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Biomedical subjects

G Herrmann

Publications and source records attributed to G Herrmann.

At least 91 records · Page 5Linked to original sources

Protein docking combining symbolic descriptions of molecular surfaces and grid-based scoring functions.

With the growing number of known 3D protein structures, computing systems, that can predict where two protein molecules interact with each other is becoming of increasing interest. A system is presented, integrating preprocessing like the computation of molecular surfaces, segmentation, and searching for complementarity in the general framework of a pattern analyzing semantic network (ERNEST). The score of coarse symbolic computations is used by the problem independent control strategy of ERNEST to guide a more detailed analysis considering steric clash and judgements based on grid-based surface representations. Successful examples of the docking system are discussed that compare well with other approaches.

Binding Sites↗

[The management of adolescents and adults with congenital heart defects: 3 years experiences with interdisciplinary consultation].

UNLABELLED: Since September 1991, 204 patients (pts), 109 male and 95 female, mean age 27.3 +/- 10.6 years, were followed in a newly established interdisciplinary outpatient clinic combining both adult and pediatric cardiologists. 61 pts predominantly presented with left-to-right shunt congenital heart disease (CHD), 32 with valvar CHD, 20 with aortic coarctation, 23 with complex acyanotic, and 49 with cyanotic CHD. The population included 19 pts with Marfan syndrome. 106 pts had had previous cardiac surgery, 32 of them with up to three reoperations. Deficits and needs in medical and social care were analyzed in 100 pts using a standardized questionnaire at the time of first examination: One-third of pts were not or only incompletely informed about their CHD, previous surgical procedures and need for antibiotic prophylaxis of endocarditis. Only a minority of pts had had vocational advice (34%) or counseling concerning contraception (40%) or pregnancy (30%). Cardiac catheterization was performed in 37 pts (18%) after being first seen in our outpatient clinic, followed by a primary surgical intervention in 19 and reoperation in eight cases. Overall, 30 pts (15%) underwent surgery (28) or interventional procedures (one closure of the arterial duct, one AV node ablation after Mustard-operation) as a consequence of admission to our unit. Successful late Fontan operations were performed in four adults aged 21 to 35 years. There was 1/30 postoperative death (M. Ebstein, thrombosis of the mechanical prosthesis). The population includes five pts with severe pulmonary vascular disease (one waiting for lung transplantation) and two pts with pulmonary artery arborisation malformations not amenable to surgery. CONCLUSION: In a population of 204 adolescents and adults with CHD, we clearly found deficits in medical and social care and, in addition, an unexpected high percentage of necessary invasive investigations (18%) and surgical or interventional procedures (15%). Interdisciplinary management of these patients is mandatory combining the special facilities of adult and pediatric cardiologists.

Activities of Daily Living↗

[Pseudo-stenosis caused by vessel wall invagination during interventional treatment of 2 coronary vessels in a patient].

We report on a 59-year-old man who underwent a combined procedure of directional coronary atherectomy (DCA) and PTCA of significant lesions of the right coronary artery (RCA) and the left circumflex artery (LCX). Already after positioning of a standard guide wire in the right coronary artery a new excentric "pseudo-stenosis" was observed in the proximal part of the right coronary artery. Since the patient remained symptom free, a 7F DCA catheter was introduced to the stenotic area in the mid RCA, which led to an extension of the narrowing, involving the total segment proximal to the DCA catheter. Directional coronary atherectomy was performed without complications. Removal of the catheter, after successful DCA, and administration of intracoronary nitroglycerin did not relieve the proximal narrowing, which disappeared spontaneously after the guide wire was pulled out. During PTCA of the left circumflex using a standard guide wire and a 3.0 mm Monorail balloon catheter, a similar tight narrowing of the origin of the LCX was observed, which could also not be influenced by vasodilator drugs, but relieved after wire removal. Until now, this phenomenon has only been described for the right coronary artery. The reason underlying intimal folding is a shifting of the intimal layer against the medial layer of the vessel wall. Our observation firstly describes this phenomenon of "pseudo narrowing" in two different vessels in one patient. We, like other authors before, recommend that interventional therapy of these pseudo-lesions should be avoided.

Angioplasty, Balloon, Coronary↗

[Pathogenetic role of HBV in liver cell carcinoma of Western European patients].

Tumour (n = 338) and corresponding liver tissue (n = 276) of liver cell carcinoma (LCC) patients including 31 Asiatic cases was studied with immunohistochemical methods (IHC) for the expression of HBs (7MABs and 2 PABs), HBc, HBe, HBx, and preS antigens. HBV-DNA was detected with in situ hybridisation (ISH) employing digoxigenin-labeled DNA probes. Furthermore, polymerase chain reaction (PCR) was done for a part of the X-ORF (1542+, 1746-). Tumours from the European patients were fibrolamellar (FLC; n = 8), hepatocellular (HCC; n = 260), mixed hepatocellular/cholangiocellular (HCC/CCC; n = 23), and pure cholangiocellular carcinomas (CCC; n = 16). Of the Asiatic cases, 56.5% contained HBs in liver and 64.5% in tumour tissue, of the European cases these were 21.7% and 29.6%, respectively. HBc, HBe, and preS antigens were found only in few cases. HBV positive rates with ISH were 82.6% and 87.1% for Asiatic, and 45.3% and 51.7% for European cases, respectively. Altogether, 93.6% of the Asiatic and 64.2% of the European patients were positive for HBV with IHC or ISH. HCC/CCC and CCC showed slightly lower HBV positive rates than HCC. Over 90% of the cases had HBx in liver and tumour tissue. PCR revealed HBV positive rates of 73.2% for liver and 90.1% for tumour tissue irrespective of patients descent and tumour type. Thus, HBV seems to represent a pathogenetic factor for LCC in Western European patients irrespective of the tumour type. The existence of the "mixed tumours" HCC/CCC as well as the frequent HBV-positivity of tumours with cholangiocellular differentiation document that CCC belong to the category LCC.

Animals↗

Microquantitative determination of lactate dehydrogenase isoenzymes in the myocardium and the conducting system.

A newly developed technique was used for the electrophoretic separation of lactate dehydrogenase (LDH) isoenzymes from lyophilized tissue samples in the nanogram range. In this study portions of 10-200 ng from the myocardium and the conducting system of cattle, sheep, pig and man were microdissected and analysed. In the heart tissues of cattle, sheep and pig, the isoforms LDH1, LDH2 and LDH3 were detected in species-specific varying amounts. In all these animals, the conducting system is marked by high LDH1 activity, which is present at a ratio of about 2:1 compared with the myocardium. The values in man, however, differ from these values, but this might be due to post-mortem changes. The findings are discussed with respect to possible aerobic-anaerobic functions.

Adult↗

T lymphocytes, CD68-positive cells and vascularisation in thyroid carcinomas.

Immunohistochemical detection and quantification of CD3- and CD45RO-positive lymphocytes and CD68-positive cells in 75 thyroid carcinomas of follicular cell origin revealed rising levels for these parameters associated with dedifferentiation. A parallel trend towards reduction of vascularisation, determined as CD31-positive blood vessels, with decreasing differentiation became evident, statistically only significant when well-differentiated follicular and anaplastic carcinomas were compared. Positive correlations could be demonstrated between the density of CD68-, CD3-, and CD45RO-positive cells as well as between the density of CD68-, and CD3-, and CD45RO-positive cells and vascularisation. These correlations were expected, as the interaction of CD68-positive cells and T lymphocytes results in the production of angiogenesis factors, ultimately leading to better vascularisation of the tumour. Nevertheless, the tumour cells themselves are variously capable of producing angiogenic substances. The obvious lack of positive correlation between the density of tumour-infiltrating cells determined in this study and vascularisation, despite reduced vascularisation in less differentiated tumours that contained increasing numbers of tumour-infiltrating cells, seems to be due to functional heterogeneity of morphologically similar tumours.

Antibodies, Monoclonal↗

Evidence for partial sympathetic cardiac reinnervation following cardiac transplantation.

Heart transplantation causes total cardiac denervation. Measurements of plasma concentrations of the main presynaptic noradrenal metabolite, dihydroxyphenylglycol (DOPEG, exclusively neuronal in origin), were used to examine the possibility of sympathetic reinnervation of the transplanted human heart. We determined arterial and coronary-venous plasma concentrations of DOPEG in 15 heart transplant recipients (28-68 years of age at the time of transplantation with the transplant ageing from 0.5 to 4 years at the time of investigation) and in nine control patients (45-75 years of age). In each of the control patients the DOPEG concentration was higher in coronary venous plasma than in arterial plasma (mean arteriovenous increment: 60 +/- 10%; P < 0.001). In the heart transplant recipients nine patients showed an arteriovenous increment in plasma DOPEG. For the mean group results it was found that the ratio of the coronary-venous to arterial DOPEG concentration was positively correlated with the time after transplantation (r = 0.92; n = 5; P < 0.05). Thus, our data provide neurochemical evidence for partial sympathetic reinnervation in some of the heart transplants. Moreover, it is suggested that the time after transplantation is unlikely to be the only determinant for the occurrence and extent of sympathetic reinnervation.

Adult↗

Systemic interleukin-1 alpha and interleukin-2 secretion in response to acute stress and to corticotropin-releasing hormone in humans.

Acute stress results in activation of the hypothalamic-pituitary-adrenal (HPA) axis. ACTH and cortisol secretion is stimulated by corticotropin-releasing hormone (CRH). It has also been shown that activation of the HPA axis during stress is accompanied by changes in the immune response. However, little is known about the influence of acute stress on the release of cytokines such as interleukin-1 (IL-1) or interleukin-2 (IL-2). In this study, we determined serum IL-1 alpha and IL-2 levels in 19 patients undergoing the acute stress of angioplasty for coronary artery disease. A second protocol was devised to determine serum IL-1 alpha and IL-2 concentrations as well as lymphocyte subpopulations in 10 normal volunteers receiving 1 microgram kg-1 human CRH intravenously. Finally, IL-1 alpha concentrations were measured in CRH-incubated mononuclear cell (MNC) and monocyte cultures. In response to the stress of angioplasty, ACTH and cortisol as well as IL-1 alpha and IL-2 concentrations were clearly above baseline levels (IL-1 alpha, mean +/- SEM, baseline: 1.39 +/- 0.34 ng ml-1, after angioplasty: 2.64 +/- 0.73 ng ml-1, P < 0.05; IL-2, baseline: 1.2 +/- 0.13 ng ml-1, after angioplasty: 2.8 +/- 1.14 ng ml, P < 0.05). A similar pattern was obtained in normal subjects in response to CRH (Il-1 alpha, baseline: 0.8 +/- 0.2 ng ml-1, after angioplasty: 3.7 +/- 1.4 ng ml-1, P < 0.05; IL-2, baseline: 1.9 +/- 0.4 ng ml-1, after angioplasty: 5.4 +/- 2.2 ng ml-1, P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Rapidly growing Epstein-Barr virus-associated pulmonary lymphoma after heart transplantation.

There is strong evidence to show an association of Epstein-Barr virus (EBV) infection with the development of post-transplant lymphoproliferative disease. We report the rapid development of a malignant lymphoma in a heart transplant recipient, which occurred within less than eight weeks. The diagnosis of this malignant high grade B-cell lymphoma was established by open lung biopsy, and classified as centroblastic lymphoma of polymorphic subtype. Immunohistochemically, the lymphoma showed reactivity with the B-cell markers L-26 (CD20) and Ki-B5 and with the activation marker Ber-H2 (CD30). Furthermore, an expression of the bcl-2 oncoprotein was detected. Monoclonal JH gene rearrangement was demonstrated by polymerase chain reaction (PCR), indicating monoclonal proliferation of B-blasts. Although serum EBV immunoglobulin M (IgM) antibodies were negative, the association to an EBV infection could be demonstrated by EBV immunostaining pattern which revealed an expression of the latent membrane protein (LMP) of EBV in the atypical blasts. The results give clear evidence of an EBV association of this rapidly growing lymphoma developed after heart transplantation.

Heart Transplantation↗

[Intervention and clinical aspects combined with endovascular irradiation of intimal hyperplasia of the vascular system].

After implantation of stents in femoropopliteal arteries we found restenosis or occlusions by intimal hyperplasia in up to 40% especially in the hunter's channel. Repeated balloon angioplasty and prophylactic endovascular radiotherapy with a surface dose of 12 Gy in the vessel wall using an iridium 192 source in the same investigational session is a new technique to reduce or eliminate further recurrence. All 18 patients had developed recurrent stenoses or occlusions 6-8 months after original stent implantations. The patients have not redeveloped recurrent obstructions after this treatment, which up to date showed no short term or long term complications. We conclude that the encouraging results of this pilot study justify further randomized trials.

Aged↗

[Hemodynamic effects of non-ionic iomeprol 350 and ionic diatrizoate 370 during levocardiography and coronary angiography--double-blind randomized comparison of 2 contrast media].

A double-blind randomized study was performed in 49 patients to compare the hemodynamic changes induced by two contrast agents: non-ionic low osmolar lomeprol 350 (IO, n = 25) and ionic high osmolar Diatrizoat 370 (DIA, n = 24). We observed significant changes in hemodynamic parameters after laevocardiography with DIA: a decrease in LVSP from 125 +/- 14 to 113 +/- 14 mmHg, a decrease in mean aortic pressure from 96 +/- 9 to 84 +/- 10 mmHg and in max dp/dt from 2086 +/- 628 to 1861 +/- 654 mm Hg/sec. LVEDP increased from 13 +/- 5 to 17 +/- 6 mmHg and cardiac output from 5.9 +/- 1.2 to 7.7 +/- 1.2 l/min. Heart-rate also rose slightly, but insignificant. IO did not alter these parameters. After selective coronary angiography both groups did not differ significantly in systolic aortic pressure, but DIA caused a drop in diastolic aortic pressure after 10 to 15 sec and a bradycardia in the first five sec, in contrast to IO. These effects can be explained by a cardiodepressive action of contrast agents on left ventricular function, an increase in circulating volume and a reduced peripheral vessel resistance. Differences between both agents are probably due to their different osmolality. IO is a safe contrast agent, compatible in contrast to DIA. In patients with borderline left-ventricular function, IO is preferable, it exerts only very slight effects on cardiovascular function.

Adult↗

[Directional coronary atherectomy: effect of vessel size on primary results and long-term results].

Of 325 consecutive patients undergoing DCA, 263 patients with 277 stenoses were successfully treated with DCA alone and had angiographic follow-up 3-6 months later. Depending upon the initial reference diameter (RD) patients were divided into two subgroups: group I (n = 159) with a RD > 3 mm and group II (n = 104) showing a RD < or = 3 mm. In contrast to other series DCA was predominantly performed with 7F atherectomy devices using balloon inflation pressures of approximately 5 atm. Angiographic data including the minimal luminal diameter (MLD), percentage of stenosis (%D) and reference diameter (RD) were assessed by quantitative computer-assisted analysis before (pre), after (post) DCA and at a 3-6 months angiographic follow-up (FU). The percentage of diameter stenosis pre/post/FU in group I was 59.9 +/- 12.6%/18.4 +/- 12.8%/29.8 +/- 17.6%, and in group II 55.6 +/- 10.8%/17.8 +/- 12.3%/33.7 +/- 16.1% with a net gain at FU of 1.0 +/- 0.89 mm for group I and 0.86 +/- 0.66 mm for group II. Based on an angiographic restenosis criterion of at least 50% diameter obstruction at FU and or recurrence of symptoms warranting interventional re-treatment of the target lesion, the incidence of restenosis in group I was 20.6% and in group II 28.0% (p: n.s.). There was no significant difference between the two groups concerning complications. Our data show that DCA leads to a satisfying long-term result.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Hyper-IgE syndrome--two case reports of unusual complications].

The hyper-IgE syndrome (HIS) is a complex immunologic disease, caused by an unknown basic defect. We report on two cases showing complications, which have not been described so far. Case 1: A 15-year-old boy suffering from HIS developed a liver tumour with severe eosinophilic infiltration and degranulation. The transformation process of the liver histologically resembled focal nodular hyperplasia. Therapy with cyclosporine A did not lead to clinical benefit. Now, a therapeutic attempt with interferon gamma is made. Case 2: In a 17-year-old female HIS patient, multiple papillomas and ulcers of the mucous membrane, caused by infection with human papilloma virus, emerged in the ENT region. Under treatment with interferon alpha, papillomatosis could be restrained. As therapy of the hyper-IgE syndrome only symptomatic treatment has been recommended so far. Future therapies should strive for systemic immunomodulation by application of cytokines or soluble cytokine receptors like interferons or sIL-4R.

Adolescent↗

Bicaval versus atrial anastomoses in cardiac transplantation. Right atrial dimension and tricuspid valve function at rest and during exercise up to thirty-six months after transplantation.

Conventional cardiac transplantation with atrial anastomoses alters atrial integrity, geometry, and possibly function. Theoretically, this may also contribute to the development of tricuspid insufficiency that is frequently observed after the operation. Thus more anatomic transplantation techniques using bicaval anastomoses were recently introduced into clinical practice. Knowledge of their efficacy, however, is scarce. Therefore right atrial size and tricuspid valve function were compared in patients with bicaval (group A) and standard atrial (group B) anastomoses in a randomized, prospective study. The results of this echocardiographic study at rest and exercise in 18 patients (bicaval n = 8; atrial n = 10) on the average 28 months after transplantation are presented. The right atrial dimension was comparable between group A patients and control subjects and larger in group B patients (p < 0.05). The incidence of tricuspid regurgitation was not different between the two groups at rest, but it was at exercise (50 watts of workload) (p < 0.05). This study suggests that up to 36 months after cardiac transplantation the technique of bicaval in contrast to atrial anastomoses preserves right atrial size and reduces tricuspid regurgitation during exercise. Whether this leads to improved hemodynamics and increased exercise capacity remains to be evaluated in a larger series of patients.

Cardiac Output, Low↗

Cyclosporin A and transplant coronary disease after heart transplantation: facts and fiction.

From published data in the currently available literature on animal experiments, it can be concluded that CyA may be involved in the development of hypertension and renal dysfunction. These side effects are probably related to a disturbed vasomotor tone and a pathologic reaction to physiologic vasoconstrictive and vasodilative agents following administration of high doses of CyA. These effects are dose related and reversible and were undetected at clinically applied levels of immunosuppression. It therefore appears to be unlikely that this pathologic response is operative in precipitating or promoting TCD, which is supported by findings of in vivo and in vitro studies on human coronary arteries as well as by comparison of immunosuppressive protocols comparing series with and without application of CyA. Chronic graft dysfunction, as depicted by late mortality in heart and isolated lung transplant recipients and by loss of kidney allograft survival, yields an annual rate of between 4 and 6% per year. It is only in heart transplantation that TCD has been tried to be associated with CyA application. If CyA-related damage were to occur in coronary arteries independent from immunologic factors, the incidence of coronary disease should be similar in heart, lung, liver, and kidney transplants. This is not the case. Although continuous investigation on the side effects of immunosuppressive agents is definitely necessary, we should concentrate our research activities on potential prophylactic and therapeutic measures to overcome the single most important risk factor of long-term surviving patients after solid organ transplantation: chronic rejection.

Animals↗

[Sialadenitis at an unusual site in acute infectious mononucleosis].

Infectious mononucleosis is found worldwide. The clinical manifestations vary widely. We report a case with impressive swelling of the hard and soft palate. Inflammation in the region of the efferent ducts of the palatinal glands resulted in congestion in the region of the mucinous salivary glands. The subsequent secretory stasis caused degeneration of the acini and rupture of a salivary retention cyst. The surrounding connective tissue was soaked with mucin, and unspecific chronic granular inflammation was found. Immunohistochemical examination with a monoclonal EBV antibody was necessary to show that the exceptional clinical picture was due to infectious mononucleosis.

Adult↗

[Neurochemical studies of adrenergic reinnervation after heart transplantation].

Heart transplantation causes sympathetic cardiac denervation. Measurements of plasma concentrations of the main presynaptic noradrenaline metabolite, dihydroxyphenylglycol (DOPEG, the plasma pool of which is exclusively neuronal in origin), were used to examine sympathetic reinnervation of the transplanted human heart. We determined arterial and coronary-venous plasma concentrations of DOPEG in 27 heart transplant recipients (transplant age ranging from 0.5 to 5 years) and in 9 control patients. In each of the control patients the DOPEG concentration was higher in coronary venous plasma than in arterial plasma (mean arterio-venous increment: 57.3 +/- 8.7%; p < 0.001). However, in heart transplant recipients, 18 out of 27 patients showed an arteriovenous increment in plasma DOPEG (mean increment in all patients 12.6 +/- 2.0%; p < 0.05). The ratio of the coronary-venous to arterial DOPEG concentration was positively correlated with the time after transplantation (p = 0.02 for individual results and p < 0.01 for mean group results). Thus, our data provide evidence for a time-dependent partial sympathetic reinnervation of the transplanted heart.

Adrenergic Fibers↗