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Biomedical subjects

B Davis

Publications and source records attributed to B Davis.

At least 37 records · Page 2Linked to original sources
PubMed2001

Spatial and temporal expression of the Cre gene under the control of the MMTV-LTR in different lines of transgenic mice.

Cre-loxP based gene deletion approaches hold great promise to enhance our understanding of molecular pathways controlling mammary development and breast cancer. We reported earlier the generation of transgenic mice that express the Cre recombinase under the control of the mouse mammary tumor virus (MMTV) long terminal repeat (LTR). These mice have become a valuable research tool to delete genes specifically in the mammary gland, other secretory organs, and the female germline. We have now characterized in depth the expression of the MMTV-Cre transgene using the ROSA26-lox-Stop-lox-LacZ reporter strain to determine the temporal and spatial activation of Cre on the level of single cells. Our results show that MMTV-mediated Cre-activation is restricted to specific cell types of various secretory tissues and the hematopoietic system. Secondly, the timing of Cre expression varies between tissues and cell types. Some tissues express Cre during embryonic development, while other selected cell types highly activate Cre around puberty, suggesting a strong influence of steroid hormones on the transcriptional activation of the MMTV-LTR. Thirdly, Cre expression in the female germline is restricted to individual mouse lines and is therefore dependent on the site of integration of the transgene. Information provided by this study will guide the researcher to those cell types and developmental stages at which a phenotype can be expected upon deletion of relevant genes.

Animals↗
PubMed2001

A method to develop a nursing intervention: the contribution of qualitative studies to the process.

AIM OF THE PAPER: To describe how to develop a patient-centred nursing intervention (NI). BACKGROUND: The stimulus for scrutinizing methods and techniques to develop a NI was a research project concerning the contribution of information and support to the sexual adaptation of women with gynaecological cancer. Within this project, a NI for sexual teaching (ST) was developed because the literature review revealed no tested NI for this purpose. How patients experience and perceive received information influences the usefulness and efficacy of a teaching intervention. Qualitative methods provide insight and understanding of patients' experience. Consequently, qualitative methods are appropriate to use when developing interventions that aim to influence patients' situations through the provision of information. METHOD: Previously reported approaches for developing an intervention did not match the goals and underlying premises identified for the intervention under development. An alternative method, consisting of a design phase and a testing phase, was developed. The goal of the design phase was to develop a working definition of the intervention and to formulate recommendations for carrying out the intervention. Written guidelines provided concrete examples of the topics to discuss and how to discuss them. During the design phase, a qualitative study was conducted to describe the lived-experience of the phenomenon that the information should influence, namely sexuality after treatment for gynaecological cancer. In the testing phase, a different type of qualitative study took place. The patients' experience of receiving information and the nurses' experience of providing it were investigated in order to refine the proposed intervention, to identify the results patients hope to achieve (or achieved) and to explore the underlying theoretical explanation of the intervention. During the testing phase, the feasibility and acceptability of the modified intervention were both established. CONCLUSION: Even when the starting point is advice from care-givers, an intervention can be developed that is in harmony with the patient perspective when qualitative studies are part of the process.

Adaptation, Psychological↗
PubMed2001

Cardiovascular T2-star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload.

AIMS: To develop and validate a non-invasive method for measuring myocardial iron in order to allow diagnosis and treatment before overt cardiomyopathy and failure develops. METHODS AND RESULTS: We have developed a new magnetic resonance T2-star (T2*) technique for the measurement of tissue iron, with validation to chemical estimation of iron in patients undergoing liver biopsy. To assess the clinical value of this technique, we subsequently correlated myocardial iron measured by this T2* technique with ventricular function in 106 patients with thalassaemia major. There was a significant, curvilinear, inverse correlation between iron concentration by biopsy and liver T2* (r=0.93, P<0.0001). Inter-study cardiac reproducibility was 5.0%. As myocardial iron increased, there was a progressive decline in ejection fraction (r=0.61, P<0.001). All patients with ventricular dysfunction had a myocardial T2* of <20 ms. There was no significant correlation between myocardial T2* and the conventional parameters of iron status, serum ferritin and liver iron. Multivariate analysis of clinical parameters to predict the requirement for cardiac medication identified myocardial T2* as the most significant variable (odds ratio 0.79, P<0.002). CONCLUSIONS: Myocardial iron deposition can be reproducibly quantified using myocardial T2* and this is the most significant variable for predicting the need for ventricular dysfunction treatment. Myocardial iron content cannot be predicted from serum ferritin or liver iron, and conventional assessments of cardiac function can only detect those with advanced disease. Early intensification of iron chelation therapy, guided by this technique, should reduce mortality from this reversible cardiomyopathy.

Adolescent↗
PubMed2001

Protective effect of pregnancy for development of uterine leiomyoma.

Many factors that can modulate the risk of developing uterine leiomyoma have been identified, including parity. Epidemiological data on decreased risk of developing this disease has been subject to different interpretations regarding whether pregnancy per se is protective or, as leiomyomas are a major cause of infertility, women that develop these tumors are less fertile and thus have lower pregnancy rates. We have utilized an animal model genetically predisposed to uterine leiomyoma to investigate the potential protective effect of pregnancy on the risk of developing this disease. Female Eker rats that carry a mutation in the tuberous sclerosis 2 (Tsc-2) tumor suppressor gene develop uterine leiomyoma with a frequency of 65% when nulliparous. These animals were bred with intact or vasectomized males and tumor incidence determined after a single pregnancy (to confirm fertility) or multiple pregnancies over the lifetime of the animals. Females with multiple litters displayed a dramatic shift in tumor incidence and presentation. Tumor incidence decreased from 71% in single litter females to 10% in females that had multiple litters (average: five litters/animal). Interestingly, females bred with vasectomized males also exhibited a reduced tumor incidence of 41%, suggesting that the hormonal changes associated with early stages of pregnancy that occur in pseudopregnant females may have contributed to the protective effect of pregnancy.

Animals↗
PubMed2001

Two cases of Kaposi's sarcoma mimicking Stewart-Treves syndrome found to be human herpesvirus-8 positive.

Although angiosarcoma is the most frequent tumor arising in the clinical setting of chronic lymphedema, as in Stewart-Treves syndrome, Kaposi's sarcoma has also been reported in this setting, although rarely. We describe two women who developed Kaposi's sarcoma in the lymphedematous arm many years after surgery for breast cancer. Case 1 is a 92-year-old and Case 2 is an 81-year-old; they underwent left total mastectomy and axillary node dissection for infiltrating breast carcinoma in 1981 and 1982 respectively. At that time, neither patient received further treatment. Except for persistent lymphedema, both women did well until over fourteen years later when each noted the development of several purple asymptomatic plaques on the edematous arm. In both, the clinical diagnosis at the time of biopsy was angiosarcoma. However, histologic findings in both cases were typical for Kaposi's sarcoma. In addition, a nested polymerase chain reaction (PCR) for the detection of a 233bp segment of KSHV/HHV8 was performed on DNA extracted from the paraffin-embedded specimens and both cases were positive for this sequence. Histologic sections of both cases were also tested for KSHV by in situ hybridization and demonstrated a positive signal in the lesional cells in each case.

Aged↗
PubMed2001

The stability of corneal topography in the post-blink interval.

PURPOSE: Videokeratoscopes provide a wealth of information about the topography of the ocular surface. Although there have been numerous studies of the accuracy and precision of videokeratoscopes with inanimate test objects, little information exists on their precision (repeatability) for real eyes. METHODS: To investigate the stability of the ocular surface in the inter-blink period, 10 patients were recruited for videokeratoscopy. Tear break-up time was measured and videokeratographs were acquired immediately post-blink and again at 4, 8, and 12 seconds post-blink. To permit statistical inferences to be drawn from the data, we acquired 24 videokeratographs for each of the four post-blink intervals. The videokeratograph data were interpolated (bilinear) to a common grid, and average and standard deviation (SD) maps were derived for each post-blink condition. t Tests were used to test the significance of changes observed in the topography. RESULTS: The instantaneous power SD maps showed increasing variation toward the periphery, with most maps showing less than +/-0.5 diopters (D) of SD in the central 4 to 5 mm and variation in the periphery often reaching more than +/-1 D SD at the edge of an 8-mm diameter. When the 4-, 8-, and 12-second average maps were subtracted from the average map acquired immediately after blinking, regions of statistically significant ( p < 0.001) change were apparent in the upper and lower regions of the maps. The upper and lower bands of change were found to correlate with the natural position of the patients' lid margins. CONCLUSIONS: For normal eyes, the central regions of videokeratographs show high stability in the inter-blink period. However, the upper and lower edges of 8-mm diameter maps show statistically significant variability, which appears to be related to the effects of eyelid pressure.

Adult↗
PubMed2001

Optimal modeling of corneal surfaces with Zernike polynomials.

Zernike polynomials are often used as an expansion of corneal height data and for analysis of optical wavefronts. Accurate modeling of corneal surfaces with Zernike polynomials involves selecting the order of the polynomial expansion based on the measured data. We have compared the efficacy of various classical model order selection techniques that can be utilized for this purpose, and propose an approach based on the bootstrap. First, it is shown in simulations that the bootstrap method outperforms the classical model order selection techniques. Then, it is proved that the bootstrap technique is the most appropriate method in the context of fitting Zernike polynomials to corneal elevation data, allowing objective selection of the optimal number of Zernike terms. The process of optimal fitting of Zernike polynomials to corneal elevation data is discussed and examples are given for normal corneas and for abnormal corneas with significant distortion. The optimal model order varies as a function of the diameter of the cornea.

Astigmatism↗
PubMed2001

Solution structure and backbone dynamics of the DNA-binding domain of mouse Sox-5.

The fold of the murine Sox-5 (mSox-5) HMG box in free solution has been determined by multidimensional NMR using (15)N-labeled protein and has been found to adopt the characteristic twisted L-shape made up of two wings: the major wing comprising helix 1 (F10--F25) and helix 2 (N32--A43), the minor wing comprising helix 3 (P51--Y67) in weak antiparallel association with the N-terminal extended segment. (15)N relaxation measurements show considerable mobility (reduced order parameter, S(2)) in the minor wing that increases toward the amino and carboxy termini of the chain. The mobility of residues C-terminal to Q62 is significantly greater than the equivalent residues of non-sequence-specific boxes, and these residues show a weaker association with the extended N-terminal segment than in non-sequence boxes. Comparison with previously determined structures of HMG boxes both in free solution and complexed with DNA shows close similarity in the packing of the hydrophobic cores and the relative disposition of the three helices. Only in hSRY/DNA does the arrangement of aromatic sidechains differ significantly from that of mSox-5, and only in rHMG1 box 1 bound to cisplatinated DNA does helix 1 have no kink. Helix 3 in mSox-5 is terminated by P68, a conserved residue in DNA sequence-specific HMG boxes, which results in the chain turning through approximately 90 degrees.

Amino Acid Sequence↗
PubMed2001

STAT4 and STAT6 regulate systemic inflammation and protect against lethal endotoxemia.

Members of the signal transducer and activator of transcription (STAT) family are transcription factors that mediate many of the effects of pro- and anti-inflammatory cytokines. The progressive systemic inflammatory response induced by endotoxin is mediated by overzealous cytokine production. Here we identify STAT4 and STAT6 as critical regulators of the systemic inflammatory response to endotoxin. Mice deficient for STAT4 or STAT6 were highly susceptible to lethal endotoxemia. In STAT4(-/-) mice, antibody blockade of IL-12 prevented mortality, suggesting that STAT4 confers protection, while another signaling pathway mediates the detrimental effects of IL-12. In STAT6(-/-) mice we observed dysregulated activation of the transcription factor NF-kappaB, resulting in augmented production of proinflammatory cytokines and chemokines. Furthermore, STAT6(-/-) mice displayed increased organ accumulation of leukocytes and significant hepatocellular injury. These findings demonstrate that STAT4 and STAT6 confer protection against endotoxin-induced death and that for STAT6 these protective effects occur through the regulation of NF-kappaB activation and subsequent production of proinflammatory cytokines and chemokines.

Animals↗
PubMed2001

An interlaboratory study of a candidate reference method for platelet counting.

A multinational interlaboratory task force explored the important variables of platelet reference counting and developed a candidate flow cytometric reference method based on the RBC/platelet ratio. A multicenter comparison was performed to determine whether the method met the necessary criteria and was precise enough to be recommended as a new reference method. Each laboratory analyzed serial dilutions of normal specimens, stabilized material, and at least 60 patient specimens with a range of platelet counts from 1 to 400 x 10(3)/microL (1-400 x 10(9)/L). Pooled analysis of the serial dilutions showed that RBC-platelet and RBC-RBC coincidence events became negligible at sufficiently high dilutions (i.e., > 1:1,000). All laboratories demonstrated excellent intra-assay and acceptable interlaboratory precision. Two antibodies (CD61 and CD41) were used for identifying platelets and individually gave acceptable results, but in a minority of samples, staining differences were observed. The optimum method thus uses a double-labeling procedure with a final dilution factor of 1:1,000. The study demonstrated that this method meets the criteria for a reference platelet count.

Anticoagulants↗
PubMed2001

Neuropsychological clusters within intelligence levels for learning disabled children.

The present study assessed 1142 learning disabled children with the Halstead Reitan Neuropsychological Battery and the Wechsler Intelligence Scale for Children-Revised. Subjects were divided into four groups based upon Full Scale IQ (i.e., 70-79; 80-89; 90-99 and 100-110). Subsequent clustering of the test data within each group suggested that while the students in the 70-79 IQ range were represented by a single Impaired Cluster, each of the other IQ groups had both an Impaired Cluster and a Non-Impaired Cluster.

Adolescent↗
PubMed2001

Additive hypotensive and anti-albuminuric effects of angiotensin-converting enzyme inhibition and angiotensin receptor antagonism in diabetic spontaneously hypertensive rats.

Angiotensin II plays a pivotal role in the development of diabetic nephropathy, but it remains controversial as to the best approach to effectively block the actions of this hormone in the kidney. The aim of the present study was to explore the effects of long-term treatment (8 months) with a combination of an angiotensin type 1 (AT1) receptor antagonist, irbesartan (15 mg/kg per day), and an angiotensin-converting enzyme (ACE) inhibitor, captopril (100 mg/kg per day), in diabetic spontaneously hypertensive rats. Captopril treatment reduced blood pressure (163+/-3 mmHg versus diabetic 201+/-3 mmHg), but not albumin excretion rate (43.8x//1.3 mg/day versus diabetic 46.8x//1.4 mg/day). Irbesartan treatment was associated with a similar reduction in blood pressure (173+/-3 mmHg) to captopril, and albumin excretion rate was reduced (14x//1.5 mg/day). The combination of irbesartan and captopril induced further reductions in blood pressure (140+/-3 mmHg) and albumin excretion rates (4.0x//1.5 mg/day). Gene expression of transforming growth factor beta-1 was reduced by all treatments to a similar level as assessed by in situ hybridization. These results demonstrate the additive hypotensive and anti-albuminuric effects of an ACE inhibitor and an AT1 receptor, suggesting that combination therapy is an approach not only more effective at reducing blood pressure, but also at retarding the development of diabetic nephropathy.

Albuminuria↗
PubMed2000

Metabolic abnormalities and cardiovascular disease risk factors in adults with human immunodeficiency virus infection and lipodystrophy.

We evaluated metabolic and clinical features of 71 HIV-infected patients with lipodystrophy by comparing them with 213 healthy control subjects, matched for age and body mass index, from the Framingham Offspring Study. Thirty HIV-infected patients without fat redistribution were compared separately with 90 matched control subjects from the Framingham Offspring Study. Fasting glucose, insulin, and lipid levels; glucose and insulin response to standard oral glucose challenge; and anthropometric measurements were determined. HIV-infected patients with lipodystrophy demonstrated significantly increased waist-to-hip ratios, fasting insulin levels, and diastolic blood pressure compared with controls. Patients with lipodystrophy were more likely to have impaired glucose tolerance, diabetes, hypertriglyceridemia, and reduced levels of high-density lipoprotein (HDL) cholesterol than were controls. With the exception of HDL cholesterol level, these risk factors for cardiovascular disease (CVD) were markedly attenuated in patients without lipodystrophy and were not significantly different in comparison with controls. These data demonstrate a metabolic syndrome characterized by profound insulin resistance and hyperlipidemia. CVD risk factors are markedly elevated in HIV-infected patients with fat redistribution.

Adolescent↗
PubMed2000

Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group.

BACKGROUND: Each year, clinical upper gastrointestinal events occur in 2 to 4 percent of patients who are taking nonselective nonsteroidal antiinflammatory drugs (NSAIDs). We assessed whether rofecoxib, a selective inhibitor of cyclooxygenase-2, would be associated with a lower incidence of clinically important upper gastrointestinal events than is the nonselective NSAID naproxen among patients with rheumatoid arthritis. METHODS: We randomly assigned 8076 patients who were at least 50 years of age (or at least 40 years of age and receiving long-term glucocorticoid therapy) and who had rheumatoid arthritis to receive either 50 mg of rofecoxib daily or 500 mg of naproxen twice daily. The primary end point was confirmed clinical upper gastrointestinal events (gastroduodenal perforation or obstruction, upper gastrointestinal bleeding, and symptomatic gastroduodenal ulcers). RESULTS: Rofecoxib and naproxen had similar efficacy against rheumatoid arthritis. During a median follow-up of 9.0 months, 2.1 confirmed gastrointestinal events per 100 patient-years occurred with rofecoxib, as compared with 4.5 per 100 patient-years with naproxen (relative risk, 0.5; 95 percent confidence interval, 0.3 to 0.6; P<0.001). The respective rates of complicated confirmed events (perforation, obstruction, and severe upper gastrointestinal bleeding) were 0.6 per 100 patient-years and 1.4 per 100 patient-years (relative risk, 0.4; 95 percent confidence interval, 0.2 to 0.8; P=0.005). The incidence of myocardial infarction was lower among patients in the naproxen group than among those in the rofecoxib group (0.1 percent vs. 0.4 percent; relative risk, 0.2; 95 percent confidence interval, 0.1 to 0.7); the overall mortality rate and the rate of death from cardiovascular causes were similar in the two groups. CONCLUSIONS: In patients with rheumatoid arthritis, treatment with rofecoxib, a selective inhibitor of cyclooxygenase-2, is associated with significantly fewer clinically important upper gastrointestinal events than treatment with naproxen, a nonselective inhibitor.

Adult↗
PubMed2000

Sensory stimulation (snoezelen) versus relaxation: a potential strategy for the management of chronic pain.

PURPOSE: The sensory environment (Snoezelen) has been advocated by those working in the field of learning disabilities and mental health as a strategy to induce relaxation. The purpose of the current study was to explore this potential within the field of pain management where the use of relaxation techniques is often employed as a strategy for the management of chronic pain. Thus the current study was designed in order to determine the use of the sensory environment compared against a traditional relaxation programme used within a District General hospital pain clinic. METHOD: Seventy three patients were randomly allocated into either a control or experimental group. Data collection involved the administration of questionnaires, which were selected in order to reflect the multidimensional nature of the chronic pain experience. Hence measures included: pain intensity, pain quality, anxiety, depression, self-efficacy, coping and sickness impact. Analysis was performed using SPSS and included Friedman two-way analysis and repeated measures analysis of variance. RESULTS: The results indicated that the experimental group experienced a significant increase in pain (p = 0.03), but they improved significantly in disability associated with sleep (p = 0.01), psychosocial (p = 0.03) and sickness impact total (p = 0.004). The experimental group experienced a significant decrease in pain (sensory - p = 0.002), (number of words chosen - p = 0.008), (pain rating index - p = 0.002). Furthermore a reduction in disability associated with physical (p = 0.009), psychosocial (p = 0.009), sleep (p = 0.001), recreation (p = 0.001) and SIP total (p = 0.001). Repeated measures analysis of variance revealed a significant improvement with the experimental group in terms of pain (p = 0.04) and self-efficacy (p = 0.02). CONCLUSIONS: The patients who attended the sensory environment did slightly better that those who attended the traditional relaxation programme in terms of self-efficacy. Thus the current study indicates the potential for future research into chronic pain management.

Adaptation, Psychological↗
PubMed2000

Metformin in the treatment of HIV lipodystrophy syndrome: A randomized controlled trial.

CONTEXT: A syndrome of lipodystrophy, characterized by fat redistribution and insulin resistance, has been estimated to affect the majority of human immunodeficiency virus (HIV)-infected individuals who are treated with combination antiretroviral therapy. There are no proven therapies for the metabolic disturbances associated with HIV lipodystrophy syndrome. OBJECTIVE: To determine the safety and efficacy of metformin therapy in HIV-infected patients with fat redistribution and abnormal glucose homeostasis. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled pilot study conducted in a university hospital between December 1998 and January 2000. PATIENTS: Twenty-six HIV-infected, nondiabetic patients with fat redistribution and abnormal oral glucose tolerance test (OGTT) results, hyperinsulinemia, or both. INTERVENTIONS: Patients were randomly assigned to receive metformin, 500 mg twice daily (n = 14), or identical placebo (n = 12), for 3 months. MAIN OUTCOME MEASURES: Insulin area under the curve (AUC), calculated 120 minutes following a 75-g OGTT at baseline vs at 3-month follow-up and compared between treatment groups. RESULTS: Patients treated with metformin demonstrated significant reductions in mean (SEM) insulin AUC 120 minutes after OGTT (-2930 [912] vs -414 [432] microIU/mL [-20349 6334 vs -2875 3000 pmol/L]; P =.01), weight (-1.3 [0.6] vs 1.1 [0.4] kg; P =.005), and diastolic blood pressure (-5 [4] vs 5 [2] mm Hg; P =.009) vs controls, respectively. Metformin therapy was associated with a decrease in visceral abdominal fat (VAT; -1115 [819] vs 1191 [699] mm(2); P =.08) and a proportional reduction in subcutaneous abdominal fat (SAT); the VAT-SAT ratio was unchanged in metformin-treated vs placebo-treated patients. No increase in lactate or liver transaminase levels was observed with metformin treatment. Mild diarrhea was the most common adverse effect of metformin. No patient discontinued therapy because of adverse effects. CONCLUSIONS: This study suggests that a relatively low dosage of metformin reduces insulin resistance and related cardiovascular risk parameters in HIV-infected patients with lipodystrophy. JAMA. 2000;284:472-477

Adult↗