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Biomedical subjects

S Davies

Publications and source records attributed to S Davies.

At least 127 records · Page 7Linked to original sources

Quantification of breath isoprene using the selected ion flow tube mass spectrometric analytical method.

We have used our selected ion flow tube mass spectrometric method (SIFT-MS) to study isoprene levels in the alveolar breath of 29 healthy volunteers during normal working hours at the varying states of nutrition occurring during this period. Quantification of the breath isoprene was achieved using O(2)(+) precursor ions to avoid complications which can arise when using H(3)O(+) precursor ions for isoprene analysis. The present data indicate that the spread of the alveolar isoprene levels in this sample of healthy individuals is 22 to 234 ppb and that the mean value is 83 ppb with a standard deviation of 45 ppb. These levels are compared with those previously determined using other techniques and are seen to be at the low end of the values previously reported. The present studies are a prelude to an investigation of the proposed correlation of breath isoprene levels with psychological, physical and biochemical stress.

Adult↗

Dose-response relationships for hepatic aflatoxin B1-DNA adduct formation in the rat in vivo and in vitro: the use of immunoslot blotting for adduct quantitation.

An immunoslot blotting (ISB) method for quantitating aflatoxin B1-DNA adduct levels has been developed and used to examine the relationship between dose and hepatic aflatoxin B1-DNA adduct levels in rats fed aflatoxin B1 (AFB1) in the diet at dose levels of between 0.5 and 10 micrograms/kg/day. The method has also been used to examine the dose-response relationship for adduct formation in precision-cut rat liver slices incubated with AFB1 at concentrations between 0.01 and 2 microM. For the feeding studies, groups of male Fisher F344 rats were given AFB1 in the diet for periods of 1 to 10 weeks and hepatic DNA adduct levels determined using ISB. The time for adduct levels to reach steady-state conditions was determined in animals given approximately 10 micrograms of AFB1/kg/day and steady-state levels at lower concentrations measured. The time course for the accumulation of AFB1-DNA adducts in rat liver slices incubated with AFB1 at 0.5 microM has been investigated and the relationship between adduct formation and AFB1 concentration over a wide concentration range in liver slices has been determined.

Aflatoxin B1↗

Models of local behavior of DNA electrophoresis peak parameters.

Many base calling algorithms implicitly or explicitly rely on predictions of local sequence parameters such as amplitude, peak time and peak width. For example, an algorithm may search for the next peak about a predicted peak time formed by adding the mean peak separation to the last position measurement. In this paper, covariance models are presented which characterize the dependence of peak parameters on those of other peaks. Based on experimental measurements, the model features an exponential decay in peak time jitter covariance with respect to base separation. Both peak amplitude and peak width are modelled as being uncorrelated with those of adjacent bases. In the model, linear expressions are given to describe the growth in peak time jitter and peak width as a function of base position while other parameters, such as amplitude variance, are modeled by constants. Together, these results form a simple model which may be used in the derivation of new sequencing algorithms or in simulations for the testing of such algorithms. We suggest that the correlation of the peak times is related to the Kuhn length of the single-stranded DNA fragments.

Algorithms↗

Lipoic acid prevents development of the hyperdynamic circulation in anesthetized rats with biliary cirrhosis.

Chronic bile duct ligation is associated with the development of oxidant injury, biliary cirrhosis, portal hypertension, and a hyperdynamic circulation. We have previously demonstrated that the hyperdynamic circulation in the partial portal vein-ligated rat can be prevented by the administration of N-acetylcysteine. To extend these findings, we have examined the effect of lipoic acid, a thiol-containing antioxidant, on hemodynamics, oxidative stress, and nitric oxide (NO) production in bile duct-ligated (BDL) cirrhotic rats. Lipoic acid was given continuously in drinking water to normal and BDL rats; control rats received ordinary drinking water, and animals were studied at 24 days following surgery. Lipoic acid prevented the development of the hyperdynamic circulation (cardiac index [CI]: 15.7 +/- 2.0 vs. 29.5 +/- 2.1 mL x min-1 x 100 g-1; P <. 05) and significantly attenuated the rise in portal pressure (PP) (12.7 +/- 0.8 vs. 15.2 +/- 0.5 mm Hg; P <.05). Hepatic nitric oxide synthase (NOS) activity and plasma nitrite/nitrate concentration increased significantly following bile duct ligation, and both of these were prevented by lipoic acid. Lipoic acid had no effect on the biochemical or histological parameters of liver function in the cirrhotic group. We conclude that lipoic acid prevents the development of the hyperdynamic circulation in the rat model of biliary cirrhosis, and that this is associated with decreased synthesis of NO.

Animals↗

Increased sensitivity to endotoxemia in the bile duct-ligated cirrhotic Rat.

Sepsis is a common complication of cirrhosis with a high mortality. In this study, we have investigated some of the pathways that may be involved in tissue injury and death. Bile duct-ligated (BDL) cirrhotic and control rats were challenged with lipopolysaccharide (LPS). Sensitivity to LPS was markedly enhanced in the BDL group, and was associated with increased liver injury and mortality. There was a 5-fold constitutive activation of nuclear factor kappa B (NFkappaB) in the liver of BDL rat controls (P <.001), and this was activated further, but to a similar extent, in the liver of both sham and BDL rats after injection of LPS. Plasma tumor necrosis factor alpha (TNF-alpha) increased more markedly in the BDL cirrhotic rats (2,463 +/- 697 pg/mL in BDL rats versus 401 +/- 160 pg/mL in the controls at 3 hours; P <.01). Plasma nitrite/nitrate concentrations were increased in the BDL controls at baseline, and increased further after LPS (P <.05), but did not differ from sham controls at 6 hours. Plasma F(2)-isoprostanes increased 6-fold in the cirrhotic rats and 2-fold in the controls (P <.01) indicative of lipid peroxidation. Esterified F(2)-isoprostanes in the liver increased 2- to 3-fold at 1 hour in control and BDL rats, but returned to baseline levels by 3 hours. Esterified F(2)-isoprostanes in the kidney increased by 2-fold in the BDL rats after LPS administration, but remained unchanged in sham controls. We conclude that there is a marked increase in sensitivity to LPS in BDL cirrhotic rats. This is associated with an enhanced TNF-alpha response and increased lipid peroxidation. These may be directly and causally related to mortality.

Animals↗

Ovarian autoimmunity: greater frequency of autoantibodies in premature menopause and unexplained infertility than in the general population.

The objective of this study was to: (1) assess the relative prevalence of ovarian, thyroid, nuclear, and cardiolipin antibodies associated with premature menopause and unexplained infertility and (2) compare ovarian and thyroid antibodies in premature menopause, unexplained infertility, and the general population. Autoantibodies were evaluated in women with premature menopause (n = 30), unexplained infertility with (n = 38) or without (n = 15) prior gonadotropin-induced ovulation, and normal cycling controls (n = 12) and in a population of women obtained from a blood bank (n = 53). Antibodies to ovary (OVAB), thyroid (THYAB; thyroid peroxidase and thyroglobulin), cardiolipin, and eight nuclear antigens were assessed by enzyme immunoassay. Organ-specific antibodies (ovary and thyroid) were present with significantly greater frequency than non-organ-specific antibodies (nuclear and cardiolipin) in premature menopause and unexplained infertility (60% (50/83) vs 16% (13/83) respectively; P < 0.0001). OVAB (53%, 44/83) were significantly more frequent than THYAB (30%, 25/83) in premature menopause and unexplained infertility (P = 0.0030). THYAB did not differ among all groups (P = 0.78). In premature menopause and treated or untreated unexplained infertility OVAB frequencies were 53, 61, and 33%, respectively, and were significantly more frequent than in the population (17%) (P = 0.0001). In unexplained infertility, individuals with no prior gonadotropin-induced ovulation had a lower frequency of OVAB than treated individuals (P = 0.07). The frequency distribution of optical density values for OVAB was significantly higher for premature menopause and unexplained infertility than for population or normal cycling women (P < 0.0001). Thus, only ovarian antibodies were significantly more frequent than other antibody markers of autoimmunity in premature menopause and unexplained infertility.

Adult↗

Amniotic fluid embolism and isolated disseminated intravascular coagulation.

PURPOSE: Disseminated intravascular coagulation (DIC) is a well-known complication of an amniotic fluid embolus. However, clinical experience has shown that, in some patients, clinical hemorrhage may be the initial presentation. Mortality in this subset of patients is high. This report describes a patient with a suspected amniotic fluid embolus who survived and in whom the initial presentation was post partum hemorrhage. CLINICAL FEATURES: During the post delivery repair of a fourth degree perineal tear a 29 yr old prima gravida was noted to have excessive vaginal bleeding despite a well contracted uterus. Laboratory investigations revealed a decrease in hemoglobin from 126 g x l(-1) to 86 g x l(-1) and a severe disseminated intravascular coagulopathy (PT 27.5 sec, APPT 149 sec, direct fibrinogen < 0.6 g x l(-1), FDP > 640 g x l(-1)). Treatment included massive blood component therapy and, eventually, total abdominal hysterectomy. The patient subsequently recovered without sequelae. In the absence of any other explanation, the coagulopathy was considered to be secondary to amniotic fluid embolus. CONCLUSION: Amniotic fluid embolus remains an important cause of maternal mortality. Clinical reports, reviews of the literature, and the development of the national registry have all contributed to our understanding of this syndrome. Contrary to earlier beliefs, not all patients present with sudden cardiorespiratory collapse. As the present case illustrates, a less common presentation is the development of an isolated DIC in the peripartum period without antecedent hemodynamic or respiratory instability. Therefore, anesthesiologists must maintain a high index of suspicion for the disorder in order to facilitate early recognition and treatment.

Adult↗

Projections of Forest and Rangeland Condition Indicators for a National Assessment.

/ This paper discusses projections of emerging geographic areas of concern with regard to forest and rangeland condition, as indicated by a model based on a set of independent econometric production functions for condition indicators at the national scale. These production functions reflect two special characteristics: (1) the independence of ecological systems from human control, and (2) the broad scale spatial nature of environmental and ecological processes. The emphasis in this paper is the model projections themselves, which are presented and discussed using national-scale maps.KEY WORDS: Resource interactions; Land management planning; Econometric production functions; Modeling; environmental outputshttp://link.springer-ny.com/link/service/journals/00267/bibs/24n3p383.html

Journal Article↗

Toxicity of ifosfamide and its metabolite chloroacetaldehyde in cultured renal tubule cells.

Renal injury is a common side effect of the chemotherapeutic agent ifosfamide. Current evidence suggests that the ifosfamide metabolite chloroacetaldehyde may contribute to this nephrotoxicity. The present study examined the effects of ifosfamide and chloroacetaldehyde on rabbit proximal renal tubule cells in primary culture. The ability of the uroprotectant medication sodium 2-mercaptoethanesulfonate (mesna) to prevent chloroacetaldehyde-induced renal cell injury was also assessed. Chloroacetaldehyde (12.5-150 microM) produced dose-dependent declines in neutral red dye uptake, ATP levels, glutathione content, and cell growth. Coadministration of mesna prevented chloroacetaldehyde toxicity while pretreatment of cells with the glutathione-depleting agent buthionine sulfoximine enhanced the toxicity of chloroacetaldehyde. Ifosfamide (1000-10,000 microM) toxicity was detected only at concentrations of 4000 microM or greater. Analysis of media collected from ifosfamide-treated cell cultures revealed the presence of several ifosfamide metabolites, demonstrating that renal proximal tubule cells are capable of biotransforming this chemotherapeutic agent. This primary renal cell culture system should prove useful in studying the cause and prevention of ifosfamide nephrotoxicity.

Acetaldehyde↗

Pleiotropic drug resistance in B-cell chronic lymphocytic leukaemia--the role of Bcl-2 family dysregulation.

B-cell chronic lymphocytic leukaemia (B-CLL) is an incurable clonal disease which shows initial responsiveness to a number of chemotherapeutic drugs. However, most treated patients become resistant to treatment and this represents a major problem in the successful management of the condition. Experimental evidence points to the fact that most chemotherapeutic drugs ultimately exert their cell killing effect through the process of apoptosis. In this study we compared the apoptotic responses of B-CLL cells in vitro following exposure to several chemotherapeutic drugs. We found that there was a correlation between ID50 values for all the drugs under investigation; particularly between Chlorambucil and Fludarabine (P = 0.0002). In addition, we analysed the expression of Bcl-2 and Bax, two proteins pivotal to the regulation of apoptosis, both immediately ex vivo and in viable and apoptotic sub-populations following exposure to drug. Our data suggest that high Bcl-2/Bax ratios may be predictive of a drug resistant phenotype in B-CLL cells and that modulation of these proteins is essential for the induction of cell death. Furthermore, it seems likely that the superior potency that has been ascribed to Fludarabine is due to it being administered in a more optimised dose. A recently reported clinical trial of Fludarabine against high-dose Chlorambucil supports this view since it showed that both treatment modalities were comparable in terms of response rate and survival times.

Antineoplastic Combined Chemotherapy Protocols↗

The biosciences in the pre-registration nursing curriculum: staff and students' perceptions of difficulties and relevance.

This paper considers the problematic position of the biological sciences in pre-registration nurse education--'The Bioscience Question'. There is no consensus and little research on the appropriate content and depth of bioscience knowledge required by nurses. Attempts to apportion curriculum time for the biosciences are confounded by the difficulty experienced by nursing students with this area. Within one university department, a survey was undertaken to investigate the perceptions of pre-registration students, and their teachers, of the teaching and learning of biological science, in comparison with other areas of the curriculum. Our findings concur with others that the biosciences are a source of disproportionate difficulty and anxiety to nursing students. Among the students, but not the lecturers, there was some, by no means universal, support for the suggestion that these problems could be reduced by a reallocation of curriculum time in favour of the biosciences. Although it was agreed that bioscience theory should be related more closely to nursing practice, there was no evidence that this lessened the students' difficulties with the subject. In contrast to lecturers, students felt the biosciences to be one of the areas of the pre-registration curriculum most relevant to clinical practice.

Adaptation, Psychological↗

Model studies on a synthetically facile series of N-substituted phenyl-N'-pyridin-3-yl ureas leading to 1-(3-pyridylcarbamoyl) indolines that are potent and selective 5-HT(2C/2B) receptor antagonists.

A model series of 5-HT2C antagonists have been prepared by rapid parallel synthesis. These N-substituted phenyl-N'-pyridin-3-yl ureas were found to have a range of 5-HT2C receptor affinities and selectivities over the closely related 5-HT2A receptor. Extrapolation of simple SAR, derived from this set of compounds, to the more active but synthetically more complex 1-(3-pyridylcarbamoyl)indoline series allowed us to target optimal substitution patterns and identify potent and selective 5-HT(2C/2B) antagonists.

Animals↗

A comparison of two methods of dietary assessment in peritoneal dialysis patients.

OBJECTIVE: To conduct a comparison of two methods of dietary assessment in patients on peritoneal dialysis. DESIGN: Comparative, cross-sectional study of two methods of dietary assessment (3-day diet diary and 24-hour recall). Data was collected simultaneously by a single experienced dietitian. Each assessment was coded and analyzed blind. SETTING: Regional speciality peritoneal dialysis training unit. PATIENTS: In this study, 30 peritoneal dialysis patients recruited prospectively and consecutively as they attended for out-patient assessment of dialysis adequacy. Age range was 22 to 77 years. Patients were excluded if unwell, younger than 18 years, or had peritonitis. OUTCOME MEASURES: Total energy and protein intakes from both methods were compared. Protein intakes from both methods were compared with the protein catabolic rate generated from urea kinetics. Data obtained from both methods were compared using paired t tests, linear regression, and Bland and Altman techniques. RESULTS: There were no significant differences in the mean daily protein (72.4 g v 76.6 g) and total energy (1757 kcals (7.35 MJ) v. 1897 kcals (7.94 MJ)) intakes determined by the two methods. Positive correlations were seen between the measurements for protein intake (r =.58, P =.0026) energy intake (r =.78, P <.00001), with mean differences of.066 g/kg/d (SD.38) 2.04 kcal/kg/day (SD 6.67), respectively. For both methods there was a similar positive correlation between dietary protein intake and protein catabolic rate. A 24-hour recall was more likely to result in successful collection of data (29 of 30) than 3-day diet diaries (25 of 30) and was less time consuming. CONCLUSION: These two methods of determining dietary protein and energy intake do not differ significantly in the information they provide. The relative success in obtaining completed records of intake, the shorter time taken and the opportunity for patient education and assessment of other nutrition related factors has led to the adoption of the 24-hour recall method in our institution.

Adult↗

Sexual desire discrepancies: effects on sexual and relationship satisfaction in heterosexual dating couples.

Sexual desire discrepancies and the associations between desire discrepancies and relationship adjustment (i.e., sexual and relationship satisfaction) in heterosexual dating couples (N = 72) were examined Desire discrepancies were assessed via two methods: (1) a couple-based index created using both individuals' reports of sexual desire and (2) an individual-based index using each person's own subjective perception of a desire discrepancy within the couple. Both indices were associated with women's adjustment, whereas only individual perceptions of discrepancies were associated with men's adjustment. The association between desire discrepancies and general relationship satisfaction was fully mediated by level of sexual satisfaction for both men and women. Women whose sexual desire level was lower than their partners' endorsed lower levels of relationship adjustment relative to women whose desire was either greater than or similar to their partners'. Implications for the assessment of sexual desire differences in couples are discussed.

Adaptation, Psychological↗

Combination therapy with fludarabine and cyclophosphamide as salvage treatment in lymphoproliferative disorders.

Seventeen patients (aged 50-85 years) with relapsed or refractory non-Hodgkin's lymphoma (NHL, 10 patients) or chronic lymphocytic leukaemia (CLL, seven patients) were treated with a combination of fludarabine 25 mg/m2/d and cyclophosphamide 250 mg/m2/d for 3 d repeated every 4 weeks. 12 patients had previously received purine analogue therapy of which four had progressive disease during treatment. The overall response rate of patients with CLL was 71% (28% CR, 43% PR) and for NHL was 50% (0% CR, 50% PR). Toxicity consisted of nausea and vomiting which was maximal in the 3 d after therapy, infections and haematological suppression which was prolonged in some patients. This combination, which is based on a rational prediction of synergistic activity, is highly effective but associated with significant problems with tolerance.

Aged↗

The educational preparation of staff in nursing homes: relationship with resident autonomy.

The following paper reports on a survey of nursing homes in three health regions in England which formed part of a wider study to evaluate educational preparation for the nursing care of older people. The aims of the survey were to describe the educational preparation of staff employed within nursing homes and to explore relationships between educational preparation and one indicator of quality of care. A self-completion questionnaire was addressed to the senior nurse within a random sample of nursing homes. The instrument included a previously validated scale to measure resident autonomy. A total of 976 questionnaires were posted and 676 were returned, a response rate of 69%. The survey revealed wide variation in the educational preparation of staff in nursing homes and in the degree of contact with local centres providing nurse education. Statistically significant associations were found between resident autonomy and a composite measure of educational preparation, the proportion of qualified staff undertaking continuing professional education and the degree of contact with educational centres. The findings have implications for both purchasers and providers of education in this field.

Adult↗

Marrow transplantation from unrelated donors for patients with severe aplastic anemia who have failed immunosuppressive therapy.

Allogeneic marrow transplantation offers curative therapy for patients with aplastic anemia. We analyzed retrospective results in 141 patients with severe aplastic anemia who received transplants between 1988 and 1995 from an unrelated volunteer donor identified through the National Marrow Donor Program (NMDP). All patients had failed one or more courses of immunosuppressive therapy. Of the patients, 121 (86%) received a radiation-containing conditioning regimen, and 20 (14%) were given chemotherapy only. Based on serologic human leukocyte antigen (HLA) typing (class I and II), 105 patients (74%) received HLA-matched marrow, and 36 (26%) received marrow mismatched for at least one HLA-A, -B, or -DR antigen. Allele-level (molecular) typing for HLA-DRB1 was available in 108 donor-recipient pairs; 77 patients received DRB -matched and 31 DRB1-mismatched transplants. All but 13% of patients were given a cyclosporine-containing regimen for graft-vs.-host disease (GVHD) prophylaxis, and 45 patients (32%) received marrow that was T cell-depleted. Among 131 evaluable patients, 116 (89%) achieved sustained engraftment and 15 (11%) did not. Among patients with engraftment, acute GVHD of grades II-IV developed in 60 patients (52%) and extensive chronic GVHD in 24 patients at risk (31%). Currently, 51 patients (36%) are surviving at 11-94 months (median 36) after transplantation. All but five have Karnofsky scores > or =80. Patients who received a serologically matched transplant fared somewhat better than did patients given a serologically mismatched transplant p = 0.03). Patients with donors matched by both serology and allele-level DRB1 typing had significantly better survival than DRB1-mismatched patients with 56 vs. 15% surviving at 3 years p = 0.001). Outcome in patients transplanted within 3 years of diagnosis was superior to that among patients transplanted with greater delay. Major causes of death were graft failure, GVHD, and infections. These data suggest that unrelated marrow transplantation offers successful therapy for a proportion of patients who have failed immunosuppressive therapy.

Adolescent↗