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Biomedical subjects

M Robinson

Publications and source records attributed to M Robinson.

At least 55 records · Page 3Linked to original sources

Adenosine provokes diastolic dysfunction in microvascular angina.

Adenosine stress echocardiography was performed in nine patients (58 (+/-3) years, eight women) with documented microvascular angina. Global ventricular function was assessed by Tc(99m) blood pool imaging and Doppler, whereas longitudinal ventricular function was assessed by simultaneous tissue Doppler echocardiography of the lateral mitral annulus. Adenosine was infused incrementally to onset of chest pain in all patients. There was no significant change in global or longitudinal systolic function. Adenosine induced global diastolic dysfunction, demonstrated by blood pool imaging and by Doppler of the transmitral flow. All patients had long axis diastolic dysfunction at peak adenosine, revealed by a ratio of early to late diastolic velocity of lateral mitral annulus <1, which was absent at rest. Adenosine, as a stress agent, provokes regional and global diastolic dysfunction in microvascular angina, which may be a consequence of subendocardial ischaemia. Long axis diastolic dysfunction can be easily revealed by tissue Doppler of the lateral annular motion.

Adenosine↗

Systematic genetic analysis with ordered arrays of yeast deletion mutants.

In Saccharomyces cerevisiae, more than 80% of the approximately 6200 predicted genes are nonessential, implying that the genome is buffered from the phenotypic consequences of genetic perturbation. To evaluate function, we developed a method for systematic construction of double mutants, termed synthetic genetic array (SGA) analysis, in which a query mutation is crossed to an array of approximately 4700 deletion mutants. Inviable double-mutant meiotic progeny identify functional relationships between genes. SGA analysis of genes with roles in cytoskeletal organization (BNI1, ARP2, ARC40, BIM1), DNA synthesis and repair (SGS1, RAD27), or uncharacterized functions (BBC1, NBP2) generated a network of 291 interactions among 204 genes. Systematic application of this approach should produce a global map of gene function.

Carrier Proteins↗

Fluconazole prophylaxis against fungal colonization and infection in preterm infants.

BACKGROUND: Invasive fungal infection is associated with substantial morbidity and mortality in preterm infants. We evaluated the efficacy of prophylactic fluconazole in preventing fungal colonization and invasive infection in extremely-low-birth-weight infants. METHODS: We conducted a prospective, randomized, double-blind clinical trial over a 30-month period in 100 preterm infants with birth weights of less than 1000 g. The infants were randomly assigned during the first five days of life to receive either intravenous fluconazole or placebo for six weeks. We obtained weekly surveillance cultures from all patients. RESULTS: The 50 infants randomly assigned to fluconazole and the 50 control infants were similar in terms of birth weight, gestational age at birth, and base-line risk factors for fungal infection. During the six-week treatment period, fungal colonization was documented in 30 infants in the placebo group (60 percent) and 11 infants in the fluconazole group (22 percent; difference in risk, 0.38; 95 percent confidence interval, 0.18 to 0.56; P=0.002). Invasive fungal infection with positive growth of fungal isolates from the blood, urine, or cerebrospinal fluid developed in 10 infants in the placebo group (20 percent) and none of the infants in the fluconazole group (difference in risk, 0.20; 95 percent confidence interval, 0.04 to 0.36; P=0.008). The sensitivities of the fungal isolates to fluconazole did not change during the study, and no adverse effects of the fluconazole therapy were documented. CONCLUSIONS: Prophylactic administration of fluconazole during the first six weeks of life is effective in preventing fungal colonization and invasive fungal infection in infants with birth weights of less than 1000 g.

Antifungal Agents↗

The landing of the NEAR-Shoemaker spacecraft on asteroid 433 Eros.

The NEAR-Shoemaker spacecraft was designed to provide a comprehensive characterization of the S-type asteroid 433 Eros (refs 1,2,3), an irregularly shaped body with approximate dimensions of 34 x 13 x 13 km. Following the completion of its year-long investigation, the mission was terminated with a controlled descent to its surface, in order to provide extremely high resolution images. Here we report the results of the descent on 12 February 2001, during which 70 images were obtained. The landing area is marked by a paucity of small craters and an abundance of 'ejecta blocks'. The properties and distribution of ejecta blocks are discussed in a companion paper. The last sequence of images reveals a transition from the blocky surface to a smooth area, which we interpret as a 'pond'. Properties of the 'ponds' are discussed in a second companion paper. The closest image, from an altitude of 129 m, shows the interior of a 100-m-diameter crater at 1-cm resolution.

Journal Article↗

Laser altimetry of small-scale features on 433 Eros from NEAR-Shoemaker.

During the Near Earth Asteroid Rendezvous (NEAR)-Shoemaker's low-altitude flyover of asteroid 433 Eros, observations by the NEAR Laser Rangefinder (NLR) have helped to characterize small-scale surface features. On scales from meters to hundreds of meters, the surface has a fractal structure with roughness dominated by blocks, structural features, and walls of small craters. This fractal structure suggests that a single process, possibly impacts, dominates surface morphology on these scales.

Journal Article↗

Imaging of small-scale features on 433 Eros from NEAR: evidence for a complex regolith.

On 25 October 2000, the Near Earth Asteroid Rendevous (NEAR)-Shoemaker spacecraft executed a low-altitude flyover of asteroid 433 Eros, making it possible to image the surface at a resolution of about 1 meter per pixel. The images reveal an evolved surface distinguished by an abundance of ejecta blocks, a dearth of small craters, and smooth material infilling some topographic lows. The subdued appearance of craters of different diameters and the variety of blocks and different degrees of their burial suggest that ejecta from several impact events blanketed the region imaged at closest approach and led to the building up of a substantial and complex regolith consisting of fine materials and abundant meter-sized blocks.

Journal Article↗

Dyspepsia: challenges in diagnosis and selection of treatment.

BACKGROUND: Despite considerable study, the pathophysiology of dyspepsia remains obscure. This and other factors have impeded development of precise and effective treatment strategies. OBJECTIVE: This paper provides a brief review of the clinical syndrome of dyspepsia and its pathophysiology, symptoms, diagnosis, and treatment. METHODS: To identify articles for inclusion in this review, a search of MEDLINE was conducted using the key word dyspepsia. Because the literature on this topic is voluminous and duplicative, the search was limited primarily to literature from the last decade and to articles concerning dyspepsia in adults. RESULTS: The symptoms of dyspepsia, which may include epigastric pain, heartburn. bloating, and early satiety, defy diagnosis in as many as 50% of patients, even after endoscopy and other appropriate studies. In the other half of patients, such causative disorders as gastroesophageal reflux disease (GERD), peptic ulcer disease, cholecystitis, pancreatitis, and gastric cancer may be diagnosed. Despite controversy regarding the selection of therapy, empiric treatment is common for apparent idiopathic dyspepsia. Histamine2-receptor antagonists, proton pump inhibitors (PPIs), promotility agents, and coating agents have all been used as empiric therapy for dyspeptic symptoms. With empiric treatment, subsequent management is directed by the therapeutic response. In the absence of a definitive diagnosis, treatment is usually selected on the basis of the type and severity of symptoms, a thorough history and physical examination, and factors such as age and the presence of Helicobacter pylori infection. Five PPIs are currently available--lansoprazole, omeprazole, rabeprazole, pantoprazole, and esomeprazole--all with established efficacy in GERD and other acid-mediated disorders. The PPIs can be expected to be useful in certain patients with dyspepsia, and may be prescribed for patients who are found to re- spond to potent antisecretory therapy. Patients' concern about their symptoms, practical considerations, and restrictions imposed by managed care organizations may all affect the choice between empiric therapy and early endoscopy in patients with dyspepsia. CONCLUSIONS: Despite the variety of therapeutic options available for the symptoms of dyspepsia, the many presentations of this condition and the uncertainty of the response to the currently available therapeutic options continue to pose a substantial clinical challenge.

Dyspepsia↗

In vivo induction of hair growth by dermal cells isolated from hair follicles after extended organ culture.

Successful hair follicle organ culture has been established for some time, but hair growth in vitro is limited and generally terminates prematurely in comparison with in vivo. The reasons why growth stops in culture are as yet unknown. In this investigation, adult rat vibrissa follicles for which growth in culture is limited to about 10 d, were maintained in vitro for a minimum of 20 d after the hair shaft stopped growing. The pattern of fiber growth and long-term follicle pathology reflected the initial hair cycle stage at the time of isolation. Furthermore, there was evidence that a group of follicles put into culture when in late anagen were attempting to cycle in vitro. Microscopy showed that, in spite of widespread pathologic changes to the follicle epithelium, dermal cells in the follicle showed remarkable resilience. Their viability was confirmed when primary cell cultures were established from isolated dermal tissue. These cells labeled positively for alpha-smooth muscle actin, an established marker of hair follicle dermal cell phenotype in vitro. Moreover, isolated dermal tissue induced hair growth when implanted into inactivated hair follicles in vivo. These data confirm that the cessation in hair growth is not due to a loss of the inductive capacity in the dermal component. Long-term organ culture may provide opportunities to investigate factors that are expressed or lost during hair growth cessation. In addition it may be possible to develop this method further to obtain a reliable and predictable model of hair follicle cycling in vitro.

Animals↗

Synergy between low-dose ranitidine and antacid in decreasing gastric and oesophageal acidity and relieving meal-induced heartburn.

BACKGROUND: The pathophysiology of recurrent postprandial heartburn and the basis for the effectiveness of antacids or low doses of histamine H2-receptor antagonists have not been well studied. METHODS: The selected subjects (n=26) had heartburn more than four times a week for at least 2 months, which was responsive to antacids. Gastric pH and oesophageal pH were measured for 1 h before, during, and 4.5 h after ingestion of a meal over 0.5 h. Heartburn severity was assessed at 15-min intervals beginning at the end of the meal. Each subject randomly received placebo, 75 mg ranitidine, 420 mg calcium carbonate, and ranitidine plus calcium carbonate. Values for pH were converted to acid concentration (mM) and integrated acidity was calculated from the cumulative, time-weighted means of the acid concentrations for every second of the postprandial recording period. RESULTS: There was a close temporal relationship between heartburn and oesophageal acidity. Most oesophageal acid exposure occurred over a 90-min period that began approximately 45 min after the end of the meal. During this period the gastric acid concentration was less than 5% of maximal. Ranitidine significantly decreased gastric but not oesophageal acidity, whilst antacid significantly decreased oesophageal but not gastric acidity. Ranitidine plus antacid significantly decreased both gastric and oesophageal acidity. Antacid alone and ranitidine plus antacid significantly decreased heartburn severity. CONCLUSIONS: Determining integrated gastric and oesophageal acidity provides novel information regarding the pathophysiology of meal-induced heartburn as well as the actions of low-dose ranitidine and antacid. For subjects with meal-induced heartburn, treatment with low-dose ranitidine plus antacid is particularly effective in decreasing gastric and oesophageal acidity as well as heartburn severity.

Antacids↗

Focal myelin swellings and tomacula in anti-MAG IgM paraproteinaemic neuropathy: novel teased nerve fiber studies.

Focal myelin swellings and tomacula in teased nerve fibers from a case of IgM anti-myelin-associated glycoprotein (MAG) paraproteinaemic neuropathy were examined using a novel technique. Five different morphologic abnormalities were identified--myelin sheath outfolding, myelin sheath infolding, enlargement of the adaxonal space, myelin degeneration, multiple increased concentric loops--and a combination of these structural abnormalities often occur in association with myelin degeneration. Similar structural changes were found in externally normal segments of teased fibers without evidence of myelin swelling or tomacula from the same case. These structural abnormalities are consistent with a disturbance of the normal adhesion functions of MAG in the maintenance of axon-myelin relationships.

Aged↗

Comparison of glycocalicin, thrombopoietin and reticulated platelet measurement as markers of platelet turnover in HIV+ samples.

It is important to distinguish between decreased platelet/megakaryocyte production or increased peripheral platelet destruction as causes of thrombocytopenia. The measurement of reticulated platelets, plasma glycocalicin and thrombopoietin (TPO) levels are potentially of use as discriminators. Thrombocytopenia occurs in many HIV+ patients, and plasma glycocalicin has previously been shown to be elevated in this patient group. Reticulated platelets, glycocalicin and TPO were measured in samples from 56 HIV+ subjects and 20 healthy normal controls. The glycocalicin index (GCI--the glycocalicin levels adjusted for the platelet count) measured in HIV+ subjects was found to be significantly elevated when compared to normal controls (mean GCI 1.5 and 1.27, p = 0.04), while the percentage of reticulated platelets and TPO levels were not. Thrombocytopenic HIV+ subjects had significantly elevated mean GCI (2.8 and 1.4, p < 0.0001), TPO (85.2 and 27.2 pg/ml, p = 0.002), percentage of reticulated platelets (15.3 and 10.8%, p = 0.01), and significantly reduced absolute numbers of reticulated platelets (16.2 and 24.5 x 10(9)/l, p = 0.0004) when compared to non-thrombocytopenic HIV+ subjects. GCI and percentage of reticulated platelets exhibited a significant positive correlation (r = 0.4, p = 0.002) in HIV+ subjects. The reticulated platelet, TPO and GCI data suggests that thrombocytopenic HIV+ subjects have normal platelet production, and increased peripheral platelet destruction.

Adult↗

Integrated acidity and the pathophysiology of gastroesophageal reflux disease.

OBJECTIVES: The aim of this study was to demonstrate that integrated esophageal and gastric acidity values, calculated from 24-h pH recordings, can provide more precise quantitative temporal data than the conventional pH parameters historically associated with gastroesophageal reflux disease (GERD) investigations. METHODS: Esophagogastroduodenoscopy results and pH tracings from 20 GERD subjects with > or =10% esophageal acid contact time were studied. Integrated gastric and esophageal acidity were calculated from time-weighted average hydrogen ion concentrations at each second of the 24-h recording period. RESULTS: Integrated esophageal acidity correlated with grade of esophagitis. Two quite distinct GERD subtypes were identified, with either a monophasic or biphasic pattern of integrated esophageal acidity. "Biphasic" subjects differed from "monophasic" subjects in terms of magnitude and pattern of integrated esophageal acidity. Although both groups had significant integrated nocturnal gastric acidity, only the biphasic GERD subjects had concomitant increases in nocturnal integrated esophageal acidity. Esophagitis grade was correlated with magnitude rather than pattern of integrated esophageal acidity, and it was possible to calculate a reflux coefficient that seems to provide an estimate of the quantitative motor disturbance present in GERD. CONCLUSIONS: Integrated esophageal and gastric acidity provide quantitative measures of GERD pathophysiology and, compared to conventional pH parameters, should enhance evaluation of therapeutic interventions.

Acids↗

Thirteen-year follow-up of children and adolescents with chronic fatigue syndrome.

OBJECTIVE: To describe the educational, social, and symptomatic outcome of children and adolescents with chronic fatigue syndrome 13 years after illness onset. METHODS: Between January 1984 and December 1987, 46 children and adolescents developed an illness suggestive of chronic fatigue syndrome. Follow-up questionnaires were obtained from 35 participants an average of 13 years after illness onset. Data were obtained concerning subsequent medical diagnoses, amount of school missed, presence and severity of current symptoms, and subjective assessment of degree of illness resolution. RESULTS: Of the 35 participants, 24 were female (68.6%) and 11 were male (31.4%). Average age at illness onset was 12.1 years. Eight participants (22.9%) had an acute onset of symptoms, 27 (77.1%) had a gradual onset. No participant received an alternative medical diagnosis that could have explained the symptom complex between illness onset and follow-up. Thirteen participants (37.1%) considered themselves resolved of illness at follow-up; 15 participants (42.9%) considered themselves well but not resolved; 4 (11.4%) considered themselves chronically ill; and 3 (8.6%) considered themselves more ill than during the early years of illness. Correlation with the Medical Outcomes Study Short Form Health Survey was good for current level of symptoms and degree of recovery. Eight participants (22.9%) missed >2 years of school, and 5 of these were still ill at follow-up. Amount of school missed correlated with both illness severity at follow-up and perceived social impact of the illness. CONCLUSIONS: These data demonstrate the presence of an illness consistent with the current definition of chronic fatigue syndrome. Eighty percent of children and adolescents affected had a satisfactory outcome from their fatiguing illness, although the majority of these participants had mild to moderate persisting symptoms. Twenty percent of participants remain ill with significant symptoms and activity limitation 13 years after illness onset. Chronic fatigue syndrome in children and adolescents may result in persistent somatic symptoms and disability in a minority of those affected.

Absenteeism↗

Development and field validation of an avidin-biotin enzyme-linked immunosorbent assay kit for bovine brucellosis.

The avidin-biotin enzyme-linked immunosorbent assay (A-B ELISA), for use in surveillance for bovine brucellosis in India was developed and calibrated using the indirect brucellosis ELISA kit of the International Atomic Energy Agency (IAEA) as a reference. The reagents used in the A-B ELISA were as follows: the smooth lipopolysaccharide of Brucella abortus strain 99 (antigen); biotinylated anti-bovine immunoglobulin G (detection antibody); avidin-horseradish peroxidase (conjugate); and O-phenylenediamine dihydrochloride (chromogen). The test results were interpreted using the IAEA software EDI version 2.1.1, which was modified for use in the A-B ELISA. The cut-off percentage positivity value was established using 500 brucellosis-positive and 500 brucellosis-negative serum samples, confirmed with reference to the sample data using the indirect ELISA kit. The overall specificity of A-B ELISA was 98.8% and overall sensitivity was 98.2%. Field validation of the A-B ELISA kit was undertaken in six laboratories in India. Screening of 7,040 cattle and 678 buffalo serum samples from 12 states revealed serological evidence of brucellosis in 8.7% of cattle and 10.2% of buffalo. This kit proved to be robust and performed with a similar sensitivity and specificity to the indirect ELISA. The kit can be supplied at a lower cost than current commercial ELISA kits.

Animals↗

Effectiveness of pharmacotherapy for body dysmorphic disorder: a chart-review study.

BACKGROUND: Research on the pharmacotherapy of body dysmorphic disorder (BDD) is limited. No placebo-controlled, continuation, maintenance, or discontinuation studies have been published. Only one augmentation study has been published. METHOD: In this chart-review study of 90 patients with DSM-IV BDD treated for up to 8 years by the first 2 authors (K.A.P., R.S.A.) in their clinical practice, response to a variety of medications, including augmentation strategies, was assessed. The relapse rate with medication discontinuation was also determined. RESULTS: All subjects received a serotonin reuptake inhibitor (SRI), with 63.2% (55/87) of adequate SRI trials resulting in improvement in BDD symptoms; similar response rates were obtained for each type of SRI. Discontinuation of an effective SRI resulted in relapse in 83.8% (31/37) of cases. Response rates to selective SRI augmentation were clomipramine, 44.4% (4/9) of trials; buspirone, 33.3% (12/36) of trials; lithium, 20.0% (1/5); methylphenidate, 16.7% (1/6); and antipsychotics, 15.4% (2/13) of trials. CONCLUSION: These findings from a clinical setting suggest that a majority of BDD patients improve with an SRI and that all SRIs appear effective. Certain SRI augmentation strategies may be beneficial. The high relapse rate with SRI discontinuation suggests that long-term treatment is often necessary. These preliminary findings require confirmation in placebo-controlled efficacy studies and effectiveness studies.

Adolescent↗