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Biomedical subjects

R Myers

Publications and source records attributed to R Myers.

At least 73 records · Page 4Linked to original sources
PubMed1995

A clinical and pharmacological study of 5-fluorouracil, leucovorin and interferon alfa in advanced colorectal cancer.

Modulation of 5-fluorouracil (FUra) using leucovorin (LV) is a standard treatment approach in patients with metastatic colorectal cancer. Modulation of FUra with interferon alfa has also shown some promise. Laboratory data have demonstrated increased cytotoxicity when FUra is combined with both LV and interferon. The current study examined the effects of double modulation of FUra using LV and interferon. Patients with measurable advanced colorectal cancer received bolus FUra 375 mg/m2 plus LV 20 mg/m2 daily for 5 days, repeated every 28 days. Recombinant human interferon alfa-2a, 3 million IU/m2 subcutaneously, was given daily on the days of chemotherapy then three times weekly. There was one complete response and nine partial responses (10/41) seen for an overall response rate of 24% (95% CI 12.0-40.0%). Overall, 70% of patients experienced one or more episodes of nonhematologic toxicity of grade 3 or more. Weight loss was common, with a mean decrease of 2.9 kg over the first two months (P < 0.0001). Improvements in tumor-related symptoms were balanced by increased fatigue and a deterioration in body weight and performance status. There was no evidence of progressive changes in FUra metabolism from interferon usage.

Adult↗
PubMed1995

Cross-tolerance between ethanol and neurotensin in mice selectively bred for ethanol sensitivity.

Neurotensin (NT), a tridecapeptide that satisfies criteria as a neurotransmitter, mimics many actions of ethanol, and evidence indicates that some of the acute effects of ethanol are mediated in part by NT. Recent studies have shown that chronic ethanol treatment produced a downregulation of NT receptors in mesolimbic brain regions of long sleep (LS) mice and that reduced NT binding capacity was associated with acquisition and decay of tolerance to ethanol-induced locomotor inhibition and hypothermia in these mice. The present study was undertaken to determine whether cross-tolerance develops between NT and ethanol and whether chronic NT infusion produces NT receptor downregulation. Animals chronically treated with ethanol were tolerant to NT-mediated locomotor inhibition at a dose of 1.8 pmol NT, ICV, and were tolerant to NT-induced hypothermia at 1.8 and 6.0 pmol NT. Following repeated injections or continuous infusion of NT ICV, LS mice showed tolerance to both NT- and ethanol-induced hypothermia and locomotor inhibition. Indeed, ethanol doses that are hypnotic in control mice (2.8 g/kg) were not effective in abolishing locomotor activity following chronic NT administration. Results with chronic saline infusion ICV indicate that stress alters sensitivity to ethanol-induced hypothermia. Chronic infusion of NT ICV produced a region-specific downregulation of high-affinity NT receptors in the striatum. The results demonstrate that cross-tolerance develops between NT and ethanol, and further support a role for neurotensinergic systems in the actions of ethanol.

Alcoholic Intoxication↗
PubMed1995

The design and physical characteristics of a small animal positron emission tomograph.

A small diameter positron emission tomography, designed specifically for small animal studies, was constructed from existing, commercially available, bismuth germanate (BGO) detectors and electronics. The scanner consists of 16 BGO detector blocks arranged to give a tomograph with a diameter of 115 mm and an axial field of view (FOV) of 50 mm. Each block is cut to produce eight (axial) by seven (radial) individual detector elements. The absence of interplane septa enables the acquisition of 3D data sets consisting of 64 sinograms. A 2D data set of 15 sinograms, consisting of eight direct and seven adjacent cross planes, can be extracted from the 3D data set. Images are reconstructed from the 2D sinograms using a conventional filtered backprojection algorithm. Two methods of normalization were investigated, based on either a rotating 68Ge rod source, or a uniform 68Ge plane source, with a uniform cylindrical 18F phantom. Attenuation of the emitted photons was estimated using a rotating 68Ge rod source. The transaxial resolution of the tomograph was measured as 2.3 mm full width at half maximum (FWHM) and 5.6 mm full width at tenth maximum (FWTM) at the centre of the FOV, degrading to 6.6 mm (radial) and 4.4 mm (tangential) FWHM and 10.4 mm (radial) and 14.4 mm (tangential) FWTM at 40.0 mm from the centre of the FOV. The axial slice width was 4.3 mm FWHM, 10.3 mm FWTM at the centre of the transaxial field of view and 4.4 mm FWHM, 10.6 mm FWTM at 20.0 mm from the centre of the FOV. A scatter fraction of 31.0% was measured at 250-850 keV, for an 18F line source centred in a 60 mm diameter, water-filled phantom, reducing to 20.4% and 13.8% as the lower energy discrimination was increased to 380 keV and 450 keV, respectively. The count rate performance was measured using a noise equivalent count rate method, and the linearity of the dead time correction was confirmed over the count rates encountered during routine scanning. In 2D mode, the absolute sensitivity of the tomograph was measured as 9948 counts s-1 MBq-1 at 250-850 keV, 8284 counts s-1 MBq-1 at 380-850 keV and 6280 counts s-1 MBq-1 at 450-850 keV.

Animals↗
PubMed1995

Mast cell tumour destruction in dogs by hypotonic solution.

Distilled water was studied as an hypoosmotic oncolysis agent to prevent mast cell tumour (MCT) recurrence following surgical excision. The results from 118 MCTs excised in 74 dogs were: surgery alone, a recurrence rate of 52.6 per cent (10/19); and surgery followed by distilled water injections into the wound, a 26.2 per cent (26/99) recurrence rate. All of 10 small MCTs (0.03 to 0.25 cm3) injected with distilled water in situ with no surgery, regressed. The present data suggest that distilled water should be considered as an adjunct to surgery for canine MCTs.

Animals↗
PubMed1995

A phase II trial of prednisone, oral etoposide, and novantrone (PEN) as initial treatment of non-Hodgkin's lymphoma in elderly patients.

This phase II study was designed to improve the outcome of elderly patients with advanced aggressive non-Hodgkin's lymphomas (NHL's) by employing a novel chemotherapy regimen PEN (prednisone, oral etoposide and mitoxantrone), as initial treatment. Between July 1991 and September 1993, 43 patients (14 male, 29 female) aged 66-82 years (median 74) received 1-8 (median 4) courses of PEN (total 192) q28 days (prednisone 50 mg od x 14 days, oral etoposide 50 mg od x 14 days and mitoxantrone 8 mg/m2 i.v. day 1) in the ambulatory setting. Pathologies of patients' tumors classified by the Working Formulation (WF) included C = 4, D = 2, E = 1, F = 7, G = 25, H = 4. Eighteen patients (42%) had stage IV, 15 (35%) stage III, 9 (21%) stage II and 1 (2%) stage I disease. Nineteen patients (44%) had B symptoms, 7 (16%) primarily extranodal disease and 15 (35%) bone marrow involvement. Patients with congestive heart failure, current anti-failure medication or pretreatment Muga left ventricular ejection fraction (LVEF) of < 45% (median pretreatment 60%) were excluded from PEN. After a median follow-up of 8.5 months (range 1-30), 14 of 33 evaluable patients (42%) have achieved CR of their disease for 8+ months (range 4-19) and 6 (18%) PR for 6+ months (range 5-10), giving an overall response rate of 61%. Ten (30%) patients did not respond to PEN and 10 were not evaluable for response. Response to PEN was not predicted by any pretreatment characteristic.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1995

Functional MR imaging correlations with positron emission tomography. Initial experience using a cognitive activation paradigm on verbal working memory.

The most established functional MR imaging technique for activation studies relies on a T2*-weighted contrast. This signal arises primarily from a blood oxygen level dependent contrast generated by an imbalance between the increase in regional cerebral blood flow and oxygen metabolism in the brain during activation. As predicted by theory, the percentage signal changes observed in functional MR imaging experiments are considerably smaller than those detected by positron emission tomography, which directly measures regional cerebral blood flow as an index of neuronal activity. Cross-validation of functional MR imaging with an established technique such as positron emission tomography would be extremely valuable for determining the correlation between functional MR image signal change and regional cerebral blood flow change and for assessing the sensitivity of the functional MR imaging technique. The authors report on such cross-validation experiments in three subjects challenged with a verbal working memory task and show that satisfactory replication of positron emission tomography results with functional MR imaging was achieved in two subjects. Limitations owing to magnetic field strength used and single-slice sampling may have contributed to the lack of signal detection in the case where no reliable activation pattern was detected with functional MR imaging.

Adult↗
PubMed1994

Effects of acute and chronic ethanol administration on neurotensinergic systems.

A summary of pharmacogenetic studies designed to test the hypothesis that NT receptors might mediate or regulate some of the actions of ethanol is presented. Indeed, there are significant genetic correlations between ethanol-induced locomotor activation and high-affinity NT receptor densities in the FC. The results suggest that further studies are needed to determine the role of NT receptors in the FC and MPFC in regulating locomotor activity. In other studies, chronic ethanol treatment, under conditions that produced tolerance to ethanol and caused NT receptor downregulation in the NA and VMB, caused tolerance to locomotor inhibitory effects of centrally administered NT and blunted the effects of intra-VTA NT on dopamine metabolism in the NA and CP. The results show a relationship between NT receptor densities and pharmacological effects of ethanol.

Alcoholism↗
PubMed1994

Artifacts due to stimulus correlated motion in functional imaging of the brain.

To assess the effect of stimulus correlated motion on the appearance of functional magnetic resonance images, conventional visual and motor protocols were each performed by four normal volunteers and an image co-registration technique was used to retrospectively monitor subject motion. In three studies synthetic data sets were constructed from single baseline images using the positional information obtained from the co-registration procedure. Cumulative difference images were then created from both the synthetic and functional image sets. Stimulus correlated motion was detected in all eight studies and the synthetic cumulative difference images showed striking similarities to the equivalent functional images in each case.

Adult↗
PubMed1994

Rejection after pediatric liver transplantation is not the limiting factor to survival.

Liver transplantation became a very successful therapy when cyclosporin A was introduced as an immunosuppressive agent. In an effort to evaluate the contribution of difficult or uncontrolled allograft rejection to mortality, the authors determined the most important factors that limited survival after liver transplantation. Eighty-two children received a total of 94 liver transplants from January 1987 to the present. Patients' records were reviewed for complications that contributed to morbidity and mortality and to assess which complications were preventable. Twelve patients died (15%), nine within 6 weeks of liver transplantation. The chief contributing cause of death was hepatic artery thrombosis (one patient), brain death after liver transplantation for fulminant hepatic failure (two patients), primary allograft nonfunction or dysfunction (two patients), allograft rejection (three patients), or other problems (four patients). Overall, hepatic artery thrombosis occurred in 3.1%, allograft rejection in 57%, fulminant hepatic failure in 7%, and donor organ dysfunction in 7%. Allograft rejection contributed directly to the cause of death in three children (4%). The authors conclude that few deaths after pediatric liver transplantation are caused by failure of immunosuppression. A high survival rate can be achieved after transplantation by eliminating the correctable complications that most frequently occur in the early postoperative period.

Adolescent↗
PubMed1993

Characterization of Ustilago maydis DNA binding protein one (UBP1).

The DNA binding properties of a protein from the lower eukaryote Ustilago maydis have been characterized. Using both filter binding and gel retention assays, we demonstrate that this protein, termed UBP1 (Ustilago binding protein one), binds preferentially to DNA molecules lacking chain interruptions. The introduction of DNA breaks by a restriction enzyme or a purified nuclease, from Ustilago maydis, causes the dissociation of protein-DNA complexes. UBP1 stimulates the relaxation of negatively supercoiled DNA, mediated by Ustilago type I topoisomerase, through a mechanism most likely involving the association of UBP1 with the DNA rather than with the topoisomerase. The prebinding of UBP1 to DNA templates, subsequently assembled into minichromosomes, results in the development of a disorganized nucleosomal array. Possible roles for UBP1 in processes that involve changes in DNA topology, such as chromatin assembly, are discussed.

DNA↗
PubMed1993

The role of positron emission tomography in the assessment of human neurotransplantation.

Positron emission tomography (PET) using tracers of the dopaminergic system has been used to measure striatal function in a small number of parkinsonian patients undergoing neurotransplantation procedures. Some postoperative scans have shown an unequivocal increase in presynaptic dopaminergic function at the graft site, providing evidence of graft survival independent of clinical assessment. Combined PET and magnetic resonance imaging (MRI) images provide the facility to explore the relationship between graft placement, survival and clinical efficacy.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1993

Trinucleotide repeat length instability and age of onset in Huntington's disease.

The initial observation of an expanded and unstable trinucleotide repeat in the Huntington's disease gene has now been confirmed and extended in 150 independent Huntington's disease families. HD chromosomes contained 37-86 repeat units, whereas normal chromosomes displayed 11-34 repeats. The HD repeat length was inversely correlated with the age of onset of the disorder. The HD repeat was unstable in more than 80% of meiotic transmissions showing both increases and decreases in size with the largest increases occurring in paternal transmissions. The targeting of spermatogenesis as a particular source of repeat instability is reflected in the repeat distribution of HD sperm DNA. The analysis of the length and instability of individual repeats in members of these families has profound implications for presymptomatic diagnosis.

Adult↗
PubMed1993

Adaptation of tibial nerve myelinated fibre parameters to reduced limb length caused by irradiation.

Irradiation of a rat hind limb at 15 days of age caused marked shortening of the limb, with a consequent reduction in nerve length. The tibial nerves of the irradiated limbs were examined qualitatively and quantitatively, and compared with the unirradiated nerve. There was no evidence of fibre degeneration and only very occasional myelin abnormalities. Myelinated fibre numbers were very slightly reduced, possibly due to irradiation effects on small myelinated fibres. Internodal lengths were reduced in proportion to limb length. Mean axon diameters were slightly increased, and myelin sheath thickness reduced. This experimental model provides a new method of altering nerve fibre parameters without surgical intervention.

Adaptation, Physiological↗