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Biomedical subjects

J Wren

Publications and source records attributed to J Wren.

14 recordsLinked to original sources
PubMed2006

Genetic associations between cathepsin D exon 2 C-->T polymorphism and Alzheimer's disease, and pathological correlations with genotype.

Genetic variations represent major risk factors for Alzheimer's disease (AD). While familial early onset AD is associated with mutations in the amyloid precursor protein and presenilin genes, only the e4 allele of the apolipoprotein E (APOE) gene has so far been established as a genetic risk factor for late onset familial and sporadic AD. It has been suggested that the C-->T (224Ala-->Val) transition within exon 2 of the cathepsin D gene (CTSD) might represent a risk factor for late onset AD. The objective of this study was to investigate whether possession of the CTSD exon 2 T allele increases the risk of developing AD, and to determine whether this modulates the amyloid pathology of the disease in conjunction with, or independent of, the APOE e4 allele. Blood samples were obtained from 412 patients with possible or probable AD and brain tissues from a further 148 patients with AD confirmed by postmortem examination. CTSD and APOE genotyping were performed by PCR on DNA extracted from blood, or from frontal cortex or cerebellum in the postmortem cases. Pathological measures of amyloid beta protein (Abeta), as plaque Abeta40 and Abeta42(3) load and degree of cerebral amyloid angiopathy were made by image analysis or semiquantitative rating, respectively. CTSD genotype frequencies in AD were not significantly different from those in control subjects, nor did these differ between cases of early or late onset AD or between younger and older controls. There was no gene interaction between the CTSD T and APOE e4 alleles. The amount of plaque Abeta40 was greater in patients carrying the CTSD T allele than in non-carriers, and in patients bearing APOE e4 allele compared with non-carriers. Possession of both these alleles acted synergistically to increase levels of plaque Abeta40, especially in those individuals who were homozygous for the APOE e4 allele. Possession of the CTSD T allele had no effect on plaque Abeta42(3) load or degree of CAA. Possession of the CTSD T allele does not increase the risk of developing AD per se, but has a modulating effect on the pathogenesis of the disorder by increasing, in concert with the APOE e4 allele, the amount of Abeta deposited as senile plaques in the brain in the form of Abeta40.

Aged↗
PubMed2004

Evaluation of three temperature measurement methods used during microwave thermotherapy of prostatic enlargement.

Three temperature measurement methods used during microwave thermotherapy of prostatic enlargement are analysed and evaluated using a phantom model. A commercial transurethral microwave thermotherapy (TUMT) system that uses a radiometric thermometer for temperature control was used to heat the phantom. The transient temperature distribution was obtained by using both fibreoptic (which is considered as gold standard) and thermocouple measurements. Both methods are subject to potential measurement errors caused by electromagnetic and/or thermal interference. The error sources are analysed and the measurement methods evaluated. The radiometric temperature and especially its relation to the transient temperature distribution was evaluated based on the fibreoptic and thermocouple measurements. These measurements in principle gave equivalent temperature distributions, and thermal interference was concluded to be the largest source of measurement error. The radiometric measurement method gave qualitative rather than quantitative readings of the temperature, and an underestimation of more than 10 degrees C was obtained for some parts of the heated area. The area that gives most of the radiometric signal was relatively close to the catheter in contrast to previously published results.

Fiber Optic Technology↗
PubMed2003

Examining child restraint use and barriers to their use: lessons from a pilot study.

OBJECTIVE: To determine the suitability of four research methods to measure the rate of child restraint device (CRD) use and incorrect use in New Zealand and obtain data on barriers to CRD use. DESIGN AND SETTING: To assess the rates of CRD use among vehicles carrying children 8 years of age and under, two methods were piloted-namely, an unobtrusive observational survey and a short interview and close inspection. A self administered questionnaire and focus group interviews were also piloted to assess CRD use, reasons for use and non-use, and to obtain information on barriers to their use. Respondents to all methods except the focus groups were approached in supermarket car park sites at randomly selected times. Focus groups were established with parents identified through early childhood organisations. All methods were assessed on criteria related to efficiency, representativeness, and ability to obtain the necessary data. RESULTS: The observational survey provided a simple method for identifying rates of CRD use, while the self administered questionnaire obtained data on demographic characteristics and reported the installation and use/non-use of CRDs. The interview/inspection addressed all the questions of both the above methods and enabled incorrect CRD use to be examined. The focus groups provided the most meaningful information of all methods on barriers to CRD use. DISCUSSION: and conclusion: Advantages and limitations of these methods are discussed and some refinements of the original instruments are proposed. The interview/inspection and focus group methods were identified as being more appropriate for efficiently obtaining reliable data on CRD use and identification of barriers to CRD use.

Accidents, Traffic↗
PubMed2001

Analysis of temperature measurement for monitoring radio-frequency brain lesioning.

During ablative neurosurgery of movement disorders, for instance therapy of Parkinson's disease, temperature monitoring is crucial. This study aims at a quantitative comparison of measurement deviations between the maximum temperature located outside the lesioning electrode and two possible thermocouple locations inside the electrode. In order to obtain the detailed temperature field necessary for the analysis, four finite element models associated with different surroundings and with different power supplies are studied. The results from the simulations show that both the power level and the power density as well as the surrounding medium affect the temperature measurement and the temperature field in general. Since the maximum temperature is located outside the electrode there will always be a deviation in time and level between the measured and the maximum temperature. The deviation is usually 2-7 s and 3-12 degrees C, depending on, for example, the thermocouple location and surrounding medium. Therefore, not only the measured temperature but also the relation between measured and maximum temperature must be accounted for during therapy and device design.

Catheter Ablation↗
PubMed2000

Treatment of separation anxiety in dogs with clomipramine: results from a prospective, randomized, double-blind, placebo-controlled, parallel-group, multicenter clinical trial.

The efficacy and tolerability of clomipramine in the treatment of separation anxiety in dogs was tested in a prospective, randomized, double-blind, placebo-controlled, parallel-group, international multicenter clinical trial. For a diagnosis of separation anxiety, dogs had to exhibit at least one of the following signs in the absence of their owner: destruction, defecation, urination and/or vocalization, as well as the behaviour suggestive of "hyper-attachment" to their owner. A total of 95 dogs were randomized to receive one of the three treatments for 2-3 months: "standard-dose" clomipramine (1 to <2 mg/kg, PO, q. 12 h); "low-dose" clomipramine (0.5 to <1 mg/kg, PO, q. 12 h); and placebo (PO, q. 12 h). All dogs received behavioural therapy. Dogs were examined at four time points (days 0, 28, 56 and 84) after the initiation of therapy. Improvement in each dog's behaviour at days 28, 56 and 84 was evaluated in comparison to its behaviour at day 0.The results showed that, compared to placebo, dogs receiving standard-dose clomipramine were rated improved at least three times faster for the signs destruction, defecation and urination. At most time points, more dogs in the standard-dose clomipramine group were rated improved for the signs destruction, defecation and urination, and in an owner's global assessment of the dog's overall behaviour (p<0.05 at certain time points). However, there were no statistically significant differences at any time point between the standard dose and the placebo groups in the sign vocalization. The low-dose clomipramine group produced no statistically significant effect when compared with placebo. Mild and transient vomiting was noted as a side effect of clomipramine in a small number of dogs.It is concluded that addition of standard-dose (1 to <2 mg/kg, PO, q. 12 h) clomipramine to conventional behavioural therapy for 2-3 months ameliorated the signs of separation anxiety in dogs.

Journal Article↗
PubMed2000

Prompt Optical Observations of Gamma-Ray Bursts.

The Robotic Optical Transient Search Experiment (ROTSE) seeks to measure simultaneous and early afterglow optical emission from gamma-ray bursts (GRBs). A search for optical counterparts to six GRBs with localization errors of 1 deg2 or better produced no detections. The earliest limiting sensitivity is mROTSE>13.1 at 10.85 s (5 s exposure) after the gamma-ray rise, and the best limit is mROTSE>16.0 at 62 minutes (897 s exposure). These are the most stringent limits obtained for the GRB optical counterpart brightness in the first hour after the burst. Consideration of the gamma-ray fluence and peak flux for these bursts and for GRB 990123 indicates that there is not a strong positive correlation between optical flux and gamma-ray emission.

Journal Article↗
PubMed1999

A comparison between in vitro studies of protein lesions generated by brain electrodes and finite element model simulations.

The aim of this study was to develop a finite element model for simulation of the thermal characteristics of brain electrodes and to compare its performances with an in vitro experimental albumin model. Ten lesions were created in albumin using a monopolar electrode connected to a Leksell Neuro Generator and a computer-assisted video system was used to determine the size of the generated lesions. A finite element model was set up of the in vitro experiments using the same thermal properties. With a very simple heat source applied to the finite element model in the proximity of the upper part of the tip, a good agreement (no deviations in width and distance from tip but a deviation in length of -1.6 mm) with the in vitro experiments (width 4.6 +/- 0.1 mm and length 7.4 +/- 0.1 mm) was achieved when comparing the outline of the lesion. In addition, a gelatinous albumin-model was set up and compared to computer simulations resulting in deviations in width of -0.4 mm, length of -2.2 mm and distance from the tip of -0.1 mm. Hence, the utilisation of finite element model simulations may be a useful complement to in-vitro experiments.

Albumins↗
PubMed1998

Computerized polymorphic marker identification: experimental validation and a predicted human polymorphism catalog.

A computational system for the prediction of polymorphic loci directly and efficiently from human genomic sequence was developed and verified. A suite of programs, collectively called POMPOUS (polymorphic marker prediction of ubiquitous simple sequences) detects tandem repeats ranging from dinucleotides up to 250 mers, scores them according to predicted level of polymorphism, and designs appropriate flanking primers for PCR amplification. This approach was validated on an approximately 750-kilobase region of human chromosome 3p21.3, involved in lung and breast carcinoma homozygous deletions. Target DNA from 36 paired B lymphoblastoid and lung cancer lines was amplified and allelotyped for 33 loci predicted by POMPOUS to be variable in repeat size. We found that among those 36 predominately Caucasian individuals 22 of the 33 (67%) predicted loci were polymorphic with an average heterozygosity of 0.42. Allele loss in this region was found in 27/36 (75%) of the tumor lines using these markers. POMPOUS provides the genetic researcher with an additional tool for the rapid and efficient identification of polymorphic markers, and through a World Wide Web site, investigators can use POMPOUS to identify polymorphic markers for their research. A catalog of 13,261 potential polymorphic markers and associated primer sets has been created from the analysis of 141,779,504 base pairs of human genomic sequence in GenBank. This data is available on our Web site (pompous.swmed.edu) and will be updated periodically as GenBank is expanded and algorithm accuracy is improved.

Computer Communication Networks↗
PubMed1997

A cost-effectiveness study of changing medical practice in early pregnancy.

Until recent years women with symptoms consistent with miscarriage either referred themselves or were referred by their doctors to the local Accident and Emergency (A&E) department. This generally resulted in admission to a gynaecological ward and delayed treatment. Examines the costs and benefits of an Early Pregnancy Assessment Clinic (EPAC), at a teaching hospital in North East England, to deal with the complications in the first trimester. The data show clear benefits together with cost savings. There is an unambiguous policy recommendation to implement the proposed clinic. Examines the delivery of service provision and the impact on referral patterns to the A&E department. Raises the issue of care provision at the margin. Finally, shows the results of an evaluative survey of the clinic from returns of a questionnaire sent to and completed by local general practitioners.

Abortion, Spontaneous↗
PubMed1992

Pediatric bacterial meningitis: is prior antibiotic therapy associated with an altered clinical presentation?

STUDY HYPOTHESIS: The clinical features of children treated with oral antibiotics before the diagnosis of bacterial meningitis differ from those who receive no antibiotics. DESIGN: Retrospective case series. SETTING: University medical center. PARTICIPANTS: Two hundred fifty-eight children 24 months old or younger with bacterial meningitis hospitalized during a 12-year period. Eighty-three children were treated with oral antibiotics before the diagnosis of meningitis, and 175 children were not. INTERVENTIONS: None. METHODS: The emergency department chart and hospital records were reviewed for presenting demographic, historical, physical examination, and laboratory features. Clinical features of pretreated and untreated patients were compared. RESULTS: Pretreated children demonstrated less frequent temperature of 38.3 C or higher, altered mental status and a longer duration of symptoms before diagnosis, with more frequent vomiting; ear, nose, and throat infections; and physician visits in the week before detection of meningitis (P less than .05 for all comparisons). There was no difference in incidence of upper respiratory symptoms, seizures, nuchal rigidity, Kernig's and Brudzinski's signs, focal neurologic signs, mortality, and length of hospitalization between groups. CONCLUSION: Clinical features of children who have taken antibiotics before the detection of meningitis differ significantly from those who have not undergone antibiotic therapy. Physicians should be aware of these differences when evaluating young children on antibiotics for the possibility of meningitis.

Anti-Bacterial Agents↗
PubMed1987

Gastroesophageal reflux in children. Clinical profile, course and outcome with active therapy in 126 cases.

A clinical profile and the course and outcome with therapy of 126 infants and children with gastroesophageal reflux (GER), diagnosed at a median age of 2.5 months and followed for 1.5 to 3.5 years is presented. Features included repeated regurgitation or rumination (99%), signs suggesting esophageal pain (49%, excessive crying "colic," sleep disturbance, Sutcliffe-Sandifer syndrome, respiratory symptoms 42%), failure to thrive (18%), and minor hematemesis (18%). Feeding problems and maternal distress were common, associated with child abuse in four cases. Therapy was initially conservative (posture, thickening of feeds, antacids, bethanechol), augmented by cimetidine in those with proven esophagitis (n = 34, 0.27%). Most (81%) were symptom-free by 18 months of age (55% by 10 months of age); 17 percent had fundoplication with good results; 2 percent have persisting symptoms beyond 2 years of age (1% failed surgery). No deaths were recorded. Surgery was performed for recurrent apneas/aspiration (6%), refractory esophagitis or stricture (5%), and failed medical management (7%). Esophagitis was a significant determinant to outcome, and the importance of selective early endoscopy is emphasized. GER is a cause of considerable morbidity in infants but, with active therapy, is self-limiting in the majority. Certain distinctive clinical signs indicate those patients who require detailed investigation and to whom more aggressive therapeutic efforts should be directed.

Child↗
PubMedDate not supplied

A hybrid equation for simulation of perfused tissue during thermal treatment.

Bio-heat equations (BHEs) are necessary for predicting tissue temperature during thermal treatment. For some applications, however, existing BHEs describe the convective heat transfer by the blood perfusion in an unsatisfactory way. The two most frequently used equations, the BHE of Pennes and the k(eff) equation, use for instance either a heat sink or an increased thermal conductivity in order to account for the blood perfusion. Both these methods introduce modelling inaccuracies when applied to an ordinary tissue continuum with a variety of vessel sizes. In this study, a hybrid equation that includes both an increased thermal conductivity and a heat sink is proposed. The equation relies on the different thermal characteristics associated with small, intermediate and large sized vessels together with the possibilities of modelling these vessels using an effective thermal conductivity in combination with a heat sink. The relative importance of these two terms is accounted for by a coefficient beta. For beta = 0 and beta = 1, the hybrid equation coincides with the BHE of Pennes and the k(eff) equation, respectively. The hybrid equation is used here in order to simulate temperature fields for two tissue models. The temperature field is greatly affected by beta, and the effect is dependent on, e.g. the boundary conditions and the power supply. Since the BHE of Pennes and the k(eff) equation are included in the hybrid equation, this equation can also be useful for evaluation of the included equations. Both these heat transfer modes are included in the proposed equation, which enables implementation in standard thermal simulation programmes.

Animals↗
PubMedDate not supplied

A cost-effectiveness study of changing medical practice in early pregnancy.

Until recent years women with symptoms consistent with miscarriage either referred themselves or were referred by their doctors to the local Accident and Emergency (A&E) department. This generally resulted in admission to a gynaecological ward and delayed treatment. This paper examines the costs and benefits of an early pregnancy assessment clinic (EPAC), at a teaching hospital in North East England, to deal with the complications in the first trimester. The data show clear benefits together with cost savings. There is an unambiguous policy recommendation to implement the proposed clinic. The paper examines the delivery of service provision and the impact on referral patterns to the A&E department and raises the issue of care provision at the margin. Finally, the authors show the results of an evaluative survey of the clinic from returns of a questionnaire sent to and completed by local general practitioners.

Abortion, Spontaneous↗