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Biomedical subjects

J Koziol

Publications and source records attributed to J Koziol.

35 records · Page 2Linked to original sources
PubMed1982

Comparison of the activity of doxorubicin analogues using colony-forming assays and human xenografts.

The potential use of nude mouse xenografts as a source of human tumor tissue for preclinical assessment of drug activity was examined by a comparison of in vitro sensitivity to four anthracycline derivatives of eight xenografts maintained in nude mice and tumor colony-forming units (CFU) from the xenografts grown in agar. Results obtained in the two systems with doxorubicin (Dx) and a new, closely related derivative (epi-doxorubicin, epi-Dx) correlated well. In vivo tumor growth delay and maximum in vitro tumor CFU kill for these two drugs showed a significant correlation (r = 0.64, P less than .01). Separation of tumors into "sensitive" and "insensitive" tumor populations on the basis of maximum in vitro CFU kill also predicted the in vivo response to these two drugs in 88% of cases. Similar analyses performed on in vitro and in vivo results with two other new anthracyclines (4'-deoxy-doxorubicin, deoxy-Dx and 4'-O-methyl-doxorubicin, O-Me-Dx) showed a significant negative correlation between in vivo and in vitro results; the in vitro system failed to predict in vivo activity of these two drugs. No significant differences in in vitro activity against normal, granulocyte/macrophage progenitors (CFU-GM) or against various tumor CFUs were detected. Thus, the selectivity (activity against normal tissue compared with that against tumor) of the four drugs appeared equal. These data suggest that in vitro screening of drugs using tumor CFUs from nude mouse xenografts may predict the in vivo activity of drugs for which pharmacologic data are available, but illustrate the difficulties in attempting to predict the in vivo activity of new drugs for which no such data are available.

Animals↗
PubMed1982

Extensive disease small cell carcinoma of the lung: trial of non-cross resistant chemotherapy and consolidation radiotherapy.

Twenty-nine patients with extensive disease, small-cell carcinoma of the lung, were treated with two cycles of intensive combination chemotherapy: HexaVAC (hexamethylmelamine, vincristine, Adriamycin, cyclophosphamide). Responders received prophylactic cranial radiation (2000 rad/10 fractions) and non cross resistant chemotherapy via a schedule of alternating cycles of CMV (cyclophosphamide, methotrexate, VP-16-213) and AMV (Adriamycin, methotrexate, VP-16-213). Whenever a complete response was achieved, consolidation radiotherapy was given to the lung primary (4000 rad/20 fractions, split dose) and abdominal metastases (2000 rad/10 fractions) synchronous with CMV therapy. The complete response rate was 14% with HexaVAC, but increased to 38% during CMV/AMV. Total response rate (complete and partial) was 59% and median survival was 42 weeks. Prophylactic brain radiation prevented clinical relapse in the brain in all 14 patients who received it. However, consolidation radiotherapy failed to prevent clinical relapse in the lung and/or liver, and therapeutic brain radiation (3000 rad) failed to prevent relapse in that site. The simultaneous administration of radiotherapy and chemotherapy was well-tolerated although two patients with poor performance status died of infectious complications while leukopenic. In spite of the high response rate, durable remissions with prolonged disease free survival were rare. Further evaluation of induction, consolidation, and maintenance modes of therapy are indicated.

Adult↗
PubMed1979

Iris tissue reaction to dacron and silk in primates: evaluation for intraocular lens fixation.

Dacron, silk, and a combination of the two were evaluated for tissue ingrowth response in the primate iris with a view towards the feasibility of using these materials for intraocular lens fixation. The materials were well tolerated by all eyes, with no inflammation after seven days and no cases of endophthalmitis occurring. Adherence to iris was strong in silk-containing materials at 14 days by gross and histologic examination, and the Dacron-silk combination was judged most suitable for potential human use.

Animals↗
PubMed1978

Experimental evaluation of anterior chamber lenses fixated with Dacron.

Four new designs for anterior chamber intraocular lenses using Dacron fibers to achieve fixation were studied. After implantation in rabbit eyes, no lens dislocation occurred. Postmortem examination found firm Dacron adherence to iris tissue in all eyes. Clinically, no difference was noted in the amount of inflammation in eyes receiving a lens with or without Dacron. One new lens design was found to have substantial advantages over the other three models. However, a high incidence of corneal edema was found following insertion of all four experimental lenses.

Animals↗
PubMed1977

Intraocular lens fixation with Dacron mesh: Part I.

Rabbits were used to demonstrate the feasibility of using Dacron fibers to fix intraocular lenses. Adhesion occurred five days after insertion and was confirmed by histologic examination to consist of fibroblastic ingrowth into the Dacron fibers. This cellular response was consistent and remained localized. Anterior and posterior placement of the acrylic portion of the lens was compared. It is our clinical impression that the risk of pupillary block is increased with posterior placement of the lens.

Animals↗
PubMed1977

Intraocular lens fixation with Dacron mesh: Part II.

We studied the feasibility of fixation of an intraocular lens in the posterior chamber by utilizing Dacron mesh to stimulate cellular ingrowth from the posterior iris surface. Tissue ingrowth into the Dacron mesh occurred five days after Dacron implantation and a firm adhesion between Dacron and the iris developed in a consistent and localized manner. Dacron fibers, when placed in contact with the posterior iris surface, induce fibroblastic and pigmented epithelial tissue ingrowth around the fibers. Fixation of the lens with and without the posterior lens capsule and vitreous is compared in vitrectomized and nonvitrectomized eyes. It is possible to achieve fixation without support from the posterior lens capsule and vitreous.

Animals↗
PubMed1975

Intravitreal injection of vancomycin in experimental staphylococcal endophthalmitis.

Toxicity, clearance, and therapeutic effectiveness of intravitreal vancomycin hydrochloride injection in experimentally induced staphylococcal endophthalmitis were evaluated. Vancomycin was found to be nontoxic in a single, 1 mg/0.1 ml intravitreal dose. Therapeutic levels of vancomycin were present in the vitreous for over 72 hours and in the aqueous during a period from 6 to 48 hours after injection. Injection of a methicillin-resistant Staphylococcus aureus produced a panophthalmitis in our systemically treated controls, whereas in the rabbits treated by intraocular injection, the course of the infection was significantly altered.

Animals↗
PubMed1975

Urokinase in experimental vitreous hemorrhage.

Toxicity of intravitreal urokinase was studied by injection of various doses of urokinase in primate eyes. Doses of 22,500 CTA units or less produced no toxic effects on the eye. Higher doses caused retinal degeneration, transient lens opacities, and cloudy vitreous. Urokinase was ineffective in clearing experimentally induced vitreous hemorrhage if injected as early as 24 hours after the intravitreal blood or as late as six months thereafter.

Animals↗