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Biomedical subjects

M Stille-Siegener

Publications and source records attributed to M Stille-Siegener.

15 recordsLinked to original sources

[Experiences with temporary vena cava filters in 114 at-risk patients with thrombosis or thromboembolism].

BACKGROUND AND OBJECTIVES: The indications for temporary implantation of a vena cava filter remain unclear and there are as yet few data about its complications and reliability. It was the aim of this study to determine the efficacy and complication rate of the temporary use of a vena cava filter (VCF) in a large group of patients at high risk of pulmonary embolism, and thus contribute to defining the indications for such temporary implantation. PATIENTS AND METHODS: Between November 1991 and October 1997 a total of 118 VCF were implanted in four groups of a total of 114 patients (67 women, 47 men; average age 45.3 +/- 19.8 [12-82] years) to prevent pulmonary embolism: those (1) with massive or fulminant pulmonary embolism (n = 54); (2) with mechanical thrombus fragmentation and (or) local catheter-delivered systemic thrombolysis in pelvic, leg or caval vein thrombosis (n = 42); (3) with systemic thrombolysis in case of floating thrombi at the femoral, iliac or caval veins (n = 7); and (4) as perioperative measure in caesarean section, venous thrombectomy, other surgical interventions or when anticoagulation had to be discontinued in patients with deep vein thrombosis (n = 11). RESULTS: Filters remained implanted for a mean of 6.1 +/- 3.4 (1-16) days. Placement had to be corrected because of filter dislocation in eight patients. Proven pulmonary embolism occurred after filter implantation in only one patient, after filter displacement into the unthrombosed contralateral iliac vein. Thrombus deposition on the filter before its removal was demonstrated in nine patients: thrombolysis was effective in seven of them, while thrombosed filters had to be removed surgically in two. Residual thrombi were found on the filter in six further patients. No pulmonary embolism occurred in connection with filter removal. Local complications at or around the site of insertion of the introducing catheter occurred in 53 of the 114 patients (46.5%): haematoma in 42, infection in 21 and brachial vein thrombosis in three patients. CONCLUSIONS: The rate of clinically relevant pulmonary embolism can probably be reduced to a minimum by the implantation of a temporary vena cava filter. The overall complication rate is high, but serious complications are rare.

Adolescent

Monocyte activation in congestive heart failure due to coronary artery disease and idiopathic dilated cardiomyopathy.

OBJECTIVE: To investigate plasma tumor necrosis factor (TNF)alpha, tumor necrosis factor alpha soluble receptor I, interleukin-1beta and neopterin concentrations as markers of monocyte activation in patients with heart failure. STUDY DESIGN: The group consisted of patients with heart failure due to dilated cardiomyopathy (n=19) and coronary artery disease (n=11). Patients without cardiac failure served as controls (n=10). RESULTS: TNFalpha concentrations were elevated only in heart failure patients with coronary artery disease (2.9+/-0.3 pg/ml versus 1.7+/-0.3 pg/ml; P<0.05). When the patients were grouped according to acute and chronic failure, TNFalpha concentrations were significantly elevated in acute failure (3.1+/-0.4 pg/ml, n=6 versus 1.7+/-0.2 pg/ml, n=8; P<0.05). TNFalpha concentrations were elevated in patients with coronary artery disease and chronic heart failure compared to coronary artery disease patients without failure (2.0+/-0.4 pg/ml, n=6 versus 1.8+/-0.3 pg/ml, n=7; P<0.05). A higher proportion of patients with myocardial insufficiency showed increased lipopolysaccharide-inducible TNFalpha concentrations (10/30 versus 0/9, P<0.05). CONCLUSIONS: TNFalpha is elevated in patients with acute cardiac decompensation. Among patients with chronic heart failure only those with coronary artery disease exhibit increased levels. Cytokine concentrations are similar in heart failure due to dilated cardiomyopathy and coronary artery disease. Monocytes of patients suffering from cardiac insufficiency show an increased sensitivity towards stimuli such as lipopolysaccharides.

Biomarkers

Coxsackievirus genome in myocardium of patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy.

Enteroviruses are known as major infectious agents for inflammatory heart diseases such as myocarditis and dilated cardiomyopathy (DCM). Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by replacement of right ventricular myocardium by fatty and fibrous tissue. In about 65% of patients inflammatory infiltrates suggest an inflammatory or infectious etiopathogenesis. To test this hypothesis, we investigated endomyocardial biopsies of patients with ARVC, with myocarditis or DCM, and from patients with non-inflammatory cardiac disorders for the presence of enteroviral genome. Enteroviral RNA with homology to coxsackieviruses type B was detected in 3 of 8 patients with ARVC (37.5%), in 7 of 23 patients with myocarditis or DCM (30.4%), but in none of 5 patient with non-infectious myocardial diseases (p < 0.05 compared to ARVC patients). These results support earlier suggestions that coxsackievirus infection of the myocardium is possibly related to the pathogenesis of ARVC.

Adult

Inhibition of coxsackievirus B3 carrier state infection of cultured human myocardial fibroblasts by ribavirin and human natural interferon-alpha.

As enterovirus infections of the heart cause myocarditis and eventually congestive heart failure, the antiviral activity of ribavirin was studied in coxsackie virus B3 (CVB3)-infected carrier cultures of human myocardial fibroblasts. Cultures were infected 7 days before application of ribavirin and effects were evaluated over a period of 16 days by plaque assays and in situ hybridization. Compared to the low antiviral activity in HeLa cells, ribavirin was highly active in reducing infectious virus yields in human myocardial fibroblasts, for example, to 2.0 x 10(3) pfu/ml with 25 microg/ml and to 1.3 x 10(2) pfu/ml with 50 microg/ml (4.3 x 10(4) pfu/ml in infected controls). Moreover, 100 microg ribavirin/ml completely suppressed infectious virus progeny in two of three cultures, and reduced the number of infected cells from 14.3 to 0.3% as determined by in situ hybridization, whereas up to 3200 microg ribavirin/ml did not result in a significant cytotoxic effect. Interaction with interferon-alpha (IFN-alpha) was additive to slightly synergistic in reducing the number of infected cells and virus yields. In conclusion, our results suggest a cell-specific high activity of ribavirin in human myocardial fibroblasts and indicate the importance of using organ-specific cells for testing antiviral agents in myocarditis. Furthermore, the usefulness of in situ hybridization for determining the long term effects of antivirals in carrier state cell cultures was demonstrated.

Antiviral Agents

[The cardiac and neurological manifestations of Lyme borreliosis in congenital first-degree AV block].

HISTORY AND CLINICAL FINDINGS: A 19-year-old youth was hospitalised because of sudden onset of incomplete lid closure and drooping mouth on the left. He regularly walked through fields and woods; three weeks before admission he had noted swelling and reddening on his neck, which he thought was due to an insect bite. When 9 years old a functional heart murmur and 1 degree AV block (P-R interval 0.25s) had been found. Physical examination showed peripheral facial paresis and a 2/6 systolic murmur over the aortic area. INVESTIGATIONS: As Borreliosis (Lyme disease) was suspected, relevant laboratory tests were performed. These revealed specific IgM antibodies against Borrelia burgdorferi. Polymerase chain reaction demonstrated B. burgdorferi-specific DNA in cerebrospinal fluid and urine. The ECG showed 1 degree AV block (P-R interval 0.28s). TREATMENT AND COURSE: Ceftriaxone was administered at once (4 g, followed by 2 g daily intravenously for 14 days). The P-R interval increased to maximally 0.31 s and transient incomplete right bundle branch block developed on the second day. Long-term ECG monitoring also revealed ventricular arrhythmias (Lown IVb), but they gradually disappeared. The neurological signs regressed completely within five days of the start of treatment, while the P-R interval had returned to its initial value of 0.25 s 3 months later. CONCLUSION: The case makes clear that an ECG should be recorded in borreliosis even in the absence of cardiac symptoms. Hospitalisation with long-term monitoring becomes necessary if it is abnormal.

Adult

Myocardial enterovirus infection with left ventricular dysfunction: a benign disease compared with idiopathic dilated cardiomyopathy.

OBJECTIVES: Endomyocardial biopsy samples from patients with idiopathic dilated cardiomyopathy were screened for the presence of enterovirus genome. Patients with enterovirus-positive samples were further studied with regard to disease course, histologic variables and response to interferon-alpha treatment. BACKGROUND: Studies of patients with idiopathic dilated cardiomyopathy have reported widely divergent clinical outcomes, suggesting that there is no unique underlying pathogenetic mechanism. METHODS: Five left ventricular endomyocardial biopsy samples were screened for the presence of the enterovirus genome by an established in situ hybridization technique in combination with a histologic, histomorphometric and immunohistologic workup. The course of the disease was then prospectively followed for up to 50 months. Virus-positive patients whose condition deteriorated were treated with interferon-alpha. RESULTS: Of 77 patients, 20 (26%) had enterovirus-positive and 57 (74%) enterovirus-negative biopsy samples. During a mean follow-up period of 25.8 +/- 13.7 months, 1 patient in the enterovirus-positive group and 11 in the enterovirus-negative group died. Four patients in the enterovirus-negative group underwent heart transplantation (p < 0.05). The surviving 19 enterovirus-positive patients had a decrease in mean left ventricular end-diastolic diameter from 66 to 61 mm (p < 0.05) and a mean increase in left ventricular ejection fraction from 0.35 to 0.43 (p < 0.05). In contrast, enterovirus-negative patients had no significant change in end-diastolic diameter or left ventricular ejection fraction. Four patients in the enterovirus-positive group whose condition deteriorated were treated with a 6-month course of subcutaneous interferon-alpha (3 x 10(6) U every second day). This treatment induced hemodynamic improvement in all four patients and eliminated the persistent enteroviral infection in two. CONCLUSIONS: Enterovirus-positive patients have a better heart transplantation-free survival rate and hemodynamic course, with fewer histologic changes, than do enterovirus-negative patients. In addition, enterovirus-positive patients respond favorably to interferon-alpha treatment. These observations indicate that myocardial enteroviral infection with associated left ventricular dysfunction is a distinct disease entity with a benign course.

Cardiac Catheterization

Cultured human myocardial fibroblasts of pediatric origin: natural human interferon-alpha is more effective than recombinant interferon-alpha 2a in carrier-state coxsackievirus B3 replication.

Cultured human myocardial fibroblasts of pediatric origin seem to be a useful species-specific model for studying various heart diseases which involve the myocardial interstitium, for example enterovirus heart disease. Cells were propagated from small samples of human ventricular tissues (0.2 g) obtained from standard surgical procedure for the correction of Fallot-tetralogy. Cultured cells exhibited typical fibroblastoid morphology over a period of 4 months and were uniformly immunoreactive with a monoclonal antibody directed against prolyl-4-hydroxylase, a marker enzyme of fibroblasts. Infection of cell cultures with coxsackievirus B3, a cardiotropic enterovirus, resulted in a typical carrier-state type of virus persistence. Average virus titers of 2.3 x 10(5) plaque-forming units/ml (SD = 9.9 x 10(4)) were maintained over a period of up to 10 weeks by productive infection of about 8-10% of the cell population. Coxsackievirus B3 carrier cultures of human myocardial fibroblasts were used to evaluate in vitro the long-term antiviral effects of recombinant interferon alpha-2a and natural human interferon-alpha. Recombinant interferon-alpha reduced virus yields by 90% with a concentration of 423 IU/ml, whereas with natural interferon-alpha a 90% reduction of virus yields was achieved with concentrations as low as 21 IU/ml. Antiviral effects of both recombinant and natural interferon-alpha were highly specific and not related to inhibition of cell-proliferation (< 50% with interferon-alpha concentrations as high as 6250 IU/ml). Since effective concentrations of interferon-alpha can be easily attained in vivo with subcutaneous application, interferon-alpha (in particular: natural interferon-alpha) may become useful in the treatment of patients with enterovirus myocarditis and enterovirus induced dilated cardiomyopathy.

Antiviral Agents

Subclassification of dilated cardiomyopathy and interferon treatment.

Seventy-seven consecutive patients with dilated cardiomyopathy underwent left ventricular endomyocardial biopsy. In 20 biopsies (26%) enteroviral RNA was detected by in-situ hybridization. After an average observation period of more than 2 years only one patient had died in the enterovirus positive (ev+) group compared with 11 deaths and four heart transplantations in the enterovirus negative (ev-) group. After a mean follow-up of 16 +/- 9 months haemodynamic evaluation of the surviving ev+ patients showed significantly better results with respect to left ventricular ejection fraction and left ventricular end-diastolic diameter. The four ev+ patients with haemodynamic deterioration were given interferon-alpha, 3 million units subcutaneously every other day for six months. No severe side effects were seen and all four patients improved according to their haemodynamic and clinical parameters. In two of the four patients enteroviral RNA was not detectable in a subsequent biopsy.

Adult

Indium-111-antimyosin Fab imaging to demonstrate myocardial involvement in systemic lupus erythematosus.

Indium-111-antimyosin Fab imaging has been used to indicate myocardial injury. This report describes antimyosin accumulation in two patients with myocardial involvement in systemic lupus erythematosus. Both patients complained of chest pain, and significant stenoses of extramural coronary arteries were ruled out by angiography. The first patient, a 64-yr-old woman, had immunopathologic findings suggestive of systemic lupus. Indium-111-antimyosin Fab imaging showed myocardial tracer uptake. This prompted endomyocardial biopsy providing evidence of systemic lupus. The patient improved under immunosuppressive therapy. The second patient, a 47-yr-old man, had systemic lupus diagnosed by immunopathologic findings and skin biopsy. He had evidence of pericarditis on electrocardiography and echocardiography. Indium-111-antimyosin Fab imaging demonstrated additional myocardial involvement, which supported the initiation of immunosuppressive therapy. Our results suggest that 111In-antimyosin Fab imaging may provide valuable diagnostic information and influence patient management in systemic lupus erythematosus with suspected myocardial involvement.

Antibodies, Monoclonal

Enterovirus-induced myocarditis: hemodynamic deterioration with immunosuppressive therapy and successful application of interferon-alpha.

In 1985, myocarditis was diagnosed by endomyocardial biopsy in a 53-year-old woman who was free of symptoms of heart insufficiency. Immunosuppressive therapy with azathioprine and prednisolone was prescribed as the patient had deteriorated to NYHA II heart insufficiency in March 1986. When application of immunosuppressive agents was terminated in 1987, serial endomyocardial biopsies revealed no signs of myocarditis, thus indicating effectiveness of immunosuppression. Nevertheless, the patient had worsened clinically and hemodynamically. At follow-up in 1991, the patient had progressed to dilated cardiomyopathy resulting in NYHA III heart insufficiency. Enterovirus infection of the heart was detected by in situ nucleic acid hybridization. In addition, retrospective serology indicated a significant increase of coxsackievirus B2 antibodies between 1985 and 1991. Investigational antiviral therapy with recombinant interferon alpha-2a was tolerated well and a favorable clinical, hemodynamic, and virologic response was observed. Thus, progression of biopsy-proven myocarditis to dilated cardiomyopathy may have been facilitated by immunosuppressive therapy in enterovirus infection. Antiviral therapy might be advantageous in patients with enterovirus myocarditis and dilated cardiomyopathy.

Azathioprine

[Myocarditis].

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Biopsy

Significance of coronary angiography, left heart catheterization, and endomyocardial biopsy for the diagnosis of idiopathic dilated cardiomyopathy.

Many physicians assume that a reliable diagnosis of idiopathic dilated cardiomyopathy can be made by noninvasive methods, mainly echocardiography. On the other hand, use of endomyocardial biopsy in those patients who have undergone left heart catheterization and who demonstrate left ventricular dysfunction of unknown origin is increasing. Therefore the purpose of this study was to investigate the yield of that diagnostic strategy in patients with the tentative diagnosis of idiopathic dilated cardiomyopathy. Between 1980 and 1988, 3.2% of our 15,442 patients were diagnosed as having idiopathic dilated cardiomyopathy on the basis of left heart catheterizations and coronary angiograms. Idiopathic dilated cardiomyopathy was diagnosed in 444 patients on the basis of clinical data and results of noninvasive tests before catheterization, but in only 295 of these cases was the diagnosis confirmed by means of coronary angiography and left heart catheterization (predictive value of noninvasive tests is 66%). The remaining 34% of patients demonstrated extensive coronary artery disease (13%), significant valvular heart disease (11%), and other or no heart disease (10%). The diagnostic sensitivity of noninvasive tools (patient history, ECG, stress test, echocardiography) was only 59%. Left heart catheterization can easily be combined with endomyocardial biopsy. With the use of histologic techniques, specific heart muscle diseases were detectable in 3.5% of 209 patients, but in only 1% could therapeutic consequences be determined. Thus coronary angiography and left heart catheterization are mandatory for the correct diagnosis of idiopathic dilated cardiomyopathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy

[Diagnosis by endomyocardial biopsy: angina pectoris as a manifestation of lupus erythematosus].

A 64-year-old female patient with a prosthetic mitral valve suffered from recurrent typical angina and dyspnea. Left heart catheterization excluded a dysfunction of the prosthesis and coronary artery disease (CAD). A stress thallium scan demonstrated an ischemic reaction. An antimyosin scintigram was positive, indicating myocytal membrane disruption. Serological tests were suspicious for systemic lupus erythematosus (SLE). Therefore, an endomyocardial biopsy (EMB) was performed and a severe alteration of an intramyocardial artery, comparable with chronic SLE, was diagnosed. EMB is a useful diagnostic tool in patients with typical chest pain, positive thallium and anti-myosin scintigrams, however exclusion of CAD.

Angina Pectoris

Experimental infection of macaques with HIV-2ben, a novel HIV-2 isolate.

Ten rhesus (Macaca mulatta) and six fascicularis (Macaca fascicularis) macaques were inoculated with HIV-2ben using three different virus preparations and two routes of inoculation. Thirteen of the 16 inoculated macaques seroconverted 2-6 weeks after infection. Three M. mulatta remained seronegative. The seroconverted animals developed antibody titres from 80 to 40,000. Their antibodies reacted with gp160 and gp130 and, in varying degrees, with gp32 and core proteins. Virus could be re-isolated from 11 of the 16 macaques. M. mulatta were transiently viraemic 6-14 weeks after infection whereas all M. fascicularis were persistently viraemic 2-7 weeks after infection onwards. In the 6-18 months after infection one M. mulatta lost 20% of its body weight and two M. fascicularis showed transient lymphadenopathy and splenomegaly; the other animals remained clinically normal. A re-isolated virus from a M. mulatta was indistinguishable from the inoculated HIV-2ben by genomic restriction enzyme analysis. M. mulatta and M. fascicularis are infectable by a single intravenous injection of cell-free HIV-2ben. Persistent viraemia in M. fascicularis represents a valuable and reliable parameter for studies on antivirals and vaccines.

Animals