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Biomedical subjects

J Griffin

Publications and source records attributed to J Griffin.

At least 19 recordsLinked to original sources

Genotyping of Mycobacterium bovis isolates from badgers in four areas of the Republic of Ireland by restriction fragment length polymorphism analysis.

An analysis of the molecular epidemiology of Mycobacterium bovis in badgers was made in four selected areas of the Republic of Ireland in which an intensive badger removal programme was being carried out over a period of five years. Tissue samples from 2310 badgers were cultured. Restriction fragment length polymorphism (RFLP) analysis with IS6110, polymorphic GC-rich sequence (PGRS) and direct repeat sequence (DR) probes was applied to the isolates from 398 badgers, and 52 different rflp types were identified. Most of the isolates belonged to seven predominant types, and the other 45 types were represented by few isolates. An analysis suggests that some of these 45 types may have been introduced by the inward migration of badgers and others may have been the result of genetic changes to one of the prevalent types. The badgers were divided into groups on the basis of the sett at which they were captured, and RFLP typing was applied to isolates from two or more badgers from 85 groups. Multiple RFLP types were identified among isolates from 50 of these groups, suggesting that badgers probably moved frequently between group territories.

Animals↗

Selamectin is a potent substrate and inhibitor of human and canine P-glycoprotein.

The transport of the antiparasitic agents, ivermectin, selamectin and moxidectin was studied in human intestinal epithelial cell monolayers (Caco-2) and canine peripheral blood lymphocytes (PBL). Both models expressed the mdr1-coded 170 kDa ATP-binding cassette (ABC) transporter P-glycoprotein (P-gp). Fluxes of the P-gp substrate rhodamine-123 (Rh-123) across Caco-2 monolayers showed that ivermectin and selamectin acted as potent P-gp inhibitors with IC50 values of 0.1 microm. In contrast, moxidectin was a weaker P-gp inhibitor with an IC50 of 10 microm. The transport of radiolabelled ivermectin, selamectin and moxidectin through Caco-2 monolayers showed that ivermectin, selamectin and moxidectin were P-gp substrates with secretory/absorptive ratios of 7.5, 4.7 and 2.6 respectively. Secretory transport of [3H]-ivermectin and [3H]-selamectin was blocked by the P-gp inhibitor, verapamil. Ivermectin and selamectin inhibited the efflux of Rh-123 from PBL and the concentration of inhibition was similar to that of verapamil. In contrast, moxidectin did not have a significant effect on Rh-123 efflux from PBL. The data suggest that ivermectin and selamectin are potent P-gp substrates, while moxidectin is a weak one.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

A modern day holy anorexia? Religious language in advertising and anorexia nervosa in the West.

OBJECTIVE: In this review we comment on the media, in particular advertisements and the internet, using religious and moralistic motifs in connection with eating and their possible role in promoting modern-day 'nutritional' consumerism and fundamentalism (diet, discipline and discipleship). METHOD: We have reviewed historically the concept of holy anorexia and have analyzed the pictorial and language content of some representative advertisements. RESULTS: Words used include 'temptation', 'decadent', 'heaven' and 'purity' and suggest a connection with eating and moral values. They also imply eating as either heaven or sin, to be yielded to in both circumstances. CONCLUSIONS: Such messages identifying eating with guilt or reward could precipitate 'atypical' eating disorders in vulnerable subjects, invoking the historical associations with extreme religiosity and anorexia. It is not clear how these 'fundamentalist' trends developed but health educators should be aware of them in dealing with at-risk subjects for eating disorders.

Advertising↗

Comparison of end-tidal and transcutaneous measures of carbon dioxide during general anaesthesia in severely obese adults.

BACKGROUND: Patients with severe obesity (body mass index (BMI) greater than 35 kg x m(-2)) present difficulties for end-tidal carbon dioxide (FE'(CO(2))) monitoring. Previous studies suggest that transcutaneous (TC) carbon dioxide measurements could be valuable, so we compared FE' and TC measures with Pa(CO(2)) in severely obese patients during anaesthesia. METHODS: We studied patients with severe obesity (BMI >or=40 kg x m(-2)) undergoing gastric bypass surgery. Carbon dioxide was measured with both FE' and TC devices. The difference between each measure (FE'(CO(2)) and TC-CO(2)) and the Pa(CO(2)) was averaged for each patient to provide one value, and data compared with a non-paired, two-way t-test, Fisher's exact test. RESULTS: We studied 30 adults (aged 18-54 yr, mean 41, SD 8.0 yr; weight: 115-267 kg, mean 162, SD 35 kg). The absolute difference between the TC-CO(2) and Pa(CO(2)) was 0.2 (0.2) (mean, SD) kPa while the absolute difference between the FE'(CO(2)) and Pa(CO(2)) was 0.7 (0.4) kPa (P<0.0001). The bias and precision were +0.1 (0.3) kPa for TC vs arterial carbon dioxide and -0.7 (0.4) kPa for FE' vs arterial carbon dioxide. CONCLUSIONS: Transcutaneous carbon dioxide monitoring provides a better estimate of Pa(CO(2)) than FE'(CO(2)) in patients with severe obesity.

Adolescent↗

Normal flow (TIMI-3) before mechanical reperfusion therapy is an independent determinant of survival in acute myocardial infarction: analysis from the primary angioplasty in myocardial infarction trials.

BACKGROUND: Whereas survival after lytic therapy for myocardial infarction is strongly dependent on early administration, it is unknown whether the otherwise excellent outcomes in patients undergoing primary PTCA for acute myocardial infarction, in whom TIMI-3 flow rates of >90% may be achieved, can be further improved by early reperfusion. METHODS AND RESULTS: Among 2507 patients enrolled in 4 PAMI trials undergoing primary PTCA, spontaneous reperfusion (TIMI-3 flow) was present in 16% at initial angiography. Compared with patients without TIMI-3 flow, those with TIMI-3 flow before PTCA had greater left ventricular ejection fraction (57+/-10% versus 53+/-11%, P=0.003) and were less likely to present in heart failure (7.0% versus 11.6%, P=0.009). Patients with initial TIMI-3 flow had significantly lower in-hospital rates of mortality, new-onset heart failure, and hypotension and had a shorter hospital stay. Cumulative 6-month mortality was 0.5% in patients with initial TIMI-3 flow, 2.8% with TIMI-2 flow, and 4.4% with initial TIMI-0/1 flow (P=0.009). By multivariate analysis, TIMI-3 flow before PTCA was an independent determinant of survival (odds ratio 2.1, P=0.04), even when corrected for by postprocedural TIMI-3 flow. CONCLUSIONS: Patients undergoing primary PTCA in whom TIMI-3 flow is present before angioplasty present with greater clinical and angiographic evidence of myocardial salvage, are less likely to develop complications related to left ventricular failure, and have improved early and late survival. These data warrant prospective randomized trials of pharmacological strategies to promote early reperfusion before definitive mechanical intervention in acute myocardial infarction.

Aged↗

The effects of a home exercise program on pain and perceived dysfunction in a woman with TMD: a case study.

There are few reports analyzing the effects of exercise on patients with temporomandibular disorders. This paper presents a case study examining whether there were additional benefits from performing neuromuscular control home exercises (NMCHE) in a patient with temporomandibular disorder who was already receiving conventional treatment. A woman, 41 years of age, completed a health status questionnaire called the TMJ Scale prior to being accepted. She completed additional TMJ Scales after receiving conventional treatment and again after conventional treatment was combined with neuromuscular control home exercises. Based on the TMJ Scale's best subscore indicator of the presence or absence of a temporomandibular disorder, the patient did not derive benefit from conventional treatment without exercise. However, she received a large benefit from the addition of NMCHE. It was concluded that exercises for patients with temporomandibular disorders may be beneficial to those who do not improve with conventional treatment alone.

Adult↗

Applications of gene replacement technology to Streptomyces clavuligerus strain development for clavulanic acid production.

Cephamycin C production was blocked in wild-type cultures of the clavulanic acid-producing organism Streptomyces clavuligerus by targeted disruption of the gene (lat) encoding lysine epsilon-aminotransferase. Specific production of clavulanic acid increased in the lat mutants derived from the wild-type strain by 2- to 2.5-fold. Similar beneficial effects on clavulanic acid production were noted in previous studies when gene disruption was used to block the production of the non-clavulanic acid clavams produced by S. clavuligerus. Therefore, mutations in lat and in cvm1, a gene involved in clavam production, were introduced into a high-titer industrial strain of S. clavuligerus to create a double mutant with defects in production of both cephamycin C and clavams. Production of both cephamycin C and non-clavulanic acid clavams was eliminated in the double mutant, and clavulanic acid titers increased about 10% relative to those of the parental strain. This represents the first report of the successful use of genetic engineering to eliminate undesirable metabolic pathways in an industrial strain used for the production of an antibiotic important in human medicine.

Cephamycins↗

Effect of soft lumbar support belt on abdominal oblique muscle activity in nonimpaired adults during squat lifting.

STUDY DESIGN: A counterbalanced repeated measures design. OBJECTIVE: To determine the effect of a soft lumbar support on abdominal oblique muscle electromyography (EMG) during lifting. BACKGROUND: Use of a soft lumbar back support is a common preventive measure to reduce the incidence of back injuries. Because the abdominal oblique muscles stabilize the spine during lifting, wearing this support may alter the activity level of these muscles. METHODS AND MEASURES: Twenty nonimpaired subjects (14 women and 6 men, mean age 28.9 +/- 8.1 years) were tested using surface electrodes to record the EMG of the right abdominal oblique muscles during lifting with and without the support. RESULTS: A paired t test revealed a significant decrease in activity of the abdominal oblique muscles during lifting with the support (29.7 +/- 3.13 mV) compared to without it (33.3 +/- 3.05 mV). Of the 20 subjects, the 14 women showed decreased EMG amplitude during the lift with the lumbar support compared to without the support, while 5 of the men showed increased EMG amplitude with the support and 1 man showed no change. CONCLUSION: This finding suggests that the soft lumbar support may play some role in the stabilization of the lumbar region during lifting.

Abdominal Muscles↗

The biology of signal transduction inhibition: basic science to novel therapies.

Developing drugs to specifically inhibit oncogenes has been a major goal of cancer research for many years. Identifying the appropriate intracellular targets and understanding the signal transduction pathways in which these molecules participate are critical to this process. A large number of the activated oncogenes implicated in the pathogenesis and progression of malignancy are tyrosine kinases. Bcr-Abl, the causative molecular abnormality in chronic myeloid leukemia (CML), is a prototypic oncogenic kinase and an attractive drug target. The tyrosine kinase inhibitor imatinib mesylate (formerly STI571, [Gleevec]; Novartis Pharmaceuticals Corp, East Hanover, NJ) was recently approved for the treatment of CML and provides proof of principle for the strategy of targeted signal transduction inhibition. This drug is effective in the chronic phase of CML, a single gene disorder driven by Bcr-Abl, and in the advanced phases of CML, showing that inhibition of a single oncogene in a multigene disorder also may be of benefit. The success of imatinib mesylate in CML led rapidly to clinical trials in other cancers associated with activation of two other tyrosine kinases known to be sensitive to imatinib mesylate, c-Kit and the platelet-derived growth factor receptor. Gastrointestinal stromal tumors, which have activating mutations in c-Kit, are now also being found to respond to kinase inhibition with the drug. The general approach of specifically targeting activated kinases with small-molecule drugs is likely to be effective in other tumors in the future.

Antineoplastic Agents↗

Runaway pacemaker: a case report and review.

We describe a case of runaway pacemaker. The differential diagnosis is discussed and a review of the literature is included for the diagnosis and treatment of pacemaker mediated tachycardia and runaway pacemaker.

Aged↗

Predictors of homelessness among participants in a substance abuse treatment program.

Risk factors for homelessness were examined prospectively among recent participants in a substance abuse treatment program. Low levels of support from friends, greater depression, and recent substance use were bivariately associated with homelessness two months following completion of the program. However, friend support was the only factor associated with homelessness after controlling for other significant bivariate predictors.

Adult↗

Guillain-Barré syndrome.

The concepts of Guillain-Barré syndrome have changed substantially over the last 10 years, and the last 2 years have been no exception. Guillain-Barré syndrome is now recognized as a heterogeneous disorder with many clinical manifestations. Most current investigations are centered on the hypothesis of molecular mimicry. The major challenge now is to identify the precise mechanisms of nerve fiber injury and to determine how to prevent immune injury.

Antigens↗

Study of restriction fragment length polymorphism analysis and spoligotyping for epidemiological investigation of Mycobacterium bovis infection.

Restriction fragment length polymorphism (RFLP) analysis with probes derived from the insertion element IS6110, the direct repeat sequence, and the polymorphic GC-rich sequence (PGRS) and a PCR-based typing method called spacer oligonucleotide typing (spoligotyping) were used to strain type Mycobacterium bovis isolates from the Republic of Ireland. Results were assessed for 452 isolates which were obtained from 233 cattle, 173 badgers, 33 deer, 7 pigs, 5 sheep, and 1 goat. Eighty-five strains were identified by RFLP analysis, and 20 strains were identified by spoligotyping. Twenty percent of the isolates were the most prevalent RFLP type, while 52% of the isolates were the most prevalent spoligotype. Both the prevalent RFLP type and the prevalent spoligotype were identified in isolates from all animal species tested and had a wide geographic distribution. Isolates of some RFLP types and some spoligotypes were clustered in regions consisting of groups of adjoining counties. The PGRS probe gave better differentiation of strains than the IS6110 or DR probes. The majority of isolates from all species carried a single IS6110 copy. In four RFLP types IS6110 polymorphism was associated with deletion of fragments equivalent in size to one or two direct variable repeat sequences. The same range and geographic distribution of strains were found for the majority of isolates from cattle, badgers, and deer. This suggests that transmission of infection between these species is a factor in the epidemiology of M. bovis infection in Ireland.

Animals↗

Cytosolic redox state mediates postischemic response to pyruvate dehydrogenase stimulation.

Augmented pyruvate oxidation via pharmacological stimulation of pyruvate dehydrogenase (PDH) during reperfusion has been related to improved recovery of postischemic hearts independent of glycolytic activity. This study examined recovery of postischemic rabbit hearts during activation of PDH with dichloroacetate (DCA) in the presence of lactate, as a source of pyruvate, to determine the response to substrate-dependent changes in cytosolic redox state. After 10 min of ischemia, isolated hearts were reperfused with either 2.5 mM or 0. 5 mM pyruvate (Pyr) or 2.5 mM lactate (Lac), with or without 5 mM DCA. (13)C-enriched substrates allowed NMR assessment of metabolic perturbations. During normal perfusion, Pyr and Lac supported similar mechanical work. Increasing Pyr oxidation restored postischemic rate-pressure product to 82 +/- 4 and 88 +/- 6% of preischemic values during reperfusion with 2.5 and 0.5 mM Pyr, respectively, vs. 61 +/- 6 and 45 +/- 14% for untreated 2.5 and 0.5 mM Pyr, respectively (P < 0.05). In contrast, increasing Lac oxidation did not benefit recovery of RPP in untreated (44 +/- 7%) vs. DCA-treated 36 +/- 4% hearts. Thus the benefit of PDH activation for contractile recovery of postischemic hearts is mediated by the source of pyruvate, which also influences cytosolic redox state.

Animals↗