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Biomedical subjects

R M Genta

Publications and source records attributed to R M Genta.

At least 163 records · Page 9Linked to original sources

Fatal disseminated strongyloidiasis in a Vietnam War veteran.

Disseminated Strongyloides stercoralis infection was the cause of death in a young immunosuppressed Vietnam War veteran. Large numbers of Americans were exposed to this potentially lethal parasite during the Southeast Asian war. Because of its characteristic autoinfectious cycle, many veterans could unknowingly harbor the parasite. As the age of this veteran population increases and more patients receive immunosuppressive therapies, greater awareness and better diagnostic methods are needed to detect and treat strongyloidiasis before immunosuppressive regimens are instituted. The risk factors and the presently available diagnostic methods are briefly reviewed.

Adult↗

Specific IgE responses in human strongyloidiasis.

IgE antibodies directed against Strongyloides stercoralis larval antigens were measured by a newly developed radioallergosorbant test (RAST). One hundred and fifty-two samples of sera from patients with parasitologically proven S. stercoralis infection were tested. One hundred and thirty-six of these (89.5%) were positive for parasite-specific IgE. Of 50 presumably non-infected North American adult control sera, 49 (98%) were negative. All sera from patients with other parasites were negative, except for two sera from subjects with Ascaris lumbricoides, who exhibited low positivity. Of eight sera from non-infected patients with allergies and high IgE levels, one was weakly positive, and the other seven were negative. Considerable individual variability was present in the levels of specific IgE as measured by the RAST in the infected patients. Significant differences were also found among the three major demographic groups which composed our study population, with Asians having higher values than Latin Americans and the latter having higher values than North American patients. We conclude that the majority of patients with strongyloidiasis develop IgE antibodies directed against antigens from filariform larvae, the invasive form of the parasite. While the functional significance of this response remains to be defined, the RAST for IgE may be a useful adjunct in the immunological evaluation of these patients.

Adolescent↗

Filaroides hirthi: hyperinfective lungworm infection in immunosuppressed dogs.

Filaroides hirthi is a pulmonary parasite found primarily in beagle dogs. The modes of transmission and the life cycle of this parasite have been described recently, and the possibility of an autoinfectious cycle has been suggested. In this paper, we report two cases of experimentally immunosuppressed beagles (4 mg/day of prednisolone for over four months) in which massive disseminated F. hirthi infections developed. Large numbers of F. hirthi adults were present in the lungs, and larvae were found in lungs, mesenteric nodes, intestinal walls, and liver. While only minimal cellular responses were associated with the adult worms, a conspicuous mononuclear cell reaction was found around the larvae in the tissues. Since our dogs were caged to minimize contact with their own feces, we suggest that autoinfection took place in these dogs. Heavy worm burdens probably were reached because the reduced immune responses against the larva facilitated their successful penetration of the intestinal wall and their recirculation within the host.

Animals↗

Experimental disseminated strongyloidiasis in Erythrocebus patas. I. Pathology.

Fatal disseminated disease was induced in ten patas monkeys infected with two Southeast Asian strains of Strongyloides stercoralis. While some animals died within 6 weeks after infection, others controlled their infections until placed on high doses of corticosteroids. Larvae were first noted in the stools 11-20 days after transcutaneous exposure to filariform larvae. Daily larval counts tended to increase as the infections progressed, but the number of larvae in the stool was not predictive of whether a monkey would control his infection or succumb to fatal disease. Hyperinfection was confirmed in the six monkeys in which counts were made of the adult female parasites in the duodenum at postmortem, as well as by pathologic findings in all animals. Clinical signs of disease were vague until dyspnea induced by terminal pulmonary hemorrhage occurred. Eosinophilia and/or basophilia were noted intermittently in some infections. Severe necrotizing duodenitis, colitis, and pulmonary hemorrhage were the most conspicuous postmortem findings. Hyperinfection has been predictably induced in a cercopithecoid monkey for the first time; a species which may lend itself to further investigations into the pathogenesis of disseminated strongyloidiasis .

Animals↗

Experimental disseminated strongyloidiasis in Erythrocebus patas. II. Immunology.

Parasite-specific humoral and cellular immune responses were evaluated in seven Erythrocebus patas monkeys experimentally infected with a Southeast Asian strain of Strongyloides stercoralis. Most animals developed high titers of anti-larval surface IgG antibody (as evaluated by the indirect immunofluorescence test), and all animals tested developed specific IgE antibody (as shown by the in vitro histamine release test). Modest lymphoproliferative responses to S. stercoralis antigens were demonstrated in most animals during the early phase of the infection (days 20-40), but disappeared later. Steroid treatment (prednisone, 12.5 mg/kg on alternate days) was given to three animals, but did not appear to significantly affect the immune parameters tested. The degree of the immune responses to S. stercoralis larval antigens did not correlate well with the course of the infection, and several animals died of disseminated disease in spite of demonstrable humoral and cellular responses to these antigens. We suggest therefore that other factors, such as local intestinal immune and nonimmune mechanisms may be of importance in protection against disseminated strongyloidiasis.

Animals↗

Immunobiology of strongyloidiasis.

Strongyloides stercoralis causes a usually silent infection that, under certain conditions of altered host-parasite balance, may become a severe, often fatal, disseminated disease. Patients, as well as experimental animals, develop specific humoral and cellular responses to the tissue-invading stage of the parasite, the filariform larvae. These responses, however, while potentially useful for diagnostic purposes, appear to be of little importance in determining the course of the disease. It is suggested that local intestinal factors may play a central role in the control of autoinfection. Until these questions are resolved and more accurate diagnostic methods are devised, preventive therapy in all patients from endemic areas that must undergo immunosuppressive therapy is advised.

Animals↗

Immunologic responses to experimental strongyloidiasis in rats.

Humoral and cellular immune responses were evaluated in Lewis rats infected with high (3000) inocula of Strongyloides ratti larvae (L3). The responses of peripheral and mesenteric node lymphocytes to crude larval antigen (by lymphocyte proliferation assay) sharply rose between days 12 and 16 of the primary infection and days 8 and 12 of the challenge, and decreased promptly to almost preinfection levels. Spleen lymphocytes failed to show any response to the primary infection, but did exhibit a modest response after challenge. The responses of peripheral lymphocytes to the mitogen phytohemagglutinin fell considerably on infection day 8 and then rose sharply to very high levels. Reinfection caused a small decrease in responsiveness, followed by another increase after 10 days. Inoculation of 3000 heat-killed larvae stimulated a response in peripheral lymphocytes similar to that elicited by the inoculation of live larvae. Spleen lymphocytes appeared to be stimulated more by the killed larvae inoculation, whereas only a limited response was found in mesenteric node lymphocytes in animals inoculated with dead larvae. IgG antibody titers against S. ratti antigen were measured by the enzyme-linked immunoabsorbent assay (ELISA). A significant elevation was noted between days 12 and 20 with a return to pre-infection levels between days 80 and 150. Challenge with 3,000 L3 induced a rapid and significant elevation. These data indicate that in rats experimentally inoculated with large numbers of S. ratti larvae a direct relationship exists between the development of cellular and humoral immune responses to larval antigens, the expulsion of the intestinal worms, and the acquisition of resistance to subsequent challenge.

Animals↗

Cellular responses in human strongyloidiasis.

Peripheral lymphocytes from 16 patients with chronic uncomplicated strongyloidiasis and 15 non-infected controls were stimulated in vitro with Strongyloides stercoralis larval antigens, other non-parasite antigens and the T cell mitogen phytohemagglutinin (PHA). In the presence of autologous plasma the patients' responses to Strongyloides antigens were similar to those of controls. When lymphocytes from nine patients were cultured in the presence of normal human serum, responses to parasite antigens were enhanced, while responses to other antigens and to PHA were unaffected. Lymphoproliferative responses to PHA were significantly lower in the patients' group than in the controls. These findings suggest that in chronic strongyloidiasis, in addition to a depression of T cell activity, factors are present in the patients' serum that inhibit parasite-specific cellular responses in vitro.

Cells, Cultured↗

Specific allergic sensitization to Strongyloides antigens in human strongyloidiasis.

Reaginic antibodies to antigens from the human parasite Strongyloides stercoralis were studied by histamine release from basophils in 15 patients with chronic uncomplicated strongyloidiasis and in 12 controls (six North Americans with no evidence of parasitic diseases, two patients with Schistosoma mansoni, two with hookworm, one with Ascaris lumbricoides, and one with Onchocerca volvulus). All of the patients had antibodies to the somatic larval antigens, and 14 of 15 patients also had antibodies to the excretory/secretory products of S. stercoralis larvae. None of the controls had a positive response to any of the antigens tested. These findings indicate that patients with chronic strongyloidiasis have parasite-specific IgE antibodies and that S. stercoralis larval allergens may have a potential role in the immunodiagnosis of strongyloidiasis.

Antigens↗

Antibodies to Strongyloides stercoralis larval surface antigens in chronic strongyloidiasis.

Antibodies to intact rhabditiform and filariform larvae of Strongyloides stercoralis were measured by indirect immunofluorescence using quantitative fluorescence microscopy. Forty-four of 48 sera from infected patients (92 per cent) were positive for IgG antibodies specific for surface antigens of filariform larvae. None of 30 North American adult control sera were positive. All sera from patients with Schistosoma mansoni, Loa loa, or hookworm infections or with idiopathic hypereosinophilia were negative. Three of nine sera from patients with Bancroftian filariasis were weakly positive. Pre- and posttreatment sera from seven patients were tested, and there was a marked decrease in antibody titers in all posttreatment sera. Twelve sera from infected patients were also tested for the presence of IgA and IgM antibodies specific for surface antigens of filariform larvae; all sera were negative for specific IgA, and only one exhibited a weak positivity for specific IgM. Nine of the IgG-positive sera were tested for the presence of IgA and IgG antibodies directed against surface antigens of S. stercoralis rhabditiform larvae. No parasite-specific IgA was detected in any of the sera, but most sera contained small amounts of parasite-specific IgG. We conclude that the majority of patients with chronic uncomplicated strongyloidiasis develop specific IgG antibodies directed against the surface of filariform larvae, the invasive stage of the parasite. such antibodies may be involved in host defenses that prevent fatal hyperinfection in immunocompetent individuals. In addition, our results confirm that the indirect immunofluorescence employing filariform larvae as antigen is a sensitive and specific test that may be a useful adjunct to stool examination in the diagnosis of strongyloidiasis.

Antibodies↗

The histopathology of experimental strongyloidiasis.

An investigation of the pathologic events occurring during experimental Strongyloides ratti infection in rats was done. The chronologic sequence of the cellular responses to the infecting larvae as they migrated through the skin and lungs was determined. Larvae penetrate the skin very quickly, eliciting considerable mast cell degranulation within the first few minutes, a modest neutrophil response within the first few hours, and an occasional mononuclear response within the first 2 days. The larval passage in the lungs appears to cause little damage except for microhemorrhages and an occasional microabscess. In the intestine S ratti adult worms lie in the cryptae without penetrating mucosa, and except for an increase in the number of mast cells at the time of expulsion (Days 20--25), there is no detectable cellular response. Differences from the human disease are discussed.

Animals↗

Strongyloides stercoralis: loss of ability to disseminate after repeated passage in laboratory beagles.

A strain of Strongyloides stercoralis originally isolated from a south-east Asian patient and maintained by passage in monkeys for four years was introduced into parasite-free laboratory-reared beagles. After the second passage in these dogs, the prepatent period shortened from an average of 12-14 d to 8-9 d. Up to the third generation, immunosuppressive treatment of the dogs with oral corticosteroids caused hyperinfection with dissemination, albeit limited, to extra-intestinal organs. From the fourth generation onward, neither hyperinfection nor extra-intestinal migration could be induced even by higher doses of corticosteroids. These observations suggest that the biological behaviour of populations of S. stercoralis can alter as they pass from host to host. Such changes may account, at least in part, for the diverse clinical manifestations of strongyloidiasis.

Animals↗

Comparison of biopsy sites for the histopathologic diagnosis of Helicobacter pylori: a topographic study of H. pylori density and distribution.

The histologic demonstration of characteristic curved, spiral bacilli on the gastric mucosa is considered the gold standard for the diagnosis of Helicobacter pylori infection. However, in some cases the urea breath test or serologic tests may be positive, yet gastric biopsy specimens fail to reveal H. pylori. The objectives of this study were (1) to analyze the density and distribution of H. pylori in different regions of the stomach, (2) to ascertain which area of the stomach is a preferential site for obtaining biopsy specimens, and (3) to determine whether the presence of neutrophils or lymphoid aggregates correlates with the presence of detectable organisms in the same biopsy specimen. Eighty-nine patients with H. pylori infection underwent gastric mapping. The density of H. pylori, neutrophils, and lymphoid follicles was assessed semi-quantitatively in each biopsy site. The likelihood of getting a false-negative result was also calculated for each biopsy site. All biopsy specimens from the antral lesser curvature, at or near the incisura, had detectable H. pylori. Scores for this area and the cardia were higher than scores for the gastric corpus, but most differences were not significant. Fewer than 3% of antral biopsy specimens were false-negative, compared to between 6% and 9% of those from the corpus (p = 0.02). Neutrophils were present in more than 94% of all antral biopsy specimens, compared to 60% to 86% of specimens from the corpus (p < 0.01). Lymphoid follicles were detected in approximately two-thirds of antral biopsy specimens but in fewer than half of those from the corpus.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗

Global prevalence of strongyloidiasis: critical review with epidemiologic insights into the prevention of disseminated disease.

Opportunistic disseminated strongyloidiasis is an important cause of morbidity and mortality in immunocompromised patients. However, the worldwide prevalence of Strongyloides stercoralis is difficult to determine because adequate data are lacking. In this paper more than 100 epidemiologic studies reporting on the prevalence of S. stercoralis among various populations on five continents are critically reviewed. Analysis of this information indicates that the following groups of people may be at risk: residents of an emigrants from any developing country and southern, eastern, and central Europe; travelers and veterans returning from endemic areas; natives and residents of the Appalachian region in the United States and local endemic areas in other countries; and institutionalized persons. Because disseminated infections may be prevented by early treatment of asymptomatic chronic infections, screening programs are recommended to detect latent S. stercoralis infection before the initiation of chemotherapy or immunosuppression in patients at risk. Serologic tests are sensitive and specific but are not yet widely available. Thus strong suspicion based on clinical and epidemiologic clues in conjunction with repeated stool examinations remains the best way to rule out S. stercoralis infection in these groups.

Acquired Immunodeficiency Syndrome↗

Congenital hepatic fibrosis and cerebral aneurysm in a 32-year-old woman.

Congenital hepatic fibrosis has been associated with a number of visceral abnormalities, but only rarely with cerebral aneurysms. We report a case of a 32-year-old woman with congenital hepatic fibrosis and a subarachnoid hemorrhage secondary to a ruptured cerebral aneurysm. A review of the literature reveals only two previous reports of such an association and both were also associated with polycystic kidney disease. Our patient is unique in that she does not have polycystic kidney disease but rather medullary sponge kidney.

Adult↗

Expression of carcinoembryonic antigen in ulcerative colitis, tubular adenomas and hyperplastic polyps: correlations with the degree of dysplasia.

Sections of tubular adenomas (n = 40), ulcertive colitis (n = 97) and hyperplastic polyps (n = 31) were examined by immunoperoxidase staining to carcinoembryonic antigen (CEA) in order to assess its potential diagnostic value in predicting malignant potential of these lesions. We compared the degree of epithelial abnormality in these mucosal specimens with the extent of immunoperoxidase staining for CEA. We found that CEA staining correlated with the degree of epithelial alteration in tubular adenoma and ulcerative colitis groups. Scattered weakly positive staining was found in eight of 31 hyperplastic polyps. High tissue expression of CEA, when combined with histologic dysplasia, may prove to be an additional factor in the evaluation of malignant potential in ulcerative colitis specimens and adenomas.

Adenoma↗