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Query: UMLS:C0019693 (HIV)
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Clinically apparent involvement of the central nervous system is a rare event in cases of disseminated histoplasmosis, even in HIV-infected persons. Despite therapy with amphotericin B, mortality remains very high. Reported here is the case of an HIV-infected patient with a 3-month history of fever, cough, weight loss and miliary lung infiltrates. Four weeks after initiation of tuberculostatic therapy, high-grade fever, neurological symptoms, personality changes and respiratory deterioration occurred. Magnetic resonance imaging of the brain showed multiple mass lesions, and a chest radiograph revealed worsening of pulmonary infiltrates. Methenamine silver staining of a lung biopsy specimen demonstrated Histoplasma capsulatum. Subsequently, this pathogen was cultured from lavage fluid. Following high-dose intravenous fluconazole therapy (800 mg once daily), the patient's condition improved markedly within 10 days, followed by an almost complete resolution of pulmonary and cerebral mass lesions. This is believed to be the first documented case of rapid improvement of disseminated histoplasmosis with central nervous system involvement in an HIV-infected patient upon induction of therapy with fluconazole.
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PMID:A case of HIV-associated cerebral histoplasmosis successfully treated with fluconazole. 1053 89

HIV protease inhibitors (PIs) are effective drugs for the treatment of AIDS. However, PI therapy is sometimes associated with side-effects including increased plasma lipids and altered body fat distribution, although fat redistribution may occur in some patients not treated with PIs. Overdosage with vitamin A(1) acid (all-trans-retinoic acid, ATRA) or its metabolites may cause similar changes in lipid metabolism. Moreover, the PI indinavir and retinoids have been associated with nail, skin, and hair defects, suggesting that indinavir and retinoids may exert their effects through similar molecular mechanisms. This hypothesis was tested by examining the effects of PIs on retinoid signaling in vitro. Mesenchymal stem cells (C3H10T1/2) were cultured in the presence of various PIs (amprenavir, indinavir, nelfinavir, ritonavir, and saquinavir) and synthetic retinoids, and the metabolic response was assessed by measuring the activity of a retinoid-regulated protein, alkaline phosphatase (ALP). Of the PIs tested, only indinavir stimulated ATRA-dependent ALP activity and altered stem cell morphology; the effects of indinavir occurred in the presence of ATRA, but not in its absence. Moreover, indinavir increased the effects of ATRA on lipid accumulation during fat cell differentiation. AGN 193109 (4-[[5,6-dihydro-5, 5-dimethyl-8-(4-methylphenyl)-2-naphthalenyl]ethynyl]-benzoic acid), a retinoic acid receptor (RAR) antagonist, inhibited the synergistic effects of indinavir and ATRA, indicating that indinavir increases RAR signaling. However, indinavir did not potentiate ALP activity in the presence of the RAR agonist CH55 (3,5-di-tert-butylchalcone 4'-carboxylic acid). Unlike ATRA, CH55 does not bind to cytosolic retinoic acid binding protein (CRABP), suggesting that CRABP may regulate the effects of indinavir on RAR signaling. These observations support the proposal that altered retinoid signaling promotes some of the adverse reactions associated with indinavir therapy, such as altered lipid metabolism.
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PMID:Stimulation of vitamin A(1) acid signaling by the HIV protease inhibitor indinavir. 1070 35

Bacillary angiomatosis (BA) is an infectious disease characterized by proliferative vascular lesions; it mainly affects HIV-positive patients. Multiple cutaneous nodular lesions together with fever, chills, malaise, anorexia, vomiting and headache are the most important clinical manifestations. It may also involve the heart, liver, spleen, bones, lung, muscles, lymph nodes, central nervous system and other organs. Erythromycin, 500 mg four times a day, is the drug of choice. The importance of this lesion lies in its clinical and histological similarity with other diseases. Cutaneous and oral lesions of BA clinically resemble Kaposi's sarcoma (KS). Histopathologically, BA may be confused with angiosarcoma, pyogenic granuloma and epithelioid hemangioma. We report two HIV-positive men with BA lesions in the oral mucosa. Diagnosis was confirmed by biopsy and Warthin-Starry silver staining.
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PMID:Bacillary angiomatosis affecting the oral cavity. Report of two cases and review. 1071 5

We describe a 2 year-old non-immunocompromised girl with disseminated histoplasmosis who presented with a 2-month history of fever and bloody diarrhoea. On presentation, she was severely wasted and anaemic. There were gross hepatosplenomegaly and multiple lymphadenopathy. A septic screen was negative. A subsequent stool culture isolated Salmonella enteriditis. Serial Widal-Weil Felix (WWF) titres showed serological response after 2 weeks of Ceftriaxone. However, she continued to have spiking fever, bloody diarrhoea and weight loss. She developed pancytopaenia and disseminated intravascular coagulation. A bone marrow aspirate and trephine, and lymph node biopsy showed the presence of Histoplasma capsulatum, confirmed by Gomori-Methenamine Silver staining. She responded to intravenous amphotericin B followed by fluconazole (intravenous then oral) for 6 months after discharge. Human Immunodeficiency Virus screening tests were negative. Complement and immunoglobulin levels were normal. T and B enumeration tests showed gross leucopaenia with very low T cell function with defective phagocytic function. A repeat T and B cell enumeration test and phagocytic function tests done 3 months later were normal.
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PMID:Disseminated histoplasmosis in a non-immunocompromised child. 1097 16

Rhodococcus equi is an aerobic Gram-positive and acid-fast coccobacillus that may cause cavitary pneumonia in immunocompromised hosts such as HIV-infected patients. Numerous Grocott's methenamine silver (GMS)-positive organisms were initially noted on the direct smear; a minor number of acid-fast organisms were seen in the Thin-Prep slide. Since the abundant mucous material with the attached organisms seen in conventional smears may be lost in liquid-based preparations, more sensitive stains such as Fite, as well as a more diligent search for organisms, is needed. This case illustrates the importance of careful selection and evaluation of special stains in sputum specimens.
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PMID:Fite stain positivity in Rhodococcus equi: yet another acid-fast organism in respiratory cytology--a case report. 1128 19

Two species of the gram-negative bacilli Bartonella, B. henselae and B. quintana, cause disease in HIV-infected patients. If untreated, infection can be fatal. Manifestations include bacillary angiomatosis (BA), bacillary peliosis hepatis (BP), bacteremia, or a combination of these. BA and BP present as lesions, but bacteremia may be subacute and persist for months without diagnosis. Additionally, patients may acquire cat scratch disease (CSD), but this is more common in immunocompetent patients. BA lesions are usually vascular, friable, and bleed profusely when traumatized. They may be confused with Kaposi's sarcoma (KS), pyogenic granuloma, lymphoma and various subcutaneous tumors and infections. Lesions may affect almost any organ, and appear as angiomatous papules, dry scaling lesions, subcutaneous nodules, cellulitic plaques or deep, highly vascularized, soft tissue masses. Patients may have osseus BA lesions (frequently affecting the long bones); hepatic and/or splenic lesions; bacteremia; or endocarditis. To diagnose infection, lesions should be biopsied and examined. Hematoxylin and eosin staining reveal histopathologic changes; darkly staining organisms are evident after Warthin-Starry silver staining; and electron microscopy allows visualization of the bacillus. An indirect immunofluorescence antibody test (IFA) detects bartonella-specific IgG antibodies. Treatment with erythromycin for at least three months is recommended, or with doxycycline if erythromycin is not well-tolerated. Severely ill patients should receive IV doxycycline with either gentamicin or rifampin for at least four months. To prevent infection, HIV-infected people should avoid traumatic cat contact and exposure to the body louse.
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PMID:Bartonella-associated infections in HIV-infected patients. 1136 39

Various cutaneous and mucocutaneous manifestations that are associated with HIV infection and AIDS from the superficial Candida albicans to systemic infections such as that caused by Histoplasma capsulatum are discussed. Specific topics cover superficial fungal infections such as blastomycosis, coccidioidomycosis, cryptoccosis, histoplasmosis, paracoccidioidomycosis, and sporotrichosis; and manifestations from systemic fungal infections caused by Cryptococcus neoformans and Penicillium marneffei. Diagnostic advice involving these conditions is offered. In the area of diagnosis, it is advised that when considering the possibility that a mucocutaneous lesion in an HIV-infected patient is secondary to dissemination of a systemic fungal infection, a tissue biopsy of that lesion should be performed for histologic evaluational and microbiologic cultures. Light microscopic examination after routine staining with hematoxylin-eosin and/or special staining for fungi with either periodic acid-Schiff or Gomori methenamine silver is also recommended in diagnosing a systemic fungal infection. Diagnostic molecular microbiology is making progress in expediting diagnosis of some of these infections, but it is not yet routinely available.
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PMID:Cutaneous fungal infections in HIV/AIDS. 1137 75

A 33-year-old Hispanic woman with newly diagnosed human immunodeficiency virus (HIV) infection, a CD4 T-lymphocyte count of 2, viral load of 730,000 copies/mL, candidal esophagitis, seizure disorder, a history of bacterial pneumonia, and recent weight loss was admitted with tonic clonic seizure. On admission, her vital signs were: pulse of 88, respiration rate of 18, temperature of 37.7 degrees C, and blood pressure of 126/76. Her only medication was phenytoin. On examination, the patient was found to have multiple umbilicated papules on her face, as well as painful, erythematous, large, punched-out ulcers on the nose, face, trunk, and extremities of 3 months' duration (Fig. 1). The borders of the ulcers were irregular, raised, boggy, and undermined, while the base contained hemorrhagic exudate partially covered with necrotic eschar. The largest ulcer on the left mandible was 4 cm in diameter. The oral cavity was clear. Because of her subtherapeutic phenytoin level, the medication dose was adjusted, and she was empirically treated with Unasyn for presumptive bacterial infection. Chest radiograph and head computed tomography (CT) scan were within normal limits. Sputum for acid-fast bacilli (AFB) smear was negative. Serologic studies, including Histoplasma antibodies, toxoplasmosis immunoglobulin M (IgM), rapid plasma reagin (RPR), hepatitis C virus (HCV), and hepatitis B virus (HBV) antibodies were all negative. Examination of the cerebrospinal fluid was within normal limits without the presence of cryptococcal antigen. Blood and cerebrospinal cultures for bacteria, mycobacteria, and fungi were all negative. Viral culture from one of the lesions was also negative. The analysis of her complete blood count showed: white blood count, 2300/microl; hemoglobin, 8.5 g/dL; hematocrit, 25.7%; and platelets, 114,000/microl. Two days after admission, the dermatology service was asked to evaluate the patient. Although the umbilicated papules on the patient's face resembled lesions of molluscum contagiosum, other infectious processes considered in the differential diagnosis included histoplasmosis, cryptococcosis, and Penicillium marnefei. In addition, the morphology of the ulcers, particularly that on the left mandible, resembled lesions of pyoderma gangrenosum. A skin biopsy was performed on an ulcer on the chest. Histopathologic examination revealed granulomatous dermatitis with multiple budding yeast forms, predominantly within histiocytes, with few organisms residing extracellularly. Methenamine silver stain confirmed the presence of 2-4 microm fungal spores suggestive of Histoplasma capsulatum (Fig. 2). Because of the patient's deteriorating condition, intravenous amphotericin B was initiated after tissue culture was obtained. Within the first week of treatment, the skin lesions started to resolve. Histoplasma capsulatum was later isolated by culture, confirming the diagnosis. The patient was continued on amphotericin B for a total of 10 weeks, and was started on lamivudine, stavudine, and nelfinavir for her HIV infection during hospitalization. After amphotericin B therapy, the patient was placed on life-long suppressive therapy with itraconazole. Follow-up at 9 months after the initial presentation revealed no evidence of relapse of histoplasmosis.
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PMID:Disseminated histoplasmosis presenting as pyoderma gangrenosum-like lesions in a patient with acquired immunodeficiency syndrome. 1170 24

The failure of some candidate HIV-1 vaccines may result from inducing very weak neutralization activity against representative primary viral isolates. Based on our hypothesis that epitope-vaccine may be a new strategy to induce high levels of neutralizing antibodies against HIV-1, we designed two candidate multi-epitope-vaccines, EP1 [C-G-(ELDKWA-GPGRAFY)2-K] and EP2 (CG-GPGRAFY-G-ELDKWA-G-RILAVERYLKD), containing three neutralizing epitopes (GPGRAFY, ELDKWA and RILAVERYLKD) on HIV-1 envelope protein, and expected them to induce epitope-specific antibodies of predefined epitope-specificity. The two peptides were conjugated to carrier protein bovine serum albumin (BSA) and used for immunization of rabbits. Proteins were purified from the rabbit sera induced by both candidate multi-epitope-vaccines (EP1-BSA and EP2-BSA) through affinity chromatography with epitope-peptide-conjugated sepharose-column, and identified as antibodies in silver-staining and immunoblotting. These antibodies were demonstrated to recognize three neutralizing epitopes on peptides and the recombinant gp41 in ELISA-assay and immunoblotting. These results indicated that both candidate multi-epitope-vaccines could induce high levels of antibodies of predefined epitope-specificity which recognized a few of neutralizing epitopes on peptides and protein, providing experimental evidence for the new strategy to develop an effective neutralizing-antibody-based multi-epitope-vaccine against HIV-1.
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PMID:Immunogenicity and specificity of the candidate multi-epitope-vaccines against HIV-1. 1179 8

The minus DNA strand of HIV-1 presents an open reading frame that is complementary to the HIV-1 envelope messenger, is highly conserved among HIV-1 isolates, and may encode a hydrophobic protein. In previous studies, the antisense transcript has been identified both in various HIV-infected cell lines and in leukocytes of HIV-1(+) patients. The expression of the corresponding antisense protein (ASP) during natural HIV-1 infection has been indirectly evidenced by the identification of anti-ASP antibodies in the sera of HIV(+) patients. We have used immunoelectron microscopy procedures (ultra-small gold particles coupled to silver enhancement) to establish direct evidence of ASP production. ASP has then been detected in chronically and acutely HIV-1-infected cell lines. The protein, found mostly associated with various cellular membranes as well as with the virions released from the cells, indicated that ASP is a bona fide component for the virions and may participate in the particle formation.
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PMID:Immunolocalization studies of an antisense protein in HIV-1-infected cells and viral particles. 1187 21


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