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Biomedical subjects

A Tobin

Publications and source records attributed to A Tobin.

At least 19 recordsLinked to original sources

Intravenous salbutamol: too much of a good thing?

OBJECTIVE: To review the evidence for the use of intravenous salbutamol, its systemic effects and the potential complications that may occur in patients with severe asthma. DATA SOURCES: A review of articles reported on intravenous salbutamol in patients with acute asthma. SUMMARY OF REVIEW: Intravenous salbutamol is recommended in the treatment of severe asthma when there is failure to respond to nebulised beta2-agonists. To date, however, there are no published trials that establish the efficacy or safety of the combination of inhaled salbutamol and a continuous intravenous salbutamol infusion over inhaled salbutamol alone for treatment of severe acute asthma. beta2-agonists have numerous systemic actions that may adversely affect patients with severe respiratory compromise. The most important of these is the potential for beta2-agonists to cause a lactic acidosis, which, by increasing respiratory demands, could precipitate respiratory failure. CONCLUSIONS: Systemic salbutamol has metabolic effects that may worsen respiratory function in asthma and should not be given by intravenous infusion to asthma patients outside of clinical trials. For patients who fail to respond to inhaled beta2-agonists, ipratropium and systemic steroids, consideration should be given to other therapies such as non-invasive ventilation rather than increasing the dose of a drug that may paradoxically worsen respiratory function.

Journal Article↗

Transvenous liver biopsy via the femoral vein.

AIM: To study the safety, effectiveness and diagnostic value of transvenous forceps biopsy of the liver in 54 patients with coagulopathy, gross ascites or morbid obesity and suspected liver disease in whom percutaneous liver biopsy was contraindicated. MATERIAL AND METHODS: Forceps biopsy of the liver via the femoral vein was attempted in 54 adult patients with advanced liver disease of unknown aetiology who had coagulation disorders (41 cases), gross ascites (11 cases) or morbid obesity (two cases). In each patient two to six biopsies (average four) were taken using a radial jaw forceps inserted via the right or left femoral vein. RESULTS: The procedure was successful in 53 cases. Hepatic vein catheterization failed in one patient. Adequate liver tissue for diagnosis was obtained in 84% of cases. One patient developed delayed haemorrhage at 12 h from a capsular leak that was undetected during the biopsy procedure. This patient required blood transfusions and laparotomy to control bleeding. There were no deaths in the 53 patients studied. Transient minor chest and shoulder pain was encountered during sheath insertion into a hepatic vein in 23 patients. Three patients developed a femoral vein haematoma, which resolved with conservative treatment. CONCLUSION: Transvenous liver biopsy via the femoral vein is another safe, effective, simple alternative technique of biopsy when the percutaneous route is contraindicated.

Adult↗

Retraining the injured spinal cord.

The present review presents a series of concepts that may be useful in developing rehabilitative strategies to enhance recovery of posture and locomotion following spinal cord injury. First, the loss of supraspinal input results in a marked change in the functional efficacy of the remaining synapses and neurons of intraspinal and peripheral afferent (dorsal root ganglion) origin. Second, following a complete transection the lumbrosacral spinal cord can recover greater levels of motor performance if it has been exposed to the afferent and intraspinal activation patterns that are associated with standing and stepping. Third, the spinal cord can more readily reacquire the ability to stand and step following spinal cord transection with repetitive exposure to standing and stepping. Fourth, robotic assistive devices can be used to guide the kinematics of the limbs and thus expose the spinal cord to the new normal activity patterns associated with a particular motor task following spinal cord injury. In addition, such robotic assistive devices can provide immediate quantification of the limb kinematics. Fifth, the behavioural and physiological effects of spinal cord transection are reflected in adaptations in most, if not all, neurotransmitter systems in the lumbosacral spinal cord. Evidence is presented that both the GABAergic and glycinergic inhibitory systems are up-regulated following complete spinal cord transection and that step training results in some aspects of these transmitter systems being down-regulated towards control levels. These concepts and observations demonstrate that (a) the spinal cord can interpret complex afferent information and generate the appropriate motor task; and (b) motor ability can be defined to a large degree by training.

Animals↗

Identification of an ATP-binding cassette transporter for export of the O-antigen across the inner membrane in Rhizobium etli based on the genetic, functional, and structural analysis of an lps mutant deficient in O-antigen.

For O-antigen lipopolysaccharide (LPS) synthesis in bacteria, transmembrane migration of undecaprenyl pyrophosphate-bound O-antigen oligosaccharide subunits or polysaccharide occurs before ligation to the core region of the LPS molecule. In this study, we identified by mutagenesis an ATP-binding cassette transporter in Rhizobium etli CE3 that is likely responsible for the translocation of the O-antigen across the inner plasma membrane. Mutant FAJ1200 LPS lacks largely the O-antigen, as shown by SDS-polyacrylamide gel electrophoresis and confirmed by immunoblot analysis. Furthermore, LPS isolated from FAJ1200 is totally devoid of any O-chain glycosyl residues and contains only those glycosyl residues that can be expected for the inner core region. The membrane component and the cytoplasmic ATP-binding component of the ATP-binding cassette transporter are encoded by wzm and wzt, respectively. The Tn5 transposon in mutant FAJ1200 is inserted in the wzm gene. This mutation resulted in an Inf- phenotype in bean plants.

ATP-Binding Cassette Transporters↗

Predictors of compliance with neuroleptic medication among inpatients with schizophrenia: a discriminant function analysis.

OBJECTIVE: To identify clinically useful predictors of adherence to medication among persons with schizophrenia. METHOD: We evaluated levels of compliance with neuroleptic medication among 32 consecutive admissions with DSM-III-R schizophrenia from a geographically defined catchment area using a compliance interview. We also assessed symptomatology, insight, neurological status and memory. RESULTS: Less than 25% of consecutive admissions reported being fully compliant. Drug attitudes were the best predictor of regular compliance, symptomatology the best predictor of noncompliance, and memory the best predictor of partial compliance with neuroleptic medication. CONCLUSIONS: These data emphasise the complexity of factors that influence whether a person adheres to his medication regimen. Furthermore, they suggest that these factors may vary within the same person over time.

Adolescent↗

Genetic locus required for antigenic maturation of Rhizobium etli CE3 lipopolysaccharide.

Rhizobium etli modifies lipopolysaccharide (LPS) structure in response to environmental signals, such as low pH and anthocyanins. These LPS modifications result in the loss of reactivity with certain monoclonal antibodies. The same antibodies fail to recognize previously isolated R. etli mutant strain CE367, even in the absence of such environmental cues. Chemical analysis of the LPS in strain CE367 demonstrated that it lacked the terminal sugar of the wild-type O antigen, 2,3,4-tri-O-methylfucose. A 3-kb stretch of DNA, designated as lpe3, restored wild-type antigenicity when transferred into CE367. From the sequence of this DNA, five open reading frames were postulated. Site-directed mutagenesis and complementation analysis suggested that the genes were organized in at least two transcriptional units, both of which were required for the production of LPS reactive with the diagnostic antibodies. Growth in anthocyanins or at low pH did not alter the specific expression of gusA from the transposon insertion of mutant CE367, nor did the presence of multiple copies of lpe3 situated behind a strong, constitutive promoter prevent epitope changes induced by these environmental cues. Mutations of the lpe genes did not prevent normal nodule development on Phaseolus vulgaris and had very little effect on the occupation of nodules in competition with the wild-type strain.

Carbohydrate Sequence↗

Increased expression of GAD65 and GABA in pancreatic beta-cells impairs first-phase insulin secretion.

The functional role of glutamate decarboxylase (GAD) and its product GABA in pancreatic islets has remained elusive. Mouse beta-cells express the larger isoform GAD67, whereas human islets express only the smaller isoform GAD65. We have generated two lines of transgenic mice expressing human GAD65 in pancreatic beta-cells (RIP7-hGAD65, Lines 1 and 2) to study the effect that GABA generated by this isoform has on islet cell function. The ascending order of hGAD65 expression and/or activity in beta-cells was Line 1 heterozygotes < Line 2 heterozygotes < Line 1 homozygotes. Line 1 heterozygotes have normal glucose tolerance, whereas Line 1 homozygotes and Line 2 heterozygotes exhibit impaired glucose tolerance and inhibition of insulin secretion in vivo in response to glucose. In addition, fasting levels of blood glucose are elevated and insulin is decreased in Line 1 homozygotes. Pancreas perfusion experiments suggest that GABA generated by GAD65 may function as a negative regulator of first-phase insulin secretion in response to glucose by affecting a step proximal to or at the K(ATP)(+) channel.

Animals↗

Prone ventilation--it's time.

Prone positioning to improve oxygenation in acute lung injury was first reported over 20 years ago. Although this and several subsequent studies have shown that prone positioning improved oxygenation in the majority of patients, it has failed to become common practice in intensive care units. This paper reviews the mechanism by which prone positioning improves oxygenation and the clinical studies of its use to date.

Humans↗

An outbreak of hepatitis A among Irish haemophiliacs.

BACKGROUND: An outbreak of hepatitis A (HAV) occurred in 1992 in Irish haemophilia A patients treated with high purity solvent-detergent (SD) treated factor VIII. Similar outbreaks were reported in Italy, Germany and Belgium. The aim of this study was to investigate the outbreak, and to test the hypothesis that it was caused by exposure to SD-treated factor VIII. METHODS: A case-control study was started in early 1993. Haemophilia A cases with acute HAV (n = 29) were compared with haemophilia A controls for exposure to SD-treated factor VIII and other environmental factors. Details of factor VIII usage were obtained from the National Haemophilia Register and environmental data were obtained by a telephone-administered questionnaire. The response rate was approximately 90%. RESULTS: The incidence of acute HAV infection among haemophilia A patients exceeded the notified national incidence of HAV by a factor of approximately 300. The incidence was higher in younger patients and those with more severe bleeding disorders. Contact with hepatitis, with children, and exposure to factor VIII were associated with increased risk. The association with factor VIII was the strongest risk factor after controlling for other factors (odds ratio = 27.6, 95% confidence interval [CI] 6.5-117.3). A dose-response effect was demonstrated. CONCLUSIONS: Although person-to-person transmission is likely to have caused a few of the cases, the results of our investigation suggest that the major contributing factor was exposure to certain batches of SD-treated factor VIII.

Adolescent↗

Helicobacter pylori infection in elderly dyspeptic patients.

The association between Helicobacter pylori (HP) and gastritis is well established. As there is evidence that HP infection increases with age we reviewed the clinicopathological records of 119 consecutive patients aged 65-85 years (mean 71.1 years) on whom gastroscopy had been performed for dyspeptic symptoms. All patients had two antral biopsies--one was assessed for histological evidence of gastritis and the other was independently assessed for evidence of HP infection. Thirty-six patients (30%) had duodenal ulceration, of whom 32 (89%) had an associated HP-positive gastritis. Forty-nine patients (41%) had antral gastritis without ulceration, of whom 38 (78%) were HP positive and 11 (22%) were HP negative. Ninety-one per cent of HP-negative gastritis patients had a history of recent ingestion of non-steroidal anti-inflammatory drugs (NSAID) compared with 29% of HP-positive gastritis patients. Ten patients (8%) had normal antral mucosa but had evidence of reflux oesophagitis (one of these patients was HP-positive). Nineteen patients (16%) had normal antral mucosa and normal endoscopic findings and one of these was HP positive. We conclude that HP infection is associated with the majority of cases of symptomatic gastritis in elderly patients. HP-positive gastritis is associated with the majority of duodenal ulcers. The most important cause of HP-negative gastritis is NSAID ingestion.

Age Factors↗

Identification and preliminary characterization of protein-cysteine farnesyltransferase.

Ras proteins must be isoprenylated at a conserved cysteine residue near the carboxyl terminus (Cys-186 in mammalian Ras p21 proteins) in order to exert their biological activity. Previous studies indicate that an intermediate in the mevalonate pathway, most likely farnesyl pyrophosphate, is the donor of this isoprenyl group. Inhibition of mevalonate synthesis reverts the abnormal phenotypes induced by the mutant RAS2Val-19 gene in Saccharomyces cerevisiae and blocks the maturation of Xenopus oocytes induced by an oncogenic Ras p21 protein of human origin. These results have raised the possibility of using inhibitors of the mevalonate pathway to block the transforming properties of ras oncogenes. Unfortunately, mevalonate is a precursor of various end products essential to mammalian cells, such as dolichols, ubiquinones, heme A, and cholesterol. In this study, we describe an enzymatic activity(ies) capable of catalyzing the farnesylation of unprocessed Ras p21 proteins in vitro at the correct (Cys-186) residue. This farnesylating activity is heat-labile, requires Mg2+ or Mn2+ ions, is linear with time and with enzyme concentration, and is present in all mammalian cell lines and tissues tested. Gel filtration analysis of a partially purified preparation of protein farnesyltransferase revealed two peaks of activity at 250-350 kDa and 80-130 kDa. Availability of an in vitro protein farnesyltransferase assay should be useful in screening for potential inhibitors of ras oncogene function that will not interfere with other aspects of the mevalonate pathway.

Alkyl and Aryl Transferases↗

The safety and efficacy of tripotassium dicitrato bismuthate (De-Nol) maintenance therapy in patients with duodenal ulceration.

Seventy-one patients whose duodenal ulcers had healed after a 4-week treatment period with tripotassium dicitrato bismuthate (TDB) were randomly allocated to receive maintenance treatment with either one TDB swallow tablet nocte (equivalent to 120 mg Bi2O3) or an identical placebo. During 12 months of follow-up, no side-effects were reported by TDB-treated patients, blood bismuth levels did not rise above discontinuation threshold concentrations (greater than 50 micrograms/L in the first 6 months, or greater than 100 micrograms/L in the second 6 months), and there were no adverse effects on haematological or biochemical indices. Ulcer relapse was significantly less in TDB-treated patients (P less than 0.025). Cumulative relapse rates at 6 and 12 months were 51% and 66%, respectively, for placebo-treated patients and 26% and 31%, respectively, for those who received TDB. It is likely that TDB is a safe and effective maintenance treatment for patients with duodenal ulcer disease.

Adult↗

Criteria of case definition in Crohn's disease and ulcerative colitis.

The diagnosis of inflammatory bowel disease is usually made on a combination of clinical, radiologic, endoscopic, and histologic grounds. In the differential diagnosis, endoscopy and histologic evaluation of biopsy specimens can help to make a specific diagnosis. Site of disease is important in documentation and can determine drug choice and clinical course. Disease activity indices are important to assess a patient objectively, particularly in multicentre studies. There is poor correlation between disease activity indices and macroscopic and histologic findings. The Severity Activity Index for Crohn's disease has both clinical and laboratory variables and is a valuable tool for the definition of Crohn's disease. An ulcerative colitis activity index that correlates significantly with microscopic and macroscopic scores, using both clinical symptoms and laboratory findings, is proposed.

Colitis, Ulcerative↗