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Biomedical subjects

J Davis

Publications and source records attributed to J Davis.

At least 55 records · Page 3Linked to original sources
PubMed2003

DNA-methyltransferase 1 mRNA is selectively overexpressed in telencephalic GABAergic interneurons of schizophrenia brains.

A down-regulation of reelin and glutamic acid decarboxylase (GAD) 67 mRNAs was detected in gamma-aminobutyric acid (GABA)ergic cortical interneurons of schizophrenia (SZ) postmortem brains (10), suggesting that the availability of GABA and reelin may be decreased in SZ cortex. In situ hybridization of the mRNA encoding for DNA-methyltransferase 1, which catalyzes the methylation of promoter CpG islands, shows that the expression of this mRNA is increased in cortical GABAergic interneurons but not in pyramidal neurons of SZ brains. Counts of reelin mRNA-positive neurons in Brodmann's area 10 of either nonpsychiatric subjects or SZ patients show that the expression of reelin mRNA is decreased in layer-I, -II, and -IV GABAergic interneurons of SZ patients. These findings are consistent with the hypothesis that the increase of DNA-methyltransferase 1 expression in telencephalic GABAergic interneurons of SZ patients causes a promoter hypermethylation of reelin and GAD(67) and perhaps of other genes expressed in these interneurons. It is difficult to decide whether this dysfunction of GABAergic neurons detected in SZ is responsible for this disease or is a consequence of this disorder. Although at present we cannot differentiate between these two alternatives, it is important to consider that so far a molecular pathology of cortical GABAergic neurons appears to be the most consistent finding associated with SZ morbidity.

Adult↗
PubMed2003

Continuous passive motion following total knee arthroplasty.

BACKGROUND: Knee arthroplasty (KA) is a common intervention that can enhance the quality of life for patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Post-surgery rehabilitation protocols often include continuous passive motion (CPM). However, CPM protocols vary considerably amongst institutions. OBJECTIVES: The purpose of the current meta-analysis is to evaluate the effectiveness of continuous passive motion following total knee arthroplasty. SEARCH STRATEGY: An electronic search of MEDLINE (1966 to 2002), EMBASE (1988 to 2002), CINAHL (1982 to 2002), HEALTH STAR (1991 to 1994) and CURRENT CONTENTS (1997 to 2002) was conducted to identify randomized controlled trials. SELECTION CRITERIA: Following an a priori protocol, only randomized controlled trials of CPM for the treatment of participants post KA were eligible. Subjects were 18 years of age or older and had a pre-surgery diagnosis of degenerative joint disease. Both the experimental and control groups received physiotherapy. In addition to the physiotherapy intervention, the experimental group received CPM. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion. Data were then extracted and the quality of the trial assessed using predetermined forms. Outcome measures of interest were: active and passive knee range of motion (ROM) length of hospital stay, pain, swelling and quadriceps strength. A fixed effects model was used throughout for continuous variables, except where heterogeneity existed; in which case, a random effects model was used. Results were analyzed as weighted mean differences (WMD) with 95% confidence intervals (CI). Standardized mean differences (SMD) were used when different scales were used to measure the same concept (e.g. pain). Dichotomous outcomes were presented as a relative risk. MAIN RESULTS: Fourteen trials were retained for analysis. Results favouring CPM were found for the main comparison of CPM combined with physiotherapy (PT) versus PT alone at end of treatment. For the primary outcomes of interest, CPM combined with PT was found to statistically significantly increase active knee flexion (WMD 4.30 degrees, 95% CI: 1.96, 6.63) and decrease length of stay (WMD -0.69 days, 95% CI: -1.35, -0.03). CPM was also found to decrease the need for post-operative manipulation (RR 0.12, 95% CI: 0.03, 0.53). CPM did not significantly improve passive knee flexion and passive or active knee extension. REVIEWER'S CONCLUSIONS: CPM combined with PT, may offer beneficial results compared to PT alone in the short term rehabilitation following total knee arthroplasty.

Arthroplasty, Replacement, Knee↗
PubMed2003

Deriving the real-ear SPL of audiometric data using the "coupler to dial difference" and the "real ear to coupler difference".

OBJECTIVE: The purpose of the study was to compare the measured real-ear sound pressure level (SPL) of audiometer output with the derived real-ear SPL obtained by adding the coupler to dial difference (CDD) and real-ear to coupler difference (RECD) to the audiometer dial reading. DESIGN: The real-ear SPL and RECD were measured in one ear of 16 normally hearing subjects using a probe-tube microphone. The CDD transform and the RECD transfer function were measured in an HA1 and an HA2 2-cc coupler using an EAR-LINK foam ear-tip or a customized earmold. The RECD transfer function was measured using the EARTone ER 3A and the Audioscan RE770 insert earphone. RESULTS: The procedures were very reliable with mean differences on retest of less than 1 dB. The mean difference between the measured and derived real-ear SPL was generally less than 1 dB and rarely exceeded 3 dB in any subject. CONCLUSIONS: The CDD measured for an individual audiometer and the RECD measured for an individual ear can be used to derive a valid estimate of real-ear SPL when it has not been possible to measure this directly.

Acoustic Impedance Tests↗
PubMed2003

Cytokines in the seronegative spondyloarthropathies and their modification by TNF blockade: a brief report and literature review.

Rheumatoid arthritis (RA) is a disease well characterised by proinflammatory cytokine secretion (particularly tumour necrosis factor, interferon gamma, interleukin (IL) 1, and IL6). Less has been reported about the cytokine profiling in the spondyloarthropathies (SpA). Several trials suggest that, similar to RA, proinflammatory cytokines are globally expressed in the SpA. However, other studies report a down regulation of these cytokines in the SpA, with a relative anti-inflammatory polarisation (featuring increases in IL4, IL5, and IL10). This review summarises current published reports and the variation in cytokine data in the SpA. Additionally, results of cytokine profiles in patients with ankylosing spondylitis before and after treatment with etanercept are reported.

Antirheumatic Agents↗
PubMed2003

International ASAS consensus statement for the use of anti-tumour necrosis factor agents in patients with ankylosing spondylitis.

OBJECTIVE: To obtain an international consensus about the use of anti-tumour necrosis factor alpha (anti-TNF alpha) for treating patients with ankylosing spondylitis (AS). METHODS: These recommendations were developed by a review of published reports in combination with expert opinion, including a Delphi exercise, and a consensus meeting of the ASsessments in AS (ASAS) Working Group. RESULTS: The final consensus comprises the following requirements: (1) For the initiation of anti-TNF alpha therapy: (a) a diagnosis of definitive AS; (b) presence of active disease for at least four weeks as defined by both a sustained Bath AS Disease Activity Index (BASDAI) of at least 4 and an expert opinion based on clinical features, acute phase reactants, and imaging modalities; (c) presence of refractory disease defined by failure of at least two non-steroidal anti-inflammatory drugs during a single three month period, failure of intra-articular steroids if indicated, and failure of sulfasalazine in patients with peripheral arthritis; (d) application and implementation of the usual precautions and contraindications for biological therapy. (2) For the monitoring of anti-TNF alpha therapy: both the BASDAI and the ASAS core set for clinical practice should be followed regularly. (3) For the discontinuation of anti-TNF alpha therapy: in non-responders, consideration should be made after 6-12 weeks' treatment. Response is defined as improvement of (a) at least 50% or 2 units (on a 0-10 scale) of the BASDAI, (b) expert opinion that treatment should be continued. CONCLUSION: This consensus statement on anti-TNF alpha treatment in AS may be used for guidance in clinical decision making and as the basis for the development of guidelines. Evaluation of the healthcare consequences of this consensus is subject to further research by the ASAS group.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2002

Adaptive evolution of small heat shock protein/alpha B-crystallin promoter activity of the blind subterranean mole rat, Spalax ehrenbergi.

Blind mole rats have degenerated subcutaneous eyes that are visually nonfunctional. In this investigation, we have compared the tissue specificity of the small heat shock protein (shsp)/alphaB-crystallin promoter of the mole rat superspecies, Spalax ehrenbergi, with that of the mouse. Earlier experiments showed that mouse shsp/alphaB-crystallin promoter/enhancer activity is high in the lens and moderate in the heart and skeletal muscle of transgenic mice. Here, we show in transgenic mouse experiments using the firefly luciferase reporter gene that, despite relatively few changes in sequence, the mole rat shsp/alphaB-crystallin promoter/enhancer has selectively lost lens activity after 13.5 days of embryogenesis (E13.5). The ratios of mole rat/mouse promoter activity were 0.01 for lens, 1.7 for heart, and 13.6 for skeletal muscle in 8-wk-old transgenic mice. Our data indicate that the shsp/alphaB-crystallin promoter/enhancer has undergone adaptive changes corresponding to the subterranean evolution of the blind mole rat. We speculate that selective pressures on metabolic economy may have contributed to these tissue-specific modifications of promoter/enhancer function during adaptation to life underground.

Animals↗
PubMed2002

Phase I trial of intraperitoneal injection of the E1B-55-kd-gene-deleted adenovirus ONYX-015 (dl1520) given on days 1 through 5 every 3 weeks in patients with recurrent/refractory epithelial ovarian cancer.

PURPOSE: Resistance to chemotherapy in ovarian cancer is frequently associated with mutations in the p53 gene. The adenovirus dl1520 (ONYX-015) with the E1B 55-kd gene deleted, allowing selective replication in and lysis of p53-deficient tumor cells, has shown preclinical efficacy against p53-deficient nude mouse-human ovarian carcinomatosis xenografts. PATIENTS AND METHODS: We undertook a phase I trial of intraperitoneal dl1520 in patients with recurrent ovarian cancer. Sixteen women with recurrent/refractory ovarian cancer received 35 cycles (median, two cycles) of dl1520 delivered on days 1 through 5 in four dose cohorts: 1 x 10(9) plaque forming units (pfu), 1 x 10(10) pfu, 3 x 10(10) pfu, and 1 x 10(11) pfu. RESULTS: The most common significant toxicities related to virus administration were flu-like symptoms, emesis, and abdominal pain. One patient receiving 1 x 10(10) pfu developed common toxicity criteria grade 3 abdominal pain and diarrhea, which was dose-limiting. The maximum-tolerated dose was not reached at 10(11) pfu, and at this dose level patients did not experience significant toxicity. There was no clear-cut evidence of clinical or radiologic response in any patient. Blood samples were taken for adenovirus DNA and neutralizing antibodies. Polymerase chain reaction data indicating presence of virus up to 10 days after the final (day 5) infusion of dl1520 are suggestive of continuing viral replication. CONCLUSION: This article therefore describes the first clinical experience with the intraperitoneal delivery of any replication-competent/-selective virus in cancer patients.

Adenoviridae↗
PubMed2002

Optimal wire-number range for high x-ray power in long-implosion-time aluminum Z pinches.

Experiments performed on the 8-MA Saturn accelerator to investigate the effects of interwire gap spacing on long-implosion-time Z pinches have resulted in the observation of a regime of optimal wire number. The experiments varied the wire number of 40 and 32 mm diam arrays, resulting in interwire gaps from 3.9 to 0.36 mm, with fixed mass and length. aluminum K-shell powers up to 3.4 TW were measured, with long, slow rising, lower power x-ray pulses for interwire gaps greater than 2.2 mm and less than 0.7 mm, and short, fast rising, higher power pulses for interwire gaps in the range 0.7-2.2 mm.

Journal Article↗
PubMed2002

Transscleral Coulomb-controlled iontophoresis of methylprednisolone into the rabbit eye: influence of duration of treatment, current intensity and drug concentration on ocular tissue and fluid levels.

The major problems associated with the use of corticosteroids for the treatment of ocular diseases are their poor intraocular penetration to the posterior segment when administered locally and their secondary side effects when given systemically. To circumvent these problems more efficient methods and techniques of local delivery are being developed. The purposes of this study were: (1) to investigate the pharmacokinetics of intraocular penetration of hemisuccinate methyl prednisolone (HMP) after its delivery using the transscleral Coulomb controlled iontophoresis (CCI) system applied to the eye or after intravenous (i.v.) injection in the rabbit, (2) to test the safety of the CCI system for the treated eyes and (3) to compare the pharmacokinetic profiles of HMP intraocular distribution after CCI delivery to i.v. injection. For each parameter evaluated, six rabbit eyes were used. For the CCI system, two concentrations of HMP (62.5 and 150mg ml(-1)), various intensities of current and duration of treatment were analyzed. In rabbits serving as controls the HMP was infused in the CCI device but without applied electric current. For the i.v. delivery, HMP at 10mg kg(-1)as a 62.5mg ml(-1)solution was used. The rabbits were observed clinically for evidence of ocular toxicity. At various time points after the administration of drug, rabbits were killed and intraocular fluids and tissues were sampled for methylprednisolone (MP) concentrations by high pressure liquid chromatography (HPLC). Histology examinations were performed on six eyes of each group. Among groups that received CCI, the concentrations of MP increased in all ocular tissues and fluids in relation to the intensities of current used (0.4, 1.0 and 2.0mA/0.5cm(2)) and its duration (4 and 10min). Sustained and highest levels of MP were achieved in the choroid and the retina of rabbit eyes treated with the highest current and 10min duration of CCI. No clinical toxicity or histological lesions were observed following CCI. Negligible amounts of MP were found in ocular tissues in the CCI control group without application of current. Compared to i.v. administration, CCI achieved higher and more sustained tissue concentrations with negligible systemic absorption. These data demonstrate that high levels of MP can be safely achieved in intraocular tissues and fluids of the rabbit eye, using CCI. With this system, intraocular tissues levels of MP are higher than those achieved after i.v. injection. Furthermore, if needed, the drug levels achieved with CCI can be modulated as a function of current intensity and duration of treatment. CCI could therefore be used as an alternative method for the delivery of high levels of MP to the intraocular tissues of both the anterior and posterior segments.

Animals↗
PubMed2002

Quantitative study of breast cancer progression: different pathways for various in situ cancers.

The chromatin pattern in nuclei from breast ductal proliferative lesions was quantitatively evaluated with the objective of deriving measures of tumor progression. A total of 110 cases were analyzed. There were 38 cases of normal tissue or benign proliferative lesions, 41 cases of ductal carcinoma in situ (DCIS), and 31 cases of microinfiltrating DCIS and of infiltrating cancer. A total of 9424 nuclei were analyzed. High-resolution images were digitally recorded. For each nucleus, 93 karyometric features descriptive of the spatial and statistical distribution of the nuclear chromatin were computed. Data analysis included establishing a profile of relative deviations of each feature from "normal," called the nuclear signature, and of lesion signatures as well as of trends of lesion progression. Two trends of evolution could be discerned: one from normal to hyperplasia, atypical hyperplasia, and comedo DCIS as representative of high-grade lesions; and the other from normal to hyperplasia to cribriform DCIS, solid DCIS, and infiltrating cancer, representing lower grade lesions. The nuclei in microinfiltrating foci are distinctly different from nuclei in high-grade comedo DCIS. The nuclei in microinfiltrating foci have a statistically significantly lower nuclear abnormality. They may represent outgrowing clones.

Breast↗
PubMed2002

Storage of cane toad (Bufo marinus) sperm for 6 days at 0 degrees C with subsequent cryopreservation.

We investigated the recovery of motility of cane toad (Bufo marinus) sperm after storage for 6 days at 0 degree C (on ice) and after subsequent cryopreservation. Sperm suspensions were prepared from testes macerated in either simplified amphibian Ringer (SAR) or 10% (w/v) sucrose diluents, with 15% or 20% (v/v) glycerol or Me2SO as cryoprotectants, and were stored for 6 days. Alternatively, suspensions were prepared in either SAR or 10% (w/v) sucrose diluent and stored for 6 days, after which some of these suspensions were kept in diluents alone or, alternatively, had 15% or 20% (v/v) glycerol or Me2SO added. All treatments (suspensions) were then cryopreserved. Sperm motility was measured at Day 1 and Day 6 (before and after cryopreservation). A substantial and variable proportion (range 0%-40%) of sperm was immotile in suspensions immediately after preparation from testes macerates. Sperm stored in either SAR or 10% (w/v) sucrose diluent maintained approximately 75% motility for 6 days, but few sperm survived cryopreservation. After storage and cryopreservation, recovery of motility was substantially higher with Me2SO than in glycerol. However, both cryoprotectants exhibited toxicity at high concentrations. Glycerol was more toxic than Me2SO in 10% (w/v) sucrose than in SAR diluent, both before and after cryopreservation. The addition of some cryoprotectants to suspensions before storage gave greater recovery both before and after cryopreservation. After cryopreservation, the highest rate of sperm recovery was in suspensions with 10% (w/v) sucrose and 15% (v/v) Me2SO added prior to storage (mean (+/-SEM) 46 +/- 7% relative to initial; 39 +/- 6% absolute). Sperm were also stored for 6 days at 0 degrees C in suspensions or testes (with suspensions then prepared from testes) and cryopreserved. Sperm maintained higher recovery and membrane integrity both before and after cryopreservation when stored in suspensions rather than in testes.

Animals↗
PubMed2002

REELIN and schizophrenia: a disease at the interface of the genome and the epigenome.

The downregulation of the Reelin gene (RELN) that occurs in schizophrenic brains, which are characterized by pyramidal neurons with shortened dendrites and by reduced expression densities of dendritic spines, may well result from hypermethylation of the RELN promoter. In the adult mammalian brain, gamma-aminoburytic acid-secreting (GABAergic) interneurons release RELN into the extracellular matrix, where it binds with high affinity to the integrin receptors present at dendritic spine postsynaptic densities and likely plays a role, elaborated in this article, in synaptic plasticity. In heterozygous reeler mice, which are haploinsufficient in RELN, inhibitors of histone deacetylase increase DNA demethylase activity and restore RELN expression. Such inhibitors could thus be of therapeutic value in mitigating vulnerability to schizophrenia among high-risk individuals.

Animals↗
PubMed2002

Anti-tumour necrosis factor alpha therapy for ankylosing spondylitis: international experience.

The conventional approach to treatment of patients with spondyloarthritis (SpA), particularly ankylosing spondylitis (AS), has serious limitations, adding a sense of urgency to the evaluation of new treatments for these rheumatic disorders. Tumour necrosis factor alpha (TNFalpha) is a cytokine that has been shown to mediate inflammatory and regulatory activities in SpA and other immune mediated diseases, including other arthritides and inflammatory bowel disease. Positive results have been reported in several international open label and randomised controlled trials of infliximab and etanercept, the two main biological agents targeting TNFalpha, which have included approximately 300 patients with SpA. Specifically, TNFalpha-directed therapy resulted in significant improvements in disease activity, function, and quality of life in these patients, most of whom had AS and received infliximab. Preliminary evidence from open label, long term extension trials suggests clinical benefit with continued use. Serious side effects were rare and consistent with experience from patient groups receiving infliximab or etanercept treatment for inflammatory bowel disease or rheumatoid arthritis. Together, these findings herald an age of more effective treatment of patients with AS with anti-TNFalpha and other emerging biological agents.

Aged↗
PubMed2001

Efficient multi-keV underdense laser-produced plasma radiators.

Novel, efficient x-ray sources have been created by supersonically heating a large volume of Xe gas. A laser-induced bleaching wave quickly ionizes the high- Z gas, and the resulting plasma emits x rays. This method significantly improves the production of hard x rays because less energy is lost to kinetic energy and sub-keV x rays. The conversion efficiency of laser energy into L-shell radiation between 4-7 keV is measured at approximately 10%, an order of magnitude higher than efficiencies measured from solid disk targets. This higher flux enables material testing and backlighting in new regimes and scales well to future high-powered lasers.

Journal Article↗