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Biomedical subjects

F A Neva

Publications and source records attributed to F A Neva.

At least 73 records · Page 4Linked to original sources

A clinical trial with pre- and post-treatment manometry comparing pneumatic dilation with bouginage for treatment of Chagas' megaesophagus.

The physiologic similarities between the megaesophagus of Chagas' disease and idiopathic achalasia are well documented. Therefore, it would seem reasonable that comparisons of controlled trials of therapy for the more common Chagas' megaesophagus could be applied to idiopathic achalasia, where the paucity of cases makes such a controlled comparison difficult. We had the opportunity to study 18 patients with achalasia secondary to Chagas' disease. All of the patients were from the mid central states of Brazil, all had symptoms of dysphagia and radiographic documentation of dilated esophagus and abnormal peristalsis (Rezende Groups II and III), as well as positive serologic evidence of Chagas' disease. Perfused intraluminal manometric studies were performed on all patients. Resting sphincter pressures ranged from 20-35 mm./Hg., mean of 25 (normal 5-12 mm./Hg.) with aperistalsis. Patients were randomly dilated with either bouginage (44-55 ff catheter) or pneumatic dilator (4-4.5 kg./6.5 cm.2 x 2 min.). Although all patients reported symptomatic improvement several days after either procedure, repeat manometric tracings demonstrated no change in the sphincter pressure in the bouginage group. The pneumatically dilated group, however, demonstrated a decrease in sphincter pressure to normal levels (mean 12 mm./Hg.). Follow-up studies one year after the procedure confirmed the persistence of normal sphincter pressure in the pneumatically dilated group but no change, as well as return of initial symptoms, in the bouginage group.

Adult↗

Specific allergic sensitsation to filarial antigens in tropical eosinophilia syndrome.

Reaginic antibodies to antigens from the human filarial parasites Wuchereria bancrofti and Brugia malayi and the animal parasite Dirofilaria immitis were studied by histamine release from basophils in 7 patients with tropical eosinophilia (T.E.) and 18 patients with other manifestations of filarial infection (lymphatic changes or symptomless microfilaraemia). All the patients had antibodies to all three filariae but T.E. patients were more highly sensitised. T.E. patients responded more to antigens from microfilariae than did patients with non-T.E. filariasis and responded more to microfilarial antigens from the human parasites than to those from the animal parasite. These findings support the view that T.E. is a form of occult filariasis which results from host hypersensitivity to the microfilarial stage of parasites which, in other individuals, cause the more common lymphatic manifestations of filarial disease.

Adolescent↗

Cutaneous leishmaniasis--a case with persistent organisms after treatment in presence of normal immune response.

A Peace Corps volunteer in Senegal, West Africa contracted cutaneous leishmaniasis which had several noteworthy features. One of the three presenting cutaneous ulcers was associated with subcutaneous nodules and viable organisms were recovered from healing lesions after multiple courses of treatment, including amphotericin B. Yet, the patient was found to exhibit both humoral and cell mediated features of normal immunologic responsiveness. Ultimately, clinical and parasitological cure occurred. The patient's organism was found to produce lesions in the foot pads of mice.

Adult↗

Failure of chloroquine in human babesiosis (Babesia microti): case report and chemotherapeutic trials in hamsters.

The failure of a 3-week course of chloroquine to eliminate an infection of Babesia microti acquired on Martha's Vineyard led to tests of selected drugs in hamsters infected with the strain from this patient. The results showed response to several antitrypanosomal drugs (pentamidine and 4,4'-diazoaminobenzamidine) but not to antimalarial drugs (chloroquine, sulfadiazine, and pyrimethamine).

Animals↗

The acquisition and loss of antigen-specific cellular immune responsiveness in acute and chronic schistosomiasis in man.

To characterize the development and evolution of cellular immune responsiveness in individuals infected with the parasite Schistosoma mansoni, we studied fifteen patients with acute, subacute and chronic schistosomiasis. Lymphocytes from the three acutely infected patients responded vigorously to schistosome antigens in an in vitro blastogenic assay. By contrast, cells from nine chronically infected individuals were essentially unreactive to these same antigens. Patients infected for an intermediate period of time (9 months) generated responses between those of acute and chronic patients. The diminished responsiveness of chronically infected individuals was specific for schistosome antigens and did not extend to humoral immune responses. Following treatment of the infection with niridazole, these patients temporarily regained responsiveness to schistosome antigens. From these data we speculate that during the course of this parasitic helminth infection there develops a progressive and specific modulation of antigen recognition and proliferation by lymphocytes to schistosome antigens, and that such diminished immune reactivity may be important in maintaining the unique biological relationship which exists between a host and its parasites.

Acute Disease↗

A complement-fixing antigen from Trypanosoma cruzi grown in cell cultures.

A complement-fixing (CF) antigen was prepared from amastigotes and trypomastigotes of Trypanosoma cruzi (Ernestina strain) grown in beef embryo cell cultures. Multiple lots of the antigen, which consisted of a supernate of washed and disrupted organisms, required material from 10(6) to 10(7) total organism per ml for optimum CF activity. Antibody at dilutions up to 1:256 was demonstrable in various sera from infected animals or patients. Contaminating beef cells from infected cultures were shown to be partly responsible for crossreactions of the antigen by CF with sera from cases of cutaneous leishmaniasis in whom concomitant infection with T. cruzi could be excluded. There were no cross-reactions with syphilitic sera and the frequency of positive reactions with normal sera was very low. Some characterisitics of the antigen included stability to storage at -20 degrees C and -70 degrees C for months, inactivation at 60 degrees C and by lyophilization, and an estimated molecular size of between 50,000 and 100,000 on the basis of membrane filtration.

Animals↗

Comparison of cell culture with epimastigote antigens of Trypanosoma cruzi.

Various epimastigote antigens of Trypanosoma cruzi were compared with an amastigote-trypomastigote antigen from infected cell cultures by complement fixation (CF) and gel diffusion (Ouchterlony). CF results with human Chagasic sera showed that the amastigote-trypomastigote antigen was usually more sensitive than epimastigote antigens tested. In addition, cross-reactions with normal and other sera were no greater and perhaps less frequent than with crude epimastigote antigens. Specificity of the amastigote-trypomastigote antigen, however, was less than with a protein extract of epimastigotes. Gel diffusion results with human Chagasic and hyper-immunized rabbit sera indicated differences between epimastigote and amastigote-trypomastigote antigens whereas differences by CF with the same sera were equivocal.

Animals↗

Tropical eosinophilia. A human model of parasitic immunopathology, with observations on serum IgE levels before and after treatment.

The diverse clinical syndromes characterized by asthmatic symptoms, transient pulmonary infiltrates, and eosinophilia have tended to obscure the specific association of one such entity with filarial infections. Serum IgE levels were determined before and after therapy in a group of well-characterized patients with tropical eosinophilia (TE), studied earlier in Singapore. The mean serum IgE level in 14 cases before treatment with diethylcarbamazine was 2,355 ng. per milliliter, with a trend but statistically nonsignificant decrease in levels to 600-1,000 ng. occurring 8 to 12 weeks after therapy. Leukocyte and eosinophil counts showed a rapid reduction after treatment, and although mean complement-fixing (cf) titers to Dirofilarial antigen tended to decrease, they were not significantly reduced until 5 to 6 weeks. The historical development of evidence supporting the filarial etiology of TE was reviewed. Many basic questions engendered by the clinical syndrome of tropical eosinophilia make it an excellent model for study of the immunopathology of parasitic infections.

Antibodies↗

Serum complement and immunity in experimental simian malaria. I. Cyclical alterations in C4 related to schizont rupture.

Previous studies indicated that the level of whole serum complement (C') falls during malaria, and that the fall in C' is linked to schizont rupture and the appearance of humoral antibody. For a more detailed study of the role of C' in malaria, levels of C4 were monitored in rhesus monkeys infected with Plasmodium coatneyi. After one to two weeks of infection, significant and abrupt declines in C4 levels occurred, and these were temporally related to the process of schizont rupture. The level of C4 began to fall within a few hours after the onset of schizont rupture and fell to values as low as 2% of prerupture levels. Over the next 24-36 hr, C4 returned to normal levels, and fell again during the next cycle of schizont rupture. In general, the decline in C4 levels was positively correlated with the onset of immune response (functional and serologic) and degree of parasitemia. This marked cyclincal depletion of C4 indicates tremendous turnover of C' in primates with malaria.

Animals↗

Serum complement and immunity in experimental simian malaria. II. Preferential activation of early components and failure of depletion of late components to inhibit protective immunity.

The role of complement in the control of parasitemia was examined. Depletion of late components (3-9) by cobra venom factor did not alter either the degree or course of parasitemia during the pre-immune or immune stages of infection. The pattern of consumption of complement components was therefore examined. Concomitant with schizont rupture there was depletion of early-acting components (C1, C4, and C2) of the clasical complement pathway. The magnitude and remporal relationships of the fall were similar for these three components. Serum levels returned to prerupture values over 36-48 hr, and then the cycle was repeated. There was no simultaneous change in the levels of C3, C3 proactivator, or C6. These results delineate a new pattern of cyclical consumption of early components of the classical complement pathway associated temporally with schizont rupture and suggest that the late-acting components are not required for protective host immunity in malaria.

Acute Disease↗

Detection of circulating antigen in acute experimental infections with Toxoplasma gondii.

Although many serologic tests are available for determination of antibody to Toxoplasma gondii, circulating antigen has not been studied in infections with this organism. Presence of circulating antigen was sought by immunologic methods in experimental infections (Rh strain) of mice and rabbits. In mice, which succumbed to infection within four days; circulating antigen was detectable in serum by counter-current immunoelectrophoresis and agar gel diffusion on days 2-4 of infection. In rabbits; which succumbed to infection within eight days; serum antigen could not be detected by countercurrent immunoelectrophoresis or agar gel diffusion; Affinity chromatography, with use of cyanogen bromide-activated Sepharose and binding of the antigen to hyperimmune rabbit antiserum to Toxoplasma, permitted isolation of serum antigen on days 3, 5, 7, and 8 of infectionmalthough infected micce and rabbits may have parasitemia of 10-2--10-4 organisms/ml of blood, this concentration did not produce precipitin reactions with antiserum that detected antigenemia. Preliminary characterizations of the column-extracted antigen revealed heat inactivation by 56 C for 30 min, complete inactivation by trypsin, and a molecular weight of greater than 100,000 daltons, as determined by chromatography on a Sephadex column.

Acute Disease↗

Relationship of serum complement levels to events of the malarial paroxysm.

Malarial paroxysms due to Plasmodium vivax were studied for alterations in whole serum complement (C') and certain C' components. The objective was to relate C' values with events of the parasite cycle during schizogony and with the febrile pattern. Substantial decreases in C' were found in 9 of 18 paroxysms studied during relapse. In contrast, only one of 22 paroxysms occuring during the primary attack was associated with a striking depression in C', and this case exhibited certain characteristics of a relapse paroxysm. The mean change in C' levels during paroxysms in relapse (-23%) was significantly different from paroxysms of the primary attack (-2%). Depletion of C' was associated directly with degree of parasitemia and presence of complement-fixing (CF) antibody. Lowest levels of C' were found within a few hours after completion of schizont repture and peak fever. C4 levels reflected changes in whole serum C' and appeared to be a more sensitive indicator of C' alterations during malaria. While the alterations in C4 as well as C1 and C2 indicated that the classical C' pathway was involved, some preliminary results showed little or no depletion of late components, C3 and C6. Overall results are compatible with C' activation and depletion during or soon after schizont repture if parasite density is sufficiently high and if CF antibody is present.

Adult↗