range of TFE concentrations that result in aggregation. We have found that the tendency to aggregate correlates inversely with the conformational stability of the native state of the protein in the different mutants. In accord with this, the most strongly destabilized acylphosphatase variant forms amyloid fibrils in aqueous solution in the absence of TFE. These results show that the aggregation process that leads to amyloid deposition takes place from an ensemble of denatured conformations under conditions in which non-covalent interactions are still favoured. These results support the hypothesis that the stability of the native state of globular proteins is a major factor preventing the in vivo conversion of natural proteins into amyloid fibrils under non-pathological conditions. They also suggest that stabilizing the native states of amyloidogenic proteins could aid prevention of amyloidotic diseases.

Acid Anhydride Hydrolases↗
PubMed2000

Managements for people with disorders of sexual preference and for convicted sexual offenders.

BACKGROUND: The reviewers recognise that it may be thought that convicted sex offenders and those with disorders of sexual preference are quite different groups. In combining them within this review we have taken the view that legal process alone should not define the population. Illegal behaviours in one jurisdiction may not be considered so in others. Studies of those who are convicted of sexual offending describe reconviction rates for sexual offences of up to 40-60%. It would seem important to know if there are interventions that might reduce this high rate of re-offending. This review examines antilibidinal management of those who have been convicted of sexual offences or who have disorders of sexual preference. OBJECTIVES: To determine the effectiveness of a range of management techniques to assist people who have disorders of sexual preference and those who have been convicted of sexual offences. SEARCH STRATEGY: Biological Abstracts, the Cochrane Schizophrenia Group Register of Trials, The Cochrane Library, EMBASE, MEDLINE, and PsychLIT were searched. Further references were sought from published trials and their authors. Relevant pharmaceutical manufacturers were contacted. SELECTION CRITERIA: All relevant randomised controlled trials. DATA COLLECTION AND ANALYSIS: Reviewers evaluated data independently and analysed on an intention-to-treat basis. Data were extracted for short and medium term outcomes. MAIN RESULTS: A single trial (McConaghy 1988) found the effect of antilibidinal medication (medroxyprogesterone acetate) plus imaginal desensitisation was no better than imaginal desensitisation for problematic/anomalous sexual behaviour and desire. A relapse prevention programme was trialed by Marques (Marques 1994) and participants were followed up for an average of 3 years. What data there are suggest that although there is no discernable effect on the outcome of sex offending (OR 0.76 CI 0. 26-2.28) those treated with response prevention do have less non-sexual violent offences (OR 0.3, CI 0.1-0.89, NNT 10 CI 5-85). In addition those committing both sexual and violent offences also declined in the response prevention group (OR 0.14 CI 0.02-0.98, NNT 20 CI 10-437). A large pragmatic trial investigated the value of group therapy for sex offenders (Romero 1983). This study finds no effect on recidivism at ten years. REVIEWER'S CONCLUSIONS: It is disappointing to find that this area lacks a strong evidence base, particularly in light of the controversial nature of the treatment and the high levels of interest in the area. The relapse prevention programme did seem to have some effect on violent reoffending but large, well-conducted randomised trials of long duration are essential if the effectiveness or otherwise of these treatments are to be established.

Humans↗
PubMed2000

Carbamazepine for schizophrenia and schizoaffective psychoses.

BACKGROUND: A sizeable minority of people with schizophrenia do not have complete remission of symptoms. A variety of adjunctive treatments have been used to treat schizophrenia, carbamazepine being one. OBJECTIVES: To review the effects of carbamazepine and its derivatives for the treatment of schizophrenia and schizoaffective psychoses. SEARCH STRATEGY: Biological Abstracts (1980-1998), The Cochrane Library (Issue 3, 1998), The Cochrane Schizophrenia Group's Register of Trials (August 1998), EMBASE (1980-1998), MEDLINE (1966-1998), PsycLIT (1886-1998) and PSYNDEX (1974-1998) were searched. Citations from included trials were also inspected and relevant companies and authors contacted for additional data. SELECTION CRITERIA: All randomised controlled trials comparing carbamazepine, or compounds of the carbamazepine family, to placebo or no intervention, whether as sole treatment or as an adjunct to antipsychotic medication for the treatment of schizophrenia and/or schizoaffective psychoses. DATA COLLECTION AND ANALYSIS: Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were extracted independently by at least two reviewers. Dichotomous data were analysed using Peto odds ratio (OR) and the 95% confidence interval (CI) estimated. Where possible the number needed to treat (NNT) or number needed to harm statistics were calculated. MAIN RESULTS: There is no clear effect of carbamazepine as the sole maintenance treatment for those with schizophrenia. Eight trials provided very limited data on the value of carbamazepine as an adjunct to antipsychotics. Studies were small and poorly reported. Currently no published data provides convincing evidence that adjunctive carbamazepine has an effect on global functioning, mental state, side effects or acceptability of treatment. REVIEWER'S CONCLUSIONS: Based on currently available randomised trial-derived evidence, carbamazepine cannot be recommend for routine clinical use for treatment or augmentation of antipsychotic treatment of schizophrenia. However, for those with a past history of being responsive to carbamazepine, or for those with associated EEG abnormalities, a trial of the drug may be warranted. More data is expected from trialists and the results of this review may be changed by their inclusion. At present large, simple well designed and reported trials are justified especially if focusing on those with both schizophrenia and EEG abnormalities or violent episodes and people with schizoaffective disorders.

Antimanic Agents↗
PubMed2000

Validation of a highly sensitive ICP-MS method for the determination of platinum in biofluids: application to clinical pharmacokinetic studies with oxaliplatin.

ELOXATIN (Oxaliplatin) is a novel platinum containing anti-cancer agent with a diaminocyclohexane carrier ligand which has been approved in several major European countries. Clinical studies have demonstrated that the compound exhibits marked activity against colorectal cancers in combination with 5-fluorouracil (5-FU). The aim of this work was to develop and validate a highly sensitive inductively coupled plasma mass spectrometry assay for the determination of oxaliplatin-derived platinum in plasma ultrafiltrate, plasma and whole blood and to apply this technique to clinical pharmacokinetic studies with oxaliplatin. Ultratrace detection of platinum in plasma ultrafiltrate was achieved using ultrasonic nebulisation combined with ICP-MS. This technique allows detection of platinum at the 0.001 microg Pt/ml level in only 100 microl of matrix. Assays in blood and plasma utilised a standard Meinhardt nebuliser and spray chamber, achieving detection limits of 0.1 microg Pt/ml in 100 and 200 microl of matrix, respectively. The assays were validated (accuracy and precision within +/- 15%) over the concentration ranges: 0.001-0.250 microg Pt/ml in plasma ultrafiltrate and 0.1-10 microg Pt/ml for plasma and whole blood. The effect of sample digestion. dilution, long term frozen storage and quantitation in the presence of 5-FU were also investigated and validated. The method was used to monitor platinum exposure following oxaliplatin administration (130 mg/m2) to cancer patients. Following a 2 h i.v. infusion, peak platinum levels declined in a triphasic manner in all blood compartments. Free platinum was detected in plasma ultrafiltrate at low levels (0.001 0.010 microg Pt/ml) for up to 3 weeks. In conclusion, a highly sensitive and specific assay has been developed for the determination of platinum in biofluids. This method enabled characterisation of the long term exposure to platinum in patients following oxaliplatin treatment.

Antineoplastic Agents↗
PubMed2000

The multifunctional properties and characteristics of vitamin D-binding protein.

In recent years, our understanding of the many physiological, biochemical, and molecular functions and attributes of vitamin D-binding protein (DBP) has seen exciting and significant advances. Since its identification in 1959, many important functions of this abundant serum protein have been discovered. These range from the transport of vitamin D metabolites to possible roles in the immune system and host defense. With these discoveries, many questions regarding the biology of DBP have been raised and many remain to be answered. Our current understanding of the classic and less-recognized activities of DBP is discussed here.

Amino Acid Sequence↗
PubMed2000

Growth hormone receptor gene expression in porcine skeletal and cardiac muscles is selectively regulated by postnatal undernutrition.

During mild postnatal undernutrition, growth hormone receptor (GHR) mRNA abundance decreases in liver but increases in longissimus dorsi muscle. We tested the following hypotheses: 1) GHR gene expression is related to the metabolic and contractile characteristics of different muscles, and 2) the GHR response to nutrition depends on muscle type. Eight pairs of littermate pigs were weaned at 3 wk and given an optimal [60 g/(kg.d)] or low [(20 g/(kg.d)] food intake for the next 3 wk. All pigs grew, but at a slower rate in the low food intake group (P: < 0.001). Functionally distinct muscles were assessed for GHR mRNA (RNase protection analysis), oxidative myofibers (succinate dehydrogenase histochemistry) and type I slow myofibers (myosin immunocytochemistry). There were striking muscle-specific differences in GHR gene expression (P: < 0.001) and in its regulation by nutritional status. Relative expression of GHR mRNA in the optimal food intake group occurred in ascending order as follows: longissimus < diaphragm approximately rhomboideus < cardiac < soleus. There was a positive correlation with the proportion of oxidative myofibers (P: < 0.001) but not with type I myofibers (P: > 0.10). Compared with the high intake pigs, hepatic GHR mRNA was downregulated in the low intake pigs by 59% (P: < 0.01), whereas in the four muscles examined it was upregulated as follows: longissimus, 124% (P: < 0.05); rhomboideus, 19% (P: > 0.4); soleus, 65% (P: < 0. 05); cardiac, 51% (P: < 0.05). Moreover, the proportion of skeletal muscle fibers with high oxidative capacity was also greater in the low intake group (P: < 0.05). We conclude that postnatal GHR gene expression and its regulation by mild undernutrition are related to the metabolic, contractile and specific functional properties of different muscles.

Animals↗
PubMed2000

Survival, morbidity, and quality of life after discharge from intensive care.

OBJECTIVE: To assess survival, morbidity (physical and psychological), quality of life (QOL), and employment status of intensive care survivors up to 12 months after discharge from the intensive care unit (ICU). DESIGN: Prospective study. SETTING: University hospital adult ICU. PATIENTS: Between August 1, 1995, and July 31, 1996, 370 patients were admitted. Of these patients, 29% died in the ICU. Three months after discharge from the ICU, 227 patients were alive, and 143 agreed to participate. Cumulative mortality was calculated using the original complete cohort. MEASUREMENTS AND MAIN RESULTS: Demographic data, severity of acute illness (Acute Physiology and Chronic Health Evaluation [APACHE] II), admitting specialty, primary diagnosis, and length of stay were recorded. Physical and ICU-related psychological morbidity (Hospital Anxiety and Depression scale score) were recorded. Health-related QOL was assessed using the Short-Form 36. All the questionnaires were completed in the clinic at 3 months. Assessment of physical morbidity and employment status at 6 and 12 months were conducted by telephone. The cumulative mortality was 39% at 3 months, 41% at 6 months, and 43% at 12 months. Deaths after 3 months occurred in the group who refused follow-up. The median age for the follow-up group was 51 yrs; the gender split was 68 women and 75 men; the mean admission APACHE II score was 18.79 (SD 6.15); and the median length of ICU stay was 3.8 days. At 3 months, approximately 80% of all patients interviewed were satisfied with their QOL. Older men (>65 yrs) and younger women (<65 yrs) demonstrated significantly better health with respect to some subdomains of the Short-Form 36 compared with their counterparts. The prevalence of psychological distress (Hospital Anxiety and Depression scale score, > or =8) was low: 11.9% had heightened anxiety, and 9.8% were depressed. There were high levels of fatigue, poor concentration, and sleep disturbance; the latter was more marked in women (p = .022). Improvement in all three symptoms occurred during the next 9 months. Significantly more women reported loss of hair (p < .0001). Men were slower to return to employment; 75% of women had returned by 6 months compared with only 65% of men at 1 yr. CONCLUSION: Assessment of outcome after ICU stay must include QOL measurements. Three months after discharge, there is a low incidence of ICU-related psychological or psychiatric illness and the majority of patients are satisfied. Differences in the incidence and nature of morbidity exist between the genders.

APACHE↗
PubMed2000

Matching response to context in complex political emergencies: 'relief', 'development', 'peace-building' or something in-between?

There is an ongoing debate over the value and pitfalls of the policy and practice of 'linking relief and development' or 'developmental relief' in aid responses to complex political emergencies (CPEs). Driven by concerns about relief creating dependence, sometimes doing harm and failing to address root causes of emergencies despite its high cost, pursuit of both relief and development has become a dominant paradigm among international aid agencies in CPEs as in 'natural' disasters. In CPEs a third objective of 'peace-building' has emerged, along with the logic that development can itself help prevent or resolve conflict and sustain peace. However, this broadening of relief objectives in ongoing CPEs has recently been criticised on a number of counts, central concerns being that it leads to a dilution of commitment to core humanitarian principles and is overly optimistic. This paper addresses these issues in the light of two of the CPEs studied by the COPE project: Eritrea and Somalia/Somaliland. It is argued that the debate has so far suffered from lack of clarity about what we mean by 'relief', 'development' and, for that matter, 'rehabilitation' and 'peace-building'. The wide spectrum of possible aid outcomes does not divide neatly into these categories. The relief-development divide is not always as clear-cut, technically or politically, as the critics claim. Moreover such distinctions, constructed from the point of view of aid programmers, are often of little relevance to the concerns of intended beneficiaries. Second, there has been insufficient attention to context: rather than attempting to generalise within and across CPE cases, a more productive approach would be to examine more closely the conditions under which forms of aid other than basic life support can fruitfully be pursued. This leads to consideration of collective agency capacity to respond effectively to diverse needs in different and changing circumstances.

Africa, Eastern↗