In vitro effect of interleukin-12 on antigen-specific lymphocyte proliferative responses from persons infected with human immunodeficiency virus type 1

The relationship between CD4 lymphocyte count and the in vitro effect of interleukin (IL)-12 on lymphocyte proliferative responses to Candida, tetanus toxoid, and streptokinase antigens was studied in peripheral blood mononuclear cells (PBMC from 30 human immunodeficiency virus (HIV)-infected persons and 10 seronegative controls. IL-12 significantly increased proliferative responses to microbial recall antigens of PBMC from HIV-infected persons with >200 CD4 lymphocytes/mm3 but had little effect on PBMC from patients with more advanced disease. The greatest increase was seen in patients with 200-500 CD4 cells/mm3. Results of limiting dilution analysis suggested that the increase in antigen-specific lymphocyte proliferation in the presence of IL-12 was due to an increase in the number of responding cells rather than an increase in the extent of proliferation of a fixed number of responder cells.     

Varicella-zoster virus infection in children with underlying human immunodeficiency virus infection

This article describes a prospective longitudinal study of varicella-zoster virus (VZV) infections in human immunodeficiency virus (HIV)-infected children, designed to determine their natural history of VZV infection and possible effects of VZV on the progression of HIV infection. Varicella was usually not a serious acute problem, and it did not seem to precede clinical deterioration. The rate of zoster was high: 70% in children with low levels of CD4+ lymphocytes at the time of development of varicella. It is predicted that immunization with live attenuated varicella vaccine is unlikely to be deleterious to HIV-infected children. Moreover, if they are immunized when they still have relatively normal levels of CD4+ lymphocytes, they may have a lower rate of reactivation of VZV than if they were allowed to develop natural varicella when their CD4+ cell counts have fallen to low levels as a result of progressive HIV infection.     

Association of non-acquired immunodeficiency syndrome-defining cancers with human immunodeficiency virus infection

Kaposi's sarcoma and non-Hodgkin's lymphoma were among the earliest recognized manifestations of the acquired immunodeficiency syndrome (AIDS) epidemic. Excluding these two tumors, the overall risk of all other cancers in human immunodeficiency virus (HIV)-infected individuals is similar to that of the general population. However, varying levels of evidence link several additional neoplasms to HIV infection. The evidence is strongest for an association with Hodgkin's disease, with lower relative and absolute risks than for non-Hodgkin's lymphoma. Anogenital intraepithelial neoplasia also appears to be HIV associated, but increases of invasive disease are still uncertain for both cervical and anal cancers. Various studies have suggested associations with testicular seminoma, multiple myeloma, oral cancer, and melanoma, but the data are inconsistent. Leiomyosarcoma and benign leiomyomas have increased in incidence in HIV-infected children but are unusual in HIV-infected adults. Conjunctival carcinoma is seen in HIV-infected individuals in sub-Saharan Africa but it is uncommon in Western countries. Most other cancers do not seem to have increased incidences in HIV infection. The etiologic mechanisms of HIV-related cancer likely differ among these diverse cancers and do not globally increase cancer risk.     

Cerebellar degeneration associated with human immunodeficiency virus infection

Cerebellar disorders associated with HIV infection are typically the result of discrete cerebellar lesions resulting from opportunistic infections such as toxoplasmosis and progressive multifocal leukoencephalopathy or primary CNS lymphoma. Clinical symptoms and pathologic abnormalities related to the cerebellum may also be observed with HIV dementia. A primary cerebellar degeneration with HIV has not previously been reported. Ten patients were identified over an 8-year period at five medical centers. All patients had clinical, laboratory, and radiologic evaluations, and three had neuropathologic examinations. Patients presented with progressively unsteady gait, slurred speech, and limb clumsiness. Examination revealed gait ataxia, impaired limb coordination, dysarthria, and abnormal eye movements. Cognition, strength, and sensory function remained normal. CD4 lymphocyte counts varied between 10 and 437 cells/mm3. Neuroimaging studies showed prominent cerebellar atrophy. Neuropathology showed focal degeneration of the cerebellar granular cell layer and unusual focal axonal swellings in the brainstem and spinal cord. Cultures, histopathology, and immunochemical studies showed no conclusive evidence of infection. We report a syndrome of unexplained degeneration of the cerebellum occurring in association with HIV infection.     

Timing of lymphocyte activation in neonates infected with human immunodeficiency virus

PURPOSE: To report the results of vitreoretinal surgery for the management of complications associated with congenital retinoschisis in children. METHODS: We conducted a review of consecutive children with complications of congenital retinoschisis treated with advanced vitreoretinal techniques. Nine eyes of seven patients with congenital retinoschisis had vitreoretinal surgery for one of the following complications of congenital retinoschisis: hemorrhage within a large schisis cavity with a dense vitreous hemorrhage; rapid progression of schisis threatening the macula; obscuration of the macula by the overhanging inner wall of a schisis cavity; a combined schisistraction retinal detachment; or a combined schisis-rhegmatogenous retinal detachment. Vitreoretinal surgery consisted of vitrectomy, inner schisis wall retinectomy, fluid-gas exchange, endolaser treatment, and perfluoropropane gas injection. After vitreoretinal surgery, patients were followed up for a mean of 26 months (range, 9 to 67 months). Retinal reattachment, visual acuity, and visual fields were used as outcome measures. RESULTS: Eight of nine eyes had successful retinal reattachment. Six eyes postoperatively had improved visual acuity or visual field, or both. One eye had stabilization of visual acuity, and two eyes had a decrease in visual acuity. CONCLUSION: In children with complications of congenital retinoschisis, vitreoretinal surgery with excision of the inner wall of the peripheral schisis cavity may be effective in achieving retinal reattachment, thereby improving visual acuity or visual field size.     

Neopterin and human immunodeficiency virus infection

We report a 53-year-old female autopsy case of multiple sclerosis with bilateral continuous cystic lesions along the lateral ventricles and caudate-callosal angles (Wetterwinkel). The pathophysiological mechanisms underlying these peculiar huge cystic lesions can be explained by the appearance of necrotic tissue during the recurrent relapsing stages of the disease, and then, by the absorption and scavenging of activated microglias. Poor astrocytic gliosis, which might be an effect of frequent use of corticosteroids during the clinical course makes the cavities bigger.     

Primary pulmonary hypertension associated with human immunodeficiency virus infection

Several cardiorespiratory diseases can complicate human immunodeficiency virus infection. Primary pulmonary hypertension is a rare clinical disorder which carries a bad prognosis. More than 90 cases of HIV-associated primary pulmonary hypertension have been reported to date. Although its pathogenesis remains unknown, some evidence suggests a possible role for the virus itself in its development. Genetic susceptibility may also be implicated. The clinical and histopathologic features of this entity do not differ from those of classic primary pulmonary hypertension. The diagnosis requires a high degree of clinical suspicion and a careful evaluation to rule out causes of secondary pulmonary hypertension. In addition to supportive measures, anticoagulation and vasodilators have been used to treat this disorder, although sufficient data regarding long-term results with these therapies are lacking.     

Fever among outpatients with advanced human immunodeficiency virus infection

BACKGROUND: Fever is common among persons with human immunodeficiency virus (HIV) infection. However, the clinical implications of fever in this population have not been evaluated. We therefore undertook a prospective study of fever in persons with advanced HIV infection to determine the incidence and etiology of fever in this patient group. METHODS: Prospective natural history study of 176 patients with advanced HIV infection followed up at Memorial Sloan-Kettering Cancer Center, New York, NY, from April 1, 1990, through December 31, 1990. RESULTS: Fever occurred in 46% of patients. A diagnosis was made in 83% of episodes, with acquired immunodeficiency virus-defining illnesses accounting for half of the diagnosed cases. Patients whose conditions required more than 2 weeks to diagnose most often had lymphoma, Mycobacterium avium-intracellulare bacteremia, or Pneumocystis carinii pneumonia. Four patients had persistent unexplained fever without a clear source. Only one patient had fever that clearly responded to antiretroviral therapy. CONCLUSIONS: Fever is common among outpatients with advanced HIV infection. Human immunodeficiency virus itself is rarely the cause of fever in such patients; the cause of the fever should be thoroughly evaluated.     

Intestinal mucosal inflammation associated with human immunodeficiency virus infection

The role of the human immunodeficiency virus type-1 (HIV) in producing intestinal disease was studied prospectively in 74 HIV-infected individuals with (43) or without (31) the acquired immunodeficiency syndrome (AIDS). Thirty-one subjects had enteric infections; all but one had AIDS. Alteration in bowel habits was the most common symptom and occurred independently of enteric infections. Abnormal histopathology was present in 69% of cases, and the finding was associated with altered bowel habits. An HIV-associated protein, p24, was detected in 71% of biopsies by ELISA assay. Tissue p24 contents varied with disease stage and were highest in HIV-infected individuals without AIDS (Walter Reed classes 3 and 4). Tissue p24 detection was associated with both altered bowel habits and histologic mucosal abnormalities. Tissue contents of the cytokines, tumor necrosis factor-alpha and interleukin-1 beta, were higher in HIV-infected individuals than in controls and their elevations were independent of enteric infection. We conclude that HIV reactivation in the intestinal mucosa may be associated with an inflammatory bowel syndrome in the absence of other enteric pathogens.     

Otolaryngologic manifestations of human immunodeficiency virus infection

Patients infected with HIV have become a steadily increasing part of most medical practices. Because most patients with HIV-related problems have manifestations in the head and neck, it is important that these be understood and recognized. This article briefly reviews the various otolaryngologic manifestations of HIV infection, including otologic, nasal, and paranasal sinus; oral cavity, pharynx, and larynx; and the neck.     

Renal pathology of human immunodeficiency virus infection

Renal complications of HIV infection are clinically and morphologically diverse. These may affect the glomerular, tubulointerstitial, and vascular compartments. Tubulointerstitial injury predominates in most autopsy-based studies, whereas glomerular disease is most frequently identified in biopsy-based studies. The most common glomerular lesion is HIV-associated focal segmental glomerulosclerosis and related mesangiopathies (collectively termed HIV-associated nephropathy). Increasingly, a variety of immune complex-mediated glomerular diseases such as membranoproliferative glomerulonephritis, IgA nephropathy and lupus-like nephritis, as well as hemolytic uremic syndrome/thrombotic thrombocytopenic purpura have been reported. The spectrum of tubulointerstitial lesions includes acute tubular necrosis, interstitial nephritis, diffuse infiltrative lymphocytosis syndrome, renal infection, and neoplasms including lymphoma and Kaposi's sarcoma. The pathological features of these conditions are reviewed with emphasis on clinical-pathological correlations and pathogenesis.     

Musculoskeletal infections in patients with human immunodeficiency virus infection

Musculoskeletal infections constitute an unusual clinical manifestation in patients with human immunodeficiency virus (HIV) infection. Available information about patients' characteristics and their clinical course has been obtained mainly from case reports and small retrospective studies. Our retrospective study is the largest in the literature providing detailed information about the clinical and laboratory characteristics of HIV-infected patients with different musculoskeletal infections. We identified 30 patients with various infections of the musculoskeletal system during a 5-year period among a cohort of 3,000-4,000 HIV-infected patients, and we describe them along with all cases of musculoskeletal infections in patients with HIV reported in the literature since 1985. Septic arthritis was the most commonly reported infection of the musculoskeletal system. It usually affects young men with a median CD4 count of 241. The exact contribution of a previous history of intravenous drug abuse in the pathogenesis of septic arthritis is unclear from the present and previous studies. Staphylococcus aureus was the most commonly isolated agent (31.3%). Numerous atypical pathogens were also identified as causes of septic arthritis. Approximately 90% of patients recovered with appropriate antibiotic treatment. Osteomyelitis was a more serious infection which also affected young individuals but with lower CD4 counts (median, 41). Half the cases were due to atypical mycobacteria. The mortality rate in the previously reported cases and in our series was high (20%). Pyomyositis is an increasingly recognized infection of the striated muscles in HIV-infected patients. It affects almost exclusively males with advanced HIV infection (median CD4 count, 24). Most cases are due to Staphylococcus aureus (67%). Drainage of the involved muscle(s) accompanied by proper antibiotic treatment resulted in resolution of the infection in the majority of patients (90%). Although the incidence of musculoskeletal infections in patients with HIV from this and previous studies appears to be low (0.3%-3.5%), these infections add a significant morbidity and mortality in the affected individuals. Better understanding of their pathogenesis and clinical course would aid the proper diagnosis and management of these infections.     

Virological aspects of human immunodeficiency virus infection

At the cellular level, the respiratory tract has a variety of defense mechanisms to prevent bacterial infection. Recent data have demonstrated that the respiratory epithelium plays a very active role in host defense. In this review we start by examining the respiratory epithelia and its function in mucociliary clearance, and extend our review to include its role in the secretion and regulation of inflammatory cytokines and production of antimicrobial factors. Furthermore, we examine how recent advances in understanding cystic fibrosis have provided useful insights into the pathogenesis of lower respiratory tract infection. In addition, we examine how two common respiratory pathogens, Streptococcus pneumoniae and Pseudomonas aeruginosa, subvert the defense mechanisms at the cellular level. Finally, we attempt to identify new or potential therapeutic approaches that have arisen from some of the insights into the pathogenesis of lower respiratory tract infections.     

Incidence of enteropathogens in patients with human immunodeficiency virus infection

BACKGROUND: To establish the incidence of diarrhea and its evolution over time, the causal microorganisms, recurrence and associated mortality in patients with AIDS or severe immunologic alterations (CD4 lymphocytes lower than 0.5 x 10(9)/l). METHODS: A prospective longitudinal study was carried out from 1984 to 1992. The following patients were included in the study: 1) all those patients with diarrhea in whom a pathogenic microorganism was identified in the stools, and 2) patients with fever and positive blood cultures for enteropathogenic bacteria. The patients belonged to a series of 1,456 patients with infection by HIV. RESULTS: Of the 1,456 controlled patients, 253 (17%) had infection by enteropathogenic microorganisms. The incidence was greater in homosexual patients (26%) than in drug addicts (12%). The most frequent germs were Cryptosporidium, in 104 episodes and Salmonella sp. in 78 episodes (31 as isolated bacteria). The mortality in the 15 days following isolation was 2%, the referred microorganisms being the most frequent responsible for the deaths. The mean of CD4 lymphocytes in the patients with enteropathogens was 0.17 x 10(9)/l). SD 0.14 x 10(9)/l). In patients with infection by Cryptosporidium the CD4 lymphocyte count was lower than that observed in the cases of infection by Isospora belli. Prior to 1988, 21% of the patients had infection by enteropathogenic bacteria and 23% by parasites, those percentages being 3% and 6%, respectively in 1991. CONCLUSIONS: Infections by enteropathogenic microorganisms in patients with infection by the human immunodeficiency virus in an advanced stage are frequent, particularly, in homosexuals. The patients with enteritis by Cryptosporidium have a greater grade of immunosuppression (CD4 lymphocytes lower than 0.1 x 10(9)/l) than patients with infection by other enteropathogenic microorganisms. In the last few years, the incidence of enteropathogenic bacteria, especially Salmonella sp. and protozoa has decreased [corrected].