Limited incision cholecystectomy.

Eighty-one consecutive cholecystectomies were retrospectively reviewed; five were dropped because of incomplete data. The remaining 76 were divided into group A, patients who underwent a limited incision cholecystectomy (LIC) defined as less than 10 centimeters, and group B, those who underwent a standard subcostal incision (STD). An STD was used for 18 patients in 1984 and an LIC for subsequent patients unless anatomy dictated extension of the incision for safe surgical exposure. The groups were evaluated for possible benefits and disadvantages of the LIC approach. Multivariate analysis was done to contrast the approaches regarding operative time, operative and postoperative complications, postoperative pain, and hospital stay. The operative time was comparable between the two groups. The LIC approach was superior with less postoperative pain and shorter hospital stay. There were no intraoperative complications or mortality in either group. The postoperative complications were also comparable. No differences were noted in body size, weight, sex, or whether the patient was suffering from acute or chronic disease. The limited incision cholecystectomy can be utilized in the majority of patients with cholecystitis without added operative time or complications when compared to the traditional approach. The benefits of less postoperative pain, shorter hospital stay and better cosmetic results afford a higher degree of patient acceptance. This procedure should be considered when open cholecystectomy is required.

Sinefungin as treatment for American Leishmania in sensitive BALB/c and resistant C57BL/6 mice.

Using inbred BALB/c and C57BL/6 mice as animal models for American cutaneous leishmaniasis, we evaluated the inhibitory effect of sinefungin on foot-pad infection produced by 5 different Leishmania isolates. When treatment was initiated a few days, or even 2 weeks, after infection, an obvious leishmanicidal effect was detected on mice infected with Leishmania mexicana or L. braziliensis isolates, which lasted at least 50 weeks for all isolates studied. The optimal dose schedule was 4 mg/kg body weight/day, injected ip for 10 consecutive days; lower doses produced only a short leishmanistatic effect. The optimal dose found was 50-fold lower than the LD50. In vitro studies using Leishmania-infected murine peritoneal macrophages showed sinefungin as a powerful inhibitory drug, mean ED50 for the several Leishmania isolates studied being 50 ng/ml. No correlation was found between in vitro sensitivity of culture promastigotes and in vivo sensitivity to sinefungin of an American Leishmania isolate.

Differences in allopurinol and 4-aminopyrazolo(3,4-d) pyrimidine metabolism in drug-sensitive and insensitive strains of Trypanosoma cruzi.

Most freshly isolated Trypanosoma cruzi blood trypomastigotes were insensitive to allopurinol (HPP) and 4-aminopyrazolo(3,4-d)pyrimidine (APP). Strains EP and Ya were, however, strongly inhibited by both drugs while strains DS and A-35 were HPP-insensitive but APP-sensitive. In contrast, epimastigotes resulting from one in vitro passage of all eleven T. cruzi strains were highly sensitive to both drugs. While hypoxanthine/guanine and adenine phosphoribosyltransferase and succino-AMP synthetase activities were similar in trypomastigotes of sensitive and insensitive T. cruzi strains, the uptake and metabolism of [14C]HPP and [14C]APP was significantly slower in T. cruzi trypomastigotes of insensitive strains than in sensitive strains. The results suggest the importance of drug uptake rates in determining the pyrazolopyrimidine sensitivity of different T. cruzi strains.

Trypanosoma cruzi: 4-aminopyrazolopyrimidine in the treatment of experimental Chagas' disease.

An allopurinol metabolite, 4-aminopyrazolopyrimidine, was tested on two different strains of mice (NMRI-IVIC and C57Bl/6J) that had been infected 4 days earlier with the virulent Ya strain of Trypanosoma cruzi. Low doses of 4-aminopyrazolopyrimidine (0.125-0.500 mg/kg body wt/day) for 10 days induced a significant reduction in parasitemia (direct counts and subinoculation experiments) and increased survival time (without any evidence of toxicity) compared with untreated animals. When tested in vitro, 4-aminopyrazolopyrimidine was sixfold more active than allopurinol as a trypanostatic drug. The low therapeutic doses of 4-aminopyrazolopyrimidine suggest that this drug may be useful in the treatment of acute Chagas' disease.

Delayed-type hypersensitivity and immunoglobulin E in American cutaneous leishmaniasis.

Delayed-type hypersensitivity (DTH) and both total and specific immunoglobulin E (IgE) antibody levels were studied during an outbreak of American cutaneous leishmaniasis. Direct correlations were detected between DTH reactivity and either age or the period of evolution of the infection, and a clear association with sex (strongest response in females) was observed. Extremely high, age-dependent, total serum IgE levels were measured in the study group, probably due to concurrent intestinal helminthiasis. A low proportion of the group also had detectable levels of specific anti-Leishmania IgE antibody. Total and specific IgE levels were also sex dependent (lowest in females), and an inverse correlation was found between these levels and DTH responsiveness, possibly reflecting the intervention of regulatory influences of T-lymphocyte activity.

Cutaneous leishmaniasis in mice: resistance to glucan immunotherapy, either alone or combined with chemotherapy.

Leishmania braziliensis, L. mexicana, and L. garnhami were studied for their ability to produce American cutaneous leishmaniasis, using C57BL/6 female mice as the animal model. No significant difference in the clinical course of mouse foot pad infection was found between the three American Leishmania species studied. In general, the incubation period varied from 2-4 weeks. Mice developed only local swelling and sometimes ulceration at the sites of inoculation. After 4 weeks of progress lesions began to decrease without obvious impact on the general health of the mice. When glucan immunotherapy (120 - 240 mg/kg body weight) was initiated previous to, or simultaneously with, infection the development of foot pad lesions was not significantly inhibited, this despite clear evidence of generalized stimulation of the reticuloendothelial system. On the other hand, pentavalent antimony at high doses (1,000 - 1,500 mg/kg) induced only a significant lengthening of the latent period. However, different combinations of glucan and pentavalent antimony (various doses of each drug, timing of administration, or changes in the sequence of use of both drugs) did not significantly alter the clinical course of American Leishmania infection as compared with pentavalent antimony alone. Thus, not only were glucan or glucantime alone unable to cure the infection (as evidenced by some animals which showed rapidly growing lesions some time after the end of treatment), but no potentiation was observed.

Tests with three antigens in leprosy-endemic and non-endemic areas.

A study comparing the 48-h and 30-day reactions produced by three antigens was made in areas of low and high leprosy endemicity in Venezuela and in areas of Chile, a non-endemic country. The antigens used for the intradermal tests were standard Mitsuda antigen, supernatant from standard Mitsuda antigen, and PPD. The results indicate that there is no difference in the Mitsuda reaction of persons living in areas of high or low endemicity, but they show a statistically significant difference between the reactions in persons who live in endemic areas and those of persons living in a country where the disease has not been described. The difference in the Fernandez reaction obtained with the supernatant was not statistically significant between the two population groups in the endemic country, but was highly significant when comparing the endemic and the non-endemic countries.