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Biomedical subjects

J Meyer

Publications and source records attributed to J Meyer.

At least 181 records · Page 10Linked to original sources

Are morphological or functional changes in the carotid artery wall associated with Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, or herpes simplex virus infection?

BACKGROUND AND PURPOSE: Chronic infection with Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus (CMV), and herpes simplex virus (HSV) has been implicated in the pathogenesis of atherosclerosis. The carotid intima-media thickness (IMT) can be taken to indicate early atherosclerosis, the presence of a carotid stenosis is a marker of a manifest carotid atherosclerosis, and an increase in arterial stiffness is used as marker of structural and functional changes in an atherosclerotic vessel wall. METHODS: In 504 patients (75% men; mean age 62.9 [SD 10] years), we measured the IMT and the elastic pressure modulus (EP; n=445) of the common carotid artery and the prevalence of a internal or external carotid artery stenosis. Blood samples were taken, and antibodies against C pneumoniae, H pylori, CMV, and HSV types 1 and 2 were evaluated. Statistical evaluation was performed with regression procedures and multivariate logistic regression analyses. RESULTS: Seropositivity for C pneumoniae was an independent predictor for a combined end point of highest category of IMT and carotid artery stenosis (OR 1.8, 95% CI 1.1 to 3.1; adjusted) for IgG titers. Independently, CMV increased the risk for the combined end point (OR 1.7, 95% CI 1.1 to 2.8; adjusted) for IgG titers and for IgA titers (OR 2.3, 95% CI 1.1 to 4. 9; adjusted). We found a significant correlation between IgG antibodies against CMV and EP; HSV type 2 IgG titers were associated with IMT and carotid stenosis, but the latter results were no longer significant after adjustment. There was no association with H pylori or HSV type 1. CONCLUSIONS: We found a significant association of IgG antibodies against C pneumoniae and CMV with early and advanced carotid atherosclerosis. CMV was also correlated to functional changes of the carotid artery, but this could not be confirmed after adjustment.

Arteriosclerosis↗

Some limitations in the practical delivery of intensity modulated radiation therapy.

The resolution characteristics of intensity modulated beam (IMB) profiles produced by milled compensators and by multileaf collimators (MLCs) are independently investigated with respect to the primary fluence. It is shown that both methods have different characteristics in the longitudinal and lateral direction and, as a consequence, the resolutions of the longitudinal and lateral delivered IMB profiles differ. For both methods, the restrictions are identified. For compensators, the maximum slopes in the machining process, which should not be exceeded, are quantified. For MLCs, emphasis is given to the direction perpendicular to leaf movement. A number of test modulations were created and the effect of different size MLCs on the intensity profile revealed that unacceptable errors can be introduced if the profiles are heavily modulated. The production of intensity modulated radiation therapy (IMRT) beams by both machined compensators or by MLCs is limited by physical constraints. Having identified these constraints, some steps should now be taken to accommodate them either in the objective function for the calculation of the beam profiles or in the delivery system.

Equipment Design↗

A health visitor for older people in an accident and emergency department.

Published studies indicate that older people have special needs on discharge from accident and emergency (A&E) departments that are not always fully met. The literature reflects that although a significant proportion of older people have a decrease in functional independence and an increased need for services following discharge from A&E, social and functional assessment by A&E staff can be inadequate, as can the arrangement of follow-up community services. As part of a wider study into the organization of care for older people in A&E, a health visitor for older people was funded to work part-time in the A&E department of a large NHS Trust. The health visitor identified potential clients through reviewing the A&E documentation of patients aged 75 years or over discharged directly from A&E. Telephone calls or home visits were used to follow up those individuals deemed to be vulnerable by the health visitor. Interventions included health education, referral to other agencies and patient or family counselling. None of the clients followed up by the health visitor (n = 212) had been referred by A&E to a specialist in gerontology, which suggests that these clients would otherwise not have received the potential benefit of specialist intervention. The pilot study described here highlights a number of practical issues in relation to the health visitor post for older people in A&E, including the importance of dedicated office space and access to a telephone. Data collected during the study, plus the positive evaluation of the role by a small group of A&E staff confirm the claims made in other studies (e.g. Runciman et al, 1996) that health visitors for older people may be of value in meeting the post-discharge needs of these people.

Accidental Falls↗

Pathophysiology of impaired right and left ventricular function in chronic embolic pulmonary hypertension: changes after pulmonary thromboendarterectomy.

STUDY OBJECTIVES: This study sought to evaluate the pathophysiology of left and right heart failure in patients with chronic thromboembolic pulmonary hypertension (CTEPH) who were hospitalized to undergo pulmonary thromboendarterectomy (PTE). DESIGN: Thirty-nine patients (16 women and 23 men; mean +/- SD age, 55+/-12 years) with severe CTEPH were examined before and 13+/-8 days after PTE by way of transthoracic echocardiography and right heart catheterization. MEASUREMENTS AND RESULTS: Examination results confirmed in all cases that before surgery the right ventricles were enlarged and systolic function was impaired. Moderate to severe tricuspid valve regurgitation was observed. Left ventricular eccentricity indexes reflected a leftward displacement of the interventricular septum. End-diastolic left ventricular size and systolic function had decreased, and the left ventricular filling pattern showed impaired diastolic function. After surgery, mean pulmonary artery pressure was significantly lower (48+/- 10 mm Hg vs. 25+/-7 mm Hg; p<0.05). The calculated end-diastolic and end-systolic right ventricular areas had decreased: 30+/-7 cm(2) vs 21 +/-5 cm(2) (p<0.05) and 24+/-6 cm(2) vs. 14+/-4 cm(2) (p<0.05), respectively. Right ventricular fractional area change had increased (20+/-7% vs. 33+/-8%; p<0.05). Most of the patients exhibited a marked decrease in the severity of tricuspid regurgitation. Septal motion, left ventricular systolic function, and diastolic filling pattern returned to normal values (early to late diastolic left ventricular inflow ratio, 0.70+/-0.33 vs. 1.35+/-0.51; p<0.05). The mean cardiac index also improved (2.7+/-0.6 L/min/m(2) vs. 3.7+/-0.8 L/min/m(2)). CONCLUSIONS: In CTEPH, functions are impaired in the right as well as the left ventricles of the heart. Improved lung perfusion and the reduction of right ventricular pressure overload are direct results of PTE, which in turn bring a profound reduction of right ventricular size and a recovery of systolic function. Normalization of interventricular septal motion as well as improved venous return to the left atrium lead to a normalization of left ventricular diastolic and systolic function, and the cardiac index improves.

Adult↗

[Physiological effects of destruction of the tip links of cochlear hair cells. Significance for noise-induced hearing loss].

Sound overexposure is known to cause damage to cochlear structures and can induce permanent or temporary hearing loss and tinnitus. Perhaps the most sensitive of these structures to sound overexposure are the tip links. In this paper the electrophysiological effects of pharmacological destruction of the tip links of outer hair cells was investigated. Outer hair cells treated with elastase (20 U/mL) or BAPTA (5 mM) no longer responded to sinusoidal stimuli. In contrast to common belief, transduction channels opened due to loss of tip links. Such opened channels can allow K+ and Ca2+ to enter the cell from the endolymphatic space and cold lead to permanent depolarization. This influx of cations caused by loss of tip links, together with the subsequent hair-cell depolarization, might be a source of sensorineural hearing loss and tinnitus associated with acoustic trauma.

Animals↗

Clostridial iron-sulphur proteins.

Iron-sulfur proteins are ubiquitous catalysts of a wide range of biological reactions, and are particularly abundant in clostridia which lack the ability to synthesize hemes. The development of research on these metalloproteins has therefore been strongly associated with biochemical investigations of clostridial metabolism. Major breakthroughs in the field, from the first isolation of an iron-sulfur protein in 1962, to the recent determination of an Fe-hydrogenase structure, have been made with clostridia. These data, as well as others obtained through studies on clostridia, are transferable to many other bioenergetic machineries, due to the strong phylogenetic conservation of some important components. For instance, clear homologies exist between constituents of the anaerobic electron transfer chains in clostridia and aerobic respiratory chains. The contribution of iron-sulfur proteins to the biotechnological and medical significance of clostridia is also discussed. Structural and functional genomics are expected to bring forth a wealth of novel data on clostridia and iron-sulfur proteins.

Bacterial Proteins↗

[Antimicrobial effects of tea tree oil (Melaleuca alternifolia) on oral microorganisms].

The essential oil of Melaleuca alternifolia (tea tree oil) exhibits antimicrobial activity against a wide range of Gram-positive and Gram-negative bacteria, yeasts and fungi. In this study the bacteriostatic and bacteriocidal/fungicidal activity of a tea tree oil solution, of a new tea tree oil (Tebodont) and the respective placebo-gel, of a chlorhexidindigluconate-solution and of PlakOut was tested in vitro against ten different oral microorganisms. Minimum inhibitory concentrations were in the range from 0.0293% to 1.25% for the tea tree oil solution and from 0.0082% to 1.25% for the tea tree oil gel. The values for minimum bacteriocidal/fungicidal concentrations were in the range from 0.0521% to 2.5% for the tea tree oil solution and from <0.0098% to 3.33% for the tea tree oil gel. The most susceptible microorganisms were Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum, and Porphyromonas gingivalis, whereas Streptococcus mutans and Prevotella intermedia were the least susceptible ones. Both for the chlorhexidindigluconate solution and for PlakOut the values for the minimal inhibitory concentration and for the minimal cidal concentration were between <0.0002% and 0.0125%.

Anti-Infective Agents, Local↗

Suggestive linkage of chromosome 10p to schizophrenia is not due to transmission ratio distortion.

The genome scan of the European-American schizophrenia families from the Human Genetics Initiative of the National Institute of Mental Health (NIMH) reported a suggestive linkage to chromosome 10p. Subsequently, Paterson and Petronis [1999] reported evidence for transmission ratio distortion on 10p to females. They suggested that transmission ratio distortion to females might have created spurious evidence for linkage to 10p. To address this issue, we reanalyzed our 10p data using only male-male affected sibling pairs. The two chromosome 10p markers that gave the most evidence for linkage in our prior report continued to show evidence for linkage: D10S1423 (NPL Z = 3.0, P = 0.001) and its neighbor D10S582 (NPL Z = 2.9, P = 0.002). These data suggest that our prior report of suggestive linkage of schizophrenia to markers on 10p cannot be attributed to the transmission ratio distortion to females reported by Paterson and Petronis. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:607-608, 1999.

Chromosomes, Human, Pair 10↗

A nonhealing ulcer diagnosed as extramedullary plasmocytoma of the limb eight years after cardiac transplantation.

A 63-year-old man was hospitalized for a nonhealing ulcer of the left lower leg that appeared 8 years after orthotopic cardiac transplantation under immunosuppressive therapy including cyclosporine. Serum protein electrophoresis, immunofixation, and urinalysis revealed a monoclonal gammopathy IgG kappa. The final diagnosis of an extramedullary plasmocytoma was made by biopsy of the ulcer, which showed formations of plasmablastic cells. We report a rare case of extramedullary plasmocytoma as a posttransplantational malignancy.

Cyclosporine↗

Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 double-blind randomised trial.

BACKGROUND: Bolus fibrinolytic therapy facilitates early efficient institution of reperfusion therapy. Tenecteplase is a genetically engineered variant of alteplase with slower plasma clearance, better fibrin specificity, and high resistance to plasminogen-activator inhibitor-1. We did a double-blind, randomised, controlled trial to assess the efficacy and safety of tenecteplase compared with alteplase. METHODS: In 1021 hospitals, we randomly assigned 16,949 patients with acute myocardial infarction of less than 6 h duration rapid infusion of alteplase (< or = 100 mg) or single-bolus injection of tenecteplase (30-50 mg according to bodyweight). All patients received aspirin and heparin (target activated partial thromboplastin time 50-75 s). The primary outcome was equivalence in all-cause mortality at 30 days. FINDINGS: Covariate-adjusted 30-day mortality rates were almost identical for the two groups--6.18% for tenecteplase and 6.15% for alteplase. The 95% one-sided upper boundaries of the absolute and relative differences in 30-day mortality were 0.61% and 10.00%, respectively, which met the prespecified criteria of equivalence (1% absolute or 14% relative difference in 30-day mortality, whichever difference proved smaller). Rates of intracranial haemorrhage were similar (0.93% for tenecteplase and 0.94% for alteplase), but fewer non-cerebral bleeding complications (26.43 vs 28.95%, p=0.0003) and less need for blood transfusion (4.25 vs 5.49%, p=0.0002) were seen with tenecteplase. The rate of death or non-fatal stroke at 30 days was 7.11% with tenecteplase and 7.04% with alteplase (relative risk 1.01 [95% CI 0.91-1.13]). INTERPRETATION: Tenecteplase and alteplase were equivalent for 30-day mortality. The ease of administration of tenecteplase may facilitate more rapid treatment in and out of hospital.

Aged↗

Highly efficient liposome-mediated gene transfer of inducible nitric oxide synthase in vivo and in vitro in vascular smooth muscle cells.

OBJECTIVE: The efficient introduction of regulatory genes into vascular smooth muscle cells (SMCs) is one of the most promising options for gene therapy of cardiovascular diseases. Cationic liposome-mediated gene transfer may become a favorable transfection technique with regard to patient's safety for in vivo administration. However, this method until now has its limitation in a low transfection efficiency. Therefore, the present study was designed to improve cationic liposome-mediated transfection of rabbit vascular SMCs in vitro and in vivo, in order to enhance transfection efficiency and present an optimized system which may offer a potential therapeutic benefit for in vivo application. METHODS AND RESULTS: Optimized lipofection of rabbit SMCs with the mammalian expression vector pE-N1 and the reporter gene green fluorescent protein resulted in a mean transfection efficiency of about 50%. The unique transfection of rabbit SMCs in vitro and in vivo with the inducible isoform of human nitric oxide synthase (NOSII), using the same vector, resulted in a successful transient transcription and translation of a functionally active human NOSII in rabbit SMC, persisting 5-6 days. We could further demonstrate that the transfection procedure and the transgene product did neither induce necrosis nor apoptosis under the conditions chosen and did not result in the induction of endogenous NOSII of transfected SMCs. CONCLUSION(S): These findings indicate potential therapeutic relevance for this nonviral gene transfer system for in vivo gene therapy for cardiovascular diseases.

Animals↗

A [2Fe-2S] protein from the hyperthermophilic bacterium Aquifex aeolicus.

Overexpression in Escherichia coli of the fdx4 gene from Aquifex aeolicus has allowed isolation and characterization of the first hyperthermophilic [2Fe-2S](Scys)(4) protein, a homodimer of M = 2 x 12.4 kDa with one [2Fe-2S] cluster per subunit. This protein is undamaged by heating to 100 degrees C for at least three hours. The primary structure, in particular the characteristic distribution of the four cysteine ligands of the metal site, and the spectroscopic properties of the A. aeolicus protein relate it to well characterized [2Fe-2S] proteins from Clostridium pasteurianum and Azotobacter vinelandii. These proteins are also homologous to subunits or domains of hydrogenases and NADH-ubiquinone oxidoreductase (Complex I) of respiratory chains. The A. aeolicus [2Fe-2S] protein is thus representative of a presumably novel protein fold involved in a variety of functions in very diverse cellular backgrounds.

Amino Acid Sequence↗

Hospital discharge. Smooth passage.

The introduction of care co-ordinators into a medical directorate two years ago has reduced bed blocking and cut length of stay from 8.5 to 5.9 days. All those appointed were already working in the hospital. There have been some tensions over boundaries with nursing and social work.

Case Management↗

Vaccination against tick-borne encephalitis under therapeutic immunosuppression. Reduced efficacy in heart transplant recipients.

Patients after organ transplantation are at an increased risk of microbial infections and might benefit from active vaccination. Due to therapeutic immunosuppression the efficacy of immunizations is, however, reduced and difficult to predict. Efficacy of vaccination against tick-borne encephalitis (TBE) using an abbreviated immunization schedule was compared in 31 heart transplant recipients (age: 54.5 +/- 11.5 years, mean time after transplantation: 53.5 +/- 23.7 months) under cyclosporine-based immunosuppression and 29 controls. TBE vaccination was well tolerated by the transplant recipients; spectrum and frequency of adverse events were similar to controls. In the transplant patients, seroconversion rate (35% versus 100%; p < 0.001) and the geometric mean of post-vaccinal antibody titres (0.98 (SF: 2.3) U/ml versus 5.46 (2.2) U/ml; p < 0.001) were markedly reduced in comparison to the control group. No clinical or demographic predictors of vaccination success could be established in the transplant patients. Due to the limited efficacy, TBE vaccination cannot be recommended as a routine procedure in heart transplant recipients at risk of TBE virus infection. TBE vaccination may be performed safely in selected cases, but repeated titre controls to confirm vaccination success would be required.

Adult↗

[Nicorandil: acute hemodynamic effects of 2 different oral doses of a potassium channel opener in patients with coronary heart disease].

BACKGROUND: In medical treatment of angina pectoris the 3 major groups of antianginal agents are nitrates, beta blockers and calcium antagonists. Now a new class of drugs is introduced in the therapy: the potassium channel openers. One of the first potassium channel openers is nicorandil. We examined the acute hemodynamic effects of 2 different oral nicorandil doses in patients with coronary heart disease. PATIENTS AND METHODS: Twenty patients with angiographic proven coronary heart disease and stable angina pectoris were treated with a dose of 2 x 10 mg Nicorandil on day 1 and 2 x 20 mg Nicorandil on day 2, while being hemodynamically monitored on an intensive care unit with a pulmonary artery catheter. RESULTS: Through the hemodynamic monitoring a dose dependent, significant reduction of systolic blood pressure was found (6%/9%), while the heart rate increased dose dependently (6%/11%). The rate pressure product as a marker of myocardial oxygen demand did not increase significantly. CONCLUSION: The oral application of nicorandil causes an acute, dose dependent, significant decrease in systolic blood pressure and induces a reflextachycardia.

Administration, Oral↗

Structural similarities between the N-terminal domain of Clostridium pasteurianum hydrogenase and plant-type ferredoxins.

An N-terminal domain of Clostridium pasteurianum hydrogenase I, encompassing 76 residues out of the 574 composing the full-size enzyme, had previously been overproduced in Escherichia coli and shown to form a stable fold around a [2Fe-2S] cluster. This domain displays only marginal sequence similarity with [2Fe-2S] proteins of known structure, and therefore, two-dimensional 1H NMR has been implemented to elucidate features of the polypeptide fold. Despite the perturbing presence of the paramagnetic [2Fe-2S] cluster, 57 spin systems were detected in the TOCSY spectra, 52 of which were sequentially assigned through NOE connectivities. Several secondary structure elements were identified. The N terminus of the protein consists of two antiparallel beta strands followed by an alpha helix contacting both strands. Two additional antiparallel beta strands, one of them at the C terminus of the sequence, form a four-stranded beta sheet together with the two N-terminal strands. The proton resonances that can be attributed to this beta2alphabeta2 structural motif undergo no paramagnetic perturbations, suggesting that it is distant from the [2Fe-2S] cluster. In plant- and mammalian-type ferredoxins, a very similar structural pattern is found in the part of the protein farthest from the [2Fe-2S] cluster. This indicates that the N-terminal domain of C. pasteurianum hydrogenase folds in a manner very similar to those of plant- and mammalian-type ferredoxins over a significant part (ca. 50%) of its structure. Even in the vicinity of the metal site, where 1H NMR data are blurred by paramagnetic interactions, the N-terminal domains of hydrogenase and mammalian- and plant-type ferredoxins most likely display significant structural similarity, as inferred from local sequence alignments and from previously reported circular dichroism and resonance Raman spectra. These data afford structural information on a kind of [2Fe-2S] cluster-containing domain that occurs in a number of redox enzymes and complexes. In addition, together with previously published sequence alignments, they highlight the widespread distribution of the plant-type ferredoxin fold in bioenergetic systems encompassing anaerobic metabolism, photosynthesis, and aerobic respiratory chains.

Amino Acid Sequence↗