PubMed Health⌕ Search

Biomedical subjects

R Marsh

Publications and source records attributed to R Marsh.

At least 19 recordsLinked to original sources
PubMed2005

Analysis of the binding of monoclonal and polyclonal antibodies to the glycoproteins of antigenic variants of human respiratory syncytial virus by surface plasmon resonance.

The surface glycoproteins of human respiratory syncytial virus (hRSV), F and G, are the major protective antigens of the virus. Both are antigenically variable, although to different degrees, but the role of antigenic variation in the pathogenesis of hRSV disease has not been fully evaluated. Assessment of immunity to different virus strains is difficult with conventional antibody assays where differing properties of the virus antigens, other than antigenicity, may influence the outcome of the assay. Here, we have developed BIAcore surface plasmon resonance based assays for antibodies to the glycoproteins of hRSV which allow valid comparison of antibody titres against multiple hRSV strains. Glycoproteins from a number of lineages of hRSV sub-group A were captured from lysates of infected cells onto the dextran coated surface of a BIAcore sensor chip via primary monoclonal antibodies (MAbs) to conserved epitopes. For the G glycoprotein, primary MAbs were conjugated directly to the dextran of the sensor chip via free amide groups. For the F glycoprotein, direct conjugation was found to inactivate the MAb and primary MAb was immobilised on the chip via rabbit anti-mouse Fc antibody fragments in an indirect system. Using monoclonal antibodies as secondary MAbs, the glycoproteins in both systems were shown to exhibit a sub-set of conserved and variable epitopes, with some epitopes of both sorts being unavailable, presumably blocked by the primary antibody. Polyclonal anti-hRSV sera raised against viruses of different genotype bound equally to both F and G glycoproteins from homologous and heterologous viruses suggesting that mice immunised systemically with lysates of cells infected with recent isolates of virus do not respond well to genotype specific epitopes.

Animals↗
PubMed2005

Spontaneous regression of subungual keratoacanthoma with reossification of underlying distal lytic phalynx.

A 45-year-old man presented with a rapidly enlarging keratotic lesion of the distal subungual right middle finger. An X-ray of the digit revealed a well-defined cup-shaped lytic lesion of the phalynx underlying the subungual nodule. The lesion resolved spontaneously with reossification of the underlying bony defect. The clinical history and X-ray is consistent with a diagnosis of spontaneously resolving subungual keratoacanthoma.

Fingers↗
PubMed2004

Detection of human respiratory syncytial virus genotype specific antibody responses in infants.

Infection and reinfection of infants with human respiratory syncytial virus (HRSV) occur despite the presence of serum anti-viral glycoprotein antibodies similar to those, which afford protection in animal models of infection. Antigenic variation of the viral glycoproteins between different genotypes of the virus which co-circulate in the population may contribute to the ability of the virus to escape from antibody-mediated protection. In this study, we have investigated whether human infants infected with HRSV produced antibody responses recognising the antigenic differences between different contemporary genotypes of virus. Acute and convalescent sera from 26 infants were analysed for antibody responses to the glycoproteins of the virus isolated from their respiratory tract and to representative viruses of homologous and heterologous genotypes. All infants developed antibodies with similar reactivity for viruses of all contemporary isolates and genotypes when measured in an immunofluorescence assay against unfixed virus infected cells. However, when antibody responses to the individual glycoproteins were measured in a surace plasmon resonance (SPR) assay, although all infants developed genotype cross-reactive antibodies to the F glycoprotein, anti-G antibodies were detectable in only half of the infants and in all cases these were genotype specific. Possession of no or only genotype specific antibodies to the G glycoprotein may contribute to the susceptibility of infants to reinfection. In both assays, reactivity of anti-glycoprotein antibodies with the sub-group A archetypal strain, A2, was markedly lower than with any contemporary virus tested indicating that this strain alone is unsuitable for accurate assessment of infant antibody responses. .

Antibodies, Viral↗
PubMed2003

Therapeutic transcatheter arterial embolization in the management of intractable haemorrhage from pelvic urological malignancies: preliminary experience and long-term follow-up.

OBJECTIVE: To evaluate the feasibility, efficacy and complications of internal iliac artery embolization as a palliative measure in the control of intractable haemorrhage from advanced pelvic urological malignancies. PATIENTS AND METHODS: Six patients (mean age 80 years, range 76-87) with advanced pelvic malignancies (three each with bladder carcinoma and prostate carcinoma) underwent embolization between September 1997 and July 2001, using permanent coils in the anterior division of internal iliac artery bilaterally. RESULTS: All patients had undergone conservative treatment before embolization for a mean of 2 days. The mean requirement for transfusion before embolization was 3.2 units. All patients except one were successfully embolized in a single setting with no complications. Bleeding was successfully controlled in one patient at the second attempt of embolization. There were minor complications, e.g. nausea, vomiting or fever, for a mean of 2 days, responding well to conservative treatment. At a mean follow-up of 22 months, no patient had a recurrence of bleeding. CONCLUSION: Internal iliac artery embolization is a feasible, effective and minimally invasive option in managing advanced pelvic urological malignancies presenting with intractable bleeding; it should be bilateral and permanent.

Adenocarcinoma↗
PubMed2002

Fractal pharmacokinetics of the drug mibefradil in the liver.

We explore the ramifications of the fractal geometry of the key organ for drug elimination, the liver, on pharmacokinetic data analysis. A formalism is developed for the use of a combination of well-stirred Euclidean and fractal compartments in the body. Perturbation analysis is carried out to obtain analytical solutions for the drug concentration time evolution. These results are then fitted to experimental data collected from clinically instrumented dogs [see, A. Skerjanec et al., J. Pharm. Sci. 85, 189 (1995)] using the drug mibefradil. The thus obtained spectral fractal dimension has a range of values that is consistent with the value found in independently performed ultrasound experiments on the liver.

Animals↗
PubMed2002

A rare co-existence of focal xanthogranulomatous pyelonepheritis, angiomyolipoma and renal cysts simulating renal cell carcinoma.

A 70-year-old male presented with left flank pain and history of gross, total painless haematuria of 6 months duration. Investigations revealed a large solid and cystic mass suggestive of renal cell carcinoma in left kidney with possible infiltration of left psoas muscle. Histology of radical nephrectomy showed angiomyolipoma with multiple cysts lined by columnar epithelium suggestive of tuberous sclerosis and focal area of xanthogranulomatous pyelonepheritis. The rare combination of such lesions leading to diagnostic dilemma has not been reported in medical literature to the best of our knowledge.

Aged↗
PubMed2002

Palliative stenting of malignant large bowel obstruction.

OBJECTIVE: Untreated malignant large bowel obstruction is rapidly fatal. Short-term palliation of symptoms can be achieved by formation of a stoma in those patients for whom resection surgery is inappropriate. In the final months of life, a stoma represents a significant burden for both patients and carers. Palliative endoluminal stenting may therefore be an attractive alternative option for this poor prognosis group. In this paper, we examine our experience of palliative endoluminal colonic stenting. PATIENTS: Twenty patients, 11 males and 9 females of median age 81 years were referred for stenting. All had left sided colonic cancers. Ten patients had confirmed metastases on presentation, four had fixed rectal cancers and the remainder had severe comorbidity limiting surgical options. Stents were placed endoscopically using a radiologically controlled 'stent over wire' technique. RESULTS: Stenting successfully relieved the obstruction in 18 of the 20 patients attempted. In one patient the stricture could not be negotiated and the procedure was abandoned. Eleven patients have died of their disease, their median duration of palliation was 50 days (3-152 days). The rest of the patients continue in follow-up and have had 80 days median palliation (14-257 days). One stent-related complication has been observed in a patient who suffered anal pain due to fracture and migration of part of a stent into the low rectum. This complication occurred after 250 days and the distal stent fragment was removed with further symptom relief. CONCLUSION: Carefully selected patients benefit from colonic endoluminal stenting with relief of obstructive symptoms. They may be spared the potential problems associated with palliative stoma formation.

Journal Article↗
PubMed2001

Roman Catholic couples: wrath and religion.

Qualitative methods were used to research the effects of the religious beliefs and practices of ten Roman Catholic couples on the ways in which they managed anger and conflict in their marital relationship. The couples were interviewed separately, twice each, using Grounded Theory techniques in the first, semi-structured interview, and Repertory Grids in the second. Religious beliefs supported a broad range of positions on anger management from self-control through to the thoughtful expression of anger. It is suggested that religious beliefs and practices can be thought of as expanding or restricting "space" by reducing the intensity of anger experienced and by providing an opportunity for reflection which enabled participants to take greater responsibility for their part in conflicts. The relationship with God affected the "space" in the couple relationship by meeting some of the unmet needs of individuals and by detouring anger away from the spouse to God where it was felt to be safely contained. This procedure was used more by wives; their husbands seemed more often to fear and avoid conflicts and the expression of anger. Links were made between the marital relationship and the relationship with God. It was proposed that these systems are both evolving interactively with changes in one resulting in changes in the other. However, there can be a delay before changes in one system can be integrated with conflicting beliefs or practices in the reciprocal system, which may result in ambivalent attitudes toward anger and conflict. Clinical implications and directions for future research were suggested.

Adaptation, Psychological↗
PubMed1998

The navigational feats of green sea turtles migrating from Ascension Island investigated by satellite telemetry.

Previous tagging studies of the movements of green turtles (Chelonia mydas) nesting at Ascension Island have shown that they shuttle between this remote target in the Atlantic Ocean and their feeding grounds on the Brazilian coast, a distance of 2300 km or more. Since a knowledge of sea turtle migration routes might allow inferences on the still unknown navigational mechanisms of marine animals, we tracked the postnesting migration of six green turtle females from Ascension Island to Brazil. Five of them reached the proximity of the easternmost stretch of the Brazilian coast, covering 1777-2342 km in 33-47 days. Their courses were impressively similar for the first 1000 km, with three turtles tracked over different dates following indistinguishable paths for the first 300 km. Only the sixth turtle made some relatively short trips in different directions around Ascension. The tracks show that turtles (i) are able to maintain straight courses over long distances in the open sea; (ii) may perform exploratory movements in different directions; (iii) appropriately correct their course during the journey according to external information; and (iv) initially keep the same direction as the west-south-westerly flowing current, possibly guided by chemical cues.

Animals↗
PubMed1998

Characterization of 101-kDa transglutaminase from Physarum polycephalum and identification of LAV1-2 as substrate.

Plasmodial transglutaminase of Physarum polycephalum was purified by anion exchange and hydrophobic chromatography. Gel filtration and SDS-polyacrylamide gel electrophoresis indicate that it is a monomer of 96-101 kDa. It is Ca2+-dependent, with half-maximal activity at 0. 7 mM Ca2+. Optimal activity occurs at pH 7.5 and at 50 mM KCl. Inactivation by N-ethylmaleimide indicates that it is a thiol enzyme. With N,N-dimethylcasein as substrate, the Km for monodansylcadaverine is 33.9 +/- 1.8 microM. Damage of plasmodia by brief treatment with 15% ethanol activates the transglutaminase, with rapid accumulation of cross-linked proteins unable to enter gels during SDS-polyacrylamide gel electrophoresis. Added monodansylcadaverine is conjugated principally to LAV1-2, a plasmodia-specific 40-kDa protein with four EF-hand sequences believed to bind Ca2+. Actin is seen as an additional substrate only in plasmodial homogenates. Immunoblots show that upon ethanol treatment, a portion of LAV1-2 is modified quickly and shifts to 36 kDa; another portion is cross-linked to itself or other proteins. The modification of LAV1-2 may lead to localized release of Ca2+ and activation of transglutaminase for walling off damaged areas of plasmodia. No significant increase in amount of the transglutaminase occurs during starvation-induced differentiation of plasmodia to form spherules, but a 50% reduction in the amount of total protein leads to a doubling in the specific mass of the TGase. Neither the transglutaminase nor LAV1-2 is found in the ameboid form of the organism.

Actins↗
PubMed1998

Reversibility of scrapie inactivation is enhanced by copper.

The only known difference between the cellular (PrPC) and scrapie-specific (PrPSc) isoforms of the prion protein is conformational. Because disruption of PrPSc structure decreases scrapie infectivity, restoration of the disease-specific conformation should restore infectivity. In this study, disruption of PrPSc (as monitored by the loss of proteinase K resistance) by guanidine hydrochloride (GdnHCl) resulted in decreased infectivity. Upon dilution of the GdnHCl, protease resistance of PrP was restored and infectivity was regained. The addition of copper facilitated restoration of both infectivity and protease resistance of PrP in a subset of samples that did not renature by the simple dilution of the GdnHCl. These data demonstrate that loss of scrapie infectivity can be a reversible process and that copper can enhance this restoration of proteinase K resistance and infectivity.

Animals↗
PubMed1998

The use of 3D conformal radiotherapy (3D CRT) to spare the cochlea in patients with medulloblastoma.

PURPOSE: Radiation therapy in combination with cis-platinum chemotherapy is associated with ototoxicity due to destruction of cochlear hair cells. This is a significant problem, especially in pediatric patients, because it may lead to difficulties with communication, speech, language, and development of learning skills. The use of 3D conformal radiotherapy (3D CRT) may be useful in sparing auditory structures. This paper discusses a technique using 3D CRT to spare the cochlea in patients with medulloblastoma. METHODS AND MATERIALS: Five pediatric patients with medulloblastoma were planned using 3D CRT. All had MRI and CT obtained specifically for treatment planning. Multiple structures were contoured, including the cochlea and posterior fossa, and conformal beams designed in beam's eye view and dose distribution analysis were edited to provide 3D dose coverage to the target while sparing the inner ear. Patients received 36 Gy to the craniospinal axis followed by an 18-20 Gy boost to the posterior fossa. RESULTS: A 3D CRT cochlear sparing technique was designed, using an axial pair of posterior oblique fields to treat the posterior fossa while sparing the cochlea for all patients in this analysis. Dose-volume information, obtained from 3D calculations, demonstrates that the average dose received by the cochlea was 65% of the prescribed dose using the cochlear sparing plan, as compared to 101% using standard opposed-lateral beams. Both plans delivered > or = 100% of the prescribed dose to the posterior fossa. CONCLUSION: 3D CRT allows for cochlear sparing in the treatment of medulloblastoma. Further follow-up is necessary to determine the long-term benefit in these patients.

Cerebellar Neoplasms↗
PubMed1998

Cloning and characterization of Physarum polycephalum tectonins. Homologues of Limulus lectin L-6.

Previous investigators have reported the presence of two dominant proteins, tectonin I (25 kDa) and tectonin II (39 kDa), in nuclei and nuclear matrix from plasmodia of Physarum polycephalum. We demonstrate, by a modification of the nuclear isolation protocol and by protease sensitivity, that the tectonins are not nuclear proteins but rather are located on the exterior surface of the plasma membrane. We report the sequences of cDNAs of tectonins I and II, which encode 217 and 353 amino acids, respectively. Tectonin I is homologous to the C-terminal two-thirds of tectonin II. Both proteins contain six tandem repeats that are each 33-37 amino acids in length and define a new consensus sequence. Homologous repeats are found in L-6, a bacterial lipopolysaccharide-binding lectin from horseshoe crab hemocytes. The repetitive sequences of the tectonins and L-6 are reminiscent of the WD repeats of the beta-subunit of G proteins, suggesting that they form beta-propeller domains. Tectonin II has an additional N-terminal domain that includes a 47-residue sequence highly similar to the galactoside-binding sequence of the B-chain of ricin. The tectonins may be lectins that function as part of a transmembrane signaling complex during phagocytosis.

Amino Acid Sequence↗
PubMed1998

The Ottawa telehealth project.

OBJECTIVE: To examine the telehealth system as a means of improving access to cardiac consultations and specialized health services in remote areas of Ontario. METHODS: The University of Ottawa Heart Institute has set up a telehealth test program, Healthcare and Education Access for Remote Residents by Telecommunications (HEARRT), in collaboration with industry and the provincial and federal government, as well as several remote clinical test sites. The program makes off-site cardiology consultations possible. History taking and physical examinations are conducted by video and electronic stethoscope. Laboratory results and echocardiograms are transmitted by document camera and VCR. The technology is being tested in both stable outpatient and emergency situations. Various telecommunications bandwidths and encoding systems are being evaluated, including satellite and terrestrial-based asynchronous transfer-mode circuits. Patient satisfaction and cost-effectiveness are also being assessed. RESULTS: Bandwidths from as low as 384 kbps using H.320 encoders to 40 Mbps using digital transport of NTSC video signals have been evaluated. Although lower bandwidths are sufficient for sending echocardiographic and electrocardiogram data, bandwidths with transport speeds of 4 to 6 Mbps appear necessary to capture the nuances of the cardiac physical examination. A preliminary satisfaction survey of 19 patients noted that all felt that they could communicate effectively with the cardiologist by video, and each had confidence in the advice offered. None reported that he or she would rather have traveled to the doctor in person. Initial and projected examination of the costs suggested that telehealth will effectively reduce overall health care spending while decreasing travel expenses for rural patients. CONCLUSION: Telehealth technology is sufficiently sophisticated to allow off-site cardiology assessments. Preliminary results suggest there is a sound business case for the implementation of telehealth technology to meet the needs of remote residents in northern Ontario. Working closely with government and industry, we will develop a marketing and commercialization plan to support the use of this technology throughout Ontario and expand application to patient education and continuing medical education.

Cardiology↗
PubMed1997

Low grade glioma in intractable epilepsy: lesionectomy versus epilepsy surgery.

In approximately 30% of patients with intractable partial epilepsy, an intra-axial cerebral lesion is the aetiology of the seizure disorder. Lesions adjacent to mesiotemporal structures often result in secondary epileptogenicity in the same region. The authors present 22 cases of low-grade gliomas associated with intractable epilepsy. In 15 cases the location was temporal (8 extra-hippocampal and 7 with invasion of the amygdalo-hippocampus), 7 cases were extratemporal in eloquent areas. The eight extra-hippocampal tumours were originally treated with lesionectomy. The seizure outcome was class 1 in only 4 cases, the remaining 4 were class 4 according to Engel's classification. The 4 cases with class 4 outcome required additional temporal lobectomy associated with amygdalo-hippocampectomy for seizure control. The 2 cases with associated hippocampal atrophy at MRI after lobectomy had outcome class 1. The 2 cases without hippocampal atrophy at MRI presented outcome class 2. The 7 cases with invasion of amygdala and hippocampus were treated with selective lesionectomy+amygdalo-hippocampectomy. In all these cases convergence of focal structural abnormality, ictal onset of epileptiform EEG abnormality and interictal epileptiform EEG abnormality provided powerful evidence of focal epileptogenicity. All these patients had a favourable epilepsy outcome (class 1-2). In the seven extratemporal cases the first step was lesionectomy. In 1 case located in the parietal region intraoperative mapping was required. 5 had class 1 outcome, one case had outcome class 2 and one case had an outcome class 4. The last patient required a second step operation with intraoperative strip and deep electrode monitoring that led subsequently to a frontal lobectomy. This patient is seizure free 2 years after surgery. There was no perioperative mortality and post-operative morbidity was 3/22. This study indicates that lesionectomy may be the first step procedure if the structural abnormality is localized to extra-temporal eloquent cortex and concordance is documented. Patients may subsequently be candidates for a cortical resection as a second step procedure if the lesionectomy does not provide an adequate reduction in seizure tendency. Since MRI identified hippocampal atrophy was predictive in this study of an unsatisfactory seizure outcome after lesionectomy, MRI defined dual pathologies consisting of a temporal lesion plus hippocampal atrophy necessitate temporal lobectomy+amygdalo-hippocampectomy. In patients with negative MRI findings of hippocampal atrophy and temporal lobe lesions, intraoperative electrocorticography and deep electrode monitoring are indicated for planning the surgical strategy.

Adolescent↗
PubMed1997

Design and analysis of an immobilization and repositioning system for treatment of neck malignancies.

Recent applications of three-dimensional treatment planning using non-coplanar treatment angles have demonstrated the potential for improved target dose homogeneity as well as normal tissue sparing for tissues in the neck, notably the parotid gland. Implementation of these highly targeted treatments requires a reliable method for accurate daily reproduction of the treatment position, as patient setup error could lead to significant decreases in target dose and normal tissue sparing. Additionally, the constrained geometry of this anatomic site requires the freedom to deliver treatments from any arbitrary angle in order to maximize the expected benefit. In order to permit accurate setup while maintaining access from most angles, a hybrid immobilization system has been developed, consisting of a custom thermoplastic mask with attachment to a foam cradle shaped to the back of the patient. To evaluate the accuracy of this system, setup errors were measured in 20 patients treated while immobilized with the positioning aide. Two orthogonal film sets consisting of anterior and lateral projections, one set taken at the beginning of treatment and a second 4-5 weeks into therapy, were compared to baseline simulator films or digitally reconstructed radiographs. The average setup deviation in any direction ranged from 0.8 to 1.4 mm and the largest single setup error observed was 4.5 mm. For the film sets taken late in treatment only 3 of the 20 patients required setup adjustment followed by repeat filming to obtain an acceptable film pair. This system has been implemented for routine clinical use since March 1995.

Equipment Design↗