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Biomedical subjects

R Guderian

Publications and source records attributed to R Guderian.

10 recordsLinked to original sources

Onchocercacidal effects of amocarzine (CGP 6140) in Latin America.

An open clinical trial of amocarzine was carried out in onchocerciasis patients in Ecuador and Guatemala. Administration after food was more effective than that during fasting. The most effective and best tolerated regimen, 3 mg/kg twice daily after food for 3 days (in 312 patients), killed 73% of 1477 female worms at nodulectomy 4 months after treatment. The mean microfilarial skin count was greatly reduced within a week (6-11% Of day 0 value on day 8) and it remained low at least 6 months (14-18% on day 180). Follow-up of a higher dose 3 day regimen taken while fasting showed microfilaridermia of 7-9% of the day 0 value 2 years after treatment.

Adult

Uptake of chloroquine by Onchocerca volvulus in vivo and in vitro.

Patients infected with Onchocerca volvulus in the Cayapa River focus in north-east Ecuador were given 500 mg chloroquine diphosphate (CQ) orally prior to nodulectomy. The concentrations of CQ were determined in parasite fragments and host tissue dissected from the nodules, in skin overlying the nodules, and in plasma at 3, 4, 7, and 24 hours after dosing. Onchocerca volvulus took up CQ rapidly, in some cases accumulating the drug to concentrations of over 600 pmol mg-1 worm tissue by three hours, and maintaining similar concentrations through 24 hours. These amounts were markedly higher than peak concentrations in plasma (3.16 pmol microliters-1) and in host tissues (78 pmol mgm-1) and skin (up to 93 pmol mg-1). In vitro uptake of CQ by females of O. volvulus was greater under alkaline conditions (pH 8.4) than at pH 6.8 and 7.4. Uptake reached equilibrium after one to two hours, with final concentrations being approximately 10 times lower than those reached in vivo. Inhibitory effects of chloroquine and its major metabolite desethylchloroquine on the motility of O. volvulus and other filariae have been observed previously in vitro; whether or not the drug had adverse effects on adult parasites in vivo was not determined in these experiments. However, the results illustrate the accessibility of O. volvulus to blood borne agents in vivo, and the potential importance of pharmacodynamic characteristics in the search for new macrofilaricidal agents.

Animals

Estimating impacts on developing countries of the decrease in U.S. training opportunities for foreign medical graduates.

Between 1973 and 1983, the number of foreign nationals from developing nations who entered the United States for graduate medical education decreased by approximately 90%. Many of those who would have studied in the United States if this decrease had not occurred would have returned home to serve their countries. To estimate the impact of this loss, a survey was conducted in six major cities in Latin America between 1983 and 1989. Selected local medical students interviewed 554 physicians who had returned home after U.S. training and 60 of their classmates who had not trained there. The findings indicate that the returned physicians had given approximately twice as much time to teaching, research, and medical administration as did those who had not left home. The authors maintain that this and related findings show how the curtailment of opportunities for training foreign nationals in the United States is detrimental to both the aspirations of developing nations and the influence of the United States in world affairs.

Adult

Abdominal sparganosis in Ecuador: a case report.

Sparganosis, infection with plerocercoids of the pseudophyllidean tapeworm Spirometra, rarely has been described in Ecuador. We report the details of a human case of sparganosis identified serendipitously in the course of an abdominal hernia repair. The parasite was found moving freely upon the external oblique fascia adjacent to the site of a direct abdominal hernia. The organism was recovered intact, photographed while alive and preserved for subsequent detailed morphological studies. The presumed route of entry into this patient was percutaneous, after application of a poultice of snake flesh to the site of a painful abdominal hernia. The literature on sparganosis in South America is reviewed. This is the second case of human sparganosis reported from Ecuador.

Abdominal Muscles

Concentrations of amocarzine in plasma of 71 Ecuadorian patients of two different races receiving 3 mg/kg b.i.d. and 5 mg/kg o.d. oral postprandial doses for 3 days.

The possible influence of sex, race and of postprandial administration conditions (either immediately after the end of meal or one hour later) on the plasma concentrations of amocarzine and its N-oxide metabolite, CGP 13 231, was investigated. 71 Ecuadorian patients (48 males and 23 females) of two different races (Indio and Negro) infected with Onchocerca volvulus participated in the study. The concentrations were measured on day 3 at times 3 and 6 h after postprandial administration in the morning of a treatment with either a dose of 5 mg/kg of amocarzine once daily (12 patients) or 3 mg/kg twice daily (59 patients) for 3 days. The concentrations of unchanged drug and of CGP 13 231 measured after the 5 mg/kg treatment were in the low range of those expected from dose proportionality by the comparison with the 3 mg/kg. After the 3 mg/kg dose, no significant difference in concentration of both compounds were detected between the male and female patients between Indio and Negro patients, between the administration immediately after food intake and one hour later. The only detected difference (P = 0.05) was that between Indio and Negro patients for the concentrations of CGP 13 231 at time 3 h. This difference was not confirmed at time 6 h. Therefore, the administration of amocarzine either immediately or one hour after food intake appeared to produce reproducible absorption conditions which were not influenced by sex and race.

Absorption

Microfilaricidal effect of amocarzine in skin punch biopsies of patients with onchocerciasis from Latin America.

Skin punch biopsies were performed in 54 selected patients with onchocerciasis participating in a clinical trial with amocarzine (CGP 6140) in Ecuador and Guatemala. Skin snipping for counting microfilariae of Onchocerca volvulus was done before treatment (day 0) and day 4 and 8 following start of the therapy which consisted of 3 mg/kg amocarzine postprandially twice daily for three consecutive days. The mean microfilarial skin density has been reduced by 45% on day 4 and 95% on day 8. Skin punch biopsies were taken on day 5, within 1 cm from the snip site on the iliac crest. Histopathologic examination revealed that the vast majority of the microfilariae in the upper as well as in the deeper dermis were degenerated or necrotic, surrounded often (57%) by minute foci of fibrinoid change of the collagen. There was usually slight, less frequently moderate eosinophilic, lympho-plasmocytic and initial histocytic inflammatory reaction in the vicinity. Microfilariae were frequently (69%) found at the dermal-epidermal junction and in the epidermis. Occasionally (7%) intra-epidermal microabscesses were noted. Microfilariae were detected also in the lumen of some dermal lymphatic vessels. Therefore it is concluded that amocarzine showed marked microfilaricidal effects in the skin of patients with onchocerciasis as evidenced histologically by mainly destroyed or moribund microfilariae which induced a mild to moderate inflammatory cell reaction.

Adult

Longterm follow-up of onchocerciasis patients in Latin America after treatment and retreatment with amocarzine. Preliminary results.

Amocarzine has been reported to have onchocercacidal effects. Four months posttherapy the majority of adult worms were dead or moribund. The effect of skin microfilariae lasted up to one year as reflected by markedly reduced microfilaridermia. Since the duration of the onchocercacidal effect of amocarzine beyond one year was unknown and since such an effect may influence the planning of future control strategies, efforts were made to follow-up the already treated amocarzine patients for a second year. The present study from Latin America showed that various amocarzine drug regimens produced a prolonged reduction of microfilaridermia at the end of the second year following the initial therapy, the best levels were about 7-17% of the initial parasite load in the skin for some three days amocarzine regimens. Such an effect occurring in a transmission area of onchocerciasis in Latin America provides additional, although indirect, evidence of a macrofilaricidal effect of amocarzine. Similar experiences of a prolonged amocarzine effect on skin microfilariae has also been observed in West Africa (Ghana, Mali). Preliminary results of retreatment schedules at the start of the third year post-initial therapy showed that simplified postprandial dose regimen of one or two days were well tolerated. It is premature at the time of this report to judge upon their ultimate efficacy, but they had significantly reduced levels of moderate microfilaridermia.

Animals

Onchodermatitis--correlation between skin disease and parasitic load in an endemic focus in Ecuador.

Onchocerciasis is a chronic parasitic infection in which infiltration of the skin by microfilariae has been associated with a number of different pathological changes. This survey compared the prevalence of different forms of skin disease in two villages, one of which was located within the endemic zone for onchocerciasis (Zapallo Grande), in a lowland rain forest area of western Ecuador. The commonest skin diseases in both villages were scabies, pyoderma and pityriasis versicolor. In addition changes closely correlated with the presence of microfilariae in skin snips were found in Zapallo Grande--such as atrophic gluteal changes, and acute and chronic papular dermatitis. The only other skin disease associated with onchocerciasis was widespread tinea corporis due to T. rubrum. The Amerindians in the endemic onchocerciasis area were more likely than Negroes to have generalized atrophic changes of the skin, whereas in the latter group significant numbers of individuals had no obvious skin lesions but large numbers of microfilariae were detected in skin snips. Acute papular dermatitis was common in both groups and in biopsied lesions microfilariae could usually be identified within the epidermis or close to the dermo-epidermal junction. One patient had developed severe reactive onchodermatitis (Sowda). Swabs taken from onchocercal skin lesions showed no evidence of skin surface carriage of Staphylococcus aureus. Changes classically associated with onchocerciasis such as pretibial hypopigmentation (leopard skin) and hanging groin were notably absent in this population.

Adolescent

[Prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae in 3 groups of Ecuadorian women with different sexual behaviors].

In order to examine the relationship between sexual conduct and infection with Chlamydia trachomatis and Neisseria gonorrhoeae (gonococcus), the prevalence of these two microorganisms was studied in three groups of Ecuadorean women with different patterns of sexual behavior: 116 prostitutes, 136 women from Borbón Parish who had numerous sexual partners, and 61 pregnant women who had sexual relations with only one partner. The prevalence of infection from one or both of the agents was 53.4% in the prostitutes (n = 62), 34.5% in the women from Borbón (n = 47), and 1.6% in the pregnant women (n = 1). These results bear out the relationship between sexual behavior and risk of sexually transmitted disease.

Adolescent

[Human sparganosis in Ecuador: report of a case in the province of Esmeraldas].

The second case of human sparganosis in Ecuador is reported in a male patient, of an indigenous tribe Chachi, from the province of Esmeraldas, who presented with a nodule localized in the left scapular region. Upon extirpation, a cestode classified as Spirometra was found, but the species could not be determined.

Adult