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A Heim

Publications and source records attributed to A Heim.

At least 37 records · Page 2Linked to original sources
PubMed1997

Conserved sequences in the fibers of epidemic keratoconjunctivitis associated human adenoviruses.

The fiber gene sequences of the human adenovirus types 19 and 37 were determined. The predicted polypeptides exposed a high homology. Ad8, Ad19, and Ad37 can cause epidemic keratoconjunctivitis (EKC), whereas Ad9 only infrequently causes acute follicular conjunctivitis. Comparison of the fiber knobs of Ad8, Ad9, Ad19, Ad37, and other previously published fiber sequences revealed that only two amino acid residues were conserved in the fiber knobs of Ad8, Ad19, and Ad37. Since the knob is responsible for interaction with the cell receptor, these two amino acid residues could play an important role in the pathogenicity of EKC causing adenoviruses.

Adenoviridae↗
PubMed1997

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↗
PubMed1996

Recombinant Interferons beta and gamma have a higher antiviral activity than interferon-alpha in coxsackievirus B3-infected carrier state cultures of human myocardial fibroblasts.

We compared the antiviral activities of three recombinant human interferons (IFN-alph2a, IFN-beta, and IFN-gamma) in cultured human myocardial fibroblasts to select a candidate for trial in heart disease induced by cardiotropic enterovirus, e.g., coxsackievirus B3 (CVB3). Cells were exposed to CVB3, and after 7 days, when a persistent infection had developed, IFN was added. Virus yields were measured on alternate days for the next 7 or 16 days, and IFN activity was assessed as the percentage reduction in yield. IFN-gamma and IFN-beta were both highly active and reduced virus yields by 2 log (EC(99)) at concentrations of 23.4 IU/ml (SD = 8.6) and 10.1 IU/ml (SD = 3.2), respectively; with 250 IU/ml of either IFN, no infectious virus was formed. Unexpectedly, IFN-alpha2a (EC(99)> 1250 IU/ml) was at least 120 times less active than IFN-beta; after use for 8 days or more, the minor effects it produced were no longer related to the concentration applied. Despite the pharmacokinetic advantages of IFN-alpha2a, our data suggest that IFN-beta should in preference be evaluated in the clinic.

Antiviral Agents↗
PubMed1996

General pharmacology of insulin lispro in animals.

[Lys(B28),Pro(B29)]-human insulin (insulin lispro, CAS 133107-64-9, LY275585, Humalog) is a quick acting insulin analog which is currently undergoing clinical evaluation for the treatment of diabetes. The potential secondary pharmacological activity of insulin lispro was profiled in studies for the evaluation of effects on the central and autonomic nervous system, the cardiovascular system, urine and electrolyte excretion, and gastrointestinal function. In vivo doses ranged from 0.03 to 10 U/kg, administered by the subcutaneous route, while pharmacologic activity in vitro was examined in smooth and cardiac muscle at concentrations of 1 x 10(-9) to 1 x 10(-5) mol/l. Insulin lispro exhibited secondary pharmacological activity in central nervous system tests only at higher doses with the most prominent observations being sedation and decreased responsiveness. Insulin lispro was essentially inactive in tests of autonomic (smooth and cardiac muscle), cardiovascular (mean arterial pressure, heart rate, systolic pressure, diastolic pressure, and pulse pressure), renal (urine and electrolyte excretion) and gastrointestinal (motility) function. In summary, insulin lispro had minimal effect in these pharmacodynamic studies indicating that insulin lispro has minimal potential to produce adverse pharmacological side effects at clinically relevant doses.

Animals↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

Comparison of carbamazepine and lithium in the prophylaxis of bipolar disorders. A meta-analysis.

BACKGROUND: This meta-analysis assessed the equipotency of carbamazepine and lithium prophylaxis in bipolar disorder. METHOD: We selected only randomised, double-blind, controlled studies comparing carbamazepine with lithium from a manual and computerised search, and subjected them to a quality inventory. Their statistical results were weighted by their quality score and combined. RESULTS: Four studies met our criteria, yielding, overall, P = 0.15. This result is not straightforward because the studies showed significant heterogeneity (P < 0.01). CONCLUSION: Differences in statistical power and sensitivity of outcome measure explain this heterogeneity and the conflicting results of the studies. Therefore, the prophylactic efficacy of carbamazepine remains questionable.

Bipolar Disorder↗
PubMed1994

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↗
PubMed1994

Abnormal regional CBF response in left hemisphere of dysphasic children during a language task.

This study used xenon 133 inhalation and single-photon computed tomography to measure regional cerebral blood flow during a quiet resting condition, a simple auditory task, and an auditory phonemic discrimination task in 3 age-matched groups of children suffering from developmental language disabilities: expressive dysphasia, expressive-receptive dysphasia, and attention-deficit hyperactivity disorder. An absence of left hemisphere activation was observed in the expressive-receptive group during the phonemic discrimination task as compared to both expressive and attention-deficit hyperactivity disorder children, together with an absence of left inferior parietal region activation in dysphasics as compared to hyperactive children. These results favor the hypothesis of an abnormal lateralization for language in dysphasic children and point toward possible different pathologic localizations in the different clinical subtypes of dysphasia.

Aphasia↗
PubMed1993

[Myocarditis].

Explore the source record for details and available documents.

Biopsy↗
PubMed1992

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↗
PubMed1992

Synergistic interaction of interferon-beta and interferon-gamma in coxsackievirus B3-infected carrier cultures of human myocardial fibroblasts.

The antiviral effects of human interferon-beta (IFN-beta) and human recombinant interferon-gamma (rIFN-gamma) were studied in persistently coxsackievirus B3-infected carrier cultures of human myocardial fibroblasts over a period of 21 days. Synergism was observed with concentrations as low as 30 IU of IFN-beta plus 10 IU of rIFN-gamma/mL, reducing mean viral titers from 6.0 x 10(7) to 1.3 x 10(4) pfu/mL and number of infected cells from 14.4% to 0.1% as determined by quantitative in situ hybridization. Higher concentrations of IFNs (both > or = 30 IU/mL) were associated with transient antagonism followed by antiviral synergism. With 100 IU of IFN-beta plus 30 IU of rIFN-gamma/mL, elimination of infectious virus was consistently achieved and sustained for 6 weeks after cessation of IFN application, whereas at least threefold higher concentrations were required with single drugs. In summary, our data support a concept of low-dose IFN combination schedules that might become useful in the treatment of enteroviral heart disease.

Cells, Cultured↗
PubMed1991

Radioimmunoimaging of subacute infective endocarditis using a technetium-99m monoclonal granulocyte-specific antibody.

Immunoscintigraphy with a technetium-99m murine monoclonal IgG1 antibody directed against non-specific cross-reacting antigen (NCA-95) and carcinoembryonic antigen was performed with 20 patients with suspected subacute infective endocarditis (SIE) and 6 controls with suspected inflammatory/infectious disease elsewhere in the body. Immunoscintigraphy and echocardiography localised SIE in 11 of 15 patients in whom the disease could be confirmed. In 4 patients with validated SIE, the immunoscan was abnormal, and the echocardiogram was normal. In another 4 patients, the result was exactly the opposite. These findings suggest that the combination of immunoscintigraphy and echocardiography improves diagnostic efficacy in patients with suspected SIE.

Adolescent↗