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[Development of a case of Mycobacterium avium complex disease from right pleural effusion].

Moist pleurisy in patients with Mycobacterium avium Complex (MAC) is rarer than tuberculosis. We encountered an extremely rare case of MAC disease in a 75-year-old man who initially had only right pleural effusion. Gaffky VII was detected in the pleural effusion, and Mycobacterium avium was identified by culture and PCR. Although administration of antitubercular agents (RFP, INH, EB, and SM) + CAM and thoracic lavage were repeated, the Gaffky persisted strongly. Accordingly, pulmonary decortication and filling of the cavity with an omental flap were performed as surgical treatments. However, fistulas were formed between the remaining empyema cavity and the surgical wounds. Fenestration was also carried out. Postoperatively, centriacinar abnormalities appeared on computed tomography (CT). It has been reported that MAC disease begins with centriacinar abnormalities and the incidence of the lymphatic developmental pattern was low. Tuberculosis (the idiopathic pleuritis type) is considered to be caused this pattern from the primary infection focus. Therefore, the onset of unilateral effusion is extremely rare in patient with MAC disease, suggesting that the lymphatic developmental pattern occurs less frequently in patients with MAC disease. Furthermore, in this case, we speculated that centriacinar abnormalities were the MAC infection foci and could be detected by CT due to surgical invasion.

Aged↗

Urticarial vasculitis, immune complex disease, and an infected ventriculoatrial shunt.

Shunt nephritis syndrome consists of glomerulonephritis, mixed cryoglobulinemia, and persistent bacteremia. A 37-year-old woman with a prior history of a ventriculoatrial shunt presented complaining of urticaria. A skin biopsy specimen from one lesion showed findings consistent with vasculitis. Because microscopic hematuria was seen on urinalysis, systemic disease was suspected. The ensuing diagnostic workup revealed the syndrome of "shunt nephritis." To our knowledge, cutaneous findings of urticaria and vasculitis have not been previously reported in this interesting syndrome.

Adult↗

Hepatitis B as an immune complex disease.

Evidence has accumulated which indicates that several of the extrahepatic syndromes associated with HBV infection--the prodromal arthritis-dermatitis syndrome, systemic necrotizing vasculitis, and glomerulonephritis--result from immune complex-mediated injury; however, our understanding of their pathogenesis remains incomplete. Other disorders--essential mixed cryoglobulinemia and polymyalgia rheumatica--have also been linked to HBV, but these associations are more controversial. In most patients with HBV infection, circulating immune complexes are of no pathogenetic importance, but may reflect normal mechanisms for immune clearance of viral antigens. Little insight has been gained into the factors which predispose to immune complex-mediated tissue injury in only a small proportion of patients with type B hepatitis, and few options are available for the management of patients with these extrahepatic disorders. Finally, circulating immune complexes do not appear to contribute to the pathogenesis of liver disease associated with HBV infection.

Glomerulonephritis↗

Immune complex disease associated with an infected ventriculojugular shunt: a curable form of glomerulonephritis.

A 22-year-old man with a ventriculojugular shunt had edema, hematuria, proteinuria, hypocomplementemia, azotemia, and S epidermidis bacteremia. Initial percutaneous renal biopsy showed a diffuse proliferative glomerulonephritis. Subendothelial and intramembranous deposits were seen on electron microscopy. Immunofluorescent studies were positive for IgG and C3. A repeat percutaneous renal biopsy six weeks after cessation of antibiotic therapy revealed a mild proliferative glomerulonephritis with some evidence of resolution. No deposits were seen on electron microscopy and immunofluorescent studies were negative. At elective shunt revision three months after cessation of therapy, culture of the jugular portion of the removed shunt revealed S epidermidis. Early recognition of immune complex glomerulonephritis occurring with an infected ventriculovascular shunt should permit early treatment (antibiotic therapy and removal of the infected foreign body) and a favorable outcome.

Adult↗

Limited cleavage of human immunoglobulins by elastase of human neutrophil polymorphonuclear granulocytes. Possible modulator of immune complex disease.

Human polymorphonuclear lysosomal granules contain a neutral protease which is capable of digesting human immunoglobulins. The protease is located in the azurophil granules and enzymatically cleaves IgG, producing a Fab-like piece which is recoverable. The Fc-like fragment is not crystallized. The Fab-like fragment competes effectively for ligands formed by native antibody from which the fragments were produced.

Epitopes↗

A review of major histocompatibility complex-disease associations in man and dog.

The organization and biology of the Major Histocompatibility Complexes (MHC) of man (HLA) and dog (DLA) are reviewed, and a summary is presented of laboratory techniques used to define allotypes. The nomenclature of this field and the mechanisms of disease association with the MHC are discussed. Currently recognized HLA-disease associations are enumerated, with emphasis on the value of the complement C4 marker. DLA-disease association studies into autoimmune disease, allergy and neoplasia are reviewed.

Animals↗

Immune complex disease and gynecomastia.

A man with arthritis, gynecomastia and a rash histologically showing leukocytoclastic vasculitis, dermatitis herpetiformis and immunoglobulin G deposits at the dermoepidermal junction is reported. In contrast to cases of systemic lupus erythematosus (SLE) associated with vesiculobullous eruptions and similar histological features, our patient had neither bullae nor serological evidence of SLE. Conversely, no men already reported had evidence of feminization. Thus, our case appears to be unique.

Adult↗

Pityriasis lichenoides, an immune complex disease?

Nine biopsies from skin lesions of 5 patients with pityriasis lichenoides acuta and three biopsies from skin lesions of 3 patients with pityriasis lichenoides chronica were examined by means of the direct immunofluorescence technique. IgM deposits along the dermoepidermal junction were found in only two biopsies. In the majority of bioipsies, complement (C3) deposits were found along the dermo-epidermal junction and in the vessel walls. Immunoglobulin and C3 deposits were not found concomitantly in the vessel walls.

Complement C3↗

Preventing disseminated Mycobacterium avium complex disease in patients infected with human immunodeficiency virus.

Disseminated Mycobacterium avium complex (MAC) infection is an important late-stage complication of infection with the human immunodeficiency virus. Since MAC is widely dispersed in the environment, the source of infection for patients with disseminated MAC generally cannot be determined. Therefore, specific recommendations for avoiding exposure are not supported at this time. Routine screening of stools and sputum to detect MAC colonization as a means of targeting prophylaxis for disseminated disease is also not recommended at present. Two randomized, placebo-controlled trials have demonstrated that prophylactic use of rifabutin in persons with low CD4 lymphocyte counts results in a 50% decrease in MAC bacteremia as well as a reduction in some signs, symptoms, and laboratory abnormalities associated with MAC disease. Thus a prophylactic daily dose of rifabutin (300 mg) should be considered for adults who have had a previous AIDS-defining opportunistic illness and who have a CD4 lymphocyte count of < 75/microL. Many experts would consider prophylaxis appropriate only when the CD4 lymphocyte count is < 50/microL, particularly when there has not been a previous AIDS-defining opportunistic infection. Clinicians should be aware of drug interactions and potential adverse effects associated with the use of rifabutin. Preliminary reports of randomized, placebo-controlled trials suggest that chemoprophylaxis with clarithromycin is also effective in the prevention of disseminated MAC disease, and evaluation of other agents is under way. Prophylaxis for disseminated MAC infection in children has not been evaluated but is presumed to be as effective as that in adults. Decisions regarding initiation of MAC chemoprophylaxis should be individualized.

AIDS-Related Opportunistic Infections↗

Immune complex disease. VI. Some determinants of the varieties of glomerular lesions in the chronic bovine serum albumin-rabbit system.

Glomerular lesions were evaluated by light, electron, and immunofluorescence microscopy in rabbits given daily injections, for prolonged periods of time, of either 12.5 mg. of bovine serum albumin (BSA) (group I) or increasing doses of BSA, paralleling the immune response (group II). In animals clearing 12.5 mg. or more of BSA per day (excluding those dying of anaphylaxis or unknown causes), marked differences were noted in the incidence of membranous glomerulonephritis (GLN) (50 per cent in group I versus 15.4 per cent in group II), of crescentic GLN (none in group I versus 26.9 per cent in group II), and of mesangiopathic GLN (11.1 per cent in group I versus 30.8 per cent in group II). On the basis of these variations and immunofluorescence microscopy findinds, it is concluded that the occurrence of membranous GLN is favored by the presence in the circulation of small concentrations of soluble immune complexes, whereas crescentic GLN results from the presence of high concentrations of such complexes. When BSA injections were discontinued in group I animals having membranous GLN, the immune deposits were sequestered by membranous transformation so that they were not readily solubilized by injections of large amounts of BSA; one such animal developed crescentic GLN. The observation that BSA was difficult to detect in the lesions of mesangiopathic GLN suggests that this lesion results from the deposition of complexes formed at equivalence or in antibody excess.

Animals↗

Differentiation of autoimmune thrombocytopenia from thrombocytopenia associated with immune complex disease: systemic lupus erythematosus, hepatitis-cirrhosis, and HIV-1 infection by platelet and serum immunological measurements.

A method and approach are described to differentiate classic autoimmune thrombocytopenia (ATP) from immune complex-associated thrombocytopenia in systemic lupus (SLE), hepatitis/chronic liver disease (LIV-ITP) and HIV-1 related thrombocytopenia (HIV-1-ITP). The platelet immunologic profile of IgG, C3C4 and IgM was measured with a solid-phase ELISA, employing 125I-staphylococcal protein A to detect indicator antibody binding. Polyethylene glycol was employed to precipitate immune complexes (PEG-IC). Platelet-associated IgG (PAIgG) was 2.8-, 5.6- and 5.8-fold higher in SLE, LIV-ITP and HIV-1-ITP patients respectively compared to ATP patients: platelet C3C4 was 3.2-, 4.8- and 4.5-fold higher respectively; platelet IgM was 2.2-, 3.7- and 3.8-fold higher respectively; serum PEG-IC levels were 4.2-, 4.8- and 2.1-fold higher respectively. With all parameters measured, there was no overlap between the 75th percentile for ATP patients and the 25th percentile for all three cohorts. The likelihood of having a platelet C3C4 level higher than the highest ATP level was 69% for SLE, 90% for LIV-ITP and 94% for HIV-1-ITP respectively; with PEG-IC measurements the likelihood was 83%, 100% and 100% respectively. Serum IgG, C3, C4, IgM and PEG-IC were examined for a possible relationship with platelet measurements. Except for a positive correlation between serum and platelet IgM in ATP, r = 0.5, P < 0.04, there was no positive correlation with any of the parameters measured. An inverse correlation was noted between PEG-IC level and platelet C3C4 in SLE, r = 0.7, P < 0.04. Thus platelet immunologic profile and serum PEG-IC level measurements differentiated classic ATP from immune complex-associated thrombocytopenias (SLE, LIV-ITP, HIV-1-ITP). Except for IgM measurements in ATP, platelet measurements could not be attributed to their respective serum concentration.

Acquired Immunodeficiency Syndrome↗

[Therapeutic plasmapheresis in immune complex diseases].

We studied the dependence of the plasma protein and volume on the exfusion volume, type and composition of the substitution solution in 140 plasmapheresis procedures given to patients with immune thrombocytopenic purpura and bronchial asthma. The change of blood protein system corresponded to the procedure regime. The procedure does not entail adverse reactions if it removes up to 30% of the plasma circulating volume (replacement with salt solution), 50% of the plasma circulating volume (replacement with dextran solution) or 95% of that with replacement with albumin. We have tested 3 simple mathematic models for postplasmapheresis proteinemia and recommend the regression equation Ct = a0 + a1.Co as the most adequate model.

Algorithms↗

Is autoimmunity a common denominator in immune complex diseases?

In normal circumstances, antibodies reactive with native DNA appear in the plasma during the course of many clinical conditions associated with inflammation. These antibodies seem to be elaborated in response to the release of exceptional amounts of DNA by nucleated cells. As a result, DNA/anti-DNA complexes can be demonstrated in the cryoprecipitable fraction of plasma from patients with various inflammatory diseases. A significant proportion of these immune complexes contain low-molecular-weight polynucleotide antigens. These polynucleotides are derived from DNA which has been degraded by plasma DNAase. Because of the digestion of DNA in the plasma a spectrum of antigen/antibody complexes forms. While large, relatively insoluble complexes would be expected to be rapidly cleared by the reticuloendothelial system, low-molecular-weight complexes are removed more slowly. It is proposed that the action of plasma DNAase upon both free and immune bound-DNA can lead to a preponderance of small, soluble, polynucleotide/anti-DNA complexes. Under appropriate conditions of vascular permeability, these soluble complexes may be deposited in vessel walls. Hence, regardless of the initiating infectious or inflammatory agent, polynucleotide antigen/anti-DNA antibody complexes form and can result in immune-mediated inflammatory phenomena in diverse disease states.

Animals↗

Current and investigational therapies for AIDS-associated Mycobacterium avium complex disease.

The epidemiology, pathogenesis, clinical manifestations, and treatment of Mycobacterium avium complex (MAC) infection are reviewed. MAC infection is one of the most common infections in AIDS patients. Its pathogenesis is poorly understood, but it is believed to develop by gastrointestinal colonization followed by systemic invasion. The relatively poor response to treatment may be partly accounted for by the tremendous mycobacterial load present by the time patients develop systemic symptoms. Clinically, MAC infection is difficult to differentiate from the signs and symptoms of AIDS or from other opportunistic infections. Signs and symptoms include fever, malaise, anorexia, night sweats, and weight loss; diarrhea and abdominal pain may also be present. There is no established therapy for MAC infection, although combinations of three to five antimicrobial agents are typically used. There has been consistently poor correlation between in vitro results and in vivo outcomes in the treatment of MAC infection. Currently, the role of treatment is mainly to suppress the progression of infection and to relieve symptoms. Recent in vitro studies and animal studies have revealed possible alternative agents and combinations of agents (e.g., macrolide antibiotics, quinolones, amikacin, cytokines) that may influence therapy of MAC infection. No known therapy for MAC has been shown to prolong survival in AIDS patients, possibly because of the high organism load that exists once patients become symptomatic. Research is needed to find improved methods for earlier detection of MAC infection, determine optimal dosage regimens of current antimycobacterial agents, develop better antimycobacterial drug-delivery systems (e.g., liposomes), and discover new antimicrobials with better activity against MAC and methods of immune modulation that will overcome immune system defects.

Acquired Immunodeficiency Syndrome↗

Testing for Genetic Interactions in Complex Disease With Distance Correlation.

Understanding epistasis (genetic interaction) may shed some light on the genomic basis of common diseases, including disorders of maximum interest due to their high socioeconomic burden, like schizophrenia. Distance correlation is an association measure that characterizes general statistical independence between random variables, not only the linear one. Here, we propose distance correlation as a novel tool for the detection of epistasis from case-control data of single-nucleotide polymorphisms. On the methodological side, we highlight the derivation of the explicit asymptotic null distribution of the test statistic. We show that this is the only way to obtain enough computational speed for the method to be used in practice, in a scenario where the resampling techniques found in the literature are impractical. Our simulations show satisfactory calibration of significance, as well as comparable or better power than existing methodology. We conclude with the application of our technique to a schizophrenia genetics dataset, obtaining biologically sound&#xa0;insights.

Epistasis, Genetic↗

[The peripartal disease complex of the mother sow in the industrial swine facility. 3. Slaughter findings of old sows with anamnesis of peripartal diseases].

In an industrial pig production unit ten sows were selected at random. All the sows had a puerperal disease in their anamnesis. The sows were slaughtered after weaning and subjected to pathological examination. The mammary glands, uteri and bladder of ten slaughtered sows were examined for gross pathological alterations. All the sows showed symptoms of chronic mastitis (abscess, granuloma, fibrosis or cysts). Four of the examined uteri showed pathological alterations. Nine out of the ten bladders examined revealed pathological findings.

Abattoirs↗