Biomedical subjects

Mark Rogers

Publications and source records attributed to Mark Rogers.

15 recordsLinked to original sources

PubMed2007

Association study between the TNXB locus and schizophrenia in a Japanese population.

The chromosome 6p21-24 region, which contains the human leukocyte antigen (HLA) region, has been suggested as an important locus for a susceptibility gene for schizophrenia. Recently, a significant association between schizophrenia and the TNXB locus, located immediately telomeric of the NOTCH4 locus in the HLA region, was observed. Few studies have further investigated the region in schizophrenia. In the present study, we investigated the region in a Japanese population. Subjects included 241 patients with schizophrenia and 290 controls. Twenty-six single nucleotide polymorphisms (SNPs) and the corresponding haplotypes were analyzed. As a result, exactly the same SNPs in the TNXB locus (rs1009382 and rs204887) as in the previous study were associated with schizophrenia (P = 0.034 and 0.034, respectively, uncorrected). A SNP (rs2071287) in the NOTCH4 locus and haplotype around it were also suggested to associate with the disease, consistent with another previous study (P = 0.041 and permutation P = 0.024, respectively, uncorrected). Although these associations became insignificant after Bonferroni correction, the findings might provide support for the association of the TNXB locus or its adjacent region of the NOTCH4 locus with schizophrenia.

Adult↗

PubMed2006

Urinary biomarker profiling in transitional cell carcinoma.

Urinary biomarkers or profiles that allow noninvasive detection of recurrent transitional cell carcinoma (TCC) of the bladder are urgently needed. We obtained duplicate proteomic (SELDI) profiles from 227 subjects (118 TCC, 77 healthy controls and 32 controls with benign urological conditions) and used linear mixed effects models to identify peaks that are differentially expressed between TCC and controls and within TCC subgroups. A Random Forest classifier was trained on 130 profiles to develop an algorithm to predict the presence of TCC in a randomly selected initial test set (n = 54) and an independent validation set (n = 43) several months later. Twenty two peaks were differentially expressed between all TCC and controls (p < 10(-7)). However potential confounding effects of age, sex and analytical run were identified. In an age-matched sub-set, 23 peaks were differentially expressed between TCC and combined benign and healthy controls at the 0.005 significance level. Using the Random Forest classifier, TCC was predicted with 71.7% sensitivity and 62.5% specificity in the initial set and with 78.3% sensitivity and 65.0% specificity in the validation set after 6 months, compared with controls. Several peaks of importance were also identified in the linear mixed effects model. We conclude that SELDI profiling of urine samples can identify patients with TCC with comparable sensitivities and specificities to current tumor marker tests. This is the first time that reproducibility has been demonstrated on an independent test set analyzed several months later. Identification of the relevant peaks may facilitate multiplex marker assay development for detection of recurrent disease.

Adult↗

PubMed2006

Insertional polymorphism of endogenous retrovirus HERV-K115 in schizophrenia.

Retroviruses are implicated in the pathogenesis of schizophrenia. Human endogenous retrovirus type K115 (HERV-K115) is a full-length, potentially transcriptional retrovirus and is also polymorphic. We investigated the frequency of HERV-K115 in Japanese schizophrenia patients and healthy controls. No difference was found in the frequency between patients and controls (8.4% versus 9.4%, respectively). However, a marginal difference was observed in age at onset between the HERV-K positive and negative patients (p=0.057). The HERV-K115 insertion appeared to be more frequent in patients with younger onset than those with later onset. These results preliminarily suggest that HERV-K115 may not be associated with schizophrenia in general, but that it could play a partial role in early precipitation of the disease.

Adult↗

PubMed2006

Association study of the dysbindin (DTNBP1) gene in schizophrenia from the Japanese population.

Dysbindin (DTNBP1: dystrobrevin binding protein 1), located on 6p22.3, is a candidate susceptibility gene for schizophrenia. Several studies, mostly in Caucasians, have provided evidence for an association between schizophrenia and the gene, although no common polymorphism or haploytpe has been established. In Asian populations, two studies investigated a limited number of single nucleotide polymorphisms (SNPs) of dysbindin and observed support for the association. In the present study, we investigated 12 SNPs of dysbindin, including those examined in previous Asian studies, and the corresponding haplotypes in a Japanese people with schizophrenia. As a result, no significant difference was observed between patients and controls in allelic frequencies or genotypic distributions of the 12 SNPs. Permutation test however showed significant differences in frequencies of the estimated 10-marker haplotypes between patients and controls (global p = 0.006). The present study may provide further support for an association between dysbindin and schizophrenia in Asian populations. The results might be similar to a previous Asian study, but specific haplotypes suggested for the association differed between the studies. Studies with more markers and subjects may be required before firm conclusions can be reached.

Adult↗

PubMed2006

No evidence for an association between the BDNF Val66Met polymorphism and schizophrenia or personality traits.

Brain-derived neurotrophic factor (BDNF) is a member of the nerve growth factor family, which plays a critical role in neurodevelopment. Based on the neurodevelopmental hypothesis, the BDNF gene has been a candidate locus for schizophrenia. In Caucasians, recent studies identified an association with the Val66Met polymorphism, which has been suggested to affect episodic memory and hippocampal function in humans. However, in other populations, the association has not been replicated. In the present study, we investigated the association between the Val66Met polymorphism of the gene and schizophrenia in 401 Japanese patients with schizophrenia and 569 controls. As a result, we did not observe a significant difference in genotypic distribution or allele frequencies between the patients and controls (chi2=0.56, df=2, p=0.76 and chi2=0.39, df=1, p=0.53, respectively). We also investigated the association between the polymorphism and personality traits in the controls; however, no significant association was observed. Thus, the present study did not provide evidence for an association between the BDNF gene and schizophrenia or personality traits in the Japanese population.

Asian People↗

PubMed2005

Seasonality of schizophrenia births in the Japanese population: increased winter births possibly confined to the north area.

A number of North American and European studies have observed a higher proportion of winter births in schizophrenia patients. Thus, seasonal fluctuation of unknown environmental factors may affect brain development in ways that alter susceptibility to schizophrenia. Specification of these factors may help elucidate the etiopathological mechanism of the disease, about which little is certain. A small number of studies have investigated this issue in Asian populations, and the findings are not as consistent as those of Western populations. No remarkable excess of winter births has been observed in Japanese or Korean studies, while some studies have reported a significant decrease of summer births. We further investigated the issue in Japanese patients with schizophrenia (n=3927). No significant excess of winter births was observed, but a decrease in the summer births was found in male subjects. This is largely consistent with previous Japanese studies; however, when the subjects were confined to those born in a colder and higher latitude area of Japan (n=1338), a consistent trend for both a winter increase, and a summer decrease, was found. However, the results did not consistently reach statistical significance, possibly due to the lack of statistical power. Environmental factors that correlate with latitude might play a role in the development of the seasonality of births in schizophrenia. Further studies in a larger sample size are required to test these possibilities.

Catchment Area, Health↗

PubMed2005

Parahippocampal activation evoked by masked traumatic images in posttraumatic stress disorder: a functional MRI study.

Posttraumatic stress disorder (PTSD) has been widely studied, but its neural mechanism is still unclear. The purpose of this study is to identify dysfunctional areas in PTSD throughout the whole brain to help to elucidate the neural mechanisms of PTSD. Sixteen patients with PTSD and sixteen healthy controls participated in this study. Traumatic images under perceptual threshold including scenes of earthquakes, traffic accidents, ambulances, emergency rooms, and crimes were presented to the participants, and brain activation was measured using functional MRI. Functional brain images of both groups were evaluated with random effect analysis for the whole brain. In the control group, activation in the ventral frontoparietal areas correlated significantly with presentation of the masked traumatic stimuli. In the PTSD group, activation was not observed in these areas, but significant activation correlated with the masked traumatic stimuli in the parahippocampal region including the left parahippocampal gyrus and tail of the left hippocampus. These results suggest that in PTSD patients activation in the ventral frontoparietal network associated with visual attention processing is attenuated, while the left hippocampal area associated with episodic and autobiographical memory is abnormally easily activated. This pattern of activation corresponds well to the clinical characteristics of PTSD, in which even slight traumatic stimuli tend to induce intrusive recollection or flashbacks, despite a general decrease in attention and ability to concentrate.

Adult↗

PubMed2005

Blood-meal analysis for the identification of reservoir hosts of tick-borne pathogens in Ireland.

The results of analysis of blood-meal remnants in unfed nymphs, despite relatively low detection levels (49.4%, n = 322), support the conclusion from an earlier study that small rodents are relatively unimportant as reservoir hosts of B. burgdorferi s.l. in this particular area, and suggest that songbirds (Passeriformes) are the most significant hosts in this respect. Tick (Ixodes ricinus) abundance was greater in the present study, but the overall Borrelia burgdorferi s.l.-infection prevalence of nymphal ticks was the same (12.2%), and the relative proportions of the various Borrelia burgdorferi s.l. genospecies were similar. B. garinii and B. valaisiana were the most frequent, B. burgdorferi s.s the least frequent, and B. afzelii of intermediate frequency. An unusually high proportion of nymphs (39%) with multiple infections of different B. burgdorferi genospecies was detected, and Borrelia spp. related to relapsing-fever spirochetes were detected in Ireland for the first time. The results of the present study contribute to the validation of blood-meal analysis as a means of determining the host origin of certain pathogens in unfed questing ticks, and raise some questions concerning the extent of B. burgdorferi s.l. host specificity.

Animals↗

PubMed2005

Intensive versus modified conventional control of blood glucose level in medical intensive care patients: a pilot study.

BACKGROUND: Critically ill postsurgical patients fare better with intensive control of blood glucose level. The link between glucose control and outcome is less well studied for medical intensive care patients. Whether intensive glucose control requires additional staffing is unclear. OBJECTIVES: To compare intensive glucose control with modified conventional control in the medical intensive care unit and to assess compliance with glucose targets, incidence of hypoglycemia, and staffing adequacy. METHODS: Medical intensive care patients who had been receiving mechanical ventilation for less than 24 hours were randomized to intensive or modified conventional protocols for glucose control. Nurses were trained before participating in the study and were interviewed after its completion. RESULTS: Five subjects were randomized to each protocol. Mean blood glucose levels were 5.8 (SD 1.5) mmol/L (105.3 [SD 26.3] mg/dL) for the intensive group and 9.8 (SD 2.5) mmol/L (177.4 [SD 45.5] mg/dL) for the modified conventional group (P < .001). Fifty percent of glucose levels met target values in the intensive group, and 72% of glucose levels met target values in the modified conventional group (P < .001). Severe hypoglycemia (glucose <2.2 mmol/L [<40 mg/dL]) occurred rarely and without complication. Nurses suggested protocols might be improved by using smaller steps in adjusting insulin dosage and reported that simultaneously caring for more than 1 study subject was taxing. CONCLUSIONS: Target levels for blood glucose were achieved with both protocols. Severe hypoglycemia was rare and uncomplicated regardless of type of glucose control. Additional staffing may be needed for intensive glucose control.

Adult↗

PubMed2004

Subclinical bovine spongiform encephalopathy infection in transgenic mice expressing porcine prion protein.

The bovine-porcine species barrier to bovine spongiform encephalopathy (BSE) infection was explored by generating transgenic mouse lines expressing the porcine prion protein (PrP) gene. All of the porcine transgenic (poTg) mice showed clinical signs of BSE after intracerebral inoculation with a high-titer BSE inoculum. The protease-resistant PrP (PrP(res)) was detected in 14% (3 of 22) of the BSE-infected poTg mice by immunohistochemical or immunoblot analysis. Despite being able to infect 42% (5 of 12) of control mice, a low-dose BSE inoculum failed to penetrate the species barrier in our poTg mouse model. The findings of these infectivity studies suggest that there is a strong species barrier between cows and pigs. However, after second-passage infection of poTg mice using brain homogenates of BSE-inoculated mice scoring negative for the incoming prion protein as inoculum, it was possible to detect the presence of the infectious agent. Thus, porcine-adapted BSE inocula were efficient at infecting poTg mice, giving rise to an incubation period substantially reduced from 300 to 177 d after inoculation and to the presence of PrP(res) in 100% (21 of 21) of the mice. We were therefore able to conclude that initial exposure to the bovine prion may lead to subclinical infection such that brain homogenates from poTg mice classified as uninfected on the basis of the absence of PrP(res) are infectious when used to reinoculate poTg mice. Collectively, our findings suggest that these poTg mice could be used as a sensitive bioassay model for prion detection in pigs.

Amino Acid Sequence↗

PubMed2004

A dual closed-loop control system for mechanical ventilation.

OBJECTIVE: Closed-loop mechanical ventilation has the potential to provide more effective ventilatory support to patients with less complexity than conventional ventilation. The purpose of this study was to investigate the effectiveness of an automatic technique for mechanical ventilation. METHODS: Two closed-loop control systems for mechanical ventilation are combined in this study. In one of the control systems several physiological data are used to automatically adjust the frequency and tidal volume of breaths of a patient. This method, which is patented under US Patent number 4986268, uses the criterion of minimal respiratory work rate to provide the patient with a natural pattern of breathing. The inputs to the system include data representing CO2 and O2 levels of the patient as well as respiratory compliance and airway resistance. The I:E ratio is adjusted on the basis of the respiratory time constant to allow for effective emptying of the lungs in expiration and to avoid intrinsic positive end expiratory pressure (PEEP). This system is combined with another closed-loop control system for automatic adjustment of the inspired fraction of oxygen of the patient. This controller uses the feedback of arterial oxygen saturation of the patient and combines a rapid stepwise control procedure with a proportional-integral-derivative (PID) control algorithm to automatically adjust the oxygen concentration in the patient's inspired gas. The dual closed-loop control system has been examined by using mechanical lung studies, computer simulations and animal experiments. RESULTS: In the mechanical lung studies, the ventilation controller adjusted the breathing frequency and tidal volume in a clinically appropriate manner in response to changes in respiratory mechanics. The results of computer simulations and animal studies under induced disturbances showed that blood gases were returned to the normal physiologic range in less than 25 s by the control system. In the animal experiments understeady-state conditions, the maximum standard deviations of arterial oxygen saturation and the end-tidal partial pressure of CO2 were +/- 1.76% and +/- 1.78 mmHg, respectively. CONCLUSION: The controller maintained the arterial blood gases within normal limits under steady-state conditions and the transient response of the system was robust under various disturbances. The results of the study have showed that the proposed dual closed-loop technique has effectively controlled mechanical ventilation under different test conditions.

Algorithms↗

PubMed2003

Giving a voice to the community: a qualitative study of consumer expectations for the emergency department.

OBJECTIVE: To identify consumer expectations with respect to the ED. METHODS: Semi-structured focus groups comprising representatives from a wide range of community groups. Data was analysed using a qualitative analytical approach. RESULTS: The major themes of the groups were communication, triage, waiting area, cultural issues and carers. Consumers expressed the need to be informed about how the ED functions, particularly with regard to the triage process, patient assessment and admissions procedure. Privacy at the triage desk, comfort and safety of the waiting area, provision of facilities for children, cultural awareness of staff, access interpreter services and recognition of the needs of carers were identified as key issues. CONCLUSION: The recognition of consumer needs provides the opportunity for the ED to develop strategies to match patient needs to service delivery.

Adolescent↗

PubMed2003

Detection and identification of pathogens and host DNA in unfed host-seeking Ixodes ricinus L. (Acari: Ixodidae).

In this study, we have developed molecular methods for the identification of reservoir hosts of sylvatic tick-borne zoonoses. The methods are based on the analysis of the blood meal remnant in the tick gut and include detection of pathogens and identification of the host origin of the blood meal. For host identification, a universal primer pair was used to amplify part of the vertebrate 18S rRNA gene followed by reverse line blot hybridization using subgroup-specific probes. Analyses of DNA from whole blood of vertebrates identified the correct subgroup of a broad range of vertebrate species (e.g., Ruminantia, Leporidea, Canidae, Murinae, Arvicolinae, Insectivora, Galliformes, Passeriformes) using probes based on the 18S rDNA sequences. Host DNA in the remnants of larval blood meals was detected in the gut of Ixodes ricinus nymphs maintained under natural conditions up to 9 mo after molting. For pathogen identification, a multiplex polymerase chain reaction was used that targeted parts of the 18S rRNA gene of piroplasm protozoa, the 16S rRNA gene of bacteria, and the intergenic spacer of the Borrelia burgdorferi genospecies complex. The utility of both methods was demonstrated under laboratory conditions by detecting Babesia microti (Franca) and gerbil DNA in 3-mo-old I. ricinus nymphs that had fed on B. microti-infected gerbils as larvae, and under field conditions by analyzing unfed ticks that were collected in a forest. The field study showed that the majority of ticks had fed on ruminants or birds and few on rodents, which is in accord with our knowledge of the fauna in this forest. Few pathogens were detected but the discovery of Borrelia valaisiana and B. burgdorferi s.s. in ticks that had fed on deer and Borrelia afzelii in a tick that had fed on a bird raises questions about the mode of transmission of these spirochetes and possibly about their host specificity.

Animals↗

PubMed2002

High-frequency oscillatory ventilation for acute respiratory distress syndrome in adults: a randomized, controlled trial.

Observational studies of high-frequency oscillatory ventilation in adults with the acute respiratory distress syndrome have demonstrated improvements in oxygenation. We designed a multicenter, randomized, controlled trial comparing the safety and effectiveness of high-frequency oscillatory ventilation with conventional ventilation in adults with acute respiratory distress syndrome; 148 adults with acute respiratory distress syndrome (Pa(O2)/fraction of inspired oxygen <or= 200 mm Hg on 10 or more cm H2O positive end-expiratory pressure) were randomized to high-frequency oscillatory ventilation (n = 75) or conventional ventilation (n = 73). Applied mean airway pressure was significantly higher in the high-frequency oscillation group compared with the conventional ventilation group throughout the first 72 hours (p = 0.0001). The high-frequency oscillation group showed early (less than 16 hours) improvement in Pa(O2)/fraction of inspired oxygen compared with the conventional ventilation group (p = 0.008); however, this difference did not persist beyond 24 hours. Oxygenation index decreased similarly over the first 72 hours in both groups. Thirty-day mortality was 37% in the high-frequency oscillation group and was 52% in the conventional ventilation group (p = 0.102). The percentage of patients alive without mechanical ventilation at Day 30 was 36% and 31% in the high-frequency oscillation and conventional ventilation groups, respectively (p = 0.686). There were no significant differences in hemodynamic variables, oxygenation failure, ventilation failure, barotraumas, or mucus plugging between treatment groups. We conclude that high-frequency oscillation is a safe and effective mode of ventilation for the treatment of acute respiratory distress syndrome in adults.

APACHE↗

PubMed2002

Closed-loop control if the inspired fraction of oxygen in mechanical ventilation.

OBJECTIVE: Supplemental oxygen treatment of patients on mechanical ventilation is crucial in maintaining the patients' oxygen levels in the normal range. The purpose of this study was to evaluate the effectiveness of a closed-loop controller for automatic adjustment of the fraction of inspired oxygen, FIO2. More specifically, the aim of the study was to assess the robustness of the controller in correcting hypoxemia as well as its effectiveness in prevention of hyperoxemia and oxygen toxicity. METHODS: The microprocessor-based feedback control system combines a rapid control algorithm with a proportional-integral-derivative (PID) control procedure to automatically adjust FIO2. The system is designed to prevent hypoxemia by applying a stepwise control procedure in response to rapid declines in arterial oxygen saturation while fine-tuning FIO2 and avoiding hyperoxemia by resuming to the PID control procedure when appropriate. The system includes a sophisticated safeguard unit which is designed to communicate any oxygenation problems or measurement artifacts to the medical personnel while keeping FIO2 at a safe and sufficiently high level. The control system has been tested by using computer simulations as well as animal studies. RESULTS: In response to different disturbances, the arterial oxygen saturation returned to the normal safe range within less than 20 seconds, thereby avoiding any untoward effects of hypoxemia. Under steady state conditions, the variations in arterial oxygen saturation were kept within +/- 3% of the mean value. The controller corrected hypoxemia within seconds while preventing hyperoxemia, rejecting artifacts, and minimizing exposure to high concentrations of oxygen. CONCLUSION: The results of the study attest to the reliability of the proposed closed-loop control scheme for automatic adjustment of FIO2. Further evaluation of the controller will require testing the effectiveness of the system on different patient groups.

Algorithms↗