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Biomedical subjects

G Herrmann

Publications and source records attributed to G Herrmann.

At least 109 records · Page 6Linked to original sources

Efficacy of 5-vinyl-1-beta-D-arabinofuranosyluracil (VaraU) against herpes simplex virus type 2 strains in cell cultures and against experimental herpes encephalitis in mice: comparison with acyclovir and foscarnet.

The sensitivity of different herpes simplex virus type 2 (HSV-2) strains to inhibition by 5-vinyl-1-beta-D-arabinofuranosyluracil (VaraU) was evaluated in comparison to 9-(2-hydroxyethoxymethyl)guanine (ACV; acyclovir) and trisodiumphosphonoformate (Na3PFA; foscarnet), using a plaque inhibition assay in primary rabbit testes (PRT) cells as well as in human embryonic lung fibroblast (HELF) cell cultures. The order of decreasing activity found was ACV much greater than VaraU greater than Na3PFA in PRT cells and ACV greater than VaraU much greater than Na3PFA in HELF cells, with 50% inhibition doses (ID50) of 1.8, 8.8, and greater than 110 microM for the three drugs in HELF cells, respectively. After 72hr of drug treatment, inhibition of HELF cell proliferation by VaraU (ID50, greater than 1000 microM) was less than that by ACV and Na3PFA, resulting in high selectivity indexes of greater than 100 against HSV-2 for VaraU and ACV. Their in vivo efficacy was assessed in a mouse encephalitis model. Using a treatment schedule of three daily intraperitoneal (ip) doses over a period of 5 days, only the survival times of mice were considerably prolonged by VaraU (150 or 300 mg/kg per day; P less than 0.05 or P less than 0.001, respectively). In contrast, ACV treatment (150 mg/kg per day) led to a nearly complete prevention of encephalitis and death (P less than 0.001). Similar therapy results with VaraU application through the drinking water were obtained using only one-sixth of the high ip dose (approximately 50 mg/kg per day) but over a prolonged period of treatment. Under similar conditions no therapeutic effect of oral Na3PFA was observed.

Acyclovir

A classification of cardiac allograft rejection. A modification of the classification by Billingham.

We herein propose a classification of rejection in cardiac allografts based on the original Stanford work. Our modified classification, as a work hypothesis, defines the following grades: mild acute rejection (A-1), corresponding to Billingham's "mild rejection"; mild acute rejection with probable conversion to moderate rejection (A-2); moderate acute rejection (A-3), comparable to Billingham's "moderate rejection"; and severe acute rejection (A-4), morphologically identical with the respective grade in the Billingham classification. The resolution of rejection has been classified into two grades--early (A-5a) and late (A-5b) resolution--according to the development of granulation tissues. We also grade the degree of vasculopathy (B-1, B-2) and chronic rejection (C), which is characterized by aggressive fibrosis and persistent vasculopathy. Mild rejection with possible conversion to moderate rejection is defined by an increasing quantity of retrogressive changes in myocytes. Changes not related to transplantation are characterized in our classification by descriptive diagnosis. The proposed classification was validated by 1 year of clinical experience and by the evaluation of possible prognostic aspects of the classification.

Biopsy

Effect of (E)-5-(2-bromovinyl)- and 5-vinyl-1-beta-D-arabinofuranosyluracil on Epstein-Barr virus antigen expression in P3HR-1 cells: comparison with acyclovir.

The effect of (E)-5-(2-bromovinyl)- and 5-vinyl-1-beta-D-arabinofuranosyluracil (BrVaraU, VaraU) in comparison to 9-(2-hydroxyethoxymethyl)guanine (ACV) on the proliferation of human lymphoblastoid P3HR-1 cells in culture and on the expression of Epstein-Barr virus capsid antigen (VCA) in the same cells was evaluated. After 7 days of cell growth, at 100 mumol/l the total number of new generations in drug-treated cultures was similar or 5 and 10% below that in drug-free control cultures, for VaraU, ACV, and BrVaraU, respectively. During the same time the percentage of VCA-expressing cells decreased from 6.3% in drug-free cultures to 1.3, 1.5, and 2.0% in cultures treated with VaraU, ACV and BrVaraU, respectively. In VaraU-treated cultures a further decrease in the percentage of VCA-positive cells down to 0.5% was revealed 7 days after drug removal. VaraU was also effective in reducing the proportion of VCA-expressing cells at 10 and 1 mumol/l. At 14 days after drug removal, the inhibitory effect of ACV was nearly reversed, whereas BrVaraU showed a prolonged VCA- suppressing effect.

Acyclovir

[Heart transplantation--postoperative management].

Heart transplantation represents a widely accepted therapeutic modality for patients with end-stage myocardial failure. With increasing experience, 1-year survival rates of over 75% and 5-year survival rates of over 60% have been achieved, mainly due to patient selection, standardized surgical techniques as well as improved postoperative management. During early follow-up, particular attention should focus on diagnosis and treatment of graft rejection and infection, which require individualized immunosuppression, while in the later postoperative course coronary atherosclerosis, hypertension, chronic renal insufficiency and malignancy become more important as potential complications. The general principles in the management of these patients are discussed.

Adolescent

In-situ hybridisation with HBV-cDNA as a sensitive method for the diagnosis of hepatitis B infection in persistent acute hepatitis.

Liver biopsies of 97 patients with persistent acute hepatitis, a morphologically distinct form of hepatitis with only slightly elevated transaminase values, were screened immunohistochemically for HBs and HBc, and with in-situ hybridisation for HBV DNA. Besides the 37 in part inconstantly immunohistochemically-positive patients, 47 others showed exclusively cytoplasmatic HBV DNA, localizing at least the major part of the replication of viral DNA to the cytoplasm of liver cells. A diffuse distribution pattern of HBV DNA-positive liver cells was accompanied by stronger morphological changes than focally accentuated positivity. In HBc-positive cases, distribution of HBV DNA corresponded mainly to the cytoplasmic type of HBc.

Acute Disease

Morphological changes after intra-arterial chemotherapy of the liver.

The livers of twenty patients given intra-arterial chemotherapy to treat malignant tumors of the liver or liver metastases, were examined histologically. The results show that cytostatic chemotherapy primarily affects tumor cells, but also causes toxic damage to liver tissue. Besides necrosis of single cells or groups of cells and cholestasis in about one-third of the cases sclerosing cholangitis is a major complication. After chemoembolization, which produces a more marked therapeutic effect with regard to tumor necrosis, extensive necrosis of liver tissue, arteries, bile ducts, and nerves is most conspicuous. Nevertheless, in view of the positive therapeutic effects observed, intra-arterial chemotherapy is recommended for palliative therapy.

Antineoplastic Agents

Kidney-derived urinary antigens assayed with monoclonal antibodies for the detection of renal damage.

For the quantitation of kidney-derived Urinary Antigens (UA) monoclonal antibodies specific for antigens localized in cells of defined subunits of the nephron were applied in sandwich ELISA. Antigen excretion was measured in the urine of healthy individuals, patients suffering from various diseases, kidney transplant recipients, and healthy volunteers receiving therapeutic doses of antibiotic drugs. In healthy individuals, in patients with diseases primarily affecting the glomerulus, and in inactive phases of chronic diseases antigen excretion was low. Toxic drug effects enhanced antigenuria. Excretion of some or all of the antigens always indicated tubular alterations. The tests thus provide information on location and extent of acute primary tubular damage.

Antibodies, Monoclonal

Parathyroid hormone in coronary artery disease--results of a prospective study.

Parathyroid hormone (PTH) influences the calcium metabolism of many different mammalian cell types; indeed, hypertension due to changes in muscle tone is a frequent symptom of hypercalcemic hyperparathyroidism. In a blind study of 81 patients with various forms of heart disease undergoing coronary angiography, the plasma concentrations of the midcarboxyl regional PTH immunoreactivity were determined. PTH concentrations were elevated in 26 of the 56 patients exhibiting organic coronary artery disease (CAD). The plasma PTH levels were highest in those patients with CAD affecting three vessels and in patients with evidence of myocardial infarction. PTH levels were not influenced by previous drug treatments, and did not correlate to stress hormone levels. We propose that increased PTH levels may be a marker for initiation or potentiation of calcium-dependent changes in vascular smooth muscle behavior inducing coronary functional and anatomic lesions typical of CAD.

Adult

Treatment of experimental herpes simplex virus type 1 encephalitis in mice with (E)-5-(2-bromovinyl)- and 5-vinyl-1-beta-D-arabinofuranosyluracil: comparison with bromovinyl-deoxyuridine and acyclovir.

The efficiency of (E)-5-(2-bromovinyl)- and 5-vinyl-1-beta-D-arabinofuranosyluracil (BrVaraU, VaraU) as inhibitors of three herpes simplex virus type 1 (HSV-1) strains was assessed in comparison to (E)-5-(2-bromovinyl)-2'-deoxyuridine (BrVUdR), 9-(2-hydroxyethoxymethyl)guanine (ACV), and trisodium phosphonoformate (Na3PFA) using a plaque assay in human embryonic lung fibroblast (HELF) cell cultures. The following order of decreasing activity was found: BrVaraU greater than VaraU greater than BrVU-dR greater than ACV much greater than Na3PFA. In HELF cell cultures, the selectivity indexes of VaraU and BrVaraU were 10 times higher than those of BrVUdR and ACV. Protection of mice from encephalitis and death due to intracerebral (i.c.) infection with a clinical HSV-1 isolate was nearly complete if mice were treated intraperitoneally (i.p.) with two daily doses of VaraU and BrVaraU (100 or 200 mg/kg per day) over a period of 5 or 10 days. The efficacy was similar to ACV, but, using a treatment schedule of three daily i.p. doses over 10 days, with equimolar amounts of the nucleoside analogs, VaraU and BrVaraU (140 and 180 mg/kg per day) were superior to ACV (130 mg/kg per day) (P less than 0.05).

Acyclovir

[Single vessel disease of the anterior interventricular branch as a cause of combined anterior and posterior wall infarct in comparison with 2-vessel disease of the RIVA and RCA].

Only few studies deal with the problem of an isolated stenosis of the left anterior descending coronary artery (LAD) leading to a combined anterior and inferior myocardial infarction in the ECG and VCG. In the present study patients with electrocardiographic signs of anterior and inferior myocardial infarction and either one-vessel disease of the LAD branch (n = 27; group I) or two-vessel disease including the LAD and the right coronary artery (RCA) (n = 29; group II) were investigated. Due to the anterior myocardial infarction present in all patients, unequivocal signs of posterior and posterolateral infarct location were missing in the ECG and VCG. There was a distinct variability with regard to Q-wave duration and amplitude in the inferior leads of the ECG and of the Q/R-relation in the scalar lead Y of the VCG (Frank-leads) in patients with isolated LAD disease when compared to those with combined LAD and RCA disease, but no reliable parameter was found in the ECG and VCG which allowed to allocate patients to one of the two groups. On the other hand, there were significant differences in hemodynamics and left ventricular function between the two groups. Group I patients showed a significantly higher left ventricular ejection fraction (mean 49 +/- 15%) than patients with two-vessel disease (group II) (mean 42 +/- 12%) (p less than 0.05). Left ventricular end-diastolic pressures at rest (13 +/- 7 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Catheterization

[Echocardiography detection of reduced left ventricular diastolic posterior wall motion in patients with constrictive pericarditis--incidence and correlation with hemodynamics and clinical course].

In 24 patients with chronic constrictive pericarditis (CP) proven by right and left heart catheterization, the amplitude of diastolic left ventricular posterior wall motion was evaluated by M-mode echocardiography and compared with the results of 14 healthy volunteers. The amplitude was significantly less in CP patients than in normal controls (0.3 mm vs. 4.0 mm, p less than 0.001) and no CP patient showed a higher value than 2 mm whereas none of the normal subjects had an amplitude less than 3 mm. In 11 of 13 CP patients undergoing pericardectomy, an increase in amplitude was observed; in 6 of them the amplitude was within normal limits following surgery. No significant correlation between the degree of heart failure or the level of left ventricular end-diastolic pressure and the reduction of the amplitude could be found. In addition, the level of the amplitude did not allow a clear separation between patients who could be treated medically and those requiring pericardectomy. It can be concluded that the reduction of diastolic left ventricular posterior wall motion is a valuable echocardiographic parameter for the noninvasive diagnosis of CP.

Adult

Functional radiographs of the craniocervical region and the cervical spine. A new computer-aided technique.

Disabilities of the articulations of the head and cervical spine can often be detected only by exact measurement of functional radiographs. From two radiographs, one in flexion and one in extension, not only can the total mobility of the head be measured, but also the mobility of the individual articulations can be evaluated by taking exact measurements of the position of each vertebra. A method for semi-automatic measuring of such pairs of radiographs is presented. Edges and structures of the bones that are clearly visible in both radiographs are digitized on a graphics tablet. Then, by computer program, each vertebra of the first radiograph is shifted and rotated until it fits best to the respective vertebra of the second radiograph. Thus, for each articulation, the mobility angle and the location of the mobility axis relative to the adjacent vertebra, can be computed. First experiences with this method are presented.

Adult

Anti-herpes simplex virus and cytostatic activity of some new 5-substituted 1-(4-hydroxybutyl)-and 1-(2-hydroxyethoxymethyl) uracil nucleoside analogues.

Two series of 5-substituted acyclic uracil nucleoside analogues (5-X-acyclo-U) were evaluated for their inhibitory effects against three herpes simplex virus type 1 (HSV-1) strains and one type 2 (HSV-2) strain in a plaque inhibition assay on human embryonic lung fibroblast (HELF) cell cultures as well as for their ability to inhibit the proliferation of baby hamster kidney cells in suspension (BHK-S) culture. Acyclovir [9-(2-hydroxyethoxymethyl)guanine; ACV] and (S)-9-(2,3-dihydroxypropyl)adenine [(S)-DHPA] were used as reference compounds. Only two derivatives, 1-(4-hydroxybutyl)-5-(2,2-dibromovinyl)uracil (Br2V-HBU) and 1-(2-hydroxyethoxymethyl)-5-(2,2-dibromovinyl)-uracil (Br2V-HEMU) proved active, but only at high concentrations (57-350 mumol/l) and without selectivity of anti-herpes activity, whereas ACV showed strong inhibition of HSV-1 and HSV-2 and a low cytostatic effect on BHK-S cells (50% inhibitory concentrations are 0.25-0.73, 2.1, and 240 mumol/l for HSV-1, HSV-2, and BHK-S, respectively), demonstrating a high antiherpes selectivity. In contrast, all other 5-X acyclo-U analogues [X = methyl, ethyl, propyl, butyl, vinyl, and 2-bromovinyl; acyclo = 1-(4-hydroxybutyl) and 1-(2-hydroxyethoxymethyl)] as well as the reference compound (S)-DHPA were inactive at concentrations up to 0.5-1 mmol/l. Some structure to activity relationships of acyclic pyrimidine and purine nucleoside analogues are discussed.

Acyclovir