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Increasing drug delivery to the tumor should induce improved tumor response. To study this the effect of degradable starch microspheres (DSM) and mitomycin was evaluated in 11 patients with chemoembolization of colorectal liver metastases (CRLM) and previous floxuridine (FUDR) treatment. In 10 patients access to the hepatic artery was obtained either by infusaid pump or infusion chambers. Indications for chemoembolization were: Failure of continuous FUDR treatment (n = 7), biliary sclerosis (n = 2), incomplete liver perfusion (n = 2), extensive disease (n = 2). Preliminary observations showed a wide range of required DSM dose. Therefore each individual dose was determined by the use of digital subtraction angiography (DSA). Seventy-five percent of the DSM dosage, which induced reversed flow in the common hepatic artery, was selected for treatment. DSM was then administered four times every 2 hours/day/monthly. The last DSM doses were mixed with 10 mg mitomycin C. Observed response rates, controlled by chemotherapy (CT) and tumor markers, were: complete response 1/11; partial response 3/11; stable disease 2/11; progression 5/11. The median duration of response was 6.5 (range 3-21) months. DSM application induced redistribution of arterial flow towards previously unperfused portions of the liver. The required DSM doses decreased about 20-30% from the first to the last chemoembolization cycle. Although there was no systemic toxicity, embolization was associated with several local side effects. Moderate to heavy pain in spite of morphia and neuroleptics was experienced in 55% of all treatments. Some patients demonstrated an elevation in body temperature of up to 39 degrees C. Postembolization liver biopsies revealed more intense tumor necrosis associated with more severe hepato-toxicity than was seen with continuous FUDR treatment. It is concluded that the optimal sequence and dosage of mitomycin and DSM has to be further evaluated in prospective trials before clinical application.

Fifty-two (52) patients with nonresectable hepatic-only metastases from colorectal carcinoma (tumor volume less than 75%) were treated by intraarterial FUdR, 0.2 mg/kg/d x 14 days/month (IA) using implantable pumps (Infusaid). They were randomized either for IA or for IA + systemic 5-FU 700 mg/m2/d x 3 days/month (IA/IV). Forty-six (46) patients were evaluable (26 IA; 20 IA/IV). Both groups were comparable in respect to primary tumor stage, age, liver function tests, tumor markers and extent of tumor infiltration. Twenty-six (26) patients (56%) demonstrated a complete (CR) or partial response (PR) with at least a 50% decrease in CEA levels and a significant tumor volume reduction (IA 50%; IA/IV 65%). Quality of response was significantly correlated with median survival (MS) time of 25 months for CR and PR. Approximate MS for IA and IA/IV was 16 and 19.5 months, respectively, and approximate median survival time to extra- and/or intrahepatic progression was 9 months (IA) and 11 months (IA/IV). Incidence of extrahepatic recurrence was not influenced by any treatment (IA 62%; IA/IV 60%). Overall approximate median time to occurrence of extrahepatic disease was 12.5 months (IA 13; IA/IV 10). Liver disease progression was observed in 38 patients (IA 85%; IA/IV 80%). A median time of 8 months to diagnosis of liver disease progression was calculated for IA, and IA/IV was 11.5 months. Incidence of chemical hepatitis for IA and IA/IV was 54 and 45%, while biliary sclerosis occurred in 15% and 10% of the cases, respectively, and did not correlate with response rates. Systemic side effects (25%) were only observed in the IA/IV group and induced significantly more interruptions of therapy than in the IA group. It is concluded from this study that additional systemic 5-FU treatment does not prevent the occurrence of extrahepatic disease under local 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.

In the scope of research concerning new proplylactic possibilities against mousepox we tested the resistance of a passive immunity of baby mice whose mothers had been immunized before or during pregnancy several times with either the vaccinia virus strains MVA, CVB or the so-called attenuated ectromelia virus strain "Hampstead" respectively. The vaccines CVB and "Hampstead" were found to cause the production of haemagglutination-inhibiting antibodies only. A passively-transmitted immunity of baby mice was proven to be effective against an intraperitoneal challenge-infection with a virulent ectromelia virus strain for as long a period as 3 weeks after birth, if their mothers had been vaccinated with either of the following: 10(2,0) and 10(4,0) KID50 of the "Hampstead" strain, or one of the vaccinia virus strains in a dosage 100-times as large. The vaccination did not lead to an intrauterine infection of the fetuses. After 224 tissue culture passages in mouse fibroblast cells (line 3T6), THE "Hampstead" strain was found te be still virulent for baby mice; however, female adult mice which had been intraperitoneally inoculated with 10(2,0) and then 10(4,0) KID50 two weeks later demonstrated no signs of mousepox. The possibility for using this ectromelia virus strain instead of vaccinia virus for active immunization against mousepox of young animals under the protection of a homologous passive immunity is discussed.

Mechanical factors that can modify the peak transvalvar pressure differences (delta P) in aortic stenosis were evaluated in a model. A latex rubber sac simulated the ventricle. Expansion of the walls of the sac by means of a negative pressure applied to its outer wall introduced a measure volume into the sac and placed the wall materials under tension. The stretched sac was then permitted to contract and to expel its contents through "aortic valvar" orifices of various severities of stenosis, into an aortic standpipe of selected diameters (compliances). Factors that increased the peak delta P included the strength (thickness) of the ventricular wall, the rate at which it mobilized and applied its tensile force to compress the sac contents, the unstressed volume of the sac, the total volume in the sac at onset of contraction, the severity of the valvar stenosis, the compliance of the aorta, the rate of arterial run-off, and the aortic diastolic pressure. Loss of forward stroke volume due to mitral regurgitation lowered the peak delta P. Elevations in diastolic arterial pressure also lowered delta P. All of these mechanical factors should be considered in the analysis of the severity of clinical aortic valvar stenosis and in decisions for medical therapy and surgical correction. The several factors which do not depend directly on the orifice area or on the forward stroke volume vitiate the sole use of the orifice formula in the analysis of the dynamics of aortic stenosis. The application of this approach in related problems is indicated.

An infusion chamber was implanted subcutaneously in 18 patients for intravenous systemic treatment and in 20 for intra-arterial treatment of the liver. Intravenous catheters were introduced via the cephalic vein, intra-arterial ones via the gastroduodenal artery, after exclusion of extrahepatic metastases. Six manageable complications were observed during a total implantation time of 102 months for i.v. treatment and usage over 500 days: three temporary occlusions; one infection; two extravasations. The intra-arterial chemotherapy, largely for hepatic metastases of breast carcinoma, was undertaken according to a modified FAM schema (fluorouracil, adriamycin, mitomycin C): It achieved a high response rate with two full and eleven partial remissions. Complications were rare, except for 4 temporary occlusions. Systemic side effects were almost completely absent, local toxicity was low. One problem was the fixation of the needle which connects to the infusion chamber. This was true for both intravenous and intra-arterial treatment.

2238 sera of bovines, 95 of goats, 251 of antelopes (various species), 143 of zebras and 11 of warthogs collected in Tanzania as well as 811 sera of men and females of the city and the region of Dar es Salaam were tested for haemagglutination inhibiting antibodies (Ab) to reovirus serotypes (St) 1, 2 and 3. Ab to St 1 resp. 2 could be detected in 24--39% of bovines, goats, antelopes and zebras, and in warthogs to 64%. In human beings the positive percentage was 60%. Ab to St 3 were most prevalent: Sera of domestic animals were positive in 70--84%, of wild animals in 77--100% and of the human population in 91%. These figures include the occurrence of Ab to one St alone as well as to more than one St. A further analysis showed, that Ab to St 3 are definitely dominant especially in sera of animals, whereas the simultaneous occurrence of Ab to all 3 St was more frequently observed in sera of human beings. Other Ab-type combinations were apparently of far less importance. It seems to be significant that the highest infection rate was found in humans (except zebras and warthogs) and that their contact to animals did not result in a higher Ab conversion rate as without such a possibility. The results were discussed under seroepidemiologic aspects and it is concluded that reovirus infections are facultative viral zoonoses.