Clinical Forms Of Disease Research Articles

Phylogenetic analysis of SRLV sequences from an arthritic sheep outbreak demonstrates the introduction of CAEV-like viruses among Spanish sheep

Small ruminant lentiviruses (SRLVs) cause different clinical forms of disease in sheep and goats. So far in Spain, Maedi visna virus-like (MVV-like) sequences have been found in both species, and the arthritic SRLV disease has never been found in sheep until a recent outbreak. Knowing that arthritis is common in goats, it was of interest to determine if the genetic type of the virus involved in the sheep arthritis outbreak was caprine arthritis encephalitis virus-like (CAEV-like) rather than MVV-like. Alignment and phylogenetic analyses on nucleotide and deduced amino acid sequences from SRLV of this outbreak, allowed a B2 genetic subgroup assignment of these SRLV, compatible with a correspondence between the virus genetic type and the disease form. Furthermore, an isolate was obtained from the arthritic outbreak, its full genome was CAEV-like but the pol integrase region was MVV-like. Although its LTR lacked a U3 repeat sequence and had a deletion in the R region, which has been proposed to reduce viral replication rate, its phenotype in sheep skin fibroblast cultures was rapid/high, thus it appeared to have adapted to sheep cells. This outbreak study represents the first report on CAEV-like genetic findings and complete genome analysis among Spanish small ruminants.

Expression of IFN-γ, TNF-α, IL-10 and TGF-β in lymph nodes associates with parasite load and clinical form of disease in dogs naturally infected with Leishmania ( Leishmania) chagasi

American visceral leishmaniasis is a zoonosis of the New World. Dogs are the main reservoir of the disease and there is much interest in the understanding of mechanisms implicated in protection against canine infection. Nevertheless, most studies in dogs have not been carried out in organs that are targets of infection. This work is first to report the profile of cytokines and parasite burdens, as determined by real-time PCR, in the lymph nodes of dogs naturally infected with Leishmania chagasi. With this purpose, 18 mongrel dogs were divided in three groups: control non-infected dogs ( n = 6) and naturally infected animals with L. chagasi, asymptomatic ( n = 6) and symptomatic ( n = 6). Parasite burden in lymph nodes was 73-fold greater in symptomatic than asymptomatic animals. Prescapular lymph nodes of asymptomatic dogs had the highest expression of IFN-γ and TNF-α and low parasite burden, indicating that these cytokines play a role in protection against infection. Highest expression of IL-10 and TGF-β and high parasite burden were observed in symptomatic dogs, suggesting a role for these cytokines in the progression of disease. Hence, the balance of expression of IFN-γ and TNF-α (protective) and IL-10 and TGF-β (disease progression) in lymph nodes determine parasite burden and clinical expression in naturally infected dogs.

Random amplified polymorphic DNA profiles of Trypanosoma cruzi isolates from chagasic patients with different clinical forms

The genetic variability of 61 Trypanosoma cruzi isolates from 47 chronic chagasic patients of Minas Gerais state was analyzed by random amplified polymorphic DNA polymerase chain reaction (RAPD-PCR) using M13-40, lambdagt11-F, and L15996 primers. Cluster analysis by unweighted pair group method analysis was applied to RAPD profiles, and cluster analysis used to verify a possible correlation among different clinical forms of the disease from these patients. The T. cruzi isolates showed distinct grouping on tree topology, with the isolates not being possible to establish a correlation to the clinical forms of Chagas' disease. These data showed that the T. cruzi isolates from these patients would compose a group of populations well correlated genetically.

Current understanding of the aetiology and laboratory diagnosis of footrot

Footrot is a highly contagious disease of the feet of ruminants caused by the synergistic action of certain bacterial species of which Dichelobacter nodosus ( D. nodosus) is the main transmitting agent. The infection is specific to sheep and goats, although it has also been reported in cattle, horses, pigs, deer and mouflon. The antigenic diversity of D. nodosus is due to variations in the DNA sequence of its fimbrial subunit gene ( fimA) and provides the basis for classification of the organism into at least 10 major serogroups (A–I and M), the distribution of which varies with different geographical locations. Host immune response to vaccination is serogroup specific. There are three different clinical forms of disease caused by virulent, intermediate and benign strains of D. nodosus, respectively. In order to facilitate rapid and reliable clinical diagnosis, virulence determination, strain differentiation and serogroup identification for effective control measures, immunological tests, DNA probes and PCR based techniques have been introduced. This review summarises the current understanding of the mechanisms of antigenic diversity of D. nodosus as well as advances made in its strain differentiation and diagnosis.

Cytotoxicity in patients with different clinical forms of Chagas' disease.

There are few studies on cell-mediated cytotoxicity in human Chagas' disease. In the present study, we evaluated peripheral blood mononuclear cell (PBMC) cytotoxicity activity from chagasic patients with different clinical forms of disease. To verify the cytotoxic response, we performed cell lysis assays using 51Cr-labelled K562 cells as targets. Results are reported as lytic units (LU = number of cells required for 30% lysis) per million PBMC. Exposure of patients' PBMC to Trypanosoma cruzi antigen led to an increase in cytotoxic activity compared with unstimulated patient cells against K562. Asymptomatic cardiomyopathy patients had higher responses (37.8 +/- 5.0 LU/10(6) PBMC; mean +/- s.d.) than indeterminate (11.5 +/- 3.6 LU/10(6) and symptomatic cardiomyopathy (7.8 +/- 2.5 LU/10(6)). Normal control PBMC stimulated with T. cruzi antigen had 4.36 +/- 1.31 LU/10(6)) PBMC against K562. Addition of recombinant interferon-gamma (IFN-gamma) did not lead to significant increase in cytotoxicity in any group of patients. On the other hand, recombinant human IL-12 significantly increased cytotoxic responses from symptomatic cardiomyopathy patients and normal controls who presented low levels of cytotoxicity induced by T. cruzi antigen. The combined use of IL-12 and a neutralizing anti-IFN-gamma antibody did not change IL-12-induced cytotoxic responses, showing the direct role of this cytokine on natural killer (NK) cells. NK cells were the main cells responsible for the lysis of K562 target cells as evidenced by testing cell subsets following magnetic cell sorting. These data demonstrate that chagasic patients with different clinical forms of disease have PBMC which respond to T. cruzi antigen with a cytotoxic response, and this response is up-regulated by IL-12.

Epidemiología clínica de la alopecia areata

Abstract. —Since Ikeda described in 1965 her four clinical forms of alopecia areata (common, atopic, prehypertensive, combined), several epidemiological studies have deepened in the knowledge of this disease, confirming or questioning many of the initial findings. The series of cases made with inpatient samples can overlue the frequency of severe forms (total and universal alopecia) and the prognosis of alopecia areata. Studies carried out in general population gives an incidence of 20.2 new cases/100,000 people/year, and a lifetime-prevalence figure of 1.7%. Slight and moderate cases are frequent, developing a total/universal alopecia in the evolution only 7% of patients. It was described also a distribution of uniform beginning of alopecia areata in all ages, and a gender- ratio next to 1:1. Finally, current genetic studies and clinical- epidemiological ones have found two clinical forms of disease («genetic» or severe, and «benign» or stress-related), with different HLA markers, evolution, clinical presentation and relationship with psychosocial stress. However, more population studies than clarify some unclear features of disease are needed.

Frequency of His1069Gln and Gly1267Lys mutations in Polish Wilson's disease population.

Wilson's disease is an autosomal recessive disorder. More than 60 mutations of the Wilson's disease gene have been described so far. We have analysed 148 Polish Wilson's disease patients from 95 families for His1069Gln and Gly1267Lys mutations and correlated this finding with age and clinical form of the disease at presentation. To identify these mutations, single strand conformation polymorphism analysis was performed. In our group there were 94 patients with neurological presentation, 28 with hepatic presentation, whilst 26 were in a pre-clinical stage of the disease. His1069Gln mutation was present on 171 (57%) of the 296 studied chromosomes, and Gly1267Lys mutation was present on 27 chromosomes (9.1%). Most of our patients were homozygous or heterozygous for His1069Gln mutation (39.9% and 30.4%, respectively); 4% of the patients were homozygous for Gly1267Lys mutation and 5.4% had both of these described mutations on their chromosomes. His1069Gln and Gly1267Lys mutations occurred often in our Wilson's disease patient population but we did not find any relationship between investigated mutations and the clinical form of Wilson's disease or age of first symptoms.

Anti-idiotypic antibodies in patients with different clinical forms of paracoccidioidomycosis.

Paracoccidioidomycosis (PCM) is the most prevalent systemic mycosis in Latin America. Patients with PCM show a wide spectrum of clinical and pathological manifestations depending on both host and pathogen factors. Two clinical forms of the disease are recognized: the acute or juvenile form and the chronic or adult form. The major antigenic component of the parasite is a glycoprotein of 43 kDa (gp43). All patient sera present antibodies against gp43 (anti-gp43) and, as demonstrated before by our group, spontaneous anti-idiotypic (anti-Id) antibodies (Ab2) can be detected in patient sera with high titers of anti-gp43. Since it has been postulated that anti-Id antibodies may have a modulating function, we decided to purify and characterize anti-Id antibodies in this system. The possible correlation of Ab2 titers with different clinical forms of disease was also verified. Results showed that purified human anti-Id antibodies (human Ab2) recognized specifically the idiotype of some murine monoclonal anti-gp43 (17c and 3e) but not others (40.d7, 27a, and 8a). Spontaneous anti-Id antibodies were found in all clinical forms of disease. The majority of patients (88%, n = 8) with the acute form of PCM had high titers of Ab2. However, among patients with the multifocal chronic form of the disease, only 29% (n = 14) had high titers of Ab2; 70% (n = 10) of patients with the unifocal chronic form had low titers of Ab2. A correlation between Ab2 titers and anti-gp43 titers was observed before and during antimycotic treatment. Our results suggest that titers of anti-Id antibodies correlate with the severity of PCM in humans.

Prognostic Factors in Meningococcal Disease-Reply

Dr Radetsky has raised the important point of the ability of preadmission antibiotic therapy to significantly decrease the risk of a fatal outcome. As he observed, we did not stratify the relationship between preadmission antibiotic therapy and outcome by clinical form of meningococcal disease in the primary series of patients (derivation set). Such a stratification is shown in the Table, and demonstrates that when the ability of preadmission antibiotics to improve survival was examined by clinical form of the disease, preadmission antibiotic therapy could improve survival in each of them. However, the differences were statistically significant only in the acute form and when all forms were analyzed together. The subacute form showed a trend to significance, whereas in the fulminant form, the low number of patients provided inadequate power to test the hypothesis. The assumption that preadmission antibiotic therapy was more frequent in subacute and acute forms of the disease is correct

Prognostic factors in meningococcal disease

Dr Radetsky has raised the important point of the ability of preadmission antibiotic therapy to significantly decrease the risk of a fatal outcome. As he observed, we did not stratify the relationship between preadmission antibiotic therapy and outcome by clinical form of meningococcal disease in the primary series of patients (derivation set). Such a stratification is shown in the Table, and demonstrates that when the ability of preadmission antibiotics to improve survival was examined by clinical form of the disease, preadmission antibiotic therapy could improve survival in each of them. However, the differences were statistically significant only in the acute form and when all forms were analyzed together. The subacute form showed a trend to significance, whereas in the fulminant form, the low number of patients provided inadequate power to test the hypothesis. The assumption that preadmission antibiotic therapy was more frequent in subacute and acute forms of the disease is correct

Pericardial Tamponade in Chronic Myelomonocytic Leukemia

We report four cases of malignant pleuropericardial effusions in patients with chronic phase myelomonocytic leukemia (CMML). Based on current literature, this event is rare and very poorly understood. Our cases shed light on three important clinical characteristics: (1) patients with CMML develop effusions during uncontrolled leukocytosis; (2) these effusions are very responsive to conventional chemotherapy; and (3) effusions may develop without clinical forms of disease in other sites of extramedullary hematopoiesis.

Antigenic differences of Leishmania amazonensis isolates causing diffuse cutaneous leishmaniasis

Six geographically distinct isolates of Leishmania amazonensis causing diffuse cutaneous leishmaniasis (DCL) (from Bahia and Maranhão, in Brazil and Guarico, in Venezuela) were characterized by immunoblot analysis to see whether any geographical or strain-related differences existed in antigenic composition. Western blots of promastigote homogenates were reacted with polyclonal sera from patients infected with L. amazonensis with the various forms of clinical disease. The pattern of antigenic reactivity of these strains revealed the presence of shared antigenic components between geographically distinct L. amazonensis isolates causing DCL, when tested with the sera of the infected patients. In certain cases, however, some polyclonal sera also detected antigenic fractions unique to the strains examined. Variation was observed between the antigenic components of some isolates of L. amazonensis that were recognized by a single serum, and between the antigenic components of a single isolate of L. amazonensis that were recognized by the different patients' sera. However, no constant association was found between the antigenic components identified in these isolates and the geographical area of isolation. These results indicate that, although these parasites appear to be closely related antigenically, they also possess some strain-related antigenic differences.

Serum antibody specificities to Leishmania aethiopica antigens in patients with localized and diffuse cutaneous leishmaniasis

In order to characterize the antigenic determinants of Leishmania aethiopica, we have analysed by immunoblotting the antibody reactivity of leishmaniasis patients with either the localized (LCL) or diffuse (DCL) clinical forms of disease. In this study we have compared the reactivity of antibodies from eight LCL and DCL patients to parasites isolated from each individual, or the parasite isolates of the other LCL and DCL patients studied. The immunoblot profiles of antibodies from LCL patients differed from the antibody profiles of DCL patients. Serum antibodies from LCL patients showed limited recognition of somatic antigens of less than Mr 50,000 which were recognized by antibodies present in DCL patients. A direct comparison of individual LCL and DCL patient derived promastigotes determined that the lack of antibody to these antigens in LCL patients was not due to the differential expression of these determinants by the LCL and DCL derived promastigotes. The results of this study suggest that although either LCL or DCL derived promastigotes express a wide variety of antigenic moieties which are potentially reactive with antibodies, only a subset of antibodies against these specificities develop in any individual patient, during active infection.

Peripheral denervation in the various clinical forms of Chagas' disease

EMG examination was performed in 41 patients with Chagas' disease, belonging to the several clinical forms of the disease. Constant and direct relationship between the amount of muscle skeletal denervation and the clinical forms has been shown. In addition light peripheral axonal neuropathy was seen. Both muscular and sensory denervation was intense in the group with cardio-digestive form, moderate in the groups with either cardiac or digestive form and light in the group with the indeterminate form. The severity of the clinical symptoms was not related with the amount of peripheral denervation.

A study on antigen recognition by onchocerciasis patients with different clinical forms of disease.

Sera from 40 onchocerciasis patients from the Yemen Arab Republic with either mild localized forms of onchocerciasis, intermediate or severe localized forms of the disease or generalized forms of infection were studied with respect to their IgG and IgM response against Onchocerca volvulus antigens. Immunoblotting, performed with SDS-PAGE-separated proteins of female O. volvulus and quantified by densitometric scanning, revealed IgG and IgM antibodies against worm components in sera of all patients. Persons with intermediate or severe localized forms of onchocerciasis had a stronger IgG response against more proteins than individuals of the other groups. However, some antigens (Mr 21, 23, 30, 33 kDa) induced comparable quantities of IgG in all groups. The IgM response of patients with mild localized forms of onchocerciasis was more intensive and directed against more antigens than in the other groups. No antigens were detected that were recognized only by individuals with low levels of microfilaridermia. In all groups, varying concentrations of antibodies against cuticle, muscle/hypodermis layer and/or uterus of female O. volvulus were detected by the indirect immunofluorescence test using frozen worm sections as antigen. The highest mean antibody titres were found in patients with intermediate and severe localized forms of disease.

β2-Microglobulin and the Acquired Immunodeficiency Syndrome in a Low-Incidence Area

To the Editor.— The study of Zolla-Pazner et al 1 is important in the search for useful clinical tests for diagnosis and management of persons at high risk for the acquired immunodeficiency syndrome (AIDS). They have demonstrated that β 2 -microglobulin (β 2 M) is a highly sensitive and specific test for AIDS and AIDS-like illnesses. Furthermore, they have shown it to be of prognostic value with six of seven healthy homosexuals with elevated levels progressing to some form of clinical disease. We would like to draw attention to the fact that sensitivity and specificity data, derived from areas where the incidence and prevalence of clinical and subclinical disease are high, may not be totally relevant in areas with a lower incidence and prevalence of clinical and subclinical disease. The northeastern Ohio area contains approximately 3.5 million people, and as of Jan 1,1984, has reported 15 cases of AIDS. From

Appearance of complement components and immunoglobulins on nasopharyngeal epithelial cells following naturally acquired infection with respiratory syncytial virus.

Nasopharyngeal epithelial cells (NPEC) were collected from 144 infants and children with respiratory syncytial virus (RSV) infection, and were analyzed by fluorescent antibody techniques for the presence of cell‐bound complement (C/ 3), IgA, IgC, and IgM class of immunoglobulins (Ig), and respiratory syncytial virus antigen. Viral antigen was present on the surface of NPEC in 100% of samples obtained in the first 3 days of illness. The percentage of patients positive for RSV antigen declined steadily, so that no patient still expressed viral antigen on NPEC by 57 days after the onset of illness. Cell‐bound IgA, IgC, and IgM could be detected in most of the samples tested in the first 13 days after the onset of illness. Subsequently, the frequency of detection of cell‐bound Ig gradually declined. Only 8–3 3 % of patients tested 57 days after the onset of illness expressed IgA, IgG, or IgM on NPEC. About 45% of samples tested in the first 8 weeks after the onset of illness exhibited complement binding to NPEC. The percentage of subjects showing cell‐bound C/ 3 reached a maximum at 8–13 says after the onset of illness, while cell–bound C/3 could not be detected in any of the samples collected 57–90 days after the onset of illness. Although cell‐bound C/ 3 was generally present in association with cell‐bound Ig on NPEC, in a small percentage (4.6%) of patients cell‐bound C/3 could be detected in the absence of any cell–bound Ig. Cell‐bound C/3 and IgA, IgG, and IgM were present with equal frequency in patients with all forms of clinical disease caused by RSV, and in patients less than or greater than 6 months of age at the onset of illness.

Therapy results in Hodgkin's disease Freiburg i.Br., 1948-1966.

Of more than 600 patients with Hodgkin's disease seen at University Clinic, Freiburg, 340 patients received their primary treatment in the Clinic from 1948 to 1966. The following results are reported: 5-year survival rate, 48 per cent; 10-year survival rate, 28.7 per cent; 15-year survival rate, 21.2 per cent. The remission rate after the first treatment was 81.5 per cent; after 5 years, 24.4 per cent; after 10 years, 20.9 per cent; after 15 years, 20.9 per cent. This group of 20.9 per cent can be considered cured. Therapy results depend on stage of disease, clinical form of disease (types A and B) and on method of therapy. Marked improvement can be achieved only through radiation with tissue-destroying doses. Chemotherapy is a palliative treatment. The possibility of eradicating the disease makes it necessary that a critical plan for treatment—with cure as its objective—be worked out in all cases.