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Biomedical subjects

M Scherer

Publications and source records attributed to M Scherer.

At least 19 recordsLinked to original sources

Roles of COX-2 and iNOS in the bony repair of the injured growth plate cartilage.

Growth plate injuries often lead to bone growth defects, which primarily occur due to bony repair at injury sites. Bony repair is preceded by an injury-induced inflammatory response, which could play a role in regulating the repair process. Here, roles of two inflammatory mediators, cyclo-oxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS), in the injury responses were analysed by examining their gene expression and effects of blocking their activities, respectively, with celecoxib and aminoguanidine during 2 days prior to and until 7 days after injury in a rat tibial growth plate injury model. Quantitative RT-PCR assays revealed upregulated expression of COX-2 on days 1 and 4 and iNOS on day 1. Histological analysis of injury sites revealed significant reductions in inflammatory infiltrate (particularly neutrophils) on day 1 in treated groups compared to saline control. While bony tissue proportions at injury sites were unaffected by either treatment, mesenchymal tissue proportions were larger but cartilaginous tissue proportions were smaller on day 8 (though statistically insignificant), and bone remodelling appeared delayed with a smaller bone marrow proportion on day 14 in both treatment groups. These findings suggest that COX-2 and iNOS mediate injury-induced inflammatory response, and may play a role in enhancing mesenchymal cell differentiation to cartilaginous cells and in promoting bone remodelling during bony repair of growth plate injury sites. Furthermore, increased expression of cartilage-related (collagen-2, collagen-10, SOX-9) and bone-related molecules (osteocalcin, cbfalpha-1) suggest involvement of both endochondral and direct bone formation mechanisms during bony repair.

Animals↗

[Pragmatic and effective treatment of painful neck].

Management of a patient with atraumatic neck pain is a complex task that necessitates a careful differentiation between harmless and risky but preventable courses (red flags), with account having to be taken of psychosocial and somatic factors. At the same time diagnostic measures need to be limited to the truly necessary, and the development of chronicity must be avoided. The very fact that the clinical significance of neck pain clearly takes second place to its psychosocial and health-economic aspects points up the need to explicitly draw attention to the rare dangerous courses.

Chronic Disease↗

[Transformation of general measures by patients in heart failure].

BACKGROUND AND OBJECTIVE: Non-pharmacological treatment (NPT) and immunization with influenzal and pneumococcal vaccines are an integral part in the management of heart failure (HF). However, few data are available about the implementation of NPT in real life. The aim of this study was to analyse long-term changes in behavior and the use of self-care strategies by patients with HF. PATIENTS AND METHODS: 91 of 151 patients in HF (77 men, 14 women; mean age 68) at the Göttingen University Hospital were recruited to the study. Implementation of NPT was assessed during the hospital stay and one year after discharge by standardized interviews. Additionally, patients were also asked about their preferred sources of information about HF. RESULTS: Compared with the baseline data, NPT were more frequently named after one year (significant increase for "See the doctor in case of weight gain" [24.3% vs. 57.1%; p<0.001] and "Dietary salt restriction" [41.4% vs. 70.0%; p<0.001]. Patients who had been readmitted reported NPT more frequently than those who had not previously been admitted to hospital (3.6 vs. 3.1, n.s). The majority of patients considered general practitioners to be the most important source for information on HF. CONCLUSIONS: One year after discharge more patients had become aware of NPT. On the whole lifestyle modification is still relatively uncommon. General practitioners are seen as the most important informants on the management of HF and could use this trust to promote greater implementation of NPT by their patients.

Aged↗

Left atrial size reduction improves the sinus rhythm conversion rate after radiofrequency ablation for continuous atrial fibrillation in patients undergoing concomitant cardiac surgery.

BACKGROUND: Radiofrequency (RF) ablation can effectively restore sinus rhythm in the majority of patients with continuous atrial fibrillation (AF). However, no previous randomized studies have discussed the association of left atrial size reduction and the improvement of sinus rhythm conversion rate after radiofrequency ablation for continuous AF. METHODS: This prospective randomized study included 46 patients with continuous AF and cardiac disease. Twenty patients underwent cardiac surgery and radiofrequency ablation (group I). The other 26 patients underwent cardiac surgery and RF ablation combined with left atrial size reduction (group II). The patients were followed for one year postoperatively. Rhythm, neurological complications, and left atrial size were evaluated. RESULTS: At the one-year follow-up sinus rhythm was restored in 61.1 % of patients in group I and 77.3 % of patients in group II. LA diameter, evaluated by echocardiography, was reduced from 60 +/- 15 mm to 55 +/- 8 mm in group I and from 69 +/- 19 mm to 51 +/- 8 mm in group II. One case of stroke was observed postoperatively in each group. In group I one patient suffered a transient ischemic attack. Two patients in each group received transvenous permanent pacemaker implantation. CONCLUSION: Left atrial size reduction improves sinus rhythm conversion rate after RF ablation for continuous atrial fibrillation in patients undergoing concomitant cardiac surgery.

Adult↗

Decalcification of the mitral annulus: surgical experience in 81 patients.

OBJECTIVE: Mitral valve surgery in the presence of extensive calcification of the mitral annulus is a technical challenge and increases perioperative risk. This study reviews our experience with decalcification of the mitral annulus in patients undergoing mitral valve reconstruction or replacement. METHODS: From 1995 to 2003, 81 patients (mean age 64 +/- 13 years, 30 male, 51 female) with extensive calcification of the mitral annulus underwent mitral valve repair (n = 42) or replacement (biological n = 20, mechanical n = 19). The mean follow-up was 24 months. Patients presented with a mean EuroSCORE of 7. Concomitant surgical procedures were performed in 62 %. Patient outcomes were retrospectively assessed. RESULTS: Perioperative survival was 97.5 % (n = 79) and hospital survival was 91.3 % (n = 74). Two-year survival was 88.9 %. Eight patients needed reexploration due to bleeding and five patients required prolonged mechanical ventilation. No perioperative stroke was observed. Freedom from reoperation was 90.2 % (n = 73). Early reoperation for recurrent incompetence was necessary in 3 patients and late reoperation in 5 patients. CONCLUSIONS: Despite the elevated perioperative risk and the high risk of reoperation with this procedure, decalcification of the annulus and repair/replacement of the mitral valve could be performed with good clinical results.

Adolescent↗

Improved cerebral protection through replacement of residual intracavital air by carbon dioxide: a porcine model using diffusion-weighted magnetic resonance imaging.

BACKGROUND: Major risk of central or peripheral organ damage is attributed to air embolism from incompletely de-aired cardiac chambers after cardiac operations. Replacement of air by carbon dioxide insufflation into the thoracic cavity is widely used. Diffusion-weighted magnetic resonance imaging of the brain detects ischemia within minutes after onset. The reversibility of ischemia in cerebral tissue after massive gaseous emboli has not yet been described. METHODS: After selective catheterization of a common carotid artery in 15 pigs, boli of 1 mL/kg body weight of air (n = 5) or carbon dioxide (n = 5, "low dose") were applied. Five pigs received 2 mL/kg body weight of carbon dioxide ("high dose"). Diffusion-weighted magnetic resonance imaging of the brain was performed 2, 5, 10, 15, and 25 minutes after embolization. RESULTS: All animals of the "air" group showed important circulatory reactions leading to death of 2 animals. In the whole group, diffusion-weighted magnetic resonance imaging revealed irreversible hyperintense signals in both hemispheres. In the low-dose group, no change in signal intensity was observed in 2 pigs, and 3 others showed reversible changes in signal intensity, without important circulatory reactions. In 3 animals of the high-dose group, hyperintense signals were reversible, but 2 others presented with bilateral, irreversible signals in diffusion-weighted magnetic resonance imaging, accompanied by minor circulatory reactions. CONCLUSION: In contrast to the dramatic effect of air emboli, identical quantities of carbon dioxide injected into cerebral arteries of the pigs were not associated with major clinical symptoms. The early reversibility of ischemic reactions visualized in diffusion-weighted magnetic resonance imaging encourages the use of carbon dioxide insufflation as a protective method in cardiac surgery.

Animals↗

How psychiatric patients perceive the public's stereotype of mental illness.

BACKGROUND: It is well established that the general public has devaluating attitudes towards psychiatric patients. In order to avoid rejection, many of these patients develop coping strategies, such as withdrawal and concealing their treatment history. These efforts are in themselves stressing, which might have negative consequences for the course of the disorder. It is not clear, however, how many and which patients do actually perceive the public's stereotype as threatening and, therefore, expect rejection. METHOD: Ninety psychiatric patients and a sample of 1042 persons of the Austrian general population were asked whether they agreed with five devaluating statements about mental patients contained in a questionnaire developed by Link et al. Matched pairs comparisons and multiple logistic regression were employed in order to find out whether patients agreed with these statements to the same extent as the general population did. RESULTS: For the statements that most people believe that psychiatric patients are "less intelligent", "less trustworthy" and "taken less seriously", patients thought significantly less often than the general population that most people devalue mental patients. For two statements ("personal failure", "think less of") no difference was found. CONCLUSIONS: It seems that some psychiatric patients are less convinced than the general population that most people devalue psychiatric patients in specific respects; these patients might fear rejection less than other patients do. Those who actually fear rejection might need antistigma assistance more urgently than the first group.

Adult↗

[Thrombosed pseudoaneurysm after aortic root replacement-sternal penetration with skin perforation as a late complication].

Aortic pseudoaneurysm is a potential complication after aortic root replacement. Occurrence has been reported up to 7% of cases, and is due to dehiscence of the anastomotic suture line. We report a case of sternum erosion and skin perforation 8 years after composite graft replacement as a consequence of a ventricular-aortic dehiscence that led to a giant spontaneously healed thrombotic pseudoaneurysm. Our patient developed a secondary sternal fistula without pain or other clinical symptoms. Chest Xray examination revealed an abnormal mediastinal mass. The tumor was recognized on a computed tomography scan; the mass was identified as spontaneously healed thrombosed pseudoaneurysma with sternal penetration. Repair could be performed on the beating heart. Postoperative right heart failure with signs of myocardial infarction was attributed to the chronically occluded right coronary artery.

Adult↗

Do surface modifying additives (SMA) influence blood loss and thrombogenicity in conventional cardiopulmonary bypass for coronary artery bypass grafting?

Cardiopulmonary bypass (CPB) leads to activation of the coagulation and fibrinolytic cascades, partially associated with foreign surface contact. Hemorrhage and the need for blood products is associated with rising cost and increased risk of infection. Treatment with surface modifying additives (SMA) has been shown to reduce thrombogenicity and improve biocompatibility. 76 elective CABG-patients were randomly assigned to surface modifying additives (group I, n=39) or untreated circuits that were otherwise identical (group II, n=37). Measurements of coagulation activity and fibrinolysis, platelet count and function were made. The postoperative blood loss and blood product replacement was also assessed. Thrombin formation measured by prothrombin fragments 1+2 (5.7+/-0.4 nmol/l vs. 5.6+/-0.4 nmol/l), fibrinolytic activity measured by plasmin-antiplasmin complex (1752.6+/-216.8 microg/l vs.1180.0+/-74.8 microg/l) and the postoperative platelet count and function did not differ significantly between the two groups. Blood loss and transfusion requirements were slightly lower in the SMA group. The treatment of extracorporeal surfaces with surface modifying additives does not appear to reduce coagulation disorders and bleeding after conventional CPB.

Aged↗

Thoracic epidural anesthesia does not influence the incidence of postoperative atrial fibrillation after beating heart surgery.

BACKGROUND: At least 20 - 30 % of patients undergoing coronary artery bypass graft surgery (CABG) or beating-heart surgery develop postoperative atrial fibrillation (AF). We evaluated the effect of thoracic epidural anesthesia (TEA) on the occurrence of postoperative AF in patients submitted to CABG without cardiopulmonary bypass (OPCABG). METHODS: We performed a retrospective analysis of 125 patients undergoing myocardial revascularization. Early postoperative incidence of AF was compared between three groups of patients - 50 after conventional CABG, 45 after OPCABG, and 30 after OPCABG combined with TEA intraoperatively and postoperatively. Clinical profile of the patients, including factors with a potential influence on postoperative AF was matched for groups. RESULTS: Postoperative AF occurred in 13.3 % of the TEA-treated patients, in 17.7 % of the patients in the OPCABG group, and in 26 % of the patients in the CABG group. This difference did not carry any statistical significance. Risk factors and incidence of postoperative complications were comparable in all groups. CONCLUSION: TEA has no effect on the incidence of postoperative AF in patients undergoing beating-heart surgery.

Aged↗

Coronary endothelial dysfunction after heart transplantation predicts allograft vasculopathy and cardiac death.

BACKGROUND: Coronary endothelial dysfunction may be an early marker for cardiac allograft vasculopathy (CAV) in orthotopic heart transplant recipients. Using serial studies with intravascular ultrasound and Doppler flow-wire measurements, we have previously demonstrated that annual decrements in coronary endothelial function are associated with progressive intimal thickening. The present study tested whether endothelial dysfunction predicts subsequent clinical events, including cardiac death and CAV development. METHODS AND RESULTS: Seventy-three patients were studied yearly beginning at transplantation until a prespecified end point was reached. End points were angiographic evidence of CAV (>50% stenosis) or cardiac death (graft failure or sudden death). At each study, coronary endothelial function was measured with intracoronary infusions of adenosine (32-microgram bolus), acetylcholine (54 microgram over 2 minutes), and nitroglycerin (200 microgram) into the left anterior descending coronary artery; intravascular ultrasound images and Doppler velocities were recorded simultaneously. Of the 73 patients studied, 14 reached an end point during the study (6 CAV and 8 deaths, including 4 with known CAV, 1 graft failure, and 3 sudden). On the last study performed, the group with an end point had decreased epicardial (constriction of 11.1+/-2.9% versus dilation of 1.7+/-2.2%, P=0.01) and microvascular (flow increase of 75+/-20% versus 149+/-16%, P=0.03) endothelium-dependent responses to acetylcholine compared with the patients who did not reach an end point. Responses to adenosine and nitroglycerin did not differ significantly. CONCLUSIONS: Endothelial dysfunction, as detected by abnormal responses to acetylcholine, preceded the development of clinical end points. These data implicate endothelial dysfunction in the development of clinically significant vasculopathy and suggest that serial studies of endothelial function have clinical utility.

Acetylcholine↗

Molecular characterization of a blue-copper laccase, TILA, of Aspergillus nidulans.

Laccases are blue-copper enzymes, which oxidize phenolic substrates and thereby reduce molecular oxygen. They are widespread within fungi and are involved in lignin degradation or secondary metabolism such as pigment biosynthesis. Many fungi contain several laccases, not all of whose functions are known. In Aspergillus nidulans one, yA, is expressed during asexual development and converts a yellow precursor to the green pigment. We identified a second laccase gene, which encodes a 66.3-kDa protein 37.6% identical to laccase I of A. nidulans. The protein harbors an N-terminal secretion signal, and three characteristic copper-binding centers. The enzyme localizes at the growing hyphal tip. The gene was therefore named tilA (=tip laccase). Deletion or overexpression of the gene had no discernible phenotype under laboratory conditions.

Amino Acid Sequence↗

Aspergillus nidulans alpha-1,3 glucanase (mutanase), mutA, is expressed during sexual development and mobilizes mutan.

We established a subtractive cDNA library of Aspergillus nidulans to identify differentially expressed genes during sexual development. One of the clones displayed homology to fungal alpha-1,3 glucanases (mutanase). Since alpha-1,3 glucan is considered the main reserve material accumulated during vegetative growth as a cell wall component and consumed during sexual development, we analyzed this gene in detail. The gene, mutA, is disrupted by three introns and encodes a putative protein of 48 kDa molecular mass with a signal peptide for secretion at the N terminus. The deduced protein displays amino acids 24-42% identical to mutanases of other fungi. A proposed mutan binding domain characterized in, e.g., Penicillium is not present in A. nidulans. Mutanase transcript and GFP reporter analysis in A. nidulans revealed specific induction of the gene during sexual development in Hülle cells. To study the role of mutA during sexual differentiation, we constructed a mutA deletion strain. Although degradation of mutan was affected in this strain, it was still able to form cleistothecia at a number similar to that of wildtype. These results suggest that additional carbon sources are available during sexual development.

Amino Acid Sequence↗

Extension of generator longevity by use of high impedance ventricular leads.

The resistance of a pacing lead negatively correlates to current consumption. A prospective, randomized trial was conducted to evaluate the effect of a high impedance ventricular lead (CapSure Z) on generator longevity compared to a conventional lead (CapSure SP) eighty-nine patients were included in the study (51 male, 37 female, age 70.0+/-10.3 years). Forty-six patients received a CapSure SP lead (5024 bipolar), and 43 patients received a CapSure Z lead (5034 bipolar) in a randomized fashion. Follow-up data collected at 5 days, 3, 6, and 12 months postimplant included: lead impedance, pacing and sensing thresholds, impulse energy, and estimated time to replacement. All parameters were collected via pacemaker telemetry; the time to replacement was calculated automatically by a programmed algorithm of the pacemaker. There was no difference in the performance of the atrial lead when a dual chamber device was indicated. The CapSure Z leads displayed statistically significant higher impedance values than the CapSure SP lead in all follow-up periods. There was no significant difference in lead related complications. No significant differences were observed between pacing and sensing thresholds in both groups. The CapSure Z leads provided a significant reduction in current drain, resulting in a reduction of mean energy consumption at the 12-month follow-up from 10.4+/-5.0 microJ in the CapSure SP group to 6.6+/-1.4 microJ in the CapSure Z group (median from 9.9 microJ to 6.9 microJ, respectively), providing an estimated increase in mean longevity of more than 1 year from 81.1+/-23.5 months in the CapSure SP group to 94.5+/-13.4 months in the CapSure Z group (median: 76.5 months to 95.0 months, respectively). The use of a high resistance lead for ventricular pacing appears to result in a clinically relevant extension of generator longevity.

Aged↗

CRTR-1, a developmentally regulated transcriptional repressor related to the CP2 family of transcription factors.

CP2-related proteins comprise a family of DNA-binding transcription factors that are generally activators of transcription and expressed ubiquitously. We reported a differential display polymerase chain reaction fragment, Psc2, which was expressed in a regulated fashion in mouse pluripotent cells in vitro and in vivo. Here, we report further characterization of the Psc2 cDNA and function. The Psc2 cDNA contained an open reading frame homologous to CP2 family proteins. Regions implicated in DNA binding and oligomeric complex formation, but not transcription activation, were conserved. Psc2 expression in vivo during embryogenesis and in the adult mouse demonstrated tight spatial and temporal regulation, with the highest levels of expression in the epithelial lining of distal convoluted tubules in embryonic and adult kidneys. Functional analysis demonstrated that PSC2 repressed transcription 2.5-15-fold when bound to a heterologous promoter in ES, 293T, and COS-1 cells. The N-terminal 52 amino acids of PSC2 were shown to be necessary and sufficient for this activity and did not share obvious homology with reported repressor motifs. These results represent the first report of a CP2 family member that is expressed in a developmentally regulated fashion in vivo and that acts as a direct repressor of transcription. Accordingly, the protein has been named CP2-Related Transcriptional Repressor-1 (CRTR-1).

Amino Acid Sequence↗

The gender gap in depression reconsidered: the influence of marital and employment status on the female/male ratio of treated incidence rates.

BACKGROUND: The consistently observed predominance of female over male rates in depression - in treated as well as in untreated populations - has never been satisfactorily explained. Among the many possible biological and psychosocial explanations, marital and employment status have not been extensively studied and virtually nothing is known about the combined effect of these variables on sex differences in depression. A main reason for this lack of knowledge is the limited number of cases available in epidemiological studies. METHODS: The present paper examines the combined effects of marital and employment status on sex differences in depression rates by analysing in-patient admission rates of all depressed patients aged 18-67 admitted for the first ever time to the Department of Psychiatry of the University of Vienna from a strictly defined catchment area over a period of 42 months. Stepwise Poisson regression analyses were carried out in order to identify the relative contribution of these variables to the variance of first ever in-patient admission rates for depression. RESULTS: A total of 2599 depressed patients fulfilled the inclusion criteria. When analysed separately, sex, marital status and employment status were shown to have distinct influences, with the "not married" carrying a two-fold higher risk than the married (2:1), and female sex (1.7:1) as well as not being employed (1.7:1) showing similar but smaller effects. In the detailed combined analysis, marriage was significantly less advantageous for women than for men, while sex differences disappeared completely in the widowed group. Also, there was no sex difference in the employed divorced; in the employed widowed there was even a slight preponderance in men. The highest rates were found in not employed divorced women, the lowest in employed married men. CONCLUSION: While in-patient admissions are certainly selective in relation to epidemiological data, the large sample made it possible to perform combined analyses of sex, marital status and employment status. It was shown that the statement of a female preponderance in depression, which was found for the total sample, is a gross oversimplification. If marital and employment status are considered simultaneously, the sex differences disappear in some subgroups and in some are even reversed. We suggest that the combined influence of marital and employment status should be studied in epidemiological studies as well before conclusions about the influence of sex on depression rates are drawn.

Adolescent↗