A case of mucocutaneous leishmaniasis in Saudi Arabia caused by Leishmania major and its response to treatment.
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Biomedical subjects
Publications and source records attributed to W Peters.
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Wistar rats were injected intravenously with sporozoites from Anopheles stephensi infected with Plasmodium yoelii yoelii. The animals were subsequently treated with primaquine at doses of 30, 50 or 100 mg kg-1 at various times. Liver biopsies were made and the exoerythrocytic schizonts examined by light and electron microscopy between 45 and 50 hours. The action of the drug appeared to be principally on the parasite mitochondria, the membranes of which became thickened, then proliferated into multiple layers. Finally the whole organelles swelled up losing all structural organisation. Other parasite membranes were affected similarly and the peripheral enzyme granules disappeared. Following treatment the small, disrupted schizonts were apparently absorbed by their host cells which appeared unaffected by primaquine.
Current and new antimalarial drugs are discussed in relation to the prevention and treatment of malaria, with special reference to multiple drug resistance in P. falciparum as it affects non-immune travellers.
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The hemodynamic effectiveness and the oxygen characteristics of stroma-free hemoglobin (SFH) solutions were studied in 11 dogs. the animals were bled two-thirds of the estimated blood volume or until cardiac arrest. The shed blood was immediately replaced by equivalent amounts of either SFH or polyhemoglobin (SFH-PLP). Sixty min later, Ringer's lactate was given iv for 180 min to maintain right atrial pressure at the initial value. In a second set of experiments, the intravascular persistence of SFH-PLP was investigated in 5 dogs by withdrawal of blood (7 ml/kg bw) and immediate replacement with 131I-labeled SFH-PLP. Hemodynamic disorders after severe blood loss could be reversed by infusion of hemoglobin solutions. Due to the short intravascular persistence, cardiac output did not increase as one would expect from the degree of hemodilution. Pyridoxalation of the hemoglobin molecule reduced oxygen affinity and improved oxygen unloading at the tissue level. The short intravascular half-time of this compound could be overcome by crosslinking of the pyridoxalated hemoglobin molecules. Further studies must prove whether this polyhemoglobin can be used as a long-term oxygen-carrying blood substitute.
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Histological and ultrastructural aspects of acute and chronic pre-erythrocytic schizonts of P. yoelii yoelii were studied with: a) acute schizonts in normal rodents; b) chronic schizonts induced in rodents receiving ethionine injections or on a low methionine diet; Experimentally induced chronic schizonts frequently have the same histological aspect as those observed in wild Thamnomys from Africa. The ultrastructural evolution of the vacuole system described by Seureau et al. in acute schizonts is discussed; new evidence is presented to support the hypothesis according to which the contents of the vacuoles are enzymatic in nature. Ultrastructural studies of chronic schizonts show alterations in the sites of synthesis (zones of rough endoplasmic reticulum small and not numerous, absent in the most delayed schizonts; vesicle system poorly developed and also disturbances of nuclear development (slow division, apparently inhibited in the most retarded forms.) A peripheral accumulation of vacuoles in many chronic schizonts without discharge of their contents to the parasitophorous space, might indicate an alteration of their membranes, leaving them unable to fuse with the schizont plasmalemma.
Eighteen severely and profoundly retarded adolescents were treated in a research and demonstration project within a state institution by behavior modification methods for 30 months. Most showed traits of autism, phobias and persistant vulnerability. Restraints had acquired stimulus control. Programming, an aversive event, evoked SIB as avoidance reaction. Effect of pharmacotropic medication was transitory at best. Combination of several behavior modification techniques obtained complete suppression of SIB in 66.6%, partial in 16.7% and none in 16.7%. Non-aversive behavior modification methods, though slow-acting and time-consuming, produced permanent results in 72.7%. Aversive stimulation by remote controlled ESS suppressed SIB instantaneously and made SIB residents accessible to behavior modification and training. In 43%, durability of extinction was limited, despite concomitant intensive full-day behavior modification programs. Extinction was maintained through booster ESS. In two of seven cases ESS lost its aversive qualities. The use of ESS appears justified when non-aversive treatment modalities have failed and life-threatening situations persist.
Enzyme typing by starch gel electrophoretic techniques was carried out on 11 Leishmania isolates from Italy in laboratories in Montpellier and London. The enzymes studied in the former were ME, G-6-PD, 6-PGD, PGM, PGI, GOT (= ASAT), MDH and IDH. In London slightly different procedures were used to examine ME, 6-PGD, PGM, PGI and ASAT. In addition, SOD, ALAT, NH, and MPI were studied. The combined data revealed that four Rattus rattus and four dogs were infected with classical L. infantum (zymodème 1). In addition, two other dogs and a fox were infected with an enzyme variant (zymodème 18) which differed in four of the 12 enzymes examined. These findings raise the question of the heterogeneity of the parasites causing visceral leishmaniasis.
The treatment of the complex of diseases known as leishmaniasis, caused by infection with protozoal parasites, is often unsatisfactory. The response to chemotherapy depends not only on the species of infecting Leishmania but also on the immune reactions of the host. This creates difficulties in evaluating any new drug in clinical trials. In a Brazilian patient with diffuse cutaneous leishmaniasis, which classical antileishmanial drugs had failed to cure, antituberculous therapy of an intercurrent mycobacterial infection produced a striking remission of the leishmanial skin lesions. Subsequent studies in mice infected with the strain of L. mexicana amazonensis isolated from this patient showed that para-aminosalicylic acid was inactive and both rifampicin and isoniazid had only a moderate beneficial action. However, a pronounced degree of potentiation was observed when rifampicin and isoniazid were administered in combination. Clinical trials of this combination are recommended in further patients, as well as experimental studies on other antimycobacterial agents, alone and in various combinations.
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Amber mutants with defects in the dnaA gene of Escherichia coli K-12 were isolated after localized mutagenesis of the tna-dnaA region of the chromosome. We isolated 36 mutants defective in the initiation of deoxyribonucleic acid replication as determined by their dependence upon integrative suppression by a P2 sig5 prophage. Three of the 36 mutants were shown to contain amber mutations through the use of a temperature-sensitive amber suppressor. These mutations, which mapped between gyrB and tna, were characterized genetically and biochemically as amber mutations in dnaA.
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A description is given of two methods for investigating the action of drugs against a viscerotropic Leishmania in mice. The parasite employed was isolated from a patient with kala-azar in Ethiopia. It is designated 'L. infantum LV9' and produces a visceral infection in NMRI mice. The biochemical typing characters of the parasite are described. In Method A, infected animals were treated from the 5th or 6th day after infection (D + 5 or D + 6) for five consecutive days. They were sacrificed 24 hours after the completion of drug treatment and an estimate was made of the amastigote load in the liver. A comparison of this with untreated controls gives an index of activity of a test drug, from 0 to 3. Method B is similar except that the ED50 and ED90 are determined by graphic analysis of data from graded drug doses. A comparison is made with sodium stibogluconate used as a positive drug control to yield a 'Pentostam Index'. The course of infection in BALB/c and NMRI mice is compared with that in random-bred Swiss mice in which 'L. infantum LV9' produces an inconsistent infection. An inoculum of 10(7) amastigotes produces a peak parasite intensity between D + 15 and D + 20. The ED50 and ED90 of sodium stibogluconate (Pentostam) (as Sbv) in Method B are 22 x 5 and 46 x 5 mg/kg sc daily x 5. (By Method A the single dose figures are 65 and 280 mg/kg.) For routine use a standard dose level of 120 mg/kg sc daily x 5 of Pentostam (Sbv) is used in Method B. The ED50 and ED90 of meglumine antimoniate (Glucantime) (as Sbv) in Method B are 11 x 6 and 66 x 7 mg/kg sc daily x 5. Data are given for other antimonials in Method A. Pentamidine and diminazene aceturate proved to have a slow action which was more readily demonstrated if the observation period was prolonged. Amphotericin B was moderately active but toxic to the host. The relevance of these models and a comparison of data found in the mouse and hamster are debated.
Fragments of a mammary adenocarcinoma were implanted into transparent tissue chambers in the dorsal skin flaps of female inbred F344 rats. A chamber modification permitted repeated access to the tissue without infection, vessel disruption, or impairment of tumor growth. Tumors completely filled the chambers after 26-30 days. Development of tumor microvasculature was characterized by increase in number, length, and diameter of vessels. These changes were much more pronounced in capillaries and venules than in arterioles. Direct blood pressure measurements were performed in microvessels throughout the tumor during the first 3 weeks of growth as well as in microvessels of tumor-free control preparations containing subcutaneous tissue. Average pressures in arterioles of 40- to 11-micron diameter were between 23.0 and 17.3 cm H2O in tumors versus 25.5 and 16.2 cm H2O in controls. Average pressures in venous capillaries, venules, and veins up to 150-micron diameter were between 9.1 and 8.1 cm H2O in tumors and between 13.4 and 11.0 cm H2O in controls.