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Biomedical subjects

H Voss

Publications and source records attributed to H Voss.

At least 109 records · Page 6Linked to original sources

[Sulphated glycosaminoglycans as virus inhibitors. 4th communication: clinical aspects of zoster with the proposal of a new treatment (author's transl)].

On the base of plaque inhibition tests in at least three virus-host-systems and successful treatment of mice with experimentally induced yellow fever encephalitis a well known sulphated glycosaminoglycan (GAGPS) "L5" was used as therapeutic agent in cases of zoster infection in man. The material was applied as 1% solution in water continuously on lint and rewettet for several days until nearly complete healing was achieved. The clinical course of 18 patients of former years (12 women, 6 men) was compared with 26 cases (19 women, 7 men) treated additionally with the new substance. All of them were carefully observed in the Rudolf-Virchow-Hospital in Berlin. Besides of registrating data as age and sex of the patients and the seasonal distribution of cases the course of illness was analyzed. The mean duration before admission to the hopsital was 4,9 days in the control group and 7,2 days in the L5-patients. Signs of organ diseases possibly acting as trigger mechanism for the remanifestation of the zoster were nearly twice in number in L5 cases than in the controls. Despite of this unfavorable stiutation the main parameters showed a clear tendency to return earlier to normal values in the GAGPS group. The fever was shortened. The blood lymphocytes normalized better with mean absolute values of 2400 in the L5-group and 3029 per m(3) in the control cases. The fall of the cell number in the liquor cerebrospinalis was more rapidly in the GAGPS treatment. The mean stay in the hospital was 33,2 days in L5 cases and 44,6 days in control patients respectively in the main group of age between 60 and 80 years. One death in the GAGPS group corresponded to four in the control group. In the local skin area the edema disappeared rapidly with beginning of treatment. Confluent vesicles flattened within 24 to 48 hours and no further efflorescences were seen. Pain diminished in few days. The good results justify continued trials.

Adult↗

[Congenital aneurysms of the membranous ventricular septum (author's transl)].

In 3 patients with a congenital aneurysm of the membranous portion of the ventricular septum diagnosis could be made by angiography. One of these patients was clinically asymptomatic, while the two other patients were transferred for surgery because of right ventricular outflow tract obstruction or intracardiac left-to-right shunt. These both patients underwent successful open heart corrections. Aneurysms with a different intracardiac localization could be found. One of the cases represents an unusual association with corrected transposition of the great vessels.

Adolescent↗

[Sulphated glycosaminoglycans as virus inhibitors. 2nd communication: Inhibitory effect of glycosaminoglycanpolysulphates on yellow fever virus 17 D in animal experiments (author's transl)].

Glycosaminoglycanpolysulfates (GAGPS) have virus inhibiting properties demonstrable by means of tissue culture in the plaque method. In brain preparations of children who had died of a hyperpyretic toxicosis, cell necroses were found corresponding to the picture of tissue culture plaques. The question arose from these observations whether this inhibiting effect of GAGPS can perhaps also be demonstrated in vivo. In animal experiments, cell necroses corresponding to those of the infant brain could be observed during the course of a 17 D yellow fever encephalitis in mice. The Luitpoldt-Werk Munich placed to our disposal 13 different GAGPS for tests. Each of these substances was tested in 210 mice (fig. 1). Virus dilutions (LD 50/ml) were mixed to the same volume with the indicated concentrations of substance directly before vaccination. The differing LD 50 doses is due to the fact that each ampoule contains a different content of virus.) The toxicity of all substances is practically zero (table 2a, 2b). The effect of the inhibiting substances was evaluated at first by means of a deviation of the rate between alive and dead animals (table 1). The statistical significance of the effect of some substances was that high so that an inhibition of the virus replication has obviously to be considered. The significance for L1 and L4 - they are chemically very similar - is higher than 0.001 (table 4). The virus inhibiting effect of the substances was controlled by histopathology. 31 brains of mice were dissected and histologically evaluated; the lesions of the brains were examined and recorded (table 3). The effect of the substances was measured by absence or diminution of the lesions. The most effective substance was L1 as far as its concentration was higher than the critical limit of 625 gamma/ml.

Animals↗

[Sulphated glycosaminoglycans as virus inhibitors. 3rd communication: therapy of viral diseases by means of glycoasaminoglycanpolysulphates. Establishment of fundamentals in experiments with laboratory animals (author's transl)].

Following the in vitro and in vivo demonstration of their inhibitory effect upon 17 D yellow fever virus (Comm. I and II) it has been tried to demonstrate the therapeutic effect of three GAGPS (L1, L5, L8)1 in experimental animals. It had been found that L1 possessed the strongest inhibitory action and L5 the lowest toxicity. L8 served as control substance with different chemical structure. Mice that had been intracerebrally infected with 50 to 100 LD50 yellow fever virus were subsequently treated with L1, L5 and L8 by i.v., i.p., i.m., and oral routes. At first it was found by cytophotometric measurements that the i.c. applicated substances accumulated in the nerve cells of the hippocampus major, the cerebellum (Purkinje cells) and the cortex; the uptake was nearly doubled if a mixture with virus was used (Table 1). Following preliminary experiments to determine the adequate quantity of virus, five experiments were performed in the order mentioned. In the first series were treated groups of 30 animals after intracerebral infection with 100 mug/0.02 ml L1 by the i.m. and i.p. routes respectively, beginning from the first day p.i. for a period of seven days (Table 2). A certain difference of the rate of deaths and surfivals was seen between the treated and untreated groups. Among the treated mice delayed death was a prominent occurrence (Fig. 1). A second experiment involving a double dose of L1a (200 mug/0.02 ml) from another batch of GAGPS showed no better effect (Table 3). An explanation was given by the fact that L1a demonstrated a moderate toxicity with high doses about 5000 mug/ml in the i.c. control (Table 4 and 5). A graphic representation of both experiments can be found in Figs. 2a and 2b. The relative low virus input in the third series as shown in the virus control impedes additionly clearcut results. In the fourth experiment the infected mice were treated with GAGPS doses between 250 and 2500 mug/ml; L1 was administered by the oral, L5 and L8 by the intraveneous route. The death rate of the animals treated with low doses of L1 (250-1000 mug/ml) is diminished clearly and there was a significant difference between treated and untreated mice when L5 and L8 were applied (Table 6). Fig. 3 shows the graphic representation of experiment four. The good results of treatment were confirmed by histopathological findings (Table 7). There was a clear difference in the kind and quantal distribution of cerebral lesions in treated and untreated mice. In the last series L1 was administered by the i.v., L5 and L8 by the oral route (Table 8). Although the virus dose given in this series was rather low a protective effect was seen with low doses of L1 (312 mug/ml) and L5 )500 and 1000 mug/ml). Also these results were confirmed by histopathological examination. In summary, the GAGPS L1, L5 and L8 were found to have a clear therapeutic effect upon the experimental encephalitis of mice caused by infection with 17 D yellow fever virus, in the case of experiment four with statistical significance.

Animals↗