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Biomedical subjects

John Davis

Publications and source records attributed to John Davis.

At least 19 recordsLinked to original sources
PubMed2006

Genome reduction in Leptospira borgpetersenii reflects limited transmission potential.

Leptospirosis is one of the most common zoonotic diseases in the world, resulting in high morbidity and mortality in humans and affecting global livestock production. Most infections are caused by either Leptospira borgpetersenii or Leptospira interrogans, bacteria that vary in their distribution in nature and rely on different modes of transmission. We report the complete genomic sequences of two strains of L. borgpetersenii serovar Hardjo that have distinct phenotypes and virulence. These two strains have nearly identical genetic content, with subtle frameshift and point mutations being a common form of genetic variation. Starkly limited regions of synteny are shared between the large chromosomes of L. borgpetersenii and L. interrogans, probably the result of frequent recombination events between insertion sequences. The L. borgpetersenii genome is approximately 700 kb smaller and has a lower coding density than L. interrogans, indicating it is decaying through a process of insertion sequence-mediated genome reduction. Loss of gene function is not random but is centered on impairment of environmental sensing and metabolite transport and utilization. These features distinguish L. borgpetersenii from L. interrogans, a species with minimal genetic decay and that survives extended passage in aquatic environments encountering a mammalian host. We conclude that L. borgpetersenii is evolving toward dependence on a strict host-to-host transmission cycle.

Animals↗
PubMed2006

Developmental instability and the neural dynamics of the speed-intelligence relationship.

Two of the most securely established findings in the biology of intelligence are the relationship between reaction time (RT) and intelligence, and the heritability of intelligence. To investigate why RT may related to intelligence, researchers have used a variety of techniques to subdivide RT into cognitive and motor components. In the current study, magnetoencephalographic (MEG) dipole latencies were used to examine the speed and timing of specific brain processing stages engaged during visually cued simple and choice reaction time tasks. Simple and choice reaction time and timing of MEG sources were considered in relation to fluid intelligence (as measured by the Raven's Advanced Progressive Matrices, RAPM). To address heritability of intelligence, developmental instability (DI) was assessed, measured here as fluctuating asymmetry. DI represents the degree to which an organism is susceptible to developmental stress arising from both environmental and genomic sources. Analyses showed that choice, but not simple reaction time was negatively correlated with RAPM score. MEG revealed a set of complex relationships between the timing of regional brain activations and psychometric intelligence. The neural component associated with integration of sensory and motor information was most associated with RAPM compared to other components. Higher values of fluctuating asymmetry predicted reduced psychometric intelligence, a result suggesting that some part of the variance of the heritability of intelligence reflects DI. Fluctuating asymmetry was significantly and negatively correlated with timing during all components of task completion. These observations suggest that fluid intelligence is primarily related to speed during processing associated with decision time, while fluctuating asymmetry predicted slower processing across all stages of information processing.

Adolescent↗
PubMed2006

'Participate to learn': a promising practice for community ABI rehabilitation.

OBJECTIVE: To identify best practices and promising practices to enhance participation in meaningful and productive activities. METHOD: An electronic search of the ABI rehabilitation research literature since 1990 yielded 974 articles of which 30 focused on interventions that targeted participation and evaluated effectiveness using direct measures of participation. Three reviewers rated these articles according to the standards set out by the Centre for Reviews and Dissemination. Following the systematic review, an interpretive review of the same articles was completed. RESULTS: Only three studies were rated as strong. No best practices were identified. Three promising practices found some support. The interpretive review suggested 'Participate to learn' as a useful rehabilitation model. The model rests on roles as goals, learning by experience in real-life contexts and the use of personal and environmental support to enable participation. CONCLUSIONS: 'Participate to learn' is both a credible rehabilitation model and deserving of more study.

Brain Injuries↗
PubMed2006

Why olanzapine beats risperidone, risperidone beats quetiapine, and quetiapine beats olanzapine: an exploratory analysis of head-to-head comparison studies of second-generation antipsychotics.

OBJECTIVE: In many parts of the world, second-generation antipsychotics have largely replaced typical antipsychotics as the treatment of choice for schizophrenia. Consequently, trials comparing two drugs of this class--so-called head-to-head studies--are gaining in relevance. The authors reviewed results of head-to-head studies of second-generation antipsychotics funded by pharmaceutical companies to determine if a relationship existed between the sponsor of the trial and the drug favored in the study's overall outcome. METHOD: The authors identified head-to-head comparison studies of second-generation antipsychotics through a MEDLINE search for the period from 1966 to September 2003 and identified additional head-to-head studies from selected conference proceedings for the period from 1999 to February 2004. The abstracts of all studies fully or partly funded by pharmaceutical companies were modified to mask the names and doses of the drugs used in the trial, and two physicians blinded to the study sponsor reviewed the abstracts and independently rated which drug was favored by the overall outcome measures. Two authors who were not blinded to the study sponsor reviewed the entire report of each study for sources of bias that could have affected the results in favor of the sponsor's drug. RESULTS: Of the 42 reports identified by the authors, 33 were sponsored by a pharmaceutical company. In 90.0% of the studies, the reported overall outcome was in favor of the sponsor's drug. This pattern resulted in contradictory conclusions across studies when the findings of studies of the same drugs but with different sponsors were compared. Potential sources of bias occurred in the areas of doses and dose escalation, study entry criteria and study populations, statistics and methods, and reporting of results and wording of findings. CONCLUSIONS: Some sources of bias may limit the validity of head-to-head comparison studies of second-generation antipsychotics. Because most of the sources of bias identified in this review were subtle rather than compelling, the clinical usefulness of future trials may benefit from minor modifications to help avoid bias. The authors make a number of concrete suggestions for ways in which potential sources of bias can be addressed by study initiators, peer reviewers of studies under consideration for publication, and readers of published studies.

Antipsychotic Agents↗
PubMed2005

Rescue angioplasty after failed thrombolytic therapy for acute myocardial infarction.

BACKGROUND: The appropriate treatment for patients in whom reperfusion fails to occur after thrombolytic therapy for acute myocardial infarction remains unclear. There are few data comparing emergency percutaneous coronary intervention (rescue PCI) with conservative care in such patients, and none comparing rescue PCI with repeated thrombolysis. METHODS: We conducted a multicenter trial in the United Kingdom involving 427 patients with ST-segment elevation myocardial infarction in whom reperfusion failed to occur (less than 50 percent ST-segment resolution) within 90 minutes after thrombolytic treatment. The patients were randomly assigned to repeated thrombolysis (142 patients), conservative treatment (141 patients), or rescue PCI (144 patients). The primary end point was a composite of death, reinfarction, stroke, or severe heart failure within six months. RESULTS: The rate of event-free survival among patients treated with rescue PCI was 84.6 percent, as compared with 70.1 percent among those receiving conservative therapy and 68.7 percent among those undergoing repeated thrombolysis (overall P=0.004). The adjusted hazard ratio for the occurrence of the primary end point for repeated thrombolysis versus conservative therapy was 1.09 (95 percent confidence interval, 0.71 to 1.67; P=0.69), as compared with adjusted hazard ratios of 0.43 (95 percent confidence interval, 0.26 to 0.72; P=0.001) for rescue PCI versus repeated thrombolysis and 0.47 (95 percent confidence interval, 0.28 to 0.79; P=0.004) for rescue PCI versus conservative therapy. There were no significant differences in mortality from all causes. Nonfatal bleeding, mostly at the sheath-insertion site, was more common with rescue PCI. At six months, 86.2 percent of the rescue-PCI group were free from revascularization, as compared with 77.6 percent of the conservative-therapy group and 74.4 percent of the repeated-thrombolysis group (overall P=0.05). CONCLUSIONS: Event-free survival after failed thrombolytic therapy was significantly higher with rescue PCI than with repeated thrombolysis or conservative treatment. Rescue PCI should be considered for patients in whom reperfusion fails to occur after thrombolytic therapy.

Adult↗
PubMed2005

Combined oral contraceptives in women with systemic lupus erythematosus.

BACKGROUND: Oral contraceptives are rarely prescribed for women with systemic lupus erythematosus, because of concern about potential negative side effects. In this double-blind, randomized, noninferiority trial, we prospectively evaluated the effect of oral contraceptives on lupus activity in premenopausal women with systemic lupus erythematosus. METHODS: A total of 183 women with inactive (76 percent) or stable active (24 percent) systemic lupus erythematosus at 15 U.S. sites were randomly assigned to receive either oral contraceptives (triphasic ethinyl estradiol at a dose of 35 microg plus norethindrone at a dose of 0.5 to 1 mg for 12 cycles of 28 days each; 91 women) or placebo (92 women) and were evaluated at months 1, 2, 3, 6, 9, and 12. Subjects were excluded if they had moderate or high levels of anticardiolipin antibodies, lupus anticoagulant, or a history of thrombosis. RESULTS: The primary end point, a severe lupus flare, occurred in 7 of 91 subjects receiving oral contraceptives (7.7 percent) as compared with 7 of 92 subjects receiving placebo (7.6 percent). The 12-month rates of severe flare were similar: 0.084 for the group receiving oral contraceptives and 0.087 for the placebo group (P=0.95; upper limit of the one-sided 95 percent confidence interval for this difference, 0.069, which is within the prespecified 9 percent margin for noninferiority). Rates of mild or moderate flares were 1.40 flares per person-year for subjects receiving oral contraceptives and 1.44 flares per person-year for subjects receiving placebo (relative risk, 0.98; P=0.86). In the group that was randomized to receive oral contraceptives, there was one deep venous thrombosis and one clotted graft; in the placebo group, there was one deep venous thrombosis, one ocular thrombosis, one superficial thrombophlebitis, and one death (after cessation of the trial). CONCLUSIONS: Our study indicates that oral contraceptives do not increase the risk of flare among women with systemic lupus erythematosus whose disease is stable.

Adolescent↗
PubMed2005

Fiber-modified adenoviral vector expressing the tumor necrosis factor-related apoptosis-inducing ligand gene from the human telomerase reverse transcriptase promoter induces apoptosis in human hepatocellular carcinoma cells.

AIM: Because of a major resistance to chemotherapy, prognosis of hepatocellular carcinoma (HCC) is still poor. New treatments are required and gene therapy may be an option. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in multiple malignant tumors, and using adenoviral vectors has shown a targeted tumor-specific therapy. However, repeated administration of adenoviral vectors can lead to cell resistance, which may be caused by the initial coxsackie-adenovirus receptor (CAR). One technique to overcome resistance is the use of modified adenoviral vectors containing an Arg-Gly-Asp (RGD) sequence. In this study we constructed an adenoviral vector (designated Ad/TRAIL-F/RGD) with RGD-modified fibers, expressing the TRAIL gene from the human telomerase reverse transcriptase (hTERT) promoter, and evaluated its antitumor activity in HCC cell lines. METHODS: To investigate the effects of Ad/TRAIL-F/RGD in human HCC cell lines Hep G2 and Hep 3b, cells were infected with Ad/CMV-GFP (vector control), Ad/gTRAIL (positive control), and Ad/TRAIL-F/RGD. Phosphate-buffered saline (PBS) was used as control. Cell viability was determined by proliferation assay (XTT), and apoptosis induction by fluorescence activated cell sorting (FACS). RESULTS: Cells treated with Ad/TRAIL-F/RGD and Ad/gTRAIL showed a significantly reduced cell viability in comparison to PBS and Ad/CMV-GFP treatment in both cell lines. Whereas, treatment with PBS and Ad/CMV-GFP had no cell-killing effect. The reduced cell viability was caused by induction of apoptosis as shown by FACS analysis. The amount of apoptotic cells was similar after incubation with Ad/gTRAIL and Ad/TRAIL-F/RGD. CONCLUSION: The new RGD modified vector Ad/TRAIL-F/RGD could become a potent therapeutic agent for the treatment of HCC, adenovirus resistant tumors, and CAR low or negative cancer cells.

Adenoviridae↗
PubMed2005

The prion protein gene: identifying regulatory signals using marsupial sequence.

The function of the prion protein gene (PRNP) and its normal product PrP(C) is elusive. We used comparative genomics as a strategy to understand the normal function of PRNP. As the reliability of comparisons increases with the number of species and increased evolutionary distance, we isolated and sequenced a 66.5 kb BAC containing the PRNP gene from a distantly related mammal, the model Australian marsupial Macropus eugenii (tammar wallaby). Marsupials are separated from eutherians such as human and mouse by roughly 180 million years of independent evolution. We found that tammar PRNP, like human PRNP, has two exons. Prion proteins encoded by the tammar wallaby and a distantly related marsupial, Monodelphis domestica (Brazilian opossum) PRNP contain proximal PrP repeats with a distinct, marsupial-specific composition and a variable number. Comparisons of tammar wallaby PRNP with PRNPs from human, mouse, bovine and ovine allowed us to identify non-coding gene regions conserved across the marsupial-eutherian evolutionary distance, which are candidates for regulatory regions. In the PRNP 3' UTR we found a conserved signal for nuclear-specific polyadenylation and the putative cytoplasmic polyadenylation element (CPE), indicating that post-transcriptional control of PRNP mRNA activity is important. Phylogenetic footprinting revealed conserved potential binding sites for the MZF-1 transcription factor in both upstream promoter and intron/intron 1, and for the MEF2, MyT1, Oct-1 and NFAT transcription factors in the intron(s). The presence of a conserved NFAT-binding site and CPE indicates involvement of PrP(C) in signal transduction and synaptic plasticity.

3' Untranslated Regions↗
PubMed2005

The DNA sequence of the human X chromosome.

The human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. We have determined 99.3% of the euchromatic sequence of the X chromosome. Our analysis illustrates the autosomal origin of the mammalian sex chromosomes, the stepwise process that led to the progressive loss of recombination between X and Y, and the extent of subsequent degradation of the Y chromosome. LINE1 repeat elements cover one-third of the X chromosome, with a distribution that is consistent with their proposed role as way stations in the process of X-chromosome inactivation. We found 1,098 genes in the sequence, of which 99 encode proteins expressed in testis and in various tumour types. A disproportionately high number of mendelian diseases are documented for the X chromosome. Of this number, 168 have been explained by mutations in 113 X-linked genes, which in many cases were characterized with the aid of the DNA sequence.

Animals↗
PubMed2005

Valproate corrects the schizophrenia-like epigenetic behavioral modifications induced by methionine in mice.

BACKGROUND: Reelin and GAD(67) expression is downregulated in cortical interneurons of schizophrenia (SZ) patients. This downregulation is probably mediated by epigenetic hypermethylation of the respective promoters caused by the selective increase of DNA-methyltransferase 1 in GABAergic neurons. Mice receiving methionine (MET) provide an epigenetic model for neuropathologies related to SZ. We studied whether MET-induced epigenetic reelin promoter hypermethylation and the associated behavioral alterations can be reduced by valproate in doses that inhibit histone deacetylases (HDACs). METHODS: Mice treated with either methionine (MET) (5.2 mmol/kg/SC/twice daily) or valproate (1.5 mmol/kg/SC/twice daily) or MET+ valproate combination were tested for prepulse inhibition of startle (PPI) and social interaction (SI). S-adenosylmethionine, acetylated histone 3, reelin promoter methylation, and reelin mRNA were assayed in the frontal cortex. RESULTS: Valproate enhances acetylated histone 3 content, and prevents MET-induced reelin promoter hypermethylation, reelin mRNA downregulation, and PPI and SI deficits. Imidazenil, a positive allosteric modulator at GABA(A) receptors containing alpha(5) subunits but inactive at receptors including alpha(1) subunits, normalizes MET-induced behavioral changes. CONCLUSION: This MET-induced epigenetic mouse models the neurochemical and behavioral aspects of SZ that can be corrected by positively modulating the action of GABA at alpha(5)-containing GABA(A) receptors with imidazenil or by inhibiting HDACs with valproate, thus opening exciting new avenues for treatment of epigenetically modified chromatin in SZ morbidity.

Aggression↗
PubMed2005

Total knee replacement using the Genesis II prosthesis: a 5-year follow up study of the first 100 consecutive cases.

One hundred consecutive patients with osteoarthritis undergoing knee replacement using a prosthesis with asymmetrical posterior condyles and an asymmetrical tibial base plate (Genesis II) were followed for a minimum of 5 years after surgery. Mean flexion was 118 degrees. Seventy nine percent of the patients could ascend and descend stairs in a reciprocal manner. A lateral retinacular release was required in only three patients. Post-operative patellar tracking was excellent as determined by both patellar displacement and patellar tilt. There was excellent flexion space stability using this prosthesis configuration without having to resort to external rotation of the femoral component. Tibial coverage was obtainable in >95% of the knees due to the asymmetric configuration of the base plate. Kaplan Meir Survivorship was 98% at 5 years.

Aged↗
PubMed2005

Degenerative disorders of the lumbar and cervical spine.

Degenerative disorders in the spine are normal, age-related phenomena and largely asymptomatic in most cases. Conservative management of lumbar and cervical spondylosis is the mainstay of treatment, and most patients with symptomatic degenerative changes respond appropriately with nonsurgical management. Surgical intervention can be considered an appropriate and viable option when conservative measures have failed. Treatment options should always be directed toward the specific nature and location of the patient's individual pathology. Although current standards in the surgical management of lumbar and cervical degenerative disorders include discectomy, neural decompression, and instrumented spinal arthrodesis, new approaches that address this often-challenging clinical entity are on the horizon.

Aged↗
PubMed2005

Capsaicin receptor TRPV1 in urothelium of neurogenic human bladders and effect of intravesical resiniferatoxin.

OBJECTIVES: To study TRPV1 immunoreactivity in the urothelium of patients with neurogenic detrusor overactivity (NDO) before and after treatment with resiniferatoxin (RTX) and controls. Functional capsaicin TRPV1 receptors have been demonstrated in urothelial cells of rodent urinary bladder, and TRPV1-knockout mice exhibit diminished nitric oxide and stretch-evoked adenosine triphosphate release from urothelial cells. In patients with NDO, TRPV1 suburothelial nerve density is increased, which is reversed by successful treatment with intravesical RTX. However, the role of urothelial TRPV1 in human bladder disorders is unknown. METHODS: Flexible cystoscopic bladder biopsies were obtained from 14 patients with NDO before and after treatment with RTX and from 8 control patients. Using a specific antibody for immunostaining, TRPV1 immunoreactivity in the urothelium was quantified by image analysis. RESULTS: TRPV1 immunoreactivity was observed in basal and apical urothelial cells. Basal cell layer TRPV1 immunoreactivity was significantly increased in NDO compared with control bladders (P = 0.003). In 5 patients who responded clinically to RTX, basal cell layer and total urothelial TRPV1 immunoreactivity decreased significantly after treatment (P = 0.032 and P = 0.016, respectively). The decreases in the basal cell layer TRPV1 immunoreactivity after RTX were comparable to the decreases in suburothelial TRPV1 nerve fibers in the biopsies previously studied from the same patients. CONCLUSIONS: Increased urothelial TRPV1 in patients with NDO may play a role in the pathophysiology, in concert with increased TRPV1 nerve fibers. Although it is not known whether similar pathogenic mechanisms are involved in the increase of urothelial and neuronal TRPV1, both may be targeted by successful RTX therapy.

Administration, Intravesical↗
PubMed2005

Comparison of type-specific human papillomavirus data from self and clinician directed sampling.

OBJECTIVE(S): To compare the type-specific human papillomavirus (HPV) recovery from physician and patient-collected samples. METHODS: Three hundred thirty-four (334) women attending colposcopy clinics in three countries were enrolled in this cross-sectional study. Cervicovaginal samples were collected by patients and physicians and processed with polymerase chain reaction and reverse line blot genotyping. McNemar's Chi-squared tests and Kappa statistics were utilized to determine statistical associations between physician- versus patient-collected samples. RESULTS: Oncogenic HPV infection was identified in 23.2% of patient-collected specimens compared to 34.9% of physician-collected specimens. Physician sampling detected significantly more infections with type 16 and 52 than did self-sampling and significantly more oncogenic HPV infection overall. For non-oncogenic HPV detection, there was no statistical difference between physician- and patient-collected samples. CONCLUSION(S): Patient sampling for HPV using a single vaginal brush does not identify all oncogenic HPV subtypes.

Colposcopy↗
PubMed2005

The Recognition of Stroke in the Emergency Room (ROSIER) scale: development and validation of a stroke recognition instrument.

BACKGROUND: In patients with acute stroke, rapid intervention is crucial to maximise early treatment benefits. Stroke patients commonly have their first contact with medical staff in the emergency room (ER). We designed and validated a stroke recognition tool-the Recognition of Stroke in the Emergency Room (ROSIER) scale-for use by ER physicians. METHODS: We prospectively collected data for 1 year (development phase) on the clinical characteristics of patients with suspected acute stroke who were admitted to hospital from the ER. We used logistic regression analysis and clinical reasoning to develop a stroke recognition instrument for application in this setting. Patients with suspected transient ischaemic attack (TIA) with no symptoms or signs when assessed in the ER were excluded from the analysis. The instrument was assessed using the baseline 1-year dataset and then prospectively validated in a new cohort of ER patients admitted over a 9-month period. FINDINGS: In the development phase, 343 suspected stroke patients were assessed (159 stroke, 167 non-stroke, 32 with TIA [17 with symptoms when seen in ER]). Common stroke mimics were seizures (23%), syncope (23%), and sepsis (10%). A seven-item (total score from -2 to +5) stroke recognition instrument was constructed on the basis of clinical history (loss of consciousness, convulsive fits) and neurological signs (face, arm, or leg weakness, speech disturbance, visual field defect). When internally validated at a cut-off score greater than zero, the instrument showed a diagnostic sensitivity of 92%, specificity of 86%, positive predictive value (PPV) of 88%, and negative predictive value (NPV) of 91%. Prospective validation in 173 consecutive suspected stroke referrals (88 stroke, 59 non-stroke, 26 with TIA [13 with symptoms]) showed sensitivity of 93% (95% CI 89-97), specificity 83% (77-89), PPV 90% (85-95), and NPV 88% (83-93). The ROSIER scale had greater sensitivity than existing stroke recognition instruments in this population. INTERPRETATION: The ROSIER scale was effective in the initial differentiation of acute stroke from stroke mimics in the ER. Introduction of the instrument improved the appropriateness of referrals to the stroke team.

Aged↗
PubMed2005

Exploratory study of ovarian intraepithelial neoplasia.

PURPOSE: This was an exploratory study to test two hypotheses related to potential epithelial precursors to ovarian cancer: (a) histologically normal ovarian surface epithelium exhibited changes in the nuclear chromatin pattern, which indicate an ovarian abnormality, and (b) such changes were detectable in the ovarian surface epithelium of cancer-free subjects who were at high risk for ovarian cancer. EXPERIMENTAL DESIGN: Ovaries were carefully collected to avoid damage to the surface epithelium. Five-micron-thick histologic sections were cut and stained with H&E. High-resolution images were recorded from the ovarian surface epithelium and from the underlying stroma of ovaries from normal women (10 cases), women at high risk of developing ovarian cancer (7 cases), and histologically normal areas adjacent to ovarian cancer (3 cases). Karyometric features and measurements of nuclear abnormality were computed for 3,390 epithelial nuclei. Discriminant function analyses and unsupervised learning algorithms were employed to define deviations from normal and to identify the subpopulations of nuclei exhibiting these changes. RESULTS: Epithelium from ovaries harboring a malignant lesion had changes in the nuclear chromatin pattern consistent with a second phenotype, which were not visually detected with histopathologic surveillance. This phenotype was also present in the ovaries obtained from women at increased risk of ovarian cancer, suggesting that it may represent a premalignant abnormality. These changes were statistically significant. CONCLUSION: The observed changes in karyometric features were sufficiently distinct to warrant further study as both diagnostic and prognostic biomarkers for early detection and prevention of ovarian cancer.

Carcinoma in Situ↗