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Biomedical subjects

W L Chapman

Publications and source records attributed to W L Chapman.

At least 37 records · Page 2Linked to original sources
PubMed1986

Antileishmanial activity of liposome-encapsulated amphotericin B in hamsters and monkeys.

Visceral leishmaniasis (kala-azar) results from parasitization of the macrophages of the liver, spleen, and the rest of the visceral reticuloendothelial system with Leishmania donovani. Pentavalent antimony is the drug of choice for leishmaniasis chemotherapy; amphotericin B (AmB) is active but is rarely used, because of drug toxicity. AmB encapsulated within macrophage-directed carriers (liposomes) has been used to treat humans with systemic mycoses complicating neoplastic diseases; dosages of up to 5 mg of encapsulated AmB per kg per day for greater than 14 days are without apparent kidney or liver toxicity. In the present work, greater than 99% of L. donovani parasites were eliminated from the liver and spleen of infected hamsters by one administration of 1.5 to 11 mg of liposome-encapsulated AmB (L-Amb) per kg. A total of 98 to 99% of hepatosplenic parasites were eliminated from squirrel monkeys by three administrations of 4 mg of L-AmB per kg. L-AmB was 170 to 750 times as active as antimony in hamsters, and approximately 60 times as active as antimony in monkeys. The demonstration that apparently nontoxic human dosages of L-AmB eliminate essentially all hepatosplenic parasites in hamster and primate models suggests that this preparation should be considered for clinical trial against kala-azar.

Amphotericin B↗
PubMed1986

Experimental visceral leishmaniasis in the owl monkey.

Visceral leishmaniasis developed in eight owl monkeys (Aotus trivirgatus) after intravenous inoculation with a Khartoum strain (WR378) of Leishmania donovani. Six monkeys died within 93 days, and two monkeys recovered from the disease. Clinically, signs were weight loss, anemia, and hepatosplenomegaly. Hematologic findings included anemia, granulocytopenia, thrombocytopenia, and lymphocytosis. Analysis of serum or plasma revealed hyperbilirubinemia, azotemia, hyperglobulinemia, hypoalbuminemia, and altered hemostasis. All monkeys developed positive antibody titers to promastigotes of L. donovani and had increases in immunoglobulins M and subsequently G. Liver, spleen, bone marrow, and lymph nodes were the principal organs containing numerous parasitized macrophages. The owl monkey was highly susceptible to L. donovani infection and should be a useful animal model for the study of visceral leishmaniasis.

Anemia↗
PubMed1986

Blastogenic responses of peripheral blood leukocytes from owl monkeys experimentally infected with Leishmania braziliensis panamensis.

The relationship of the progression and regression of cutaneous lesions of 6 owl monkeys (Aotus trivirgatus) to the responses of their peripheral blood leukocytes (PBL) in vitro to mitogens and to leishmanial antigens, as well as their delayed skin test responses (DTH) in vivo to leishmanin antigen, were studied after primary and challenge infections with Leishmania braziliensis panamensis (WR 128 or WR 539). All 6 infected monkeys developed primary and satellite cutaneous leishmanial lesions which were measured for up to 30 weeks in 3 of the monkeys and up to 52 weeks in the other 3 monkeys. Two owl monkeys which had recovered from cutaneous leishmaniasis demonstrated acquired resistance when challenged with an intradermal inoculation of L. b. panamensis (WR 128). Reactivity of PBL from infected owl monkeys to PHA, Con A, and PWM was similar during primary and challenge infections to that observed prior to infection. Reactivity to leishmanial antigens was detected at 20 to 28 weeks post-infection (PI), became statistically significant after 28 weeks and remained elevated up to 52 weeks PI and after challenge infections. During primary infections DTH responses to leishmanin antigen were detected as early as 8 weeks PI, and continued up to 27 weeks PI. After challenge infections DTH reactivity was positive at 25 and 37 weeks, the only times the response was evaluated. The immunological responses of owl monkeys to L. b. panamensis were similar in many respects to those observed in humans with localized cutaneous leishmaniasis. This nonhuman primate model should be useful for future studies involving the immunology and chemotherapy of cutaneous leishmaniasis.

Animals↗
PubMed1985

Chemotherapy of visceral leishmaniasis (Leishmania donovani) in the squirrel monkey (Saimiri sciureus).

The relationship of the numbers of amastigotes in the liver to the duration of infection with two lines of a Khartoum strain of Leishmania donovani [designated the parent (P) line and the meglumine antimoniate (Glucantime) resistant (MAR) line] and the effect of meglumine antimoniate on these two lines of Leishmania were studied in the squirrel monkey. All experimental monkeys were inoculated via the saphenous vein with 32.5 X 10(6) amastigotes (per kg body weight), obtained from heavily-infected hamster spleens. Subsequently in Experiment I, liver biopsy samples were taken chronologically from all monkeys. Imprints of liver were made on glass slides and stained with Giemsa's staining solution, and parasite density per gram of liver tissue was determined. The parasites reached a maximum density of 6.2 X 10(6) amastigotes per gram between two to four weeks and 9.4 X 10(7) amastigotes per gram between four to six weeks in the monkeys receiving the P line and the MAR line, respectively. Parasite numbers then decreased, and all the livers and spleens of all monkeys became microscopically negative for Leishmania eight to 13 weeks post-infection. Comparison of the multiplication of the two lines of Leishmania indicated that the MAR line persisted longer in the livers than did the P line. A slight decrease in body weight was observed at eight weeks post-infection. Packed cell volume and haemoglobin were low at four to eight weeks post-infection, but were within the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Leishmania donovani: clinical, hematologic and hepatic changes in squirrel monkeys (Saimiri sciureus).

Clinical signs, parasite densities, and hematologic and hepatic changes were studied in 7 squirrel monkeys (Saimiri sciureus) each of which was inoculated intravenously with amastigotes (5.0 X 10(7) per kg body weight) of a Khartoum strain (WR 378) of Leishmania donovani. One control monkey was inoculated with uninfected hamster spleen homogenate. Five of the infected monkeys recovered spontaneously from visceral leishmaniasis by 8 to 15 wk postinoculation (wk PI) and 2 of the infected monkeys died at 39 and 59 days PI, respectively. All monkeys inoculated with L. donovani experienced a slight body weight loss, mild but significant anemia, lymphocytosis and an inconsistent neutropenia. Liver parasite densities could be quantitated from liver imprints from 2 to 8 wk PI and reached a maximum mean of 6.3 X 10(7) amastigotes/g liver at 4 wk PI in Experiment 1 and 13.4 X 10(7) amastigotes/g liver at 6 wk PI in Experiment 2. None of the liver imprints contained parasites at 15 wk PI. The characteristic histopathologic findings in liver biopsy and necropsy samples were multiple granulomas consisting of macrophages (some of which contained parasites), lymphocytes and plasma cells. The squirrel monkey is a moderately susceptible host for L. donovani. Squirrel monkey visceral leishmaniasis has a sustained course and certain clinical, hematologic and pathologic characteristics which are similar to human visceral leishmaniasis.

Adrenal Glands↗
PubMed1985

An enlarged aggregate of apocrine glands on the chest of karyotype I owl monkeys.

A firm circumscribed umbilicated mass in the middle of the chest, overlying the cephalad portion of the sternum, was an incidental finding in the skin of three males and one female from a group of eight (four male and four female) aged karyotype I owl monkeys (Aotus trivirgatus) released to our laboratory from the breeding colony of the Walter Reed Army Institute of Research (WRAIR). Light microscopic examination of each mass revealed an enlarged aggregate of apocrine glands which was interpreted to be the result of hyperplasia. Some degree of enlargement of the aggregate of glands was observed on all adult male karyotype I owl monkeys recently examined at WRAIR.

Aging↗
PubMed1984

Liposomes in leishmaniasis: effects of parasite virulence on treatment of experimental leishmaniasis in hamsters.

During studies on the use of liposomes as drug carriers in experimental leishmaniasis in hamsters, we noted incidentally that the apparent virulence of the infection often varied widely between different large groups of animals. When the death rates among control animals (injected only with saline) were compared with hepatic parasite counts of survivors in the same group, three distinctive types of infection were observed: type I, low death rate, low parasite count in survivors; type II, high death rate, low parasite count in survivors; type III, high death rate, high parasite count in survivors. The apparent virulence, based on death rates both at early and late stages of infection, was in the order I less than II less than III. Therapeutic efficacy of a drug (meglumine antimoniate) or liposome-encapsulated drug against each type of infection was in the order I greater than II greater than III. Liposomes reduced the drug dose required for each infection type many hundred-fold and reduced the death rate for type I to zero. However, among animals with type III (or even type II) infection certain individuals were completely refractory to treatment, even when liposome-encapsulated drug was employed, and the lowest mortality rate achieved was approximately 30%. This latter resistance to treatment may have been due to irreversible tissue damage caused by advanced disease, or it may have reflected resistance of certain virulent infections to treatment.

Animals↗
PubMed1984

Keratoconjunctivitis sicca: histopathologic study of nictitating membrane and lacrimal glands from 28 dogs.

Forty nictitating membrane glands and 9 main lacrimal glands were obtained for histologic evaluation from 28 dogs with keratoconjunctivitis sicca as the result of azosulfapyridine toxicity, canine distemper, multisystemic autoimmune disease (Sjögren's syndrome-like syndrome), congenital origin, and unilateral and bilateral idiopathic keratoconjunctivitis sicca. Similar glands from 6 control dogs were studied. The most prevalent (87%) histopathologic finding was variable degrees of multifocal chronic adenitis, characterized by acinar atrophy and replacement with increased numbers of plasma cells and lymphocytes within increased amounts of interacinar fibrous connective tissue stroma. Occasional tubular structures were dilated and filled with neutrophils and cellular debris.

Animals↗
PubMed1984

Antileishmanial activity of liposome-encapsulated meglumine antimonate in the dog.

Experimental infections of Leishmania donovani in mixed-breed dogs were induced to determine the antileishmanial efficacy of liposome-encapsulated meglumine antimoniate ( LEMA ). Each dog was inoculated IV with 1.0 +/- 0.2 X 10(8) amastigotes of a Khartoum strain of L donovani/kg of body weight. The antileishmanial agents ( LEMA or unencapsulated meglumine antimoniate ) were given once daily, IV, for 1, 4, or 10 consecutive days beginning the 12th day after inoculation. The dogs were killed 3 or 4 days after completion of therapy, and parasites in the spleens were quantified. A single injection of LEMA (0.61 mg of Sb/kg of body weight) resulted in 89% suppression and 4 consecutive daily injections of LEMA (1.94 mg of Sb/kg/day) resulted in 95.8% suppression of splenic parasites. The dose of LEMA that would give 50% suppression ( SD50 ) was estimated as approximately 0.029 mg of Sb/kg. The SD50 for unencapsulated drug was estimated as approximately 24 mg of Sb/kg. The liposome-encapsulated drug was estimated to be more than 700 times more efficacious than the unencapsulated drug. Seemingly, liposomes can markedly reduce the drug dosage required for equivalent treatment of visceral leishmaniasis in dogs.

Animals↗
PubMed1983

Leishmania braziliensis: effects of bacteria (Staphylococcus aureus and Pasteurella multocida) on the developing cutaneous leishmaniasis lesion in the golden hamster.

Experimentally induced lesions of cutaneous leishmaniasis and the effect of concurrent bacterial infection on the development of these lesions were studied in the golden hamster. Male outbred golden hamsters received intradermal injections at the base of the tail with approximately 10(7) promastigotes of Leishmania braziliensis panamensis, or promastigotes combined with Staphylococcus aureus or Pasteurella multocida or both, bacteria only, or sterile Eagle's minimal essential medium (MEME). The size of the resulting lesions was measured at least twice each week. Hamsters were killed at postinoculation Days 6, 13, 20, 27, 41, or 48, and each lesion was measured, aseptically excised, and bisected; half was used for bacteriologic culture and the other half was prepared for light microscopic examination. Lesions resulting from L. b. panamensis alone progressed from initial erythema to a granulomatous nodule and finally to a necrotic granuloma, often capped by a crateriform ulcer. Lesions resulting from a suspension of L. b. panamensis with added S. aureus or S. aureus and P. multocida, were initially larger, more erythemic and contained a greater proportion of neutrophils up to postinoculation Days 14-21 than did lesions resulting from L. b. panamensis alone. Concurrent infections with bacteria such as S. aureus and P. multocida had little effect on the development of ulcerating characteristics of lesions, but when S. aureus was present it appeared to enhance the severity of the early lesions. Between postinoculation Days 14-28, lesions produced by L. b. panamensis, with or without added bacteria had similar developmental progression of sufficient size for optimal testing of antileishmanial compounds.

Animals↗
PubMed1982

alpha-Difluoromethylornithine: a promising lead for preventive chemotherapy for coccidiosis.

alpha-Difluoromethylornithine (DFMO; RMI 71,782) given in drinking water in concentrations as low as 0.0625% inhibited infections of Eimeria tenella and minimized the development of lesions in chickens. It had approximately the same activity as a currently used anticoccidial drug, amprolium, and also had the advantage of being relatively nontoxic in chickens. Body weight gains were not reduced in chickens given 0.0635% DFMO or less for 14 days starting 8 days before they were inoculated with oocysts, but were reduced in chickens given drinking water containing 0.125 and 0.25% DFMO. The anticoccidial activity of DFMO was completely reversed by injection (intraabdominal) of putrescine hydrochloride (300 mg/kg of body weight/day), indicating that the drug may act by blocking putrescine biosynthesis. Inoculated chickens, in which coccidial lesion development was suppressed by DFMO, resisted subsequent challenge exposure with E tenella, as did nontreated infected control birds which had recovered from infection.

Animals↗