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Biomedical subjects

M Green

Publications and source records attributed to M Green.

At least 235 records · Page 13Linked to original sources

Identification of pesticide poisoning in wildlife.

The Wildlife Incident Investigation Scheme investigates incidents of suspected poisoning of wildlife (also honey bees and companion animals) by pesticides in the United Kingdom. The approach to these investigations has evolved over the past 30 years. Field investigations, post-mortem examinations, toxicological data and experience of previous poisoning incidents assist in the selection and interpretation of appropriate chemical analyses. Several 'multi-residue' and several 'individual compound' analytical methods for pesticides in wildlife are currently in use; these are described.

Animals↗

How useful is thyroid function testing in patients with recent-onset atrial fibrillation? The Canadian Registry of Atrial Fibrillation Investigators.

BACKGROUND: Patients with recent-onset atrial fibrillation often undergo routine thyroid function screening to rule out thyroid disease as a cause of atrial fibrillation. METHODS: Patients with recent (< 3 months) onset of documented atrial fibrillation or flutter were enrolled in the Canadian Registry of Atrial Fibrillation from outpatient clinics, emergency departments, and hospital wards across Canada. Seven hundred twenty-six patients underwent baseline thyroid function screening and were assessed for presence of clinical thyroid disease. Serum thyrotropin level (TSH) was measured in 707 patients (97%), and thyroxine level (T4) in 407 patients (56%). RESULTS: A TSH level less than 0.1 mU/L was present in 5 patients (0.7%). A TSH level less than normal but more than 0.1 mU/L was present in 34 patients (4.7%). No patient had definite hypothyroidism (TSH > 20 mU/L), but 56 patients (7.7%) had an elevated TSH level that was less than 20 mU/L. During 1.7 years of follow-up, only 7 patients were found to have clinical hyperthyroidism, and 11 patients (1.5%) had hypothyroidism. Logistic regression analysis showed that palpitations (odds ratio, 4.9; 95% confidence interval, 1.7-14.0) and asymptomatic presentation (odds ratio, 5.5; 95% confidence interval, 1.9-16.2) were risk factors for low TSH level, and increasing age (odds ratio, 1.32 every 10 years; 95% confidence interval, 1.01-1.66) was a risk factor for high TSH level. The positive predictive value of palpitations and asymptomatic presentation for low TSH level were 9% and 8%, respectively. CONCLUSIONS: An abnormal TSH level is common in patients with recent-onset atrial fibrillation. However, clinical thyroid disease is uncommon. Routine TSH screening of patients who have atrial fibrillation has a low yield and may be better applied to those patients at higher risk of having undiagnosed clinical thyroid disease.

Atrial Fibrillation↗

Segregation of the fragile X mutation from a male with a full mutation: unusual somatic instability in the FMR-1 locus.

Fragile X syndrome is associated with an unstable CGG-repeat in the FMR-1 gene. There are few reports of affected males transmitting the FMR-1 gene to offspring. We report on a family in which the propositus and his twin sister each had a full mutation with abnormal methylation. Their mother had an FMR-1 allele in the normal range and a large premutation, with normal methylation. The maternal grandmother had two normal FMR-1 alleles. The maternal grandfather had an unusual somatic FMR-1 pattern, with allele size ranging from premutation to full mutation. No allele was detectable by PCR analysis. Multiple Southern blot analyses identified a hybridization pattern that originated at a distinct premutation band and extended into the full mutation range. Methylation studies revealed a mosaic pattern with both unmethylated premutations and methylated full mutations. This individual declined formal evaluation but did not finish high school and has difficulty in reading and writing. The size of the premutation FMR-1 allele passed to his daughter is larger than his most prominent premutation allele. This is most likely due to gonadal mosaicism similar to that in his peripheral lymphocytes. Alternatively, this expansion event may have occurred during his daughter's early embryonic development and this large premutation allele is mitotically unstable. This pattern of FMR-1 alleles in a presumably mildly affected male is highly unusual. These findings are consistent with the absence of transmission of a full fragile X mutation through an expressing male. Studies of tissue specific FMR-1 allele expansion and FMR-1 protein expression on this individual should help to determine the correlation of the molecular findings with the phenotypic effects.

Alleles↗

Developmental and tissue-specific expression of mouse pelle-like protein kinase.

The NF-kappaB/c-Rel proteins are a family of evolutionarily conserved transcription factors activated during development that in the adult, mediate many processes including the immune response. A high degree of sequence similarity is shared between the NF-kappaB/c-Rel family of transcription factors and the Drosophila Dorsal protein as well as between its cytoplasmic inhibitor, IkappaBalpha, and the Drosophila Cactus protein. Genetic analyses of Dorsal have defined components of a signaling pathway for Dorsal activation, including a serine/threonine kinase, Pelle, placed upstream of Dorsal and Cactus. We demonstrate that this pathway is likely to be conserved in mammals by the isolation of a cDNA that encodes a novel mouse protein highly related to Pelle, mPLK (mouse Pelle-like protein kinase). Expression of mPLK mRNA is developmentally regulated in the mouse and in adult tissue mPLK expression is greatest in the liver, a tissue that expresses a high level of NF-kappaB. Recombinant mPLK produced in bacteria is a protein kinase capable of autophosphorylating and phosphorylating IkappaBalpha.

Amino Acid Sequence↗

Quadriceps strength and fatigue assessed by magnetic stimulation of the femoral nerve in man.

There is no nonvolitional method of assessing quadriceps strength which both supramaximally activates the muscle and is acceptable to subjects. In 10 normal subjects and 10 patients with suspected muscle weakness we used magnetic stimulation of the femoral nerve to elicit an isometric twitch and measured twitch tension (TwQ), surface electromyogram in addition to the maximum voluntary contraction force (MVC). Supramaximality was achieved in all subjects at a mean of 83% of maximum stimulator output. When supramaximal, TwQ was reproducible (mean coefficient of variation 3.6%, range 0.7-10.9) and correlated well with MVC (r2 = 0.83, P<0.001). In 7 normal subjects we measured TwQ before and after a fatiguing protocol; after 20 min TwQ was a mean of 55% (range 29-77%) of baseline and remained substantially reduced at 90 min. Magnetic femoral nerve stimulation is a painless, supramaximal method of assessing quadriceps strength and fatigue which is likely to be of value in clinical and physiological studies.

Action Potentials↗

In quest of outcomes: the Larimer Project.

This article illustrates Larimer County Mental Health Center's response to the intensifying demand for mental healthcare organizations to develop treatment outcome evaluation systems. It describes the integration of the Target Complaints Assessment (TCA) procedure into the everyday clinical assessment and treatment processes of the organization. The article delineates the development of the procedure's practical application and its usefulness as a feedback mechanism to senior management and line clinicians.

Documentation↗

Human aortic valve allografts elicit a donor-specific immune response.

OBJECTIVE: The nature and magnitude of the immunologic response to implantation of human cryopreserved aortic valve allografts was investigated. METHODS: Twenty aortic valve allograft recipients were investigated for donor-specific antibody and T-cell-mediated responses with serial flow cytometric and microlymphocytotoxic crossmatch assays and one-way mixed lymphocyte cultures. RESULTS: Donor-specific immunoglobulin G antibodies to class I and II human leukocyte antigens were first detected in the serum of all aortic valve allograft recipients at 30 days after implantation and persisted in substantial amounts in all but one of the recipients at day 365. Recipient T-cell alloreactivity toward donor lymphocytes was significantly increased at day 30 compared with levels before and 10 days after operation. CONCLUSIONS: Cryopreserved aortic valve allografts elicit a substantial allogeneic response in recipients. This alloreactivity may contribute to the observed morphologic changes in aortic valve allografts and eventual long-term deterioration of allograft function.

Adult↗

Emerging resistance to antibiotics: impact on respiratory infections in the outpatient setting.

OBJECTIVE: To review the major mechanisms of antibiotic resistance and provide an overview of currently available oral antibiotics. This article discusses the impact of antibiotic resistance on respiratory infections (eg, otitis media, sinusitis, and pneumonia) encountered in the outpatient setting and appropriate management strategies for these infections are proposed. DATA SOURCES: A Medline search was performed to identify recent references from the English language pertinent to this topic. Proposed management schemes for infections due to antibiotic-resistant bacteria were derived from current literature as well as the opinion of the authors. RESULTS: Currently available oral antibiotics including penicillins, cephalosporins, macrolides, trimethroprim/sulfamethoxazole, and clindamycin continue to provide effective therapeutic options despite the increasing importance of antibiotic resistance in bacteria causing respiratory tract infections in the outpatient setting. The effectiveness of a given agent may no longer be assured, leading to the need for development of updated management strategies for patients experiencing treatment failure with antibiotics. Diagnostic strategies (ie, tympanocentesis) and novel treatment algorithms (eg, use of amoxicillin in combination with amoxicillin/clavulanate) for patients experiencing clinical failures potentially due to antibiotic-resistant bacteria are proposed. CONCLUSIONS: The increasing prevalence of antibiotic resistant bacteria (especially penicillin-resistant Streptococcus pneumoniae) is leading to new approaches to the management of common respiratory infections in the outpatient setting. Additional experience and careful clinical trials are necessary to identify optimal management strategies for these infections.

Cephalosporins↗

Post-ischemic shunt following hepatic ischemia/reperfusion does not affect tissue chemokine levels of tissue injury.

Hepatic ischemia followed by reperfusion causes the release of a cascade of mediators, including tumor necrosis factor-alpha and epithelial neutrophil activating protein (ENA-78), which are important in the subsequent development of the lung and liver injury associated with this insult. We hypothesize that preferential post-ischemic shunting of blood into the nonischemic hepatic lobes at the time of reperfusion may increase the ischemic injury. To test this hypothesis, we utilized a rat model of lobar no-flow hepatic ischemia/reperfusion and removed the nonischemic hepatic lobes at the time of reperfusion to eliminate the preferential shunting of blood into the nonischemic tissues. We assessed pulmonary and hepatic tissue levels of ENA-78, pulmonary neutrophil influx and changes in pulmonary capillary permeability, and liver injury as measured by hepatic neutrophil influx and serum transaminase levels. Our results demonstrated that there were no significant differences in pulmonary and hepatic levels of ENA-78, or in the development of the lung and liver injury in animals undergoing resection of the nonischemic hepatic lobes at the time of reperfusion, as compared with animals undergoing hepatic ischemia/reperfusion alone.

Animals↗

Hepatic inflammation following 70% hepatectomy may be related to up-regulation of epithelial neutrophil activating protein-78.

Tumor necrosis factor-alpha (TNF) is known to be released after partial hepatectomy. Furthermore, TNF triggers the release of chemotactic cytokines, such as epithelial neutrophil activating protein (ENA-78), which are important for neutrophil chemotaxis, activation, and propagation of the inflammatory response. We now postulate that ENA-78 may play a role the hepatic inflammatory response that occurs following partial hepatectomy. Rats were subjected to 70% hepatectomy or sham laparotomy and were killed in a time-dependent manner. Hepatic neutrophil influx, as assessed by myeloperoxidase (MPO) levels, serum alanine aminotransferase (ALT), and hepatic TNF and ENA-78 levels, as measured by ELISA, were evaluated at 1, 6, and 12 h following operation. MPO levels became significantly elevated within 6 h of hepatectomy and remained elevated at 12 h. Serum ALT became significantly elevated within 1 h of hepatectomy and continued to rise at 12 h. Hepatic TNF and ENA-78 were also increased significantly after hepatectomy. Next, rats undergoing 70% hepatectomy were treated with neutralizing anti-ENA-78 serum; this resulted in a significant decrease in hepatic MPO and serum ALT, suggesting less hepatic injury. To determine whether ENA-78 release was induced by TNF is this model, rats were treated with neutralizing anti-TNF serum and hepatic ENA-78 levels measured 6 h posthepatectomy. ENA-78 levels were significantly decreased in the animals receiving the anti-TNF serum, suggesting that ENA-78 is released in response to TNF in this model. These data suggest that TNF triggers the release of ENA-78 following 70% hepatectomy and that ENA-78 contributes to the hepatic neutrophil influx and liver injury following 70% hepatectomy.

Alanine Transaminase↗

UDP glucuronosyltransferase in the cirrhotic rat liver.

In patients with cirrhosis, the elimination of drugs metabolized by glucuronidation is relatively preserved, in comparison with the metabolism of drugs by oxidation. This study explores this phenomenon at a molecular level. In cirrhotic rat livers the content of UDP-glucuronosyltransferase (UGT) was examined by immunohistochemistry and immunoblotting using three antibodies: (i) a polyclonal antibody directed against a broad number of UGT isoforms from both family 1 and family 2; (ii) a family 2-specific antibody; and a (iii) family 1-specific antibody. The steady state mRNA level of UGT of a family 2 isoform was also detected by northern blot analysis. The results demonstrate normal or increased UGT protein by immunohistochemistry and immunoblot in cirrhotic livers compared with controls. This was accompanied by increased steady state mRNA encoding the UGT isoform UGT2B1. In contrast, an isoform of cytochrome P450 (CYP2C11) was reduced markedly in both immunohistochemical staining and immunoblot analysis. These results suggest that in cirrhosis there is a comparative increase or at least a maintenance of UGT enzyme content and that this most likely occurs at a pretranslational level.

Animals↗

d-Sotalol decreases defibrillation energy requirements in humans: a novel indication for drug therapy.

INTRODUCTION: We assessed the effect of d-sotalol on defibrillation voltage and energy requirements in patients undergoing automatic defibrillator implantation. Drugs that primarily prolong cardiac refractoriness generally decrease the energy requirements for defibrillation in animal models. Despite the widespread use of antiarrhythmic drugs in patients with implanted cardioverter defibrillators, the effect of such drugs on defibrillation energy requirements in humans has not been well studied. Sotalol (in the d,l racemic form) is an antiarrhythmic with beta-blocking and cardiac refractoriness prolonging effects. The d-isomer of sotalol is largely devoid of beta-blocking effects; both forms decrease defibrillation energy requirements in animals. We hypothesized that d-sotalol would decrease defibrillation voltage and energy requirements in humans. METHODS AND RESULTS: Fifteen patients undergoing implanted cardioverter defibrillator implantation were studied before and 20 minutes after d-sotalol infusion (2 mg/kg IV in 15 min, followed by 1 mg/kg per hour). The estimated energy (E50) and voltage (V50) for 50% success in defibrillation (estimated from two successive defibrillation "threshold" measurements), ventricular effective refractory period, monophasic action potential duration, and mean cycle length of ventricular fibrillation were measured, along with heart rate, blood pressure, and plasma concentration of d-sotalol. There was a significant decrease in defibrillation energy (E50 = 12.4 +/- 5.0 J before and 8.4 +/- 4.0 J after d-sotalol, P < 0.003) and voltage (V50 = 440 +/- 77 V before and 354 +/- 93 V after d-sotalol, P < 0.001). Consistent with the Class III effect of d-sotalol, ventricular effective refractory period increased from 284 +/- 21 to 330 +/- 24 msec (P < 0.001), and action potential duration was prolonged from 296 +/- 28 to 340 +/- 22 msec (P < 0.001). Following d-sotalol, there was a tendency for induced tachyarrhythmia to self-terminate (23/102 episodes before vs 74/150 after sotalol, P < 0.001), and ventricular fibrillation cycle length was increased from 216 +/- 20 msec before to 274 +/- 23 msec (P < 0.001) after d-sotalol, despite the persistence of a rapid, disorganized rhythm of the surface ECG. No patient suffered adverse effects. CONCLUSIONS: d-Sotalol lowers defibrillation energy by a mean 32% +/- 27% at concentrations producing a 16% +/- 7% increase in ventricular effective refractory period. Along with its other antiarrhythmic effects, d-sotalol may increase the safety margin for defibrillation or allow lower programmed energies in patients with implanted defibrillators.

Adrenergic beta-Antagonists↗

Safety and immunogenicity of investigational Shigella conjugate vaccines in Israeli volunteers.

The safety and immunogenicity of investigational conjugates, composed of the O-specific polysaccharides of Shigella sonnei and Shigella flexneri type 2a covalently bound to Pseudomonas aeruginosa recombinant exoprotein A (rEPA), were evaluated in 192 Israeli soldiers. None had significant local reactions or fever. Fourteen days after injection, 90% of S. sonnei-rEPA recipients and 73 to 77% of S. flexneri-rEPA recipients had a fourfold or greater increase in serum immunoglobulin G (IgG) and IgA anti-lipopolysaccharide (anti-LPS) levels; at 2 years, these remained higher than at prevaccination (P < 0.01). There was a fourfold or greater increase in IgM anti-LPS in 20% of vaccinees at 2 weeks, but levels returned to prevaccination values at 6 to 12 months. IgG was the highest and most sustained class of LPS antibodies. Reinjection at day 42 did not boost antibody levels. Eighteen of 23 (78%) who received S. sonnei-rEPA and 13 of 19 (68%) who received S. flexneri-rEPA. had significant IgA-secreting cell responses. Significant IgG antibody-secreting cell responses were detected in 19 of 23 (83%) and 11 of 19 (58%) volunteers following vaccination with S. sonnei-rEPA and S. flexneri 2a-rEPA, respectively. On the basis of these data, further evaluation of the Shigella conjugates for protective efficacy in field trials in Israel was started.

Adolescent↗

Field inversion gel electrophoretic analysis of Legionella pneumophila strains associated with nosocomial legionellosis in children.

Two nosocomial cases of Legionnaires' disease occurred in children. Legionella pneumophila serogroup 1 was isolated from both patients and 30 of 39 plumbing system sites in the hospital. The patient and hospital environmental isolates yielded identical field inversion gel electrophoretic patterns which differed from patterns observed with epidemiologically unrelated strains.

Child↗