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Biomedical subjects

C Walsh

Publications and source records attributed to C Walsh.

At least 37 records · Page 2Linked to original sources

Hypercoagulable states in renal transplant candidates: impact of anticoagulation upon incidence of renal allograft thrombosis.

INTRODUCTION: Although multiple studies of demographic variables have been associated with allograft thrombosis, these results are not routinely reproducible. Are ESRD patients with hypercoagulable states (HCS) (antithrombin III deficiency, protein S or C deficiency, activated protein C resistance, and anticardiolipin antibodies) at predictably greater risk for allograft thrombosis? METHODS: Between 1996 and 1999, all renal transplant candidates were screened for hypercoagulability risk factors [HRF] (multiple arteriovenous access thromboses, prior deep vein thrombosis, prior allograft thrombosis, collagen vascular disease, multiple miscarriages, diabetes, autoimmune disease, and Fabry's disease). HRF(+) candidates were then tested for HCS status. We administered preemptive posttransplant i.v. Heparin in HCS(+) patients and observed the impact of this intervention upon the incidence of allograft thrombosis. We compared demographic data and incidence of allograft thrombosis in an historic control (346 patients transplanted between June 31, 1992, and March 5, 1996) not tested for HCS and a study cohort (502 patients transplanted between March 6, 1996, and June 31, 1999) prospectively screened for HRF. HRF(+) patients who were HCS(+) in the study cohort received i.v. heparin immediately after transplant and p.o. warfarin as outpatients. RESULTS: Demographic characteristics previously implicated in allograft thrombosis were equivalently distributed in both cohorts with the exceptions that more living-donor transplants (33.1% vs. 15.3%) were performed in study cohort, CIT>24 hr occurred in more control patients (37.3% vs. 22.1%) and more study patients (16.7% vs. 0%) received tacrolimus. Hypercoagulable states were found upon reevaluating five of seven controls (71.4%), who lost prior allografts to thrombosis. Hypercoagulable states were prospectively detected in 10 study patients with hypercoagulability risk factors. Most (9 of 10) study patients receiving anticoagulation have achieved long-term allograft function. Study group allograft thrombosis incidence was reduced (1.59% vs. 4.05%). Hypercoagulable states were demonstrated in most episodes of allograft thrombosis. Control patients who lost prior allografts to thrombosis were anticoagulated after retransplantation and 100% achieved long-term allograft function. CONCLUSIONS: Long-term allograft function has been achieved in 90% of study patients when prophylactically anticoagulating study patients with hypercoagulable states. A 2.6-fold reduction in the expected incidence of allograft thrombosis was observed in anticoagulated patients with hypercoagulable states.

Adult↗

Nontoxic doses of suramin enhance activity of paclitaxel against lung metastases.

We recently reported that acidic (aFGF) and basic (bFGF) fibroblast growth factors confer a broad spectrum chemoresistance in solid tumors, and that suramin, an inhibitor of multiple growth factors including aFGF and bFGF, enhanced the in vitro antitumor activity of several anticancer drugs including paclitaxel (Song, S., et al., Proc. Natl. Acad. Sci. USA, 97: 8658-8663, 2000). The present study investigated in vitro and in vivo interaction between paclitaxel and suramin, using human PC3-LN cells which, upon i.v. injection into immunodeficient mice, yielded lung metastases in 100% of animals. In in vitro studies, conditioned medium (CM) obtained from histocultures of rat lung metastases induced a 3-fold resistance. The addition of suramin had no effect in the absence of CM but reversed the CM-induced resistance; calculations based on the IC(50) values indicate a complete reversal in the presence of <20 microM suramin. Analysis by the combination index method indicates a synergistic interaction between paclitaxel and suramin. In in vivo studies, animals with well-established lung metastases (at least five nodules of 1 mm in diameter) were treated i.v. with paclitaxel (15 mg/kg) and suramin (10 mg/kg) administered twice weekly for 3 weeks. Single-drug therapy with paclitaxel or suramin did not reduce body weight. Suramin alone had no antitumor activity. Paclitaxel alone reduced the tumor size by approximately 75%, reduced the density of nonapoptotic cells by approximately 70% in residual tumors, and enhanced the fraction of apoptotic cells by approximately 3-fold. The addition of suramin to paclitaxel therapy enhanced the antitumor effect, resulting in an additional 5-fold reduction of tumor size, an additional 9-fold reduction of the density of nonapoptotic cells, and an additional 30% increase in the apoptotic cell fraction. These data indicate significant enhancement of the efficacy of paclitaxel by suramin and support the use of nontoxic doses of suramin with paclitaxel in the treatment of lung cancer.

Animals↗

Retrospective assessment of historic radon concentrations in Norwegian dwellings by measuring glass implanted Po-210--an international field intercomparison.

The first Norwegian study of historic radon concentrations in 17 dwellings in the high radon areas in Norway has been conducted as part of an international field intercomparison during 1998. The retrospective radon concentration is estimated via measurements of Po-210, the long-lived decay product of Rn-222 implanted in glass surfaces of objects like pictures, mirrors, cabinet-glass, etc. the method called 'surface trap'. Three different surface trap techniques to assess the implanted Po-210 activity and two different procedures to estimate retro radon from Po-210 data were used. The Po-210 and the retrospectively estimated radon results agree reasonably well over a wide range of concentrations. Historic radon concentrations were also estimated from analysis of a smaller number of 'volume trap' samples (pieces of spongy materials), and the results compared to those from 'surface traps'. The retro radon results correlate with contemporary radon results with a correlation coefficient of 0.877. To evaluate uncertainty in Po-210 measurements due to varying position on the glass a study of spatial homogeneity of three sample glasses was conducted and variations between 12% and 18% were found.

Air Pollution, Indoor↗

Correlation of 210Po implanted in glass with radon gas exposure: sensitivity analysis of critical parameters using a Monte-Carlo approach.

In recent years, 210Po implanted in glass artefacts has been used as an indicator of the mean radon gas concentration in dwellings in the past. Glass artefacts have been selected in many dwellings and the alpha-recoil implanted 210Po concentration has been measured using various techniques. Some of these retrospective techniques use a model to estimate the retrospective radon gas on the basis of this surface 210Po activity. The accumulation of 210Po on glass surfaces is determined by the deposition regime over the exposure period. The 210Po activity is determined not only by the radon progeny deposition velocities, but by other room parameters such as ventilation rate, aerosol conditions and the surface to volume ratio of the room. Up to now in using room models, a nominal or 'base-case' scenario is used, i.e. a single value is chosen for each input parameter. In this paper a Monte-Carlo analysis is presented in which a probability distribution for each parameter is chosen, based on measurements quoted in the literature. A 210Po surface activity is calculated using a single value drawn from each of the parameter distributions using a pseudo-random number generator. This process is repeated n times (up to 20,000), producing n independent scenarios with corresponding 210Po values. This process permits a sensitivity analysis to be carried out to see the effect of changes in inputs on the model output.

Aerosols↗

Integrated natural radiation exposure studies in stable Yugoslav rural communities.

The results of field investigations of natural radiation exposures of the general population in two stable rural communities in Yugoslavia are presented. The principal emphasis was on exposures to contemporary indoor radon, but measurements of external penetrating radiation absorbed dose rates in air were carried out in the majority of cases. In addition, in a limited number of dwellings, measurements of thoron gas concentrations were made. By means of making a series of sequential 3-month radon measurements, both seasonal variations and annual average radon levels in the dwellings were determined. Using passive alpha track detectors, individual radon and thoron indoor concentrations as high as 9591 Bq m(-3) and 709 Bq m(-3), respectively, were detected while absorbed dose rates in air in the dwellings as high as 430 nGy h(-1) were recorded. On the basis of these different types of measurements, assessments could be made of the integrated natural radiation exposures being received by the populations. In addition to contemporary radon measurements, retrospective radon exposure assessments in most of the dwellings were made on the basis of measurements of 210Po concentrations in both surface (glass) traps and in volume (porous materials) traps. A description is given of the sampling strategies and protocols used in this field work. It is shown that at least one stable rural community receiving high natural radiation exposures, has been clearly identified and plans for future health investigations of the population there are outlined.

Air Pollutants, Radioactive↗

Familiality of symptom dimensions in schizophrenia.

The division of schizophrenic symptoms into three core dimensions - psychomotor poverty, reality distortion, and disorganisation - is well established. When factor analytic studies have included affective symptoms they have identified two additional dimensions - manic and depressive. Whether these five dimensions represent underlying psychopathology of a genetic or environmental aetiology remains unclear. The aims of this study were to perform factor analysis of symptoms in a group of familial schizophrenic patients and to investigate the familiality of the symptom dimensions identified, and their relationship to clinical characteristics. Symptoms were recorded, using the Operational Criteria Checklist for Psychotic Illness, for 155 Caucasian subjects with an RDC diagnosis of schizophrenia, schizoaffective disorder, or psychosis of unknown origin, from 61 families multiply affected with schizophrenia. Factor analysis indicated five symptom dimensions: depressive, manic, reality distortion, disorganisation, and psychomotor poverty. The psychomotor poverty, disorganisation, and manic dimensions were shown to be familial. Psychomotor poverty, disorganisation, and reality distortion were all associated with deterioration from premorbid functioning and chronic course of the disorder. In addition, psychomotor poverty was significantly related to poor premorbid functioning, as well as to single marital status and unemployment at onset. Disorganisation was significantly related to single marital status and unemployment at onset. The familiality of the psychomotor poverty, disorganisation, and manic dimensions supports their use in the delineation of homogeneous subsets for genetic studies.

Adult↗

Enabling the chemistry of life.

Enzymes are the subset of proteins that catalyse the chemistry of life, transforming both macromolecular substrates and small molecules. The precise three-dimensional architecture of enzymes permits almost unerring selectivity in physical and chemical steps to impose remarkable rate accelerations and specificity in product-determining reactions. Many enzymes are members of families that carry out related chemical transformations and offer opportunities for directed in vitro evolution, to tailor catalytic properties to particular functions.

Biological Evolution↗

Cell cultures and retroviral particles from a tumor of a moray eel.

Until recently, fish cell culture primarily has been useful only in the propagation and study of epidemic viruses significant to the fishing industry. Such fish cell lines derived were developed by appropriating classical techniques of mammalian cell culture, with serum as the major growth supplement. Using an approach in which culture medium is formulated in a cell-type-specific manner with minimal serum and a variety of synergistic supplements, several fish cell lines have been derived that may serve multiple uses. We established cell lines from a potentially tumorous skin lesion of a green moray eel (Gymnothorax funebris) and control tissues, and identified putative retroviral particles in the medium from the tumor cells that are not present in medium from cultures of normal cells from the same eel. The relationship between the virus and the cause of the tumor is not clear, but the genomic structure of this virus should provide useful information in understanding the evolution of retroviruses in general.

Journal Article↗

Hemodynamic performance of the 21-mm Sorin Bicarbon mechanical aortic prostheses using dobutamine Doppler echocardiography.

BACKGROUND: Small-sized mechanical aortic prostheses are commonly associated with generation of high transvalvular gradients, particularly in patients with large body surface area, and can result in patient-prosthesis mismatch. This study evaluates the hemodynamic performance of 21-mm Sorin Bicarbon bileaflet mechanical prostheses using dobutamine stress echocardiography. METHODS: Fourteen patients (7 women; mean age, 63+/-8 years) who had undergone aortic valve replacement with a 21-mm Sorin Bicarbon bileaflet mechanical prosthesis 32.4+/-5.1 months previously were studied. After a resting Doppler echocardiogram, a dobutamine infusion was started at a rate of 5 microg x kg(-1) x min(-1) and increased to 30 microg x kg(-1) x min(-1) at 15-minute intervals. Pulsed- and continuous-wave Doppler echocardiographic studies were performed at rest and at the end of each increment of dobutamine. Both peak and mean velocity and pressure gradient across the prostheses were measured, and effective orifice area, discharge coefficient, and performance index were calculated. RESULTS: Dobutamine stress increased heart rate and cardiac output by 83% and 81%, respectively (both p < 0.0001), and mean transvalvular gradient increased from 15.6+/-5.5 mm Hg at rest to 35.4+/-11.9 mm Hg at maximum stress (p < 0.0001). Although the indexed effective orifice area was significantly lower in patients with a larger body surface area, this was not associated with any significant pressure gradient. The performance index of this valve was unchanged throughout the study. Regression analyses demonstrated that the mean transvalvular gradient at maximum stress was independent of all variables except resting gradient (p = 0.05). Body surface area had no association with the changes in cardiac output, transvalvular gradient at maximum stress, and effective orifice area. CONCLUSIONS: These data show that the 21-mm Sorin Bicarbon bileaflet mechanical prosthesis offers an excellent hemodynamic performance with full utilization of its available orifice when implanted in the aortic position. The lack of significant transvalvular gradient in patients with a larger body surface area suggests that patient-prosthesis mismatch is highly unlikely when this prosthesis is used.

Adult↗

Field studies on equine influenza vaccination regimes in thoroughbred foals and yearlings.

SUMMARY: The purpose of these studies was to examine the response of Thoroughbred foals and yearlings to different influenza vaccines and vaccination regimes. The horses' antibody levels against haemagglutinin, an established correlate of protection were measured by haemagglutination inhibition. The first study investigated the extent to which maternal antibodies interfered with the humoral response to a subunit vaccine. The findings suggest that repeat vaccination in the face of maternal antibodies may induce tolerance as defined by serological testing. The second study compared the immune response elicited by a subunit immune stimulating complex (ISCOM) vaccine, an inactivated whole virus vaccine and the same product containing equine herpesviruses and equine reoviruses in addition to equine influenza virus. The monovalent vaccine induced a significantly better response than the ISCOM or the multivalent vaccine. The final study demonstrated that the inclusion of an additional booster vaccination, between the second and third vaccination recommended by the vaccine manufacturers and required under the rules of racing in certain countries, is of benefit to young horses. Since these studies were performed, several of the vaccines have been updated with more recent virus strains in line with WHO/OIE recommendations. However, the general principles investigated in the studies remain relevant to these vaccines.

Animals↗

Chlamydia trachomatis infection in women: bad news, good news, and next steps in prevention.

Chlamydia trachomatis causes largely asymptomatic infections that can lead to pelvic inflammatory disease, infertility, ectopic pregnancy, and chronic pelvic pain. Screening women routinely is critical to controlling the epidemic of this disease. Testing innovations now make diagnosis easier, and simple treatment regimens may improve compliance with medications and increase cure rates, but testing and treatment must be coupled with improved screening efforts and effective partner services. Ongoing research may point to other interventions that will increase our success in fighting chlamydial infections.

Chlamydia Infections↗

A mechanical model of cerebral circulation during sustained acceleration.

BACKGROUND: High positive Gz may result in inadequate blood supply to the brain even if the central blood pressures are maintained at normal levels. We use a mechanical model to simulate the influence of sustained +Gz on cerebral circulation. METHODS: The model consists of ascending and descending tubes representing the extracranial arteries and veins, respectively, and a cranium in which the tubes are enclosed within water-filled rigid container to account for the skull and the cerebrospinal fluid. A thick-walled Tygon tube and a thin-walled surgical drain tube were used for the arteries and veins, respectively. The flow of water was driven by a pressure difference at the model ends, and the change in the gravitational vector was accomplished by tilting the model. RESULTS: The flow drops with an increasing tilt angle only if the descending arm collapses. However, when the pressures at the model ends are sufficiently elevated, the flow is restored to normal value. In the cranium model, the pressure in the water surrounding the tubes always stays close to the pressure in the surgical tubing. Consequently, the tubes in the container do not collapse. CONCLUSIONS: The principal effect of Gz on flow through the model occurs via changes in the resistance of the collapsed descending arm. As the pressures at the model ends are elevated, the descending arm opens and the flow increases. The pressure in the cranium model is dictated by the condition that the volume of the container has to remain constant.

Acceleration↗

No association of an insertion/deletion polymorphism in the angiotensin I converting enzyme gene with bipolar or unipolar affective disorders.

A recent Japanese study on the angiotensin I converting enzyme gene (ACE) insertion/deletion polymorphism reported that both the D allele (P < 0.02) and the DD genotype (P < 0.002) were significantly more frequent in affective disorder cases than in controls [Arinami et al., 1996: Biol Psychiatry 40:1122-1127]. A replication study was performed by using 157 bipolar I affective disorder cases, 169 major depressive disorder cases, and 313 controls. No significant association with this polymorphism was found in either disorder or in a combined affective disorder group. These results do not support the ACE gene having a major role in the etiology of either bipolar or unipolar affective disorders. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:733-735, 2000.

Alleles↗

Molecular mechanisms that confer antibacterial drug resistance.

Antibiotics--compounds that are literally 'against life'--are typically antibacterial drugs, interfering with some structure or process that is essential to bacterial growth or survival without harm to the eukaryotic host harbouring the infecting bacteria. We live in an era when antibiotic resistance has spread at an alarming rate and when dire predictions concerning the lack of effective antibacterial drugs occur with increasing frequency. In this context it is apposite to ask a few simple questions about these life-saving molecules. What are antibiotics? Where do they come from? How do they work? Why do they stop being effective? How do we find new antibiotics? And can we slow down the development of antibiotic-resistant superbugs?

Anti-Bacterial Agents↗

Serial volumetric intravascular ultrasound analysis of the efficacy of beta irradiation in preventing recurrent in-stent restenosis.

We compared postintervention and follow-up intravascular ultrasound findings of 25 patients from the beta-Washington Radiation for InStent restenosis Trial (in which all patients received radiation) and 75 patients from the Washington Radiation for InStent restenosis Trial (in which patients were randomized to gamma irradiation). The decrease in lumen volume was similar for beta versus gamma and less in both gamma versus placebo and beta versus placebo; the increase in intimal hyperplasia volume was similar for beta versus gamma and greater in both beta versus placebo and gamma versus placebo.

Beta Particles↗

Genetic associations with clinical characteristics in bipolar affective disorder and recurrent unipolar depressive disorder.

Genetic factors may be associated with disease subtype as well as susceptibility. We have therefore typed polymorphisms at the serotonin transporter, dopamine receptor, tryptophan hydroxylase, tyrosine hydoxylase, and monoamine oxidase A (MAOA) loci in 139 unipolar and 131 bipolar patients and investigated associations with gender, number of episodes, age of onset, history of psychotic symptoms, history of suicidal behavior, and history of substance abuse. In bipolar subjects, the promoter variable number tandem repeat (VNTR) allele 132 of MAOA was associated with history of suicide attempts, P = 0.029, particularly in females, P = 0.006. The Fnu4HI allele 1 of MAOA was also associated with history of suicide attempts in females, P = 0.0162. The serotonin transporter promoter allele 2 was associated with increasing number of manic episodes, P = 0.02, and history of psychotic symptoms, P = 0.0243. One significant association was found in the unipolar group: dopamine D2 receptor promoter allele 2 with history of psychotic symptoms, P = 0. 0165. We have tested multiple loci for a variety of different clinical variables and performed 228 tests of significance in total. It is possible that these preliminary findings are type 1 errors, because one would expect 11 of the 228 tests to reach a nominal significance level of P < 0.05 by chance alone if all the tests were independent. The associations with the MAOA and serotonin transporter loci are consistent with previous data suggesting associations with susceptibility to bipolar affective disorder. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:36-42, 2000

Base Sequence↗