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Biomedical subjects

M Robinson

Publications and source records attributed to M Robinson.

At least 163 records · Page 9Linked to original sources
PubMed1996

Effective maintenance treatment of reflux esophagitis with low-dose lansoprazole. A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To compare the efficacy of two doses of lansoprazole with that of placebo in preventing recurrence of erosive esophagitis in a 12-month period. DESIGN: Randomized, double-blind, parallel, placebo-controlled trial. SETTING: 25 U.S. medical centers. PATIENTS: 173 patients with documented healing of erosive esophagitis after 8 weeks of acid-suppressing therapy. INTERVENTION: Lansoprazole, 15 mg or 30 mg, or placebo once daily for as long as 12 months. MEASUREMENTS: Endoscopy and symptom evaluation after 1, 2, 3, 6, 9, and 12 months of treatment. Endoscopy was also done whenever symptoms suggested erosive changes. RESULTS: Lansoprazole was significantly superior to placebo in maintaining healing and preventing recurrence of symptoms. By month 1, 45% of placebo recipients remained healed compared with more than 90% of patients in either lansoprazole group. By month 12, only 24% of placebo recipients remained healed compared with 79% of patients receiving 15 mg of lansoprazole and 90% of patients receiving 30 mg of lansoprazole. During the same period, 35% of placebo recipients remained asymptomatic compared with 72% of recipients of 15 mg of lansoprazole and 67% of recipients of 30 mg of lansoprazole. The 15-mg and 30-mg lansoprazole doses did not differ significantly in maintaining healing and controlling symptoms. Follow-up after recurrence of erosion indicated that during the 12 months, 35% of placebo recipients and 2% of lansoprazole recipients had three or more recurrences. CONCLUSION: Lansoprazole effectively maintains healing of erosive esophagitis. The 15-mg and 30-mg lansoprazole doses did not differ significantly for use as maintenance treatment.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1996

Distinct 3p21.3 deletions in lung cancer and identification of a new human semaphorin.

Loss of chromosome 3p is a critical event in the pathogenesis of lung cancer. Overlapping homozygous 3p21.3 deletions in lung cancer cell lines involving GNAI2 were characterized and found to involve a region of genomic instability. A new widely expressed Semaphorin, H.SemaIV, was isolated from the GNAI2 deletion region. Reduced H.SemaIV expression allowed identification of additional cell lines with submicroscopic or larger deletions of the locus which occurred in a heterogeneous manner. We also demonstrate the presence of a distinct 3p21.3 homozygous deletion region, adjacent to the DNA mismatch repair gene, hMLH1, and identified deletions in direct tumors. This appears to represent one of the first demonstrations of homozygous deletions affecting 3p in direct lung tumors.

Amino Acid Sequence↗
PubMed1996

UBC researcher's back-pain studies focus on space travel.

Researchers at the University of British Columbia have been studying back pain that develops in astronauts in space. Their findings not only may help astronauts cope with future space travel, but also lead to new treatments for Earth-bound patients who experience back pain.

Aerospace Medicine↗
PubMed1996

Ki-ras mutations in adenomas: a characteristic of cancer-bearing colorectal mucosa.

Activating mutations in the Ki-ras2 oncogene are frequently observed in sporadic colorectal adenomas and their incidence is reported to rise in large and tubulovillous adenomas to values close to those in carcinomas. This study shows that this property is a feature of adenomas growing in large bowel that has already demonstrated its propensity to engender malignant tumours: i.e., bowel in which there is a synchronous carcinoma. Adenomas from cancer-free bowel do not share this high incidence of Ki-ras mutations. This difference in mutation incidence between adenomas from cancer-free and cancer-bearing patients does not appear to derive from sampling bias relative to adenoma size, site, or patient age, nor is it found in another gene (APC) known to be of importance in adenoma formation. Large, dysplastic adenomas from cancer-bearing bowel, however, are particularly liable to carry Ki-ras mutations when they arise in patients over 70 years old. The observations suggest that the role of Ki-ras mutations may be more subtle than merely enhancing adenoma growth. Adenoma cells of cancer-prone individuals may suffer more mutational events than those in persons selected as cancer-free.

Adenoma↗
PubMed1996

Evaluation of the in vivo genotoxic potential of three carcinogenic aromatic amines using the Big Blue transgenic mouse mutation assay.

Three genotoxic mouse carcinogens, 4-chloro-o-phenylenediamine (4-C-o-PDA), 2-nitro-p-phenylenediamine (2-N-p-PDA), and 2,4-diaminotoluene (2,4-DAT), were tested in the Big Blue transgenic mouse mutation assay. Each experiment consisted of a vehicle control group with ten Big Blue C57BL/6 mice, five of either sex, and an equally sized group treated with a high dose of the test chemical. In addition, four animals were treated with the vehicle and six animals with the test compound for the measurement of bromodeoxyuridine (BrdU) incorporation to determine cellular proliferation. Prior to the mutagenicity experiments, the maximally tolerated dose of each compound was determined using nontransgenic C57BL/6 mice. Based on these results the doses used in the main study were 200 mg/kg/day for 4-C-o-PDA, 150 mg/kg/ day for 2-N-p-PDA, and 80 mg/kg/day for 2,4-DAT. Animals were treated for 10 days over a 2 week period and were killed 10 days after the ast treatment. In an additional experiment with 2,4-DAT, animals were killed 28 days after treatment. Since all three chemicals are liver carcinogens in the mouse, the DNA of the liver was analyzed using the standard procedures for the Big Blue assay. Hepatocyte proliferation was assessed by immunohistochemical detection of proliferating cell nuclear antigen (PCNA) and, in some studies, by measuring BrdU incorporation. 4-C-o-PDA and 2-N-p-PDA did not induce an increase in PCNA expression when measured 10 days after the last treatment. There was no increase in BrdU incorporation immediately after treatment with 4-C-o-PDA or with 2,4-DAT. However, 10 days after the last treatment with 2,4-DAT, a strong mitogenic effect was found with both techniques, i.e., in the PCNA and BrdU assays. 4-C-o-PDA, a liver carcinogen in both genders of mice, induced a small, statistically significant increase of the mutant frequencies in females. No increase was found in males. 2-N-p-PDA, which has been reported to induce liver tumors only in females, was found positive in males and was clearly negative in females. 2,4-DAT, a liver carcinogen in female mice, was positive in females and negative in males when the animals were killed 10 days after the last treatment. After an expression time of 28 days, 2,4-DAT induced a statistically significant increase in both sexes. The effect in females was marginally stronger than after 10 days' expression time and almost identical to the effect observed in males under these test conditions. In conclusion, the experiments showed that the Big Blue assay detects the genotoxicity of the three carcinogenic monocyclic aromatic amines tested. However, it seems that the sex specificity of the carcinogenic effects of these compounds is not reflected by the mutagenicity data in Big Blue mice.

Animals↗
PubMed1996

Expression of E-selectin and E-selectin ligands in human liver inflammation.

Lymphocyte recruitment to tissue is regulated by homing molecules expressed on subsets of leukocytes that bind to endothelial adhesion molecules termed addressins in target tissues. The addressins and homing molecules involved in recruiting lymphocytes to inflamed human liver are not known. E-selectin, which acts as an addressin for a subset of skin-infiltrating T cells that express a distinct E-selectin ligand called the cutaneous lymphocyte antigen (CLA), can be detected on endothelium in inflammatory liver diseases suggesting it might also act as an addressin for liver-infiltrating lymphocytes. To determine whether E-selectin does play such a role we looked for concomitant expression of E-selectin on hepatic endothelium and E-selectin ligands on infiltrating lymphocytes in liver sections from patients with primary biliary cirrhosis (PBC), acute allograft rejection, alcoholic liver disease, and normal liver. E-selectin was detected on vascular endothelium in association with lymphocytic infiltrates in all three liver diseases but not on normal endothelium. However, less that 10% of infiltrating lymphocytes expressed the only known lymphocyte E-selectin ligand, CLA. We used E-selectin chimeric fusion proteins to probe for novel E-selectin ligands on liver-infiltrating lymphocytes; however, less than 10% of lymphocytes had t he ability to bind the fusion proteins. Thus, E-selectin is unlikely to act as an addressin for liver-infiltrating lymphocytes, suggesting that other molecules are involved in lymphocyte recruitment to the liver. Despite the lack of binding to lymphocytes other structures in the liver expressed CLA and bound the E-selectin fusion proteins. Inflamed, but not normal, intrahepatic bile ducts expressed CLA and bound E-selectin, suggesting that they express activation dependent carbohydrate binding receptors. Furthermore, Kupffer cells did not express CLA but bound to both E-selectin fusion proteins, suggesting that they express potentially novel E-selectin ligands.

Antibodies, Monoclonal↗
PubMed1996

Paracrine interactions of BDNF involving NGF-dependent embryonic sensory neurons.

The expression of BDNF mRNA by a proportion of embryonic dorsal root ganglion neurons has led to the proposal that BDNF acts by an autocrine loop on these neurons. To clarify the role of BDNF expression in developing sensory neurons, we measured the level of BDNF mRNA in purified populations of cranial sensory neurons that depend on either NGF or BDNF for survival. When neuronal death is taking place, the highest levels of BDNF mRNA were detected in NGF-dependent cutaneous sensory neurons. BDNF mRNA was expressed at lower levels in BDNF-dependent cutaneous sensory neurons and was undetectable in BDNF-dependent proprioceptive neurons. In coculture, NGF-dependent neurons promoted the survival of BDNF-dependent neurons by the production and release of BDNF. Depolarizing levels of KCl increased the expression of BDNF mRNA in cultured sensory neurons and this effect was partially inhibited by calcium channel antagonists. Our results suggest that during the phase of naturally occurring neuronal death, BDNF acts by a paracrine mechanism in sensory neurons and that BDNF expression is regulated by neural activity.

Animals↗
PubMed1996

Tissue distribution of 2-(2-nitro-4-trifluoromethylbenzoyl)cyclohexane-1-3-dione (NTBC): effect on enzymes involved in tyrosine catabolism and relevance to ocular toxicity in the rat.

Administration of a single oral dose of 2-(2-nitro-4-trifluoromethylbenzoyl)cyclohexane-1,3-dione (NTBC) to rats produced a marked tyrosinemia in the plasma and aqueous humor. The tyrosinemia was both time- and dose-dependent with the duration being more marked at the higher doses. The dose-response curve was very steep with a single dose of 1.5 micromol NTBC/kg (0.5 mg/kg) and above producing maximal concentrations of tyrosine in plasma of about 2500 nmol/ml and in aqueous humor of about 3500-4000 nmol/ml at 24 hr after dosing. Analysis of the key hepatic enzymes involved in tyrosine catabolism showed that 4-hydroxyphenylpyruvate dioxygenase (HPPD) was markedly inhibited soon after dosing at either 0.3 or 30 micromol/kg (0.1 or 10 mg/kg) NTBC and that the activity recovered very slowly. In response to the tyrosinemia, the activity of tyrosine aminotransferase (TAT) in the liver was induced about twofold, while the activity of homogentisic acid oxidase (HGO) was not affected. Daily oral administration of NTBC for 6 weeks induced lesions to the cornea of the eye, with a dose of 0.3 micromol/kg/day producing about a 38% incidence and a higher dose of 30 micromol/kg/day a 75% incidence. Administration of a single oral dose of [14C]NTBC at either 0.3 or 30 micromol/kg led to selective retention of radiolabel in the liver and to a lesser extent in the kidneys and the Harderian gland. Concentrations of radioactivity in the liver and kidneys remained constant over 4 days and after the lower NTBC dose were about 2 nmol/g wet wt and 0.9 nmol/g wet wt, respectively. Subcellular fractionation of the liver showed that the majority of the radiolabel, >90%, was associated reversibly with the cytosol fraction. No retention of radiolabel was detected in the cornea, the site of toxicity. Our studies indicate that NTBC binds to protein in rat liver cytosol, inhibits the hepatic cytosolic enzyme HPPD, and causes a marked and sustained tyrosinemia. We suggest that this marked and sustained ocular tyrosinemia produced by NTBC in the rat is responsible for the corneal lesions since similar corneal lesions are produced by feeding rats a high tyrosine diet.

4-Hydroxyphenylpyruvate Dioxygenase↗
PubMed1996

Simultaneous emission and transmission measurements as an adjunct to dynamic planar gamma camera studies.

Anatomical imaging provides useful information which complements functional imaging performed using a gamma camera. We have previously used transmission measurements in single-photon emission tomography acquired simultaneously with the emission scan using either a plane flood source or a moving line source for attenuation and scatter correction. This approach is equally applicable in planar imaging and provides useful information to assist in detecting patient motion and in defining regions of interest in dynamic studies. We have adapted a moving transmission line source to acquire dynamic geometric mean measurements in the study of the mucociliary clearance of inhaled technetium-99m labelled colloids with a single-headed rotating gamma camera. The line source makes a return pass for each emission acquisition frame (alternating anterior/posterior views), each pass being initiated by a signal from the gamma camera. The result is a dynamic sequence of emission and transmission measurements obtained from a single acquisition. In this application transmission measurements are used to define the lung outline for clearance determination and to check for subject movement throughout the duration of the study.

Gamma Cameras↗
PubMed1996

An analysis of the normal ranges of lymphocyte subpopulations in children aged 5-13 years.

UNLABELLED: Peripheral blood lymphocytes subsets were examined in 233 healthy school children aged 4.9-13.7 years at the time of examination. Lymphocyte subsets were characterized according to the following cluster of differentiation (CD) numbers: CD2, CD4, CD8 and CD19 and quantified according to both their absolute number and as a percentage of total lymphocytes. For the purpose of analysis, the LMS (lambda, mu, sigma) method was utilized, with a 3%-97% confidence interval. Smoothing of the generated curves, was by multiple regression analysis, using the least squares method. The results of these analyses indicate distinct trends as a child ages, both in absolute numbers and in the percentage of each cell type. CONCLUSION: We characterized lymphocyte subsets in children aged 4.8-13.7 years. These data should prove of considerable value to pediatricians dealing with patients with known or suspected immunological problems, and ought to be used in place of the commonly used, but inappropriate, adult lymphocyte subset ranges.

Adolescent↗
PubMed1996

A potential clinical method for calculating transmural left ventricular filling pressure during positive end-expiratory pressure ventilation: an intraoperative study in humans.

OBJECTIVES: This study sought to investigate whether right atrial pressure could be used to estimate pericardial pressure during positive end-expiratory pressure (PEEP). BACKGROUND: Because of elevated intrathoracic pressure during PEEP, pulmonary capillary wedge pressure may not accurately reflect left ventricular preload. An estimate of pericardial pressure during PEEP would allow assessment of transmural filling pressure. METHODS: In eight patients, at the start of cardiac surgery, pericardial and pleural pressures were recorded by balloon transducers placed over the anterolateral left ventricular wall. We also recorded intravascular pressures and left ventricular short-axis area by transesophageal echocardiography. RESULTS: A stepwise increase in PEEP from 0 to 15 cm H2O caused a linear increase in pleural pressure from 0.3 +/- 0.6 (mean +/- SEM) to 6.1 +/- 0.8 mm Hg (p < 0.01). Pericardial pressure increased from 2.3 +/- 0.5 to 5.9 +/- 0.6 mm Hg (p < 0.01). The correlation between right atrial (Pra) and pericardial pressure (Pperic) was good: Pra = 0.85 x Pperic + 1.8, r = 0.77. The correlation between changes in right atrial pressure and in pericardial pressure was better: delta Pra = 0.96 x delta Pperic -0.2, r = 0.97. Pulmonary capillary wedge pressure increased with PEEP (p < 0.05), whereas left ventricular area decreased (p < 0.05). However, there was a progressive reduction in transmural pressure, calculated as wedge pressure minus pericardial pressure (p < 0.05), and in transmural pressure, estimated as wedge pressure minus right atrial pressure (p < 0.05). The estimated transmural filling pressure correlated (r = 0.86) with end-diastolic area. CONCLUSIONS: The present observations suggest that right atrial pressure may be used to estimate changes in pericardial pressure with PEEP and that pulmonary capillary wedge pressure minus right atrial pressure is a potentially clinically useful approximation of transmural filling pressure.

Adult↗
PubMed1996

Comparison of endothelial activation during endotoxic and posttraumatic conditions by serum analysis of soluble E-selectin in nonhuman primates.

Because the presence of E-selectin, which is one of the adhesion molecules on the endothelium, cannot be determined directly in vivo except by invasive biopsy techniques, the only available kinetic information concerning its activity is the serum level of the soluble form. Therefore we tried to measure soluble E-selectin levels and compare the degree of endothelial activation in a trauma and endotoxic situation, where endothelial activation is supposed to occur. To perform these studies, an enzyme-linked immunosorbent assay with two monoclonal antibodies was set up and used in (1) a model of endotoxic shock in baboons (n = 8) (1.5 mg/kg Escherichia coli endotoxin as a 10-minute intravenous infusion), (2) a hemorrhagic traumatic shock model in baboons (n = 6), where trauma was simulated by infusion of zymosan-activated serum and hemorrhage. Soluble E-selectin was released in vivo after the application of endotoxin, and it reached a peak level after 24 hours (13.82 +/- 5.38 ng/ml). In baboons with hemorrhagic shock, much lower levels (5.03 +/- 1.98 ng/ml) of soluble E-selectin were found. A lower soluble E-selectin level indicates a lower level of endothelial activation after experimental hemorrhagic traumatic shock (with endotoxin translocation from the gut) as compared with endotoxic shock probably caused by much lower endotoxin levels in traumatic shock.

Animals↗
PubMed1996

Evaluation of a soluble E-selectin enzyme-linked immunosorbent assay under posttraumatic conditions.

The up-regulation of E-selectin, one of the adhesion molecules on the endothelium, is an important event in the mediation of the inflammatory response. Because the presence of E-selectin cannot be determined directly in vivo except by invasive biopsy techniques, the only available information concerning its activity is the serum level of the soluble form. Therefore we tried to measure soluble E-selectin levels in trauma and sepsis situations, where endothelial activation is supposed to occur. We have investigated the soluble E-selectin levels in a group of patients undergoing the trauma associated with cardiac surgery and the use of extracorporeal circulation, some of whom developed a systemic inflammatory response syndrome (SIRS). We have also confirmed that our enzyme-linked immunosorbent assay (ELISA) will detect the levels of soluble E-selectin that are produced as a result of the exposure of cultured human umbilical endothelial cells to even low levels of endotoxin. The data presented in this paper indicate that in patients with SIRS after extracorporeal circulation, the levels of circulating soluble E-selectin are numerically higher but---at least in this group of patients---not statistically significantly different from the levels in patients who have undergone the surgery. These results suggest that the measurement of serum levels of soluble E-selectin is not a reliable method for monitoring the onset of SIRS in patients having undergone surgical trauma, although we have confirmed that our ELISA will detect the levels of soluble E-selectin that are produced as a result of the exposure of cultured human endothelial cells to even low levels of endotoxin.

Adult↗
PubMed1996

Combination vigabatrin and lamotrigine therapy for intractable epilepsy.

Vigabatrin (GVG) and lamotrigine (LTG) are new antiepileptic drugs (AEDs) individually effective as add-on therapy for refractory seizures. The efficacy of GVG and LTG in combination was evaluated in a prospective audit of 42 patients with intractable epilepsy. There was a statistically significant median reduction of 62% (P < 0.025) from a median baseline monthly seizure frequency (MSF) of 29 (mean 59, 95% CI 22, 96) to a median MSF of 11 (mean 23, 95% CI 8, 38) during a median treatment period of eight months, with a greater than 50% reduction in MSF in 29 patients (69%) treated with the add-on combination of GVG and LTG. The additional MSF reduction achieved by the combination amounted to 21% (18% when GVG was added to LTG and 24% when LTG was added to GVG). The median trough plasma lamotrigine concentration was 9.9 mg/l (range 3.4-19.6 mg/l). The average daily dose of LTG was 517 mg (range, 175-800 mg) and GVG 2400 mg (range, 1500-3500 mg). Adverse events requiring alteration of therapy occurred in 24 patients (57%) with a drop-out rate of 12%. The combination of GVG and LTG should be considered as a therapeutic option in patients with intractable epilepsy. The results of the present study support the need to confirm additive efficacy of GVG and LTG by conducting controlled trials of this combination therapy.

Adolescent↗
PubMed1996

In vitro stimulation of naive mouse lymphocytes by Heligmosomoides polygyrus adult worm antigens induces the production of IgG1.

The production of high levels of IgG1, by mice chronically infected with the parasitic nematode Heligmosomoides polygyrus, has been documented for a number of years. In order to investigate this phenomenon, naive lymphocytes from B10.D2 mice were incubated in vitro with H. polygyrus adult worm homogenate (AWH) and the culture supernatants examined for immunoglobulin production. Stimulation of pooled naive splenocytes by AWH was found to produce IgG1, but not IgM, in an antigen dose dependent manner. Identical stimulation of splenocytes of individual inbred mice, indicated that this effect was reproducible but with considerable variation between mice. When the IgG1 produced was tested for specificity, it was found that there was little evidence that the immunoglobulin produced was able to bind to the inducing parasite antigens. Analysis of purified T cells reconstituted with splenocytes, demonstrated that T cells were the target lymphocytes of the stimulating molecule, contained within AWH. These results show that H. polygyrus AWH can induce the production of non-parasite specific IgG1 from naive splenocytes and that this production is crucially dependent upon the cell content of the in vitro culture. Furthermore, the production of IgG1 is not proportional to the degree of lymphocyte proliferation. It is suggested that at least part of the hypergammaglobulinaemia produced during a primary H. polygyrus infection, is due to this non-specific stimulation of mouse lymphocytes by the parasite.

Animals↗
PubMed1996

Prescribing practice and policy for hypnotics: a model of pharmacy audit.

A problem of overprescribing of hypnotic medication ('sleeping tablets') was identified and quantified within a department of health care for older people in a district general hospital. Data on the volume of prescribing were obtained from computerized pharmacy records, and this information was supplemented by a retrospective survey of case notes of 100 patients. Sixty per cent of patients were prescribed a hypnotic at some stage during their hospital stay. Twelve per cent were prescribed a sleeping tablet on admission on an 'as required' basis but never took this medication, suggesting that such prescribing was becoming routine. As part of an ongoing pharmacy audit within the department, a policy was implemented to try to improve prescribing habits. Following this, hypnotic prescribing fell, with the average monthly number of sleeping tablets prescribed falling from 2392 to 734. A further survey of 100 case notes showed overall prescribing had fallen to 25%, although 2% were still prescribed a hypnotic on admission but never took it.

Aged↗
PubMed1996

New isomer 32Alm.

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Journal Article↗