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Biomedical subjects

M Israel

Publications and source records attributed to M Israel.

At least 127 records · Page 7Linked to original sources
PubMed1981

Tibial arteriovenous fistula: successful use for limb salvage.

Embolization of atheromatous material from abdominal aortic aneurysms to the distal arterial circuit is a well-recognized clinical entity causing the "blue toe syndrome." A case is presented in which this phenomenon resulted in obliteration of the pedal arch and thrombosis of the tibial arteries. As a result, forefoot gangrene, severe leg ischemia and anterior and posterior compartment syndromes occurred. Salvage of the extremity required an extraordinary approach with the construction of an arteriovenous fistula between the posterior tibial vessels. The literature on the use of therapeutic and adjunctive arteriovenous fistulas and their physiology is discussed.

Aortic Aneurysm↗
PubMed1981

Protein-associated DNA breaks and DNA-protein cross-links caused by DNA nonbinding derivatives of adriamycin in L1210 cells.

The effects of Adriamycin derivatives on L1210 mouse leukemia cells were studied with the DNA alkaline elution assay. The exposure of exponentially growing cells to approximately equitoxic concentrations of N-trifluoroacetyladriamycin-14-valerate (13.8 microM) and its metabolites, N-trifluoroacetyladriamycin (9.0 microM) and N-trifluoroacetyladriamycinol (43.7 microM), for 1 hr in vitro resulted in a high frequency of protein-associated DNA breaks and DNA-protein cross-links. These effects were comparable to those observed with Adriamycin (2.8 microM) and with adriamycinol (26.9 microM). In contrast to Adriamycin and its metabolite adriamycinol, N-trifluoroacetyladriamycin-14-valerate and its two major metabolites do not bind to DNA. Despite the absence of this direct interaction, N-trifluoroacetyladriamycin-14-valerate and its metabolites produce alterations in DNA comparable with the effects of intercalating agents. No evidence for conversion of N-trifluoroacetyladriamycin-14-valerate to Adriamycin or adriamycinol was found in L1210 cells. The similar effects on DNA macromolecules, observed between intercalating and non-DNA-binding anthracyclines, are consistent with the concept that mechanisms other than direct interaction with DNA play a role in the toxic effects of these compounds.

Animals↗
PubMed1980

Pharmacologic studies with radiolabeled N-trifluoroacetyladriamycin-14-valerate (AD 32). Comparison of total anthracycline fluorescence and radioactivity in mouse serum and urine.

In connection with pharmacologic studies with AD 32, isotopically-labeled drug prepared from 1-[14C]-trifluoroacetic anhydride and adriamycin-14-valerate was used to determine murine serum and urine levels of radioactivity. Other studies, performed in parallel, measured serum and urinary total fluorescence. Serum fluorescence disappeared in a biphasic pattern, with an initial rapid rate of disappearance followed by a somewhat slower phase. For the first hour, serum radioactivity levels were not significantly different than those measured by fluorescence. After this, however, serum radioactivity decayed at a much slower rate than did fluorescence. Furthermore, a large fraction of the injected radioactivity was found excreted in the urine, whereas urine accounted for only a small fraction of the fluorescence. These results suggest the formation, in part, of a hitherto unrecognized nonfluorescent metabolite, most probably N-trifluoracetyldaunosamine.

Animals↗
PubMed1980

Adjunctive arteriovenous fistula with tibial and peroneal reconstruction for limb salvage.

Arteriovenous fistulas were constructed as an adjunct to femoral peroneal and tibial bypasses in 13 patients threatened by imminent limb amputation. Previous attempts at conventional vascular reconstructive procedures had failed in nine patients. Deficient or absent pedal arches were noted in all patients, as were poor quality or small crural arteries. Graft patency was achieved in 11 cases and limb salvage in 10. There was no mortality. A steal phenomenon occurred in one patient and was successfully treated by secondary popliteal vein ligation. These preliminary results clearly indicate that an adjunctive arteriovenous fistula can maintain patency in a femoral tibial or peroneal bypass graft while preserving flow into the markedly diseased distal circulation.

Aged↗
PubMed1980

Effect of the venom of Glycera convoluta on the spontaneous quantal release of transmitter.

A neurotoxin able to increase the spontaneous release of transmitter was found in the venom glands of the polychaete annelid Glycera convoluta. We studied the effect of this venom on the frog cutaneous pectoris muscle, where its application produced a prolonged (20-h), high-frequency discharge of miniature potentials. After 5 h of action, the initial store was renewed several times but no detectable ultrastructural changes were observed. After 19 h of sustained activity, nerve terminals with their normal vesicular contents were infrequent; others were fragmented and contained swollen mitochondria, abnormal inclusions, and vesicles of various sizes. In the noncholinergic crayfish neuromuscular preparation, the venom triggered an important increase in spontaneous quantal release that subsided in 1 h. An activity higher than that in resting conditions then persisted for many hours. This high electrical activity was not accompanied by any detectable structural modifications after 3 h. In the torpedo electric organ preparation, the venom elicited a burst of activity that returned to control levels in 1 h. The release of ACh (evaluated by the efflux of radioactive acetate) paralleled the high electrical activity. No morphological changes or significant depletion of tissue stores were detected. The venom of Glycera convoluta appears to enhance considerably the release of transmitter without impairing its turnover. The venom effect is Ca++ dependent and reversible by washing, at least during the first hour of action. Because the high rate of transmitter release appears dissociated from the later-occurring structural modifications, it is possible that the venom mimics one component of the double mode of action proposed for black widow spider venom.

Animals↗
PubMed1980

Remote profunda femoral bypass for limb salvage.

Patients with patency of the distal segment of the profunda femoral arteries can be subjected to a direct end-to-side bypass with either tissue or synthetic grafts to increase blood flow to the lower extremity. The effectiveness and durability of this procedure will be enhanced by patency of the popliteal artery. Diffuse profunda femoris disease, popliteal or tibial peroneal obliterative disease and gangrenous lesions tend to militate against the success of this operation as an isolated procedure without augmenting flow to the distal part of an artery in the leg. Of 18 remote profunda femoris bypasses performed during a four year period, early amputation was required in two patients because of inadequate distal flow and the inability to establish downstream reconstruction. In one patient, an early bypass to the peroneal artery was required following closure of the profunda femoris bypass. The remaining 15 bypasses resulted in limb salvage and significant relief of symptoms. Three patients subsequently required secondary downstream reconstructions. The profunda femoris is surgically accessible for a long length and can serve as an adequate source of blood to the leg and foot in selected patients.

Aged↗
PubMed1980

Structural and functional effects of adriamycin on cardiac cells in vitro.

The effects of Adriamycin (ADR) on the heart, seen clinically as transient electrocardiographic changes and cardiomyopathy, have been simulated in an in vitro cardiac cell system. Structural and functional alterations in cultured heart cells can be dissociated based upon ADR dose and length of exposure. At high ADR doses (100 to 200 micrograms/ml), cessation of beating was rapid, and structural changes consistent with the in vivo cardiomyopathic picture (vacuolization and nucleolar fragmentation) were observed. At low ADR doses (0.1 to 0.5 micrograms/ml), arrhythmias were produced in the absence of ultrastructural changes (within 48 hr); the incidence and severity of the arrhythmias were demonstrated to be dose dependent. Continued treatment of cultures at low dose levels for sustained periods of time (up to 17 days) resulted in a striking loss of muscle fiber without concomitant vacuolization and nucleolar fragmentation. An intermediate ADR dose of 10 micrograms/ml for 1 hr exposure caused vacuolization and cessation of beating, with lysis of cells within 72 hr. The parallel between the effects of ADR on in vitro cardiac cell structure and function with those seen in vivo suggests that this simple system may have value in studies directed towards the mechanism of ADR-induced cardiac toxicity and in the screening of anthracycline analogs for their potential effects on the heart.

Animals↗
PubMed1979

Comparative metabolism and excretion of adriamycin in man, monkey, and rat.

Adriamycin and its fluorescent metabolites in bile (man, monkey, and rat) and urine (man and monkey) were determined by means of a simple, rapid, and highly reproducible high-performance liquid chromatographic procedure. Species differences in metabolism and biliary excretion were observed with respect to aldoketo reductase and conjugase activities.

Animals↗
PubMed1979

Initial clinical evaluation of N-trifluoroacetyladriamycin-14-valerate (AD-32), an adriamycin analog.

N-Trifluoroacetyladriamycin-14-valerate (AD-32) is superior to Adriamycin in murine L1210 and P388 leukemias and in a number of solid tumor systems, including Ridgway osteogenic sarcoma and Lewis lung carcinoma. In preclinical toxicology studies, AD-32 was less toxic than Adriamycin in both tumor- and non-tumor-being mice and in rabbits. An initial clinical trial was carried out in 23 patients who received a total of 74 courses of AD-32 over a dose range of 100--700 mg/m2 administered at 21-day intervals. Hydrocortisone given during the period of infusion prevented all clinical manifestations of acute toxicity. The AD-32 dose-limiting toxicity, leukopenia, was comparable to that of Adriamycin at a dose of 10:1, but at these equivalently myelosuppressive doses, AD-32 induced less gastrointestinal toxicity and alopecia than Adriamycin and it did not cause local tissue damage following inadvertent paravenous extravasation. Although two responses are reported, the therapeutic activity of AD-32 cannot be assessed because of an inadequate number of patients in any given tumor type. A phase II study is being initiated at a dose of 600 mg/m2 given at 21-day intervals.

Doxorubicin↗
PubMed1978

An approach to cost analysis of clinical laboratory services.

The authors have developed a system that provides information about costs related to specific laboratory tests. These costs are derived from: (1) labor and material actually used for specific tests; (2) allocation of costs for labor and material shared by several different tests; (3) allocation of supervisory and management costs. The "cost" of a specific procedure is a theoretical construct that is significantly affected by the method chosen for allocation. We know of no cost-analysis system generally accepted by all clinical laboratories. Since third-party payers may base future reimbursement on costs rather than charges, accurate systems for clinical laboratory cost analysis may have some practical value.

Clinical Laboratory Techniques↗
PubMed1978

Hepatobiliary metabolism and excretion of adriamycin and N-trifluoroacetyladriamycin-14-valerate in the rat.

In connection with mechanism of action studies with N-trifluoroacetlyadriamycin-14-valerate (AD 32), a superior Adriamycin (ADR) analog under development in these laboratories, serial bile samples were collected from male Sprague-Dawley rats given a single i.v. dose of either ADR (4 mg/kg) or AD 32 (20 mg/kg) and were analyzed for anthracyclines by thin-layer chromatography-fluorometry and high-performance liquid chromatography. For ADR, 20% of the administered dose was accounted for at 24 hr, whereas 80% of the AD 32 dose were excreted into the bile by this time. ADR underwent little biotransformation; 80% of the 48-hr cumulative fluorescence excretion was attributable to unchanged drug, one-half the remainder was adriamycinol, and the balance was polar conjugates. In contrast, AD 32 underwent extensive metabolism to N-trifluoracetyladriamycin, N-trifluoroacetyladriamycinol, and polar conjugates, mostly glucuronides of N-trifluoroacetyladriamycin and N-trifluoroacetyladriamycinol. Based on direct and indirect evidence, ADR was not a metabolite of AD 32.

Animals↗