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M Robinson

Publications and source records attributed to M Robinson.

At least 73 records · Page 4Linked to original sources
PubMed2001

New-generation proton pump inhibitors: overcoming the limitations of early-generation agents.

Proton pump inhibitors (PPIs) are now generally considered the drugs of choice for treatment of patients with serious or refractory acid-related diseases. However, despite some popular notions to the contrary, these agents are not equivalent in their pharmacokinetic, pharmacodynamic and efficacy profiles. When the two newest PPIs, rabeprazole and esomeprazole, are compared with the older drugs in this class (omeprazole, lansoprazole and pantoprazole), the newer PPIs offer several key advantages over older agents, particularly in terms of the management of gastro-oesophageal reflux disease. Rabeprazole and esomeprazole achieve more rapid and profound inhibition of acid secretion than do older agents, and they sustain this suppression to provide acid control and symptom relief over 24 h. The balanced hepatic metabolism of rabeprazole, involving both cytochrome P450 (CYP)-mediated reactions in the liver and nonenzymatic reactions, appears to confer an advantage over older PPIs in that genetic polymorphisms for CYP 2C19 do not significantly influence rabeprazole clearance and, potentially, clinical efficacy. The metabolism of esomeprazole also involves CYP 2C19, but the pharmacokinetic effects of genetic differences in the expression of this enzyme are not known. However, esomeprazole is also intended to minimize pharmacological variability. Unlike esomeprazole, the use of rabeprazole is not complicated by clinically significant drug-drug interactions of the type that have been reported for omeprazole and the wide range of medications metabolized by CYP 2C19.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2001

Optimizing acid-suppression therapy.

Acid-related disorders are caused by an imbalance between acid secretion by the gastric parietal cells and the defensive mechanisms of the gastrointestinal tract to protect against the effects of acid. Therapy for acid-related disorders focuses on the control of acidity. Data collected throughout the last decade have demonstrated that PPIs are the most effective therapy for acid-related disorders: PPIs have proven superior to H2RAs and antacids in numerous studies. Five PPIs are currently available in the United States. While all PPIs exert their effect through the same basic mechanism of action, they do not have the same pharmacologic and clinical properties. All PPIs are effective in healing and maintenance of gastric and duodenal ulcers and GERD. The PPIs differ, however, in their ability to control symptoms rapidly and consistently. Due to its more rapid rate of activation, rabeprazole results in a faster onset of action and faster symptom control than other PPIs. Studies comparing rabeprazole to omeprazole found statistically significant differences in the rapidity of symptom relief in patients with gastric ulcer, duodenal ulcer, and GERD. Rapid symptom relief is important to the majority of patients, as their symptoms have an impact on their quality of life. Rapid symptom relief is also important in an environment where patients self-medicate on demand, depending on daily symptoms. Rabeprazole has also been shown to have a more consistent suppression of acid, including at night. Optimizing therapy with PPIs necessitates consideration not only of healing rates of the different available treatments but also of the rapidity and consistency of acid suppression that translate clinically into symptom relief.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2001

U.S. and Canadian dental school involvement in extramural programming.

This project was undertaken from July 1999 to August 2000 to identify the status of extramural programming (that is, a program that has undergraduate dental students providing any aspect of dental care to individuals in settings outside the main clinical facility of the school) in North American dental schools. A survey instrument was mailed to all United States and Canadian dental schools concerning student involvement in extramural programming. The response rate was 79.7 percent. Of the schools responding, 3.9 percent did not offer extramural programming. The type of extramural sites, the percentage of schools offering each type of site, and the mean number of weeks students are at each site were as follows: hospital clinics--71 percent, 2.5 weeks; public health clinics--65 percent, 6 weeks; schools and day care centers--49, 1.7 weeks; private dental offices--37 percent, 2 weeks; and "other"--29 percent, 2.5 weeks. The average number of weeks spent at extramural site(s) per class was: freshman 1.9 weeks (SD=4.3); sophomores 2.3 weeks (SD=4.2); juniors 2.6 weeks (SD=1.9); and seniors 5.3 weeks (SD=6.7). Of total student time in extramural programming, 43.3 percent was spent delivering basic clinical services, 24.4 percent comprehensive clinical services, 11.8 percent health education, 11.8 percent preventive dentistry, and 8.7 percent community activities. From the data collected it is apparent that the majority of North American dental schools are providing a variety of extramural experiences for their dental students. It was found that student involvement in extramural programming increases gradually from the freshman to the senior year.

Canada↗
PubMed2000

Protective effect of beta-carbolines and other antioxidants on lipid peroxidation due to hydrogen peroxide in rat brain homogenates.

Tryptoline and pinoline are two beta-carbolines isolated from the nervous system of mammals. We investigated the ability of these compounds to prevent lipid peroxidation induced by hydrogen peroxide in rat brain homogenates. We also compared their effects with other known antioxidants including melatonin, trolox and ascorbic acid. Lipid peroxidation was assessed by measuring malonaldehyde (MDA) and 4-hydroxy-alkenals (4-HDA) concentrations in the brain homogenates. Incubation with hydrogen peroxide (5 mM) increased MDA+4-HDA levels, which were totally prevented by tryptoline, pinoline, melatonin and trolox in a concentration-dependent manner. By contrast, higher MDA-4-HDA concentrations compared with control experiments were found after incubation with ascorbic acid, thus reflecting an increase of lipid peroxidation induced by this compound. Although in vivo studies are needed, the data suggest that these beta-carbolines may be potential neuroprotective agents because of their antioxidant activities.

Aldehydes↗
PubMed2000

NEAR at eros: imaging and spectral results

Eros is a very elongated (34 kilometers by 11 kilometers by 11 kilometers) asteroid, most of the surface of which is saturated with craters smaller than 1 kilometer in diameter. The largest crater is 5.5 kilometers across, but there is a 10-kilometer saddle-like depression with attributes of a large degraded crater. Surface lineations, both grooves and ridges, are prominent on Eros; some probably exploit planes of weakness produced by collisions on Eros and/or its parent body. Ejecta blocks (30 to 100 meters across) are abundant but not uniformly distributed over the surface. Albedo variations are restricted to the inner walls of certain craters and may be related to downslope movement of regolith. On scales of 200 meters to 1 kilometer, Eros is more bland in terms of color variations than Gaspra or Ida. Spectra (800 to 2500 nanometers) are consistent with an ordinary chondrite composition for which the measured mean density of 2.67 +/- 0.1 grams per cubic centimeter implies internal porosities ranging from about 10 to 30 percent.

Journal Article↗
PubMed2000

Tissue distribution of 2-(2-nitro-4-trifluoromethylbenzoyl)-cyclohexane-1,3-dione (NTBC) and its effect on enzymes involved in tyrosine catabolism in the mouse.

Administration of a single oral dose of 2-(2-nitro-4-trifluoromethyl-benzoyl)-cyclohexane-1,3-dione (NTBC) to mice increases the concentration of tyrosine in the plasma and aqueous humour. The tyrosinaemia is both time and dose-dependent with a single dose of 30 micromol NTBC/kg (10 mg/kg) producing maximal concentrations of tyrosine in plasma of about 1200 nmol/ml and in aqueous humour of about 2200 nmol/ml at 16 h after dosing. Analysis of the key hepatic enzymes involved in tyrosine catabolism, following a single dose of 30 micromol NTBC/kg, showed that 4-hydroxyphenylpyruvate dioxygenase (HPPD) was markedly inhibited soon after dosing and that the activity recovered very slowly. In response to the tyrosinaemia, the activity of hepatic tyrosine aminotransferase (TAT) was induced about two-fold, while the activity of hepatic homogentisic acid oxidase (HGO) was reduced at 4 and 5 days after dosing. Daily oral administration of NTBC at doses up to 480 micromol NTBC/kg (160mg/kg/day) to mice produced a maximal tyrosinaemia of about 600-700nmol/ml plasma, showing some adaptation relative to a single dose. Unlike the rat, no treatment-related corneal lesions of the eye were seen at any dose levels up to 6 weeks. Administration of a single oral dose of [14C]-NTBC at 30 micromol/kg led to selective retention of radiolabel in the liver and to a lesser extent the kidneys. Our studies show that NTBC is a potent inhibitor of mouse liver HPPD, which following repeat exposure produces a marked and persistent tyrosinaemia, which does not result in ocular toxicity.

4-Hydroxyphenylpyruvate Dioxygenase↗
PubMed2000

Autopsy consent practice at US teaching hospitals: results of a national survey.

BACKGROUND: Autopsy rates continue to fall despite the enduring benefit of the procedure to families and medical science, yet there are few data about the consent process itself. OBJECTIVE: To evaluate the current practice of obtaining autopsy consent, by assessing the consent forms currently in use, the knowledge and attitudes of chief residents on the procedure, and the expert opinion of pathologists in those institutions. DESIGN: Cross-sectional survey. SETTINGS AND PARTICIPANTS: One hundred twenty-seven US teaching hospitals. RESULTS: Of all autopsy consent forms we surveyed, 84.7% contained 7 of 10 elements recommended by the College of American Pathologists. Only 7.1% of institutions supplied educational materials for the physician, as recommended by the College of American Pathologists. Overall, 50.1% of chief residents reported deficiencies in their knowledge of the autopsy procedure. Correspondingly, greater than 74.5% felt that educational materials would be beneficial for physicians and the family. Finally, 93.3% of chief residents believed that a limited autopsy should be offered to families, while 68 (90%) of 76 pathologists at these institutions believed that limited autopsies are an unsatisfactory alternative to the complete procedure. CONCLUSIONS: Chief residents at US teaching hospitals reported substantial deficiencies in their knowledge about autopsy and desire more training on the consent process. Autopsy consent forms are often lacking information that might help physicians and families in making an educated choice about autopsy. Teaching institutions need to reevaluate the training for the autopsy consent practice.

Autopsy↗
PubMed2000

Effect of a short course of rhDNase on cough and mucociliary clearance in patients with cystic fibrosis.

The aim of the study was to measure the effect of a short course of recombinant human deoxyribonuclease I (rhDNase) on ciliary and cough clearance in a group of cystic fibrosis patients, using a radioaerosol and gamma camera technique. Patients were initially randomized to receive either rhDNase (2.5 mg qd) or placebo. Following the measurement of baseline clearance, patients were given a 7-day course of either rhDNase or placebo. The patient then returned on the seventh day for follow-up clearance measurements. This was followed by a 2-week washout period before the whole process was repeated with the alternative inhalation solution. On each of the study days, mucociliary clearance was initially measured for a period of 60 min (IC). This was followed by cough clearance (CC) measurements for 30 min, during which patients were requested to cough a total of 120 times. Post-cough clearance (PCC) was then measured for a further 60 min. Thirteen patients completed the study. Patients' age ranged between 18-38 years, and they had baseline values of FEV(1) of 27-103% of predicted values. Following completion of the course of rhDNase, there was a mean percent increase from baseline of 7.5% for FEV(1) and 5.4% for FVC% (P = 0. 03). There was a small, nonsignificant increase in IC (6.2 +/- 3.6%) on the rhDNase arm compared with the placebo arm (-2.3 +/- 2.9%), P = 0.1. No changes were seen in either CC (1.0 +/- 3.2% [rhDNase] vs. 1.9 +/- 2.4% [placebo], P = 0.9) or PCC (-0.7 +/- 1.5% [rhDNase] vs. 0.9 +/- 1.7% [placebo], P = 0.3). Patients who achieved a 10% or greater improvement in FEV(1) (n = 5) in response to rhDNase did not show any greater change in clearance than nonresponders. In conclusion, we were unable to demonstrate any improvements in either ciliary or cough clearance in response to a short course of rhDNase. The mechanism of action of this drug in vivo remains uncertain.

Administration, Inhalation↗
PubMed2000

High-throughput profiling of the mitochondrial proteome using affinity fractionation and automation.

Recent studies have demonstrated the need for complementing cellular genomic information with specific information on expressed proteins, or proteomics, since the correlation between the two is poor. Typically, proteomic information is gathered by analyzing samples on two-dimensional gels with the subsequent identification of specific proteins of interest by using trypsin digestion and mass spectrometry in a process termed peptide mass fingerprinting. These procedures have, as a rule, been labor-intensive and manual, and therefore of low throughput. The development of automated proteomic technology for processing large numbers of samples simultaneously has made the concept of profiling entire proteomes feasible at last. In this study, we report the initiation of the (eventual) complete profile of the rat mitochondrial proteome by using high-throughput automated equipment in combination with a novel fractionation technique using minispin affinity columns. Using these technologies, approximately one hundred proteins could be identified in several days. In addition, separate profiles of calcium binding proteins, glycoproteins, and hydrophobic or membrane proteins could be generated. Because mitochondrial dysfunction has been implicated in numerous diseases, such as cancer, Alzheimer's disease and diabetes, it is probable that the identification of the majority of mitochondrial proteins will be a beneficial tool for developing drug and diagnostic targets for associated diseases.

Animals↗
PubMed2000

A comparison of silver stain and SYPRO Ruby Protein Gel Stain with respect to protein detection in two-dimensional gels and identification by peptide mass profiling.

Proteomic projects are often focused on the discovery of differentially expressed proteins between control and experimental samples. Most laboratories choose the approach of running two-dimensional (2-D) gels, analyzing them and identifying the differentially expressed proteins by in-gel digestion and mass spectrometry. To date, the available stains for visualizing proteins on 2-D gels have been less than ideal for these projects because of poor detection sensitivity (Coomassie blue stain) or poor peptide recovery from in-gel digests and mass spectrometry (silver stain), unless extra destaining and washing steps are included in the protocol. In addition, the limited dynamic range of these stains has made it difficult to rigorously and reliably determine subtle differences in protein quantities. SYPRO Ruby Protein Gel Stain is a novel, ruthenium-based fluorescent dye for the detection of proteins in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gels that has properties making it well suited to high-throughput proteomics projects. The advantages of SYPRO Ruby Protein Gel Stain relative to silver stain demonstrated in this study include a broad linear dynamic range and enhanced recovery of peptides from in-gel digests for matrix assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry.

Acrylic Resins↗
PubMed2000

Increased risk of vitamin B12 deficiency in patients with phenylketonuria on an unrestricted or relaxed diet.

OBJECTIVE: To investigate whether dietary relaxation or cessation in patients with phenylketonuria (PKU) predisposes to vitamin B12 deficiency. STUDY DESIGN: Patients with PKU aged 11 to 38 years underwent a neurologic examination and dietetic assessment and were divided according to their diet into 1 of 3 groups: Strict - those on a strict low phenylalanine (phe) diet with amino acid, mineral, and vitamin supplements; Relaxed - those on a total protein intake of approximately 1 g/kg/d with 50% of this from natural protein and 50% from amino acid, mineral, and vitamin supplements; Unrestricted - those on no formal protein restriction and not taking amino acid supplements. Assays of blood samples were taken for vitamin B12 and folate levels by standard assays. Results were analyzed with Student t test. RESULTS: Vitamin B12 levels were significantly lower in the PKU groups on relaxed or unrestricted diets compared with the normal population (P <.0001 [unrestricted] and.0034 [relaxed]). Folate levels were significantly elevated in all PKU groups (<.0001). CONCLUSION: Patients with PKU who are no longer under strict dietary control may be at risk from vitamin B12 deficiency. We recommend that all patients should remain under medical and dietetic supervision and in particular have their vitamin B12 status monitored.

Adolescent↗
PubMed2000

The effects of capsaicin on reflux, gastric emptying and dyspepsia.

AIMS: To evaluate capsaicin's effects on heartburn, dyspepsia, gastric acidity and emptying, and gastro-oesophageal reflux, and to test the hypothesis that capsaicin induces heartburn and exacerbates symptoms by sensitizing the oesophagus. METHODS: Eleven heartburn sufferers underwent two separate pH monitoring sessions and assessments of gastric emptying (13C-octanoic acid breath test), heartburn and dyspepsia (100 mm VAS) after a non-irritant meal. The meal consisted of a sausage biscuit with egg, cheese and 30 g raw onion, 8 oz chocolate milk and a peppermint patty. Thirty minutes prior to meal consumption, subjects were administered a placebo capsule. On visit 1, subjects consumed the meal containing 100 microl 13C-octanoic acid cooked in the egg, over 15 min. On visit 2, subjects consumed the meal plus 5 mg capsaicin in gelatin capsules. RESULTS: Oesophageal and gastric pH profiles and gastric emptying were not different between meals. Capsaicin did not alter mean heartburn and dyspepsia scores (P > 0.05), but significantly decreased time to peak heartburn (120 min vs. 247 min; P < 0.003). Time to peak dyspepsia was not altered by capsaicin (P > 0.05). CONCLUSION: Capsaicin enhances noxious postprandial heartburn, presumably by direct effects on sensory neurons.

Adult↗
PubMed2000

Managing heartburn at the 'base' of the GERD 'iceberg': effervescent ranitidine 150 mg b.d. provides faster and better heartburn relief than antacids.

BACKGROUND: Many individuals with heartburn self-medicate with antacids for relief of their symptoms. AIM: To compare efficacy of effervescent ranitidine to as-needed calcium carbonate antacids in subjects who self-treat heartburn. METHODS: A total of 155 subjects with frequent antacid-responsive heartburn were randomized to receive effervescent ranitidine 150 mg tablets b.d., or as-needed calcium carbonate 750 mg for 12 weeks. Endoscopic oesophagitis severity and mucosal histology were assessed at baseline, and at weeks 6 and 12. Heartburn frequency, severity, and antacid consumption were recorded daily, and quality of life was assessed at baseline, and at weeks 6 and 12. RESULTS: Heartburn frequency and severity were significantly decreased after 1 day of ranitidine (P < 0.02). By week 6, ranitidine had significantly decreased rescue antacid consumption (7.3 tablets, P < 0.001) vs. antacids (14.1 tablets). Endoscopic oesophagitis healing (</= grade 1) was significantly better with ranitidine (55%, P=0.022) vs. antacids (29%). Quality of life was improved by both treatments; however, ranitidine was numerically superior for all quality of life parameters, statistically superior for several quality of life indices at week 6 and for the pain-related index by week 12 (P < 0. 05). CONCLUSIONS: For subjects self-administering antacids for chronic heartburn, effervescent ranitidine 150 mg b.d. is more effective than antacids in reducing heartburn, healing erosive oesophagitis, alleviating pain, and improving quality of life.

Adult↗
PubMed2000

In vivo biotinylation studies: specificity of labelling of reticulated platelets by thiazole orange and mepacrine.

Animal in vivo biotinylation studies have demonstrated that thiazole orange (TO) labels the youngest cells in the circulation. TO has since been widely used for the measurement of reticulated platelets. As recent findings suggest that at high concentrations TO also labels platelet dense granules non-specifically, the value of previous work is unclear. Mepacrine also labels platelet dense granules and can detect storage pool defects. In this study, a mouse in vivo biotinylation model was used to determine the specificity of TO and mepacrine staining on platelets recently released into the circulation. The mean life span of biotin/TO (low), biotin/TO (high) and mepacrine/TO dual-positive platelets was 1.4 d (SD 0.5), 2.2 d (SD 0.2) and 2.3 d (SD 0.3) respectively (n = 6) compared with a life span for biotin-positive platelets of 4.9 d (SD 1.6). TO (low), TO (high) and mepacrine labelled 8.0% (SD 3.1), 43.9% (SD 8.3) and 40.0% (SD 9.9) of the total platelet population respectively (results of 30 samples from six mice), which decreased to 6.8% (SD 3. 9), 26.6% (SD 6.9) and 25.7% (SD 10.6) after thrombin degranulation. The shorter life span and lack of thrombin sensitivity of TO (low)-positive platelets, suggests that TO (low) measures reticulated platelets specifically. The comparative life spans and thrombin sensitivity of TO (high) and mepacrine-positive platelets suggest that TO (high) labels platelet dense granules. These data also suggest that dense granules are lost during platelet ageing.

Animals↗
PubMed2000

The relationship between insight and clinical factors for persons with schizophrenia.

This correlational study examined the relationship of insight with positive and negative symptoms and level of functioning among persons with schizophrenia or schizoaffective disorder. Poor insight as a symptom of schizophrenia is the conceptual framework. Thirty-seven people receiving assertive community treatment, inpatient hospitalization, or outpatient treatment were assessed using 2 self-rating insight scales, the Scale for Assessment of Positive Symptoms (SAPS), the Scale for Assessment of Negative Symptoms (SANS), and the Global Assessment of Functioning (GAF). A significant negative correlation was found between insight and positive formal thought disorder. No significant relationships were found between insight and negative symptoms or level of functioning. Reactions to the self-rating insight tools suggest necessary revisions of the insight tool.

Adult↗
PubMed2000

Regional mucociliary clearance in patients with cystic fibrosis.

This paper reports on a large retrospective analysis of mucociliary clearance (MCC) studies in a group of 59 patients with cystic fibrosis (CF) and 17 age-matched healthy subjects. As many of the CF patients were studied on multiple occasions, a total of 184 patient studies are presented. MCC was measured using a radioaerosol and gamma camera technique. In addition to whole lung clearance, MCC was measured from the central, intermediate, peripheral, basal, mid and apical regions of the lung. MCC was markedly decreased in the CF patient group. Not only was whole lung clearance (14.2 +/- 1.4% vs. 28.0 +/- 3.7%) impaired, but also clearance from the central (19.1 +/- 1.9% vs. 35.6 +/- 4.3%), intermediate (10.7 +/- 1.6% vs. 25.5 +/- 3.7%), apical (12.4 +/- 2.6% vs. 31.6 +/- 4.6%) and mid (14.0 +/- 1.9% vs. 30.4 +/- 4.0%) regions. Attempts were made to identify factors that may have influenced MCC in both the normal subjects and CF patients. Age, gender, body mass index, patient genotype, penetration index, spontaneous cough, and various lung function parameters were entered into a stepwise multiple regression model, but none of the factors proved to be statistically important in determining MCC. Both intrasubject repeatability and intersubject variability estimates are presented for the patients and normal subjects that had multiple studies. The values were found to be remarkably similar for both CF patients and normal subjects and for both intra- and intersubject repeatability. With marked deviation from normal ranges and good repeatability, the measurement of MCC in CF patients would seem to be a valuable outcome measure for clinical trials involving new pharmaceuticals and physical therapy designed to improve removal of secretions from the airways.

Adolescent↗