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Biomedical subjects

J Venditti

Publications and source records attributed to J Venditti.

12 recordsLinked to original sources

[Acute monoarthritis and laryngeal obstruction as extralymphatic manifestations of non-Hodgkin's lymphoma].

Joints and larynx are uncommonly involved by non-Hodgkin's lymphoma (NHL). Synovial involvement has been reported in only 7 cases, mainly located in the knees. When this is the first location of NHL it is usually misdiagnosed. The treatment of choice is local radiotherapy followed by systemic chemotherapy. Laryngeal lymphoma can be either primary or forming part of multifocal disease. The prognosis of the primary form is usually good only with radiotherapy, whereas the prognosis of the laryngeal location of advanced disease is rather poor. The symptoms include dysphonia and slowly progressive dyspnea. A case of NHL is presented who showed initial arthritis of the knee, later evolving into severe laryngeal obstruction, an association not previously reported.

Acute Disease↗

Acute megakaryoblastic leukemia with massive myelofibrosis: complete remission and reversal of marrow fibrosis with allogeneic bone marrow transplantation as the only treatment.

We report results of allogeneic bone marrow transplantation in an 8-year-old boy with acute megakaryoblastic leukemia characterized by intense fibrosis together with 20% blast cells in the bone marrow, who was transplanted without preceding chemotherapy for remission induction. Conditioning comprised cytosine arabinoside, cyclophosphamide and total body irradiation. The donor was his HLA-identical sister. The patient is well with minor chronic graft-versus-host disease and normal hematologic values 670 days post-transplant.

Bone Marrow↗

Use of nude mouse xenografts as preclinical drug screens: in vivo activity of established chemotherapeutic agents against melanoma and ovarian carcinoma xenografts.

To evaluate the utility of nude mouse xenografts as preclinical drug screens, the activity of ten established chemotherapeutic agents was evaluated against seven melanoma and three ovarian carcinoma xenografts. Xenografts were established using primary explants from patients who had not received chemotherapy and serially passaged as sc tumors in nude mice. In vivo drug activities for dactinomycin, carmustine, vinblastine, melphalan, amsacrine, cisplatin, bleomycin, mitomycin, doxorubicin, and etoposide were evaluated by 4 weekly ip injections of 10% less than LD10 doses. Plots of relative tumor growth versus time were nearly log-linear. Analysis of in vivo activity was performed using percent control growth (treated/control tumor volume) and by calculation of a novel growth delay index obtained by fitting growth curves to a quadratic regression model. Both modes of data analysis identified alkylating agents (melphalan, carmustine, and mitomycin) as the most active drugs against human melanomas. Melphalan, mitomycin, and cisplatin showed the greatest activity against ovarian xenografts. However, complete tumor regressions were noted only with melphalan, mitomycin, and cisplatin against a single ovarian tumor xenograft. Correlation analysis suggested xenograft tumor growth rate was an important determinant of drug response. These results suggest that preclinical, new-drug screening with melanoma xenografts would identify drugs such as alkylating agents as active, and may not provide an advantage over murine leukemia screens. However, screening with ovarian xenografts may more closely reflect clinical drug activity. Criteria for detecting active drugs in such systems are discussed.

Animals↗

Metabolic activity of the lung during cardiopulmonary bypass.

Metabolic functions of the lung were examined in sixty patients undergoing coronary artery bypass surgery employing a method to separate right and left heart flow during surgery. Six study groups were employed to investigate the activity of normal serum electrolytes, minerals, enzymes and vasoactive prostanoids as they pass through the pulmonary vasculature. Various sample sites were employed to represent isolated segments of the vascular tree: pump (systemic) and right atrium (myocardium), aortic (bronchial flow). LDH, Ca++, phosphate and SGOT were documented to vary with passage through the pulmonary circulation while alkaline phosphatase, bilirubin, creatinine, urate, cholesterol, albumin and BUN remained essentially unchanged. Bronchial flow was calculated and directly related to temperature and pump flow with an average range of 15 ml/min +/- 6 ml/min. The stress of surgery produced elevated PGE2 in bronchial flow and urine that caused reproducible hypotension when rapidly reinfused into the patient. PGE2 production, though decreased with Indomethacin block, could be rapidly reversed with the stress of surgery.

Blood Pressure↗

Hemodynamic consequences of bronchial flow during cardiopulmonary bypass.

Nine patients (seven men and two women) were studied while undergoing coronary artery bypass on cardiopulmonary bypass. Selective bronchial flow samples were obtained and analyzed for prostaglandin E2 levels, and the hemodynamic effects of this vasodilator were studied. Bronchial flow collection and measurements were performed during hypothermic cardioplegic arrest while the peripheral anastomosis was being completed, as described previously. This collected sample was reinfused abruptly to the pump circuit, but samples were also analyzed for specific radioimmunoassay antiserum for prostaglandin E2 levels. Urine levels were obtained both with and without indomethacin block. All nine patients were studied for the hemodynamic effects of rapidly reinfused bronchial flow. A 34% +/- 8.8% mean drop of blood pressure and peripheral vascular resistance were recorded (p less than 0.002). Three study groups were established: In Group I, serum prostaglandin assay was performed on six patients. Prostaglandin E2 levels showed an average of increase of 159% compared to the baseline (p less than 0.02). In Group II, urine prostaglandin was measured. Nine assays were performed on six patients. Analysis of the total urine production while on cardiopulmonary bypass showed an average increase in prostaglandin E2 of 300% (p less than 0.02). In Group III, combined serum and urine prostaglandin levels were measured in three patients before and after indomethacin block (50 mg four times a day for 48 hours before the operation). All of these patients demonstrated the same hypotensive phenomena with reinfusion of the bronchial flow. The urinary prostaglandin E2 output and serum prostaglandin E2 levels in bronchial flow were elevated. Overall, this group manifested a 50% reduction in prostaglandin E2 production over baseline values with indomethacin block (p less than 0.02) and a 300% increase in production during cardiopulmonary bypass (p less than 0.02). Our data suggest that significant amounts of prostaglandin E2 are released in the lung during the stress of cardiac operations. Rapid reinfusion of bronchial flow is responsible for hypotension during cardiopulmonary bypass. Pretreatment with indomethacin will not completely block prostaglandin E2 release in the lung during stress.

Aged↗

Investigation of the antitumor activity of new epoxide derivatives. Part I: s-Triazinetrione derivatives.

The noteworthy cytostatic activity of triglycidyl-s-triazinetrione and the planned clinical testing of this new active substance induced us to subject this class of substances to closer examination. By chemical reaction of one of the three glycidyl groups present it was possible to introduce wide variations in the properties of the compounds, whilst still retaining the active principle. A number of these substances possessed very high antitumor activity as revealed in the leukemia screening test (P 388; mouse). The influence of other substituents within the glycidyl groups affecting the reactivity of the epoxides groups was also examined.

Animals↗

Investigation of the antitumor activity of new epoxide derivatives. Part II: N-glycidylated oxo-nitrogen heterocycles.

A number of N-glycidyl compounds derived from oxo-substituted nitrogen heterocycles such as diazines, triazines, diazoles, triazoles as well as condensed ring systems containing these units have been synthesised. All products were tested for their antitumor activity against leukaemia in the mouse. Almost all of the approx. 50 di- and triglycidyl compounds showed activity, whereby 5 of them exhibited an increase of lifespan of 200% and more. The most active compound was 1,2,4-triglycidyl-urazol.

Animals↗

Antitumor activity of macromomycin B (NSC 170105) against murine leukemias, melanoma, and lung carcinoma.

Mice bearing either of the two rapidly growing mouse leukemias, L1210 or P388, or the slow-growing B16 melanoma responded to i.p. injections of Macromomycin B (NSC 170105) with significant increases in life-span. The maximal increases in life-span obtained in these experiments were 37% for L1210, 68% for P388, and 120% for B16. In addition, there were 7 of 30 cures for varying doses of Macromomycin in the B16 melanoma. Activity of over 50% increase in life-span in B16 was obtained with a daily i.p. injection on Days 1 to 9 of 16 to 40 mg/kg. Animals that had received s.c. implanted Lewis lung tumors responded to either single or repeated injections (8 to 16 mg/kg) given at the site of tumor implant by a marked reduction in growth of the primary tumor, increased life-span, and some cures. The same doses were without effect when administered i.p. The reported activity of Macromomycin against L1210, P388 leukemias, B16 melanoma, and Lewis lung carcinoma make it a good candidate for development for clinical trial against human solid tumors. A new method of evaluating activity against solid tumors, "responder analysis," is also presented.

Animals↗