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Biomedical subjects

M Robinson

Publications and source records attributed to M Robinson.

At least 127 records · Page 7Linked to original sources
PubMed1998

Psyllium is superior to docusate sodium for treatment of chronic constipation.

BACKGROUND: Stool softening is a physician's first step in the management of chronic constipation. AIM: To compare stool softening (stool water content) and laxative efficacy of psyllium hydrophilic mucilloid vs. docusate sodium. METHODS: The multi-site, randomized, double-blind, parallel-design study of 170 subjects with chronic idiopathic constipation involved a 2-week baseline (placebo) phase followed by 2 weeks of treatment. The treatment phase compared psyllium (5.1 g b.d.) plus docusate placebo to docusate sodium (100 mg b.d.) plus psyllium placebo. Stools were collected and assessed. RESULTS: Compared to baseline, psyllium increased stool water content vs. docusate (psyllium 2.33% vs. docusate 0.01%, P = 0.007). Psyllium also increased stool water weight (psyllium 84.0 g/BM; docusate 71.4 g/BM; P = 0.04), total stool output (psyllium 359.9 g/week: docusate 271.9 g/week; P = 0.005), and O'Brien rank-type score combining objective measures of constipation (psyllium 475.1; docusate 403.9; P = 0.002). Bowel movement (BM) frequency was significantly greater for psyllium (3.5 BM/week) vs. docusate (2.9 BM/week) in treatment week 2 (P = 0.02), with no significant difference (P > 0.05) between treatment groups in treatment week 1 (3.3 vs. 3.1 BM/week). CONCLUSION: Psyllium is superior to docusate sodium for softening stools by increasing stool water content, and has greater overall laxative efficacy in subjects with chronic idiopathic constipation.

Adult↗
PubMed1998

Medical therapy of inflammatory bowel disease for the 21st century.

Inflammatory bowel disease therapy can be considered in several subcategories, and this review is designed to provide selective updates for some of the most important therapeutic entities currently marketed or soon to be available for the medical management of IBD. Although conventional corticosteroids have been a major component of acute inflammatory bowel disease management, steroids have many serious disadvantages; and toxicity is heightened with chronic steroid therapy. Newer corticosteroids, particularly budesonide, may be less toxic than older agents such as prednisone. Budesonide may be used as an enema in active distal ulcerative colitis (UC) or as delayed release tablets in Crohn's disease (CD). However, budesonide is not completely free from steroid side effects, and may share in some of the toxicity of older corticosteroids, particularly when high dose budesonide is administered. Topical and oral aminosalicylates are widely utilized for the treatment of mild to moderate active UC and mild active CD, and they also are efficacious for maintenance of IBD remission. Recent data continue to support the concept that higher doses and prolonged use of mesalamine-based drugs are therapeutically superior to lower doses and short term treatment. In addition, the combination of oral and rectal aminosalicylate formulations often succeeds in patients refractory to either used alone. The immunomodulatory drugs azathioprine and 6-mercaptopurine are particularly effective in treating both CD and UC, and methotrexate has also shown some promise in CD therapy. Immunosuppressive therapy for inflammatory bowel disease initially met with strong physician resistance. However, views have shifted in response to positive data on the utility of immunosuppressive agents in many cases of IBD. Although cyclosporine may be used as a 'rescue' medication in some severe IBD cases, it has been associated with severe toxic reactions. Possible candidates for cyclosporine treatment should be offered such therapy only in academic centers highly experienced with the nuances of this modality. Clinical trials of the newer entities IL-10, IL-11, tacrolimus, and anti-TNFalpha, have demonstrated variable efficacy in refractory IBD patients. Anti-TNFalpha has been very impressive, particularly in the presence of fistulizing Crohn's disease. Many physicians have utilized various antibiotics empirically as part of their 'general' management of IBD. Only metronidazole has been adequately studied in controlled CD trials, but other antibiotic studies are pending. Further exploration of antimicrobial treatment for IBD is clearly warranted. Many other investigational agents in disparate pharmaceutical categories have been employed in IBD therapy; and some of these also show varying degrees of promise, including the aloe vera derivative acemannan, several formulations of heparin, and both transdermal and intra-rectal nicotine. Despite the growing list of medications and formulations promoted for the treatment of IBD, no single drug or recognized combination has yet been confirmed as dependably clinically effective. Many additional investigations of IBD medical therapy are needed, including permutations of conventional medications, along with newer agents that may be more precisely targeted to specific aspects of IBD pathophysiology. All physicians who care for UC and CD patients enthusiastically await more optimal regimens for these challenging disorders.

Forecasting↗
PubMed1998

Sensitivity of the relative-rate test to taxonomic sampling.

Relative-rate tests may be used to compare substitution rates between more than two sequences, which yields two main questions: What influence does the number of sequences have on relative-rate tests and what is the influence of the sampling strategy as characterized by the phylogenetic relationships between sequences? Using both simulations and analysis of real data from murids (APRT and LCAT nuclear genes), we show that comparing large numbers of species significantly improves the power of the test. This effect is stronger if species are more distantly related. On the other hand, it appears to be less rewarding to increase outgroup sampling than to use the single nearest outgroup sequence. Rates may be compared between paraphyletic ingroups and using paraphyletic outgroups, but unbalanced taxonomic sampling can bias the test. We present a simple phylogenetic weighting scheme which takes taxonomic sampling into account and significantly improves the relative-rate test in cases of unbalanced sampling. The answers are thus: (1) large taxonomic sampling of compared groups improves relative-rate tests, (2) sampling many outgroups does not bring significant improvement, (3) the only constraint on sampling strategy is that the outgroup be valid, and (4) results are more accurate when phylogenetic relationships between the investigated sequences are taken into account. Given current limitations of the maximum-likelihood and nonparametric approaches, the relative-rate test generalized to any number of species with phylogenetic weighting appears to be the most general test available to compare rates between lineages.

Adenine Phosphoribosyltransferase↗
PubMed1998

On the behavioral characteristics of loud-music listening.

To provide insight into the behavioral characteristics of people who listen excessively to loud music, the 32-item Northeastern Excessive Music Listening Survey was developed and administered to 90 subjects. Results indicate that 8 of the 90 subjects scored within a range that would suggest the presence of a maladaptive pattern of music-listening behavior similar to that exhibited by substance abusers. Implications for further research and models of treatment are discussed.

Adult↗
PubMed1998

Cystic fibrosis and pregnancy.

The case records of 11 patients with cystic fibrosis (CF) who had 13 completed pregnancies between 1975 and 1995 were retrospectively reviewed to assess: (1) the changes in spirometry and body mass index (BMI) during pregnancy; and (2) maternal and neonatal complications and outcomes. Prepregnancy the mean age of the group was 24 (range 17-27) years. Two patients were exsmokers, 7 had pancreatic insufficiency and 7 had chest X-ray evidence of bronchiectasis. None of the patients had diabetes mellitus but 3 developed gestational diabetes. The mean +/- SEM (% predicted) forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) prepregnancy were 2.3 +/- 1.0 (83%) litres and 3.0 +/- 0.9 (85%) litres respectively. Five patients had normal spirometry (FEV1 and FVC >80% predicted) prior to 6 pregnancies. The mean body mass index (kg/height(m)2) for the group was 20.5 +/- 2.0. There was a significant decline in spirometry during pregnancy (FEV1 15.5 +/- 6.6% p<0.01; FVC 14.0 +/- 8.3% p<0.5). However, FVC but not FEV1 recovered to prepregnancy values by 12 months postpartum. There was a significant increase in both weight (7.1 kg) and BMI (2.6 kg/height(m)2) at the time of delivery compared with prepregnancy (p=0.0004). However, postpregnancy both weight and BMI had returned to their prepregnancy values (p<0.2). Mothers with an FEV1>80% had less decline in FEV1 related to pregnancy, better outcomes, fewer operative and instrumental deliveries, fewer preterm infants and fewer neonatal complications. Suggestions for the planning and management of pregnancy in women with CF are discussed.

Adolescent↗
PubMed1998

Temporal integration of loudness under partial masking.

This paper tests the hypothesis that the loudness ratio between equal-SPL tones with different durations is the same at all SPLs. Detection thresholds and levels required to produce equal loudness for 5- and 200-ms tones presented in quiet or in broadband noise were measured using adaptive, two-interval, two-alternative forced-choice procedures. Tone levels ranged from 5 dB SL to 90 dB SPL for the long tones and about 100 dB SPL for the short tones. Results from six listeners with normal hearing show that the amount of temporal integration, defined as the level difference between equally loud 5- and 200-ms tones, varies nonmonotonically with level and is greatest at moderate levels. The average amount of temporal integration in quiet is about 15 dB near threshold, increases to a peak of 27 dB when the 5-ms tone is about 58 dB SPL, and decreases to about 15 dB near 100 dB SPL. For masker levels of 40, 60, and 80 dB SPL, the amount of temporal integration near masked threshold remains near 15 dB. The maximum amount of temporal integration decreases as masker level increases and occurs at progressively higher levels. At high levels, the amount of temporal integration is nearly the same as in the quiet for all masker levels. Loudness functions derived by applying the equal-loudness-ratio hypothesis to the data yield excellent predictions of loudness matches between tones in the quiet and partially masked tones with the 40- and 60-dB maskers. For the 80-dB masker, clear deviations are present. These results support the equal-loudness-ratio hypothesis, but suggest that intense masking may alter the loudness ratio between 200- and 5-ms tones.

Adult↗
PubMed1998

Indole-3-acetic acid biosynthesis in colletotrichum gloeosporioides f. sp. aeschynomene

We characterized the biosynthesis of indole-3-acetic acid by the mycoherbicide Colletotrichum gloeosporioides f. sp. aeschynomene. Auxin production was tryptophan dependent. Compounds from the indole-3-acetamide and indole-3-pyruvic acid pathways were detected in culture filtrates. Feeding experiments and in vitro assay confirmed the presence of both pathways. Indole-3-acetamide was the major pathway utilized by the fungus to produce indole-3-acetic acid in culture.

Journal Article↗
PubMed1998

Clinical evaluation of hand-arm-vibration syndrome in shipyard workers: sensitivity and specificity as compared to Stockholm classification and vibrometry testing.

The hand-arm-vibration syndrome (HAVS) is a complex entity composed of circulatory, sensory, and motor disturbances, as well as associated musculoskeletal components. This study was performed to find a diagnostic testing modality with sufficient sensitivity, specificity, and predictive value to be utilized as a screening test for this disorder in a working population. A full range of testing modalities was utilized in the shipyard medical department. In addition, a clinical diagnosis of vascular and sensorineural disease was established in the workers by a combination of plethysmography, vibrometry, two point discrimination, and monofilament testing in an independent occupational medicine clinic. No one test modality met the requirements for such a definitive diagnostic test. Rather, a range of modalities was required to reach any acceptable level of predictive value, with sufficient degrees of specificity and sensitivity.

Adult↗
PubMed1997

Impact of changes in GC content on the silent molecular clock in murids.

Murid nuclear genomes are more homogeneous in GC content than those of most mammals, which leads to the question of how such important compositional changes have accumulated. This paper reports on relationships between frequencies of synonymous differences and GC change, in the lineages leading to human and murids. For this, we used the four-species approach: GC changes between human and murids were compared to the frequencies of synonymous differences, measured between two independent species without GC change (bovine and pig), by using orthologous genes common to all four species. We report three conclusions: (1) Among genes with little GC change, 60% of the variability of synonymous substitution frequencies is explained by the gene-specific rate component. (2) GC changes in murid genomes are independent of the gene-specific rate component. Slowly evolving genes in pig bovine comparison can show strong GC change in murids. (3) By using a GC-independent estimate of the substitution rate, we show that GC changes in murid genomes increase synonymous substitution frequencies. The GC homogenization considerably weakens the gene-specific conservation of substitution rates in murids, and could explain part of the increase of evolutionary rates observed in this group. We present a mechanism that can account for the evolution of the GC homogenization in murids.

Animals↗
PubMed1997

NEAR's flyby of 253 mathilde: images of a C asteroid

On 27 June 1997, the Near Earth Asteroid Rendezvous (NEAR) spacecraft flew within 1212 kilometers of asteroid 253 Mathilde. Mathilde is an irregular, heavily cratered body measuring 66 kilometers by 48 kilometers by 46 kilometers. The asteroid's surface is dark (estimated albedo between 0.035 and 0.050) and similar in color to some CM carbonaceous chondrites. No albedo or color variations were detected. The volume derived from the images and the mass from Doppler tracking of the spacecraft yield a mean density of 1.3 +/- 0.2 grams per cubic centimeter, about half that of CM chondrites, indicating a porous interior structure.

Journal Article↗
PubMed1997

Airway deposition and clearance and systemic pharmacokinetics of amiloride following aerosolization with an ultrasonic nebulizer to normal airways.

STUDY OBJECTIVES: Airway epithelial ion transport is an important component of the airway defense mechanism, and new therapies that target ion transport are being developed. Amiloride is an example of such a new drug, exerting a dose-dependent action to inhibit Na+ transport. Amiloride may be useful in cystic fibrosis, blocking the characteristic airway epithelial Na+ hyperabsorption that occurs in the disease. To evaluate airway and systemic delivery of amiloride via an ultrasonic nebulizer (Omron NE-UO7), we measured the airway surface concentrations of amiloride in normal volunteers via a novel approach, together with the systemic pharmacokinetics of amiloride. DESIGN: Direct measurement of airway surface liquid, plasma, and urine amiloride concentrations following ultrasonic nebulization. PARTICIPANTS/INTERVENTIONS: Seven normal subjects were studied in the General Clinical Research Center of the University of North Carolina. Following inhalation with amiloride (1 mg/mL, 4.5 mL) for approximately 12 min, a bronchoscopy was performed. Amiloride deposition and clearance from airway surfaces over 1 h were evaluated by transbronchoscopic sampling using preweighed filter papers. Pulmonary and systemic absorption was assessed by measuring drug concentrations in blood and urine. RESULTS: The mean volume aerosolized was 3.5+/-0.3 mL during 12 min of aerosolization time; the mean initial concentration of amiloride on airway surfaces after nebulization was 1.6 x 10(-4) mol/L, with an elimination half life of approximately 23 min. Peak plasma concentrations of amiloride (30 min, 3.36+/-0.70 ng/mL) suggest early absorption across lung surfaces, rather than via the GI route. Mean urinary excretion of amiloride over 72 h was 0.63+/-0.07 mg, with 87% excreted in the first 24 h. CONCLUSIONS: The ultrasonic nebulizer rapidly delivers amiloride to normal conducting airways as assessed by the transbronchoscopic sampling technique. Early blood concentrations of amiloride probably reflect initial absorption across lung surfaces and are a useful index of the efficiency of the machine.

Absorption↗
PubMed1997

An animal cell mutant with a deficiency in acyl/alkyl-dihydroxyacetone-phosphate reductase activity. Effects on the biosynthesis of ether-linked and diacyl glycerolipids.

In the accompanying paper (James, P. F., and Zoeller, R. A. (1997) J. Biol. Chem. 272, 23532-23539), we reported the isolation of a series of mutants from the fibroblast-like cell line, CHO-K1, that are deficient in the incorporation of the long chain fatty alcohol, hexadecanol, into complex lipids. All but one of these mutants, FAA. K1B, were deficient in long-chain-fatty alcohol oxidase (FAO) activity. We have further characterized this FAO+ isolate. FAA.K1B cells displayed a 40% decrease in [9,10-3H]hexadecanol uptake when compared with the parent strain. Although incorporation of hexadecanol into the phospholipid fraction was decreased by 52%, the cells accumulated label in alkylglycerol (20-fold over wild type). The increase in 1-alkylglycerol labeling corresponded to a 4-fold increase in alkylglycerol mass. Short term labeling with 32Pi showed a 45-50% decrease in overall phospholipid biosynthesis in FAA.K1B. Both diacyl- and ether-linked species were affected, suggesting a general defect in phospholipid biosynthesis. Mutant cells were able to partially compensate for the decreased biosynthesis by decreasing the turnover of the phospholipid pools. The primary lesion in FAA. K1B was identified as a 95% reduction in acyl/alkyl-dihydroxyacetone-phosphate reductase activity. Whole cell homogenates from FAA.K1B were unable to reduce either acyl-dihydroxyacetone phosphate (DHAP) or alkyl-DHAP, supporting the notion that the reduction of these two compounds is catalyzed by a single enzyme. These data suggest that the biosynthesis of diacyl phospholipids, in Chinese hamster ovary cells, begins with the acylation of dihydroxyacetone phosphate as well as glycero-3-phosphate and that the "DHAP pathway" contributes significantly to diacyl glycerolipid biosynthesis. Also, the severe reduction in acyl/alkyl-DHAP reductase activity in FAA.K1B resulted in only a moderate decrease in ether lipid biosynthesis. These latter data together with the observed increase in alkylglycerol levels support the existence of a shunt pathway that is able to partially bypass the enzymatic lesion.

Animals↗
PubMed1997

Molecular phylogeny of rodents, with special emphasis on murids: evidence from nuclear gene LCAT.

Phylogenetic relationships among 19 extant species of rodents, with special emphasis on rats, mice, and allied Muroidea, were studied using sequences of the nuclear protein-coding gene LCAT (lecithin:cholesterol acyltransferase), an enzyme of cholesterol metabolism. Analysis of 705 base pairs from the exonic regions of LCAT confirmed known groupings in and around Muroidea. Strong support was found for the families Sciuridae (squirrel and marmot) and Gliridae (dormice) and for suprafamilial taxa Muroidea and Caviomorpha (guinea pig and allies). Within Muroidea, the first branching leads to the fossorial mole rats Spalacinae and bamboo rats Rhizomyinae. The other Muroidea appear as a polytomy from which are issued Gerbillinae (gerbils), Murinae (rats and mice), Sigmodontinae (New World cricetids), Cricetinae (hamsters), and Arvicolinae (voles). Evidence from LCAT sequences agrees with that from a number of previous molecular and morphological studies, both concerning branching orders inside Muroidea and the bush-like radiation of rodent suprafamilial taxa (caviomorphs, sciurids, glirids, muroids), thus suggesting that this nuclear gene is an appropriate candidate for addressing questions of rodents relationships.

Animals↗
PubMed1997

Immunological interactions between Trichinella spiralis and Heligmosomoides polygyrus: cross reactivity between muscle larvae and antibodies raised to unrelated antigens.

It is documented that concurrent infections in mice with the 2 unrelated nematode parasites, Heligmosomoides polygyrus and Trichinella spiralis, can result in delayed rejection of the latter species. The basis of this immunological interference is not completely understood, but a possibility exists that antibodies induced by 1 species may interact with antigens produced by the other parasite. Therefore, it was investigated whether H. polygyrus infections may induce the production of antibodies which could cross react with T. spiralis muscle larval (m.l.) antigens. The results shown here indicate that this assumption is correct, and there is cross reactivity between antibodies produced against H. polygyrus, and T. spiralis m.l. antigens. Furthermore, antibodies which were not specific for either species were also able to bind to T. spiralis m.l. This is in agreement with recent evidence which has shown that antibodies that are not specific for H. polygyrus may still be absorbed by an H. polygyrus homogenate. It is considered that the binding of these antibodies may be involved in manipulation of the host immune response by T. spiralis.

Animals↗
PubMed1997

Non-specific binding of mouse IgG1 to Heligmosomoides polygyrus: parasite homogenate can affinity purify mouse monoclonal antibodies.

A characteristic feature of infections with the nematode parasite of mice Heligmosomoides polygyrus, is a marked IgG1 hypergammaglobulinaemia. A possible source for this immunoglobulin has recently been demonstrated, through evidence that H. polygyrus adult worm homogenate (AWH) can induce the in vitro production of non-specific IgG1 from mouse lymphocytes. To determine the interactions between this immunoglobulin and the parasite, the ability of IgG1 to bind to AWH of H. polygyrus was investigated. Protein (Western) blotting indicated that mouse monoclonal antibodies are able to bind non-specifically to selected parasite antigens. Furthermore, by binding H. polygyrus adult worm homogenate to cyanogen bromide (CNBr)-activated Sepharose CL-4B, an affinity column was prepared which could be used to efficiently purify mouse IgG1 monoclonal antibodies. These antibodies were eluted from the affinity column and still retained their original specificity. These results indicate that H. polygyrus not only induces the production of non-specific IgG1 by the host, it can also bind this immunoglobulin to its own specific proteins. Thus, it is possible that IgG1 produced during a primary infection with H. polygyrus may not entirely benefit the host.

Animals↗
PubMed1997

Heligmosomoides polygyrus superantigen: differential response with mouse and human lymphocytes.

The interaction between Heligmosomoides polygyrus superantigen and human peripheral blood mononuclear cells (PBMC) was evaluated. Parasite homogenate and excretory-secretory proteins from both L4 larvae and adult worms were examined for their ability to stimulate, and be presented by, human cells. Proliferation assays using PBMC from 3 human volunteers indicated that naïve cells were stimulated by H. polygyrus superantigen. Antigen presenting cells (APC) from a number of human donors were able to successfully present H. polygyrus' superantigen to mouse T cell hybridomas. However, this ability varied according to the source of the superantigen, and human APC, in contrast to APC from mice, could only present the superantigen contained within parasite homogenate. Also, in contrast to the situation with mice, human APC could present H. polygyrus superantigen to stimulate mouse T cells expressing not only TCR V beta 8.1, but also TCR V beta 7. Therefore, H. polygyrus superantigen can successfully stimulate, and be presented by, human PBMC of different MHC haplotypes, although the cellular mechanisms appear to be different from those observed in the mouse.

Animals↗
PubMed1997

Effects of oral rabeprazole on oesophageal and gastric pH in patients with gastro-oesophageal reflux disease.

BACKGROUND: This study examined the dose-response effects of the new proton-pump inhibitor rabeprazole on oesophageal and gastric pH in patients with gastro-oesophageal reflux disease. METHODS: This study had a single-centre, double-blind, randomized, two-way crossover design. Twenty patients were treated for two 7-day periods separated by a 7-10-day washout period. Patients were randomly assigned to receive either 20 mg of rabeprazole once daily during the first treatment period and 40 mg once daily during the second treatment period, or 40 mg during the first treatment period and 20 mg during the second treatment period. The primary efficacy variable was oesophageal acid exposure determined by 24-hour ambulatory pH monitoring. Acid-reflux time was defined as the percentage of time over 24 h that oesophageal pH was < 4. A dosage was considered effective if reflux time was reduced to < 6%, a number which has been our internal laboratory reference. RESULTS: Both rabeprazole 20 mg and 40 mg, given once daily, normalized reflux time, with decreases of 79% and 92% in acid exposure by day 7. Both dosages also decreased the mean total number of reflux episodes and the number of episodes lasting > 5 min, with no significant differences between dosages for any reflux parameter. Mean gastric pH increased with 20 mg from 1.86 at baseline to 3.71 on day 1 and 4.17 on day 7. Rabeprazole 40 mg once daily increased gastric pH from 2.01 to 4.37 on day 1, and to 4.65 on day 7. Safety analyses revealed no significant acute side-effects for either dosage. CONCLUSIONS: Pathological oesophageal acid exposure was normalized with both 20 mg and 40 mg dosages of rabeprazole, and the effects of these two doses did not differ. Rabeprazole was well-tolerated in this short-term study.

2-Pyridinylmethylsulfinylbenzimidazoles↗