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Biomedical subjects

J J Marr

Publications and source records attributed to J J Marr.

At least 19 recordsLinked to original sources
PubMed1998

Reduction of "callbacks" to the ED due to discrepancies in plain radiograph interpretation.

Retrospective and prospective chart review was conducted to study patient callbacks to the emergency department (ED) based on plain radiograph interpretation discrepancies between radiologists and emergency physicians before and after a continuous quality improvement (CQI) intervention. Patients who were called back to the ED because of radiograph interpretation discrepancies were retrospectively studied. These results were reviewed by a CQI team, which recommended greater communication and consultation. A prospective study was then performed. Before quality intervention, 0.7% of the patients were recalled; 0.4% required recall after quality assurance, a reduction of 42.9% (P = .0001). Emergency physicians in this study had a low percentage of patient recall due to discrepancies in radiologic interpretation. CQI further reduced this percentage. The proficiency of emergency physicians interpreting radiographs validates the current practice of emergency physicians rendering treatment based on their interpretations and supports the notion of emergency physicians billing for this service.

Appointments and Schedules↗
PubMed1992

Allopurinol in the treatment of American cutaneous leishmaniasis.

BACKGROUND: Pentavalent antimony, the generally accepted treatment for leishmaniasis, is given parenterally, and it is expensive and not readily available in developing countries. An inexpensive, orally administered compound would be a substantial advance in treatment. Previous studies in vitro have shown synergism between allopurinol and pentavalent antimony in tissue-culture systems. We designed this clinical study to determine whether synergism could be demonstrated in patients. METHODS: We performed a randomized, controlled study of the efficacy of allopurinol plus meglumine antimoniate (Glucantime), as compared with meglumine antimoniate alone, in patients with cutaneous leishmaniasis, who were recruited from a village in southeastern Colombia. In addition, those who declined injections were treated with allopurinol alone, and those who declined any treatment were considered controls. All the patients were followed for one year after the completion of treatment. Lesions that healed completely at three months and remained healed during follow-up were considered to be cured. RESULTS: The cure rate for patients treated with meglumine antimoniate was 36 percent; the addition of allopurinol increased the rate to 74 percent (P less than 0.001). Treatment with allopurinol alone yielded a cure rate of 80 percent (P less than 0.001). There were no cures among the untreated patients. There was no significant difference between the cure rate with allopurinol plus meglumine antimoniate and that with allopurinol alone. No major toxic effects were observed. CONCLUSIONS: For the treatment of American cutaneous leishmaniasis, the combination of allopurinol and meglumine antimoniate is significantly more effective than meglumine antimoniate alone, probably because of the efficacy of allopurinol alone, which appears to be as good as the combination.

Adolescent↗
PubMed1991

Antiprotozoal activity of 3'-deoxyinosine. Inverse correlation to cleavage of the glycosidic bond.

Two nucleosides related to the known antiprotozoal agent 1-(beta-D-ribofuranosyl)-1,5-dihydro-4H-pyrazolo-[3,4-d]pyrimidine-4-one (allopurinol riboside, 1) were prepared and evaluated against Leishmania donovani, Trypanosoma cruzi, and Trypanosoma gambiense. 3'-Deoxyinosine (2) exhibited potent antiprotozoal activity against the three protozoal pathogens with minimal toxicity for host cells. It was found to be especially effective against the Columbia strain of T. cruzi reported to be resistant to 1. The antiprotozoal activity of 2 appeared to be inversely related to the rate of cleavage of the glycosidic bond, as shown by metabolic profiles of 2 in the various pathogenic hemoflagellates and host cells. Combining the key structural elements of 1 and 2 led to the synthesis of 1-(3-deoxy-beta-D-erythro-pentofuranosyl)-1,5-dihydro-4H-pyrazolo[3,4-d] pyrimidin-4-one (3'-deoxy-allopurinol riboside, 3). which was found to be inactive as an antiprotozoal agent.

Animals↗
PubMed1991

Purine analogs as chemotherapeutic agents in leishmaniasis and American trypanosomiasis.

The metabolic pathways for purines in parasitic protozoans differ significantly from the corresponding pathways in human beings. Leishmania and Trypanosoma cruzi have particular enzymatic reactions that have relevance for chemotherapy. Certain purine analogs are metabolized by the parasites to nucleotides and aminated to the analogs of adenine nucleotides. These halt protein synthesis and cause the break-down of RNA. The most important purine analogs with respect to chemotherapeutic potential are the pyrazolo [3,4-D]-pyrimidines. The prototype, allopurinol, is nontoxic to human beings and is aminated to adenine nucleotide analogs by the organism. Studies in vitro and in vivo have demonstrated its antiparasitic action and led to its development as a chemotherapeutic agent for diseases caused by these organisms. Clinical investigations now have demonstrated the therapeutic efficacy of allopurinol in cutaneous leishmaniasis caused by Leishmania braziliensis and in chronic Chagas' Disease.

Chagas Disease↗
PubMed1990

Synthesis, structure, and antiparasitic activity of sulfamoyl derivatives of ribavirin.

The triazole nucleoside derivatives 1-(5'-O-sulfamoyl-beta-D-ribofuranosyl) [1,2,4]triazole-3-carboxamide (2), 1-(5'-O-sulfamoyl-beta-D-ribofuranosyl) [1,2,4]triazole-3-thiocarboxamide (3), and 1-(5'-O-sulfamoyl-beta-D-ribofuranosyl)-[1,2,4]triazole-3- carbonitrile (4) were synthesized. Suitably protected triazole nucleosides were converted to their corresponding 5'-sulfamoyl derivatives, which on subsequent deprotection gave the desired compounds in good yields. The structures of compounds 2-4 were confirmed by X-ray crystallographic analysis. All three compounds showed significant antiparasitic activity in vitro, while 2 showed significant activity in vivo against Leishmania donovani and Trypanosoma brucei.

Animals↗
PubMed1990

Inhibition of growth of Toxoplasma gondii by qinghaosu and derivatives.

The antimalarial compound qinghaosu (artemisinin) was tested in vitro for the ability to inhibit plaque formation by Toxoplasma gondii in fibroblasts. Qinghaosu at 0.4 microgram/ml for 5 days eliminated all plaques and microscopic foci of T. gondii. At 1.3 micrograms/ml for 14 days, qinghaosu completely eliminated T. gondii. Pretreatment of host cells or T. gondii with qinghaosu had no effect on T. gondii growth. There was no apparent toxicity to human fibroblasts in long-term studies. Of the six qinghaosu derivatives tested, dihydroqinghaosu, 1-propyl-ether-qinghaosu, and 1-butyl-ether-qinghaosu were comparable to qinghaosu. Ethyl-ether-qinghaosu (arteether) and sec-butyl-ether-qinghaosu were more effective. Methyl-ether-qinghaosu (artemether) was the most effective, with a potency approximately 10-fold greater than that of qinghaosu.

Animals↗
PubMed1990

Therapeutic efficacy of allopurinol in patients with chronic Chagas' disease.

Laboratory and animal studies have demonstrated that pyrazolopyrimidines have significant activity against Trypanosoma cruzi. This clinical investigation was to ascertain the efficacy of allopurinol in the treatment of chronic Chagas' disease. Of 307 patients studied, 91 were untreated; the remaining 216 were divided into 4 treatment groups. These corresponded to 600 or 900 mg/day of allopurinol for 60 days and benznidazole or nifurtimox at conventional dosage regimens. Patients were evaluated clinically, serologically, and parasitologically. Allopurinol was found to be as efficacious as the conventional therapeutic modalities in eliminating the parasitemia and rendering patients seronegative. Adverse reactions occurred in 11% of patients who received allopurinol and in 30% of those receiving nitrofurans. Reactions with the conventional therapy were more frequent and of a more serious nature. Oral allopurinol is as effective as the nitrofurans, but has none of the side effects.

Adult↗
PubMed1989

Purine deoxynucleoside salvage in Giardia lamblia.

Giardia lamblia is dependent on the salvage of preformed purines and pyrimidines, including deoxythymidine. Dependence on deoxynucleoside salvage is extremely unusual among eucaryotic cells (Moore, E. C., and Hurlbert, R. B. (1985) Pharmacol & Ther. 27, 167-196). The present study investigates the possibility that giardia lacks ribonucleotide reductase and depends entirely on deoxynucleoside salvage. A ribonucleotide reductase inhibitor, hydroxyurea, at concentrations up to 2 mM had no effect on the growth of giardia. This is 15-20 times the ED50 of hydroxyurea for the protozoans Trypanosoma cruzi, Trypanosoma gambiense, and Leishmania donovani. A lysate of giardia had no detectable ribonucleotide reductase. Although radiolabeled adenine, adenosine, guanine, and guanosine were readily incorporated into RNA by cultured cells, no adenine or adenosine and only trace amounts of guanine and guanosine were detectable in DNA. This is in contrast to deoxynucleosides, where 58% of deoxyadenosine and 10% of deoxyguanosine incorporated into nucleic acid were found in DNA. Phosphorylation of both deoxyadenosine and deoxyguanosine was catalyzed by a cell lysate of giardia when nucleoside kinase co-substrates were included in the assay but not when phosphotransferase co-substrates were present. The absence of detectable ribonucleotide reductase, the failure to incorporate purine nucleobases and nucleosides into DNA to any significant extent, the ready incorporation of deoxynucleosides into DNA, and the demonstration of a purine deoxynucleoside kinase suggest that giardia are dependent on the salvage of exogenous deoxynucleosides.

Animals↗
PubMed1989

Purine metabolism in Toxoplasma gondii.

We have studied the incorporation and interconversion of purines into nucleotides by freshly isolated Toxoplasma gondii. They did not synthesize nucleotides from formate, glycine, or serine. The purine bases hypoxanthine, xanthine, guanine, and adenine were incorporated at 9.2, 6.2, 5.1, and 4.3 pmol/10(7) cells/h, respectively. The purine nucleosides adenosine, inosine, guanosine, and xanthosine were incorporated at 110, 9.0, 2.7, and 0.3 pmol/10(7) cells/h, respectively. Guanine, xanthine, and their respective nucleosides labeled only guanine nucleotides. Inosine, hypoxanthine, and adenine labeled both adenine and guanine nucleotide pools at nearly equal ratios. Adenosine kinase was greater than 10-fold more active than the next most active enzyme in vitro. This is consistent with the metabolic data in vivo. No other nucleoside kinase or phosphotransferase activities were found. Phosphorylase activities were detected for guanosine and inosine; no other cleavage activities were detected. Deaminases were found for adenine and guanine. Phosphoribosyltransferase activities were detected for all four purine nucleobases. Interconversion occurs only in the direction of adenine to guanine nucleotides.

Animals↗
PubMed1989

The activity of ketoconazole and other azoles against Trypanosoma cruzi: biochemistry and chemotherapeutic action in vitro.

Trypanosoma cruzi epimastigotes in culture medium, and amastigotes and trypomastigotes in cultured human diploid lung cells were exposed to the antimycotic agent ketoconazole and their growth and/or sterol biosynthesis observed. Propagation of epimastigotes and amastigotes was impaired by concentrations of ketoconazole achievable in human serum, and amastigotes were more sensitive than were epimastigotes. Epimastigotes and trypomastigotes (non-dividing stage) displayed changes in their membrane sterol content such that the amounts of normal, end-product sterols (ergosterol, ergosta-5,7-dien-3 beta-ol, 24-ethylcholesta-5,7,22-trien-3 beta-ol, 24-ethylcholesta-5,7-dien-3 beta-ol) were notably decreased and the amounts of 14 alpha-methyl sterol precursors of these sterols (24-methylenedihydrolanosterol, obtusifoliol, lanosterol) were increased. Other azole drugs, itraconazole and fluconazole, when tested on epimastigotes, evoked the same qualitative pattern of changes in free sterols. Itraconazole was nearly as potent as ketoconazole, but fluconazole was significantly less potent. The nature of the sterols found in T. cruzi and the actions of azole drugs on their biosynthesis were similar in many respects to those observed in fungi and in Leishmania species. By analogy, it would seem that the primary mechanism of action of azole drugs on T. cruzi life-cycle stages is the impairment of the cytochrome P-450 sterol 14 alpha-demethylase. The consequent loss of normal sterols and accumulation of 14 alpha-methyl sterols may be responsible for the coincident retardation or cessation of growth.

Animals↗
PubMed1989

Treatment of American cutaneous leishmaniasis with orally administered allopurinol riboside.

Eighteen patients received 1,250 mg of allopurinol riboside (AR) four times daily for 28 d. Nine of the patients concurrently received 500 mg probenecid (PB) four times daily. Cure was assessed clinically and parasitologically. Patients who had culture-positive and nonhealing lesions 3 mo after therapy received pentavalent antimony. Of the nine patients who received AR alone, four (44%) had clinical improvement at the end of therapy and two (22%) were culture-negative. A third patient became culture negative at 2 mo after therapy. The culture-negative patients were completely healed at 1 mo and remained so at 1 y after therapy. Of the nine patients who received AR plus PB, four had complete healing and two had clinical improvement at the end of therapy; however, all patients remained culture-positive. At 2-3 mo after therapy, six (67%) of the patients were completely healed, and of these, five (56%) were culture-negative. The drug was well-tolerated.

Adult↗
PubMed1988

Suppression of recurrent genital herpes by single daily dosages of acyclovir.

Patients with frequent recurrences of genital herpes were treated with oral acyclovir tablets, 800 mg, or placebo once daily for two years. Confirmed recurrences for all patients were treated with acyclovir capsules, 200 mg orally five times per day, for five days. Of 46 patients enrolled, 18 of 22 acyclovir recipients and 14 of 24 placebo recipients completed two years of study. Patients receiving acyclovir experienced a mean of 0.184 recurrences/month compared with a mean of 0.977 recurrences/month for patients receiving placebo (p less than 0.0001). A total of 28 percent of acyclovir recipients and no placebo recipients remained free of recurrences for two years. The low rate of recurrences in the acyclovir group remained consistent throughout the study. No serious clinical or laboratory abnormalities associated with acyclovir were observed. The 800-mg acyclovir tablet given daily was well-tolerated and effective for two years in the management of recurrent genital herpes.

Acyclovir↗