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Aims: Human immunodeficiency virus (HIV)-related lymphadenopathy is characterized by a wide spectrum of histological changes. Three patterns have been described which correspond to clinical stages of HIV/acquired immune deficiency syndrome (AIDS). Castleman disease is a heterogeneous group of disorders. A recently described variant, multicentric Castleman disease (MCD), of which some cases are associated with human herpes virus-8 (HHV-8), has been reported in both HIV-seropositive and -negative patients. Considerable morphological overlap occurs between one of the patterns of HIV lymphadenopathy and this variant., Methods and Results: This retrospective histopathological study on 95 cases of HIV-reactive lymphadenopathy assessed the incidence of the different patterns and HHV-8 on immunohistochemistry (IHC). Of the 95 cases, 78 (82.1%) were HHV-8-negative, of which 46 (59.0%) were classified as pattern A, 20 (25.6%) as pattern B and 12 (15.4%) as pattern C. Nine (31.0%) of 29 cases with pattern B and 8 (40.0%) of 20 cases with pattern C were HHV-8 positive. In total 15 cases of MCD were diagnosed in this series., Conclusion: This study draws attention to the overlap between HIV lymphadenopathy and MCD. We recommend that cases of HHV-8-associated MCD should be investigated for HIV infection., (© 2012 Blackwell Publishing Ltd.)

Objective: To explore the clinicopathological correlation between CD4(+) T lymphocyte count and superficial lymphadenopathy HIV/AIDS patients., Methods: A total of 1066 HIV/AIDS patients were included in this study. The incidence of superficial lymphadenopathy, peripheral blood CD4(+) T lymphocyte counts and histological features of superficial lymphadenopathy were analyzed., Results: Among 1066 patients, 126 cases (11.8%) presented with superficial lymphadenopathy. Of the 126 cases, there were 69 cases with CD4(+) T lymphocyte counts < 100/µl and clinical diagnoses including tuberculosis (37 cases), reactive hyperplasia (8 cases), AIDS-related lymphadenopathy (18 cases), penicillium diseases (12 cases), fungal infection (5 cases) and non-tuberculous mycobacterial infection (1 case). Twenty-six cases had CD4(+) T lymphocyte counts between 100/µl to 200/µl and clinical diagnosis including tuberculosis (12 cases), reactive hyperplasia (8 cases), AIDS-related lymphadenopathy(6 cases), penicillium disease (2 cases) and non-Hodgkin lymphoma (1 case). Twenty-nine cases had CD4(+) T lymphocyte counts > 200/µl and clinical diagnoses including tuberculosis (11 cases), reactive hyperplasia (12 cases), AIDS-related lymphadenopathy (3 cases), Penicillium diseases (1 case) and non-Hodgkin lymphoma (4 cases). The CD4(+) T lymphocyte counts among patients with tuberculosis, AIDS-related lymphadenopathy and Penicillium diseases were significantly different (χ(2) = 8.861, P = 0.012). A significant correlation between the incidence of superficial lymphadenopathy and CD4(+) T lymphocyte counts was found (χ(2) = 375.41, P = 0.000)., Conclusions: The most common cause of superficial lymphadenopathy in HIV/AIDS patients is tuberculosis, followed by lymph node reactive hyperplasia, AIDS-related lymphadenopathy and Penicillium disease. Low CD4(+) T lymphocyte count correlates with an increased incidence of superficial lymphadenopathy and the risk of opportunity infection. Therefore, determination of peripheral blood CD4(+) T lymphocyte count should become an integral marker for the early diagnosis and treatment of superficial lymphadenopathy in HIV/AIDS patients.

Recently, we managed the case of a young HIV-positive man with a pyrexial illness and severe constitutional symptoms, the cause of which was elusive for several weeks. Here we review the causes of pyrexia of unknown origin in HIV-positive individuals, review appropriate investigations and discuss possible empirical treatment when this is required.

Pyrexia of unknown origin (PUO) is defined as a prolonged fever of more than 3 weeks duration and which resists a diagnosis after a week in hospital. Here we present a case admitted in our hospital with fever of prolonged duration, esophageal candidiasis, multiple systemic symptoms and infections. She was diagnosed as being infected by HIV and presenting with AIDS related complex with no clear details of the source of infection. There is no significant history of exposure, sexual transmission or blood transfusions. The only mode suggestive of acquiring HIV in this case was probably due to her repeated hospital admissions and repeated intravenous infusions. She also had history of dental procedures which may be a considerable factor.

An HIV positive black African woman presented with widespread lymphadenopathy and pancytopenia that had been ascribed to tuberculosis. Lymph node biopsy showed both Kaposi's sarcoma and multicentric Castleman's disease. Despite antiretroviral therapy and chemotherapy the patient deteriorated, developing confusion and dysphasia. A cranial magnetic resonance scan showed central pontine myelinolysis. Despite supportive therapy the patient died.

Background: Many lymph node abnormalities have been described in AIDS. These include opportunistic infections that sometimes result in spindle cell pseudotumours, Kaposi's sarcoma (KS), malignant lymphoma (Hodgkin's and non-Hodgkin's), and florid reactive hyperplasia. Among these, reactive hyperplasia is the most common manifestation of AIDS related lymphadenopathy., Aim: To examine whether human herpesvirus 8 (HHV-8), the aetiological agent of KS, can be localised in AIDS related lymphadenopathy and whether its appearance in such nodes is predictive of Kaposi's sarcoma development., Methods: A series of human immunodeficiency virus (HIV) positive men (n = 21) with AIDS related lymphadenopathy who at the time of presentation had KS or subsequently developed KS (n = 5) were examined. The prevalence of HHV-8 was assessed in these patients using solution phase polymerase chain reaction (PCR), real time TaqMan quantitative PCR, and in cell amplification techniques (PCR in situ hybridisation (PCR-ISH) and labelled primer driven in cell amplification)., Results: Using standard solution phase PCR in a nested format, only two of the 21 patients with AIDS related lymphadenopathy were positive for HHV-8. The lymph node of one of these patients contained KS lesions. Three HHV-8 positive patients were identified using TaqMan PCR (the original two positive patients and one additional patient). All of the positive patients either subsequently developed KS (n = 2) or had KS at the time of diagnosis (n = 1). Two additional patients subsequently developed KS, but were negative for HHV-8 by solution phase PCR and TaqMan PCR. Using PCR-ISH, HHV-8 amplicons were identified in some lymphoid cells (in one patient) and in spindle cells of the KS lesion in another. The positive lymphoid cells were predominantly concentrated in B cell areas of the affected lymph nodes, confirming the B cell tropism exhibited by HHV-8., Conclusions: The presence of HHV-8 in AIDS related lymphadenopathy is predictive of KS development and probably represents seeding of HHV-8 infected B cells from the peripheral blood. These findings support a role for HHV-8 in the pathobiology of KS.

During the period of 1980-1996 the dispensary observation of 50 HIV-infected patients was carried out. The clinical forms of the infection were distributed among these patients as follows: asymptomatic forms in 18 patients, persisting generalized lymphadenopathy in 8 patients, pre-AIDS in 14 patients, AIDS in 10 patients. Secondary infections were registered at the pre-AIDS stage. Dermatoses, oropharyngeal candidiasis occurred most frequently: in 52% of the HIV-infected patients. Herpes virus infection was registered in 46% of the patients. At the stage of AIDS during the generalized herpes virus and cytomegalovirus infections were registered in 5 and 7 patients respectively. Generalized forms of combined infections (herpes virus + fungi) prevailed, which caused the death of 7 patients at the terminal stage of AIDS.

Background: The natural history of a traumatic acute subdural hematoma is usually interrupted by its prompt surgical removal. Rapid spontaneous resolution within 48 hours, although infrequently reported, may be, underestimated and demonstrates a benign course of this condition. To our knowledge, this is the first case of rapid spontaneous resolution of an acute subdural hematoma in a patient with HIV encephalopathy and cerebral atrophy., Methods and Results: This 27-year-old man, an intravenous drug user with AIDS-related complex and HIV encephalopathy, suffered an acute subdural hematoma due to head injury in a car accident. The hematoma spontaneously resolved within 12 hours, resulting in a favorable outcome with nonoperative treatment., Conclusions: AIDS related cerebral atrophy may not only have predisposed the patient to the development of an extracerebral collection, but may have also favorably influenced the spontaneous resolution of the hematoma. The mechanism of the hematoma resolution and the influence of HIV related cerebral atrophy is discussed.

We used a time-dependent input rate function in the two-compartment model to simulate drug plasma concentrations after an oral administration. The input rate term has a Gaussian-like structure with two parameters, time to maximum absorption rate (tm) and measure of the duration of the absorption process (s). This structure corresponds to the scenario in which the absorption rate of the drug into the central compartment changes unimodally with respect to time after administration with a single peak at time tm. We demonstrate the applicability of this formulation in the simulation of plasma concentration of didanosine after oral administration in two Japanese hemophiliacs. We found that we were able to simulate the time courses of the didanosine plasma concentrations in both patients using the theoretical equation with the input term included, and that we were able to determine the six parameters in the equation by the least squares estimation. Pharmacokinetic values derived from the best-fit curve were almost comparable to those reported in other literature except that the Cmax and AUC0-infinity seemed to be slightly higher than those reported elsewhere. Although we are unable to verify the accuracy of this formulation because of the lack of sufficient Japanese data, we are able to demonstrate its efficacy and convenience in the application presented here.

Concurrent Sweet's syndrome and acute sarcoidosis (Löfgren's syndrome) has been reported in 4 cases. We describe a 40-year-old woman with biopsy confirmed lesions of Sweet's syndrome and erythema nodosum together with arthritis and hilar and mediastinal adenopathy. We review the association of Sweet's syndrome and malignancy or hematologic disorders, and the need to exclude malignancy when hilar adenopathy is found. Aggressive diagnostic procedures can be avoided with prompt recognition of Löfgren's syndrome.

The incidence of HD appears to have increased in HIV-infected individuals, with HIV-seropositive intravenous drug users most likely to develop the disorder. All groups at risk for HIV, however, may develop HD. The pathologic spectrum of HD in the setting of HIV infection is distinct from that seen in "de novo" HD in the United States, with the majority of patients diagnosed with the mixed cellularity subtype, as opposed to the more usual occurrence of nodular sclerosis in "de novo" disease. The presence of fibrohistiocytic stromal cells within involved tissues is also a distinct characteristic of HIV-associated HD. Epstein-Barr viral genome has been detected within tumor cell nuclei, and it may be involved in the pathogenesis of disease. Clinically, patients often present with systemic "B" symptoms and widely disseminated extranodal disease, seen in 75% to 90%. Bone marrow is involved in 40% to 50% of cases at diagnosis. Complete remission may be achieved in approximately 50% of patients after use of combination chemotherapy, but median survival is short, in the range of 12 to 18 months. Death is often due to bacterial or opportunistic infection (or both), often occurring in the setting of chemotherapy-induced neutropenia.

Anonymous antenatal and newborn screening demonstrates a positive HIV seroprevalence of one in 400 in areas of inner city London. European Collaborative Study data show a vertical transmission rate of 15% and suggests that 23% of infected children will develop clinical manifestations of AIDS before reaching 1 year of age [1], meaning that recognition of the radiological findings in vertically-acquired HIV is important. 75 serial cases of vertically-acquired HIV (age range 6 weeks to 12 years, mean age 35 months) presenting to a national referral centre over 48 months were reviewed; the radiographic findings we describe constitute a core of typical abnormalities together with a selection of the rarer manifestations of vertically-acquired HIV.

Aim: To determine the aetiology of isolated intrathoracic lymphadenopathy on chest radiographs of HIV-infected patients., Patients and Methods: Over a 40 month span in 1990-1993, 18 HIV-infected patients (13 men, 5 women) from our New York City adult HIV outpatient clinic development isolated intrathoracic lymphadenopathy (defined as intrathoracic nodal enlargement without other persistent abnormalities on chest radiographs). Serial chest radiographs (n = 18), CT scans when available (n = 7), and clinical charts (n = 18) were reviewed retrospectively., Results: Median patient age was 34 (range 25-49) years. The diagnoses associated with adenopathy were Mycobacterium tuberculosis (Mtb) in eight (44%), Mycobacterium avium intracellulare complex (MAC) in four (22%), and Mtb and MAC co-infection in three (17%). Cryptococcal infection, thymic hyperplasia, and spontaneous resolution without diagnosis or treatment occurred in one patient each. In 16 (89%) of the 18 patients, lymphadenopathy was present in more than one nodal station. Enlarged nodes were found in the following sites: paratracheal/tracheobronchial (n = 14), aortopulmonary window (n = 9), hilar (n = 7), anterior mediastinum (n = 3), subcarinal (n = 2), and left paraesophageal (n = 2)., Conclusion: Mycobacterial infection was the aetiology of isolated intrathoracic lymphadenopathy in 15 of 18 (83%) HIV-infected patients. When an inner city HIV-infected patient presents with isolated intrathoracic lymphadenopathy, we recommend an aggressive work-up for mycobacterial disease.

Background: Although neurological complications of human immunodeficiency virus (HIV) infection are common, the presence of cerebrovascular disease (CVD) has been seldom reported. The purpose of this report is to review available data on the association between stroke and acquired immunodeficiency syndrome (AIDS)., Summary of Review: A review of all literature published between mid-1976 and December 1994 was performed through a MEDLINE search with the following key words: AIDS, CVD, human T-cell lymphotropic virus type III, and HIV-1. Only reports of clinical stroke in patients with AIDS or HIV infection and autopsy series with stroke findings were selected. The type of study, population, number of stroke patients, subtype and etiology of stroke, and associated AIDS conditions were described. Six clinical series and 11 autopsy series were found, with a total of 1885 cases with AIDS, AIDS-related complex, and HIV carriers. Forty percent had a neurological complication, but only 1.3% had a stroke syndrome. Ischemic infarcts were more common than intracerebral hemorrhages. Cerebral infarcts were generally due to nonbacterial thrombotic endocarditis or concomitant opportunistic central nervous system infection, and intracerebral hemorrhages were usually associated with thrombocytopenia, primary central nervous system lymphoma, and metastatic Kaposi's sarcoma. Autopsy findings of CVD were generally not related with clinical stroke before death. Data are not available to determine the role of risk factors for AIDS in CVD., Conclusions: Because of limitations of the available data, it is still not clear whether there is an association between AIDS and stroke. Further studies are needed to better define the epidemiology of CVD in association with AIDS.

Rhodococcus equi causes a rare infection in immunocompromised hosts. We describe 24 cases of infection in patients with AIDS-related complex (ARC)/acquired immunodeficiency syndrome (AIDS). Pneumonia was always the first manifestation of R. equi infection, but extrapulmonary involvement was also observed. The main sources of bacteria were sputum, bronchial washings and blood. The strains isolated were mainly susceptible to erythromycin, vancomycin, teicoplanin, rifampicin, imipenem and aminoglycosides. Initial treatment should involve an intravenously administered antibiotic combination therapy including imipenem or vancomycin or teicoplanin, followed by orally administered maintenance combination therapy. Drug combinations should be investigated for serum bactericidal activity in vitro. Surgery does not increase survival time and should only be performed in cases that do not respond to antibiotic treatment. Presumptive risks of infection (contact with horses or farm dust, or cohabiting with people affected by R. equi infection) were present in more than 50% of patients. This finding, and the frequency of bacteria in the sputum, are not sufficient proof of transmission between humans, but do suggest the need for respiratory isolation of patients affected by R. equi pneumonia.

The relative importance of human immunodeficiency virus (HIV)-associated lymphadenopathy amongst patients presenting for lymph node biopsy in Central Africa is unknown. HIV-1 serology and histology of patients undergoing superficial lymph node biopsy during 1989-1990 in Lusaka, Zambia, were examined in a prospective cohort study of HIV serology and by retrospective review of laboratory records. Of 727 lymph nodes biopsied in Lusaka in 1989-1990, 380 (52 per cent) showed tuberculous lymphadenitis, 160 (22 per cent) histology suggestive of primary HIV lymphadenopathy and 66 (9 per cent) nodal Kaposi's disease. HIV serology was tested in 280 adults and was positive in 91 per cent (255 patients), including 89 per cent (153 of 171) of those with tuberculous lymphadenitis, 98 per cent (63 of 64) of those with histology suspicious of primary HIV lymphadenopathy and all (24 of 24) with nodal Kaposi's disease. Other HIV-associated lymphadenopathy included nodal lymphomas and lymphoepithelial cysts. HIV serology was tested in 22 children and was positive in eight, including four of 14 with tuberculous lymphadenitis. It is concluded that HIV-associated lymphadenopathy, especially tuberculous lymphadenitis, is very common amongst patients presenting for lymph node biopsy in Central Africa.

Background: Although pericardial effusion is known to be common among patients infected with HIV, the incidence of pericardial effusion and its relation to survival have never been described., Methods and Results: To evaluate the incidence of pericardial effusion and its relation to mortality in HIV-positive subjects, 601 echocardiograms were performed on 231 subjects recruited over a 5-year period (inception cohort: 59 subjects with asymptomatic HIV, 62 subjects with AIDS-related complex, and 74 subjects with AIDS; 21 HIV-negative healthy gay men; and 15 subjects with non-HIV end-stage medical illness). Echocardiograms were performed every 3 to 6 months (82% had follow-up studies). Sixteen subjects were diagnosed with effusions (prevalence of effusion for AIDS subjects entering the study was 5%). Thirteen subjects developed effusions during follow-up; 12 of these were subjects with AIDS (incidence, 11%/y). The majority of effusions (80%) were small and asymptomatic. The survival of AIDS subjects with effusions was significantly shorter (36% at 6 months) than survival for AIDS subjects without effusions (93% at 6 months). This shortened survival remained significant (relative risk, 2.2, P = .01) after adjustment for lead time bias and was independent of CD4 count and albumin level., Conclusions: There is a high incidence of pericardial effusion in patients with AIDS, and the presence of an effusion is associated with shortened survival. The development of an effusion in the setting of HIV infection suggests end-stage HIV disease (AIDS).

The purpose of this prospective randomized open trial was to investigate the impact of monitoring concentrations in serum on the efficacy and side effects of high-dose co-trimoxazole therapy. Forty consecutive patients with microscopically confirmed Pneumocystis carinii pneumonia were enrolled. Therapy was started with 5 and 25 mg of trimethoprim and sulfamethoxazole, respectively, per kg of body weight given every 6 h for 2 days and continued every 8 h either with (group A) or without (group B) monitoring and dose adjustments according to sulfamethoxazole levels in serum (target, 150 to 200 micrograms/ml) for a total of 21 days. Only 7 of 19 patients (83%). Patients who were treated for the full period and patients for whom co-trimoxazole was prematurely stopped had similar concentrations of sulfamethoxazole (157 +/- 52 versus 155 +/- 47 micrograms/ml) and trimethoprim (5.0 +/- 1.4 versus 5.6 +/- 1.0 microgram/ml). Concentrations of sulfamethoxazole and trimethoprim in group A (158 +/- 39 and 5.6 +/- 1.8 micrograms/ml, respectively) did not differ from those in group B (153 +/- 57 and 5.1 +/- 1.6 micrograms/ml, respectively), and the average daily maintenance doses for groups A (75.4 mg/kg plus 15.1 mg/kg) and B (76.4 mg/kg plus 15.3 mg/kg) were nearly identical. Although the average sulfamethoxazole concentrations were maintained within the target zone in the monitoring group (day 5, 160 +/- 44 micrograms/ml; day 10, 160 +/- 41 micrograms/ml; day 15, 168 +/- micrograms/ml; and day 21, 157 +/- 95 micrograms/ml), only 28% of the individual sulfamethoxazole levels were within the target range of 150 to 200 micrograms/ml after the dose adjustments (32% in group B without intervention). Response rates were similar in both groups. Complete response or improvement was observed in 18 of 19 (group A) and 19 of 21 (group B) patients. The method used for monitoring sulfamethoxazole levels with subsequent dose adjustment did not allow us to reliably achieve the target concentrations and did not significantly alter the incidence of side effects or the efficacy of the therapy.

Hyponatremia has been recognized as a complication in adults with acquired immunodeficiency syndrome (AIDS). We did a retrospective study evaluating the medical records of 86 children (age 4 months to 21 years) with human immunodeficiency virus (HIV-1) infection to determine the frequency and clinical associations of hyponatremia. Twenty-two children (26%) developed hyponatremia (serum sodium < 135 mEq/L; range 104 to 134 mEq/L; mean 130 mEq/L). Fourteen were male; 18 of the 22 patients were black and 4 were white. At the time of hyponatremia, the children frequently had comorbid associations, including 8 (35%) with AIDS encephalopathy; 3 (14%) with cardiomyopathy; 3 (14%) using diuretics; 1 (5%) using pentamidine; 3 (14%) with bacterial pneumonia; 2 (9%) requiring gastric lavage feedings; 2 (9%) with tuberculosis meningitis; 2 (9%) with gastroenteritis; 1 (5%) with infection caused by Mycobacterium avium-intracellulare; 1 (5%) each with brain tumor and tumor metastasis to brain. The cause of hyponatremia was attributed to syndrome of inappropriate antidiuretic hormone in 8 children; poor sodium intake and/or excessive diarrheal losses in 5; and the use of diuretics in 3 patients. Mild hyponatremia with no identifiable cause was found in 5 patients.

Background: It has previously been shown that HIV infected individuals with pneumonitis have identifiable abnormalities in alveolar macrophages obtained by bronchoalveolar lavage (BAL). In particular, alterations in the expression of alveolar macrophage surface antigens associated with macrophage function have been reported. To determine whether these changes reflect HIV infection or the respiratory episode itself, a population of HIV infected patients with no respiratory disease was studied., Methods: Twenty two HIV antibody positive individuals with a peripheral blood CD4 count of > 400/microliters and 10 healthy volunteer controls underwent bronchoscopy and BAL. Cytospin preparations from the recovered cells were stained using immunoperoxidase and double immunofluorescence techniques with monoclonal antibodies RFD1, RFD7, EBM11/CD68 (mature macrophages), UCHM1/CD14 (monocyte marker), and HLA-DR (RFDR1). Differential cell counts were also performed., Results: There was an increase in overall alveolar macrophage HLA-DR expression in the HIV population. This was not reflected in a change in the percentage of cells staining CD14 (monocytes) or CD68 (mature macrophages) positive. The relative proportions of cells staining RFD1 + RFD7- (inducer cells), RFD1 - RFD7+ (effector cells), and RFD1 + RFD7+ (suppressive cells) were unchanged between HIV and control groups., Conclusions: In a population of HIV infected individuals with normal CD4 counts and no respiratory disease there was an increase in overall alveolar macrophage HLA-DR expression which occurred independently of any alteration in the relative proportions of alveolar macrophage subpopulations.

In this study we describe a series of nine patients affected by acquired immunodeficiency syndrome (AIDS) or AIDS-related complex who had hypereosinophilia and hyperimmunoglobulinemia E (hyper-IgE) with chronic dermatitis and recurrent staphylococcal infections. These patients had features similar to those present in hyper-IgE syndrome, a primary immunodeficiency disease. In addition, immunologic characterization of these patients with human immunodeficiency virus (HIV) infection, compared with 51 HIV-positive patients without hyper-IgE, both atopic and nonatopic, and three patients affected by the primary hyper-IgE syndrome, also revealed an increase in IgA and a severe decrease in B and CD4+ lymphocytes. Spontaneous in vitro synthesis of IgE by peripheral blood mononuclear cells was confirmed in both hyper-IgE conditions, together with increased levels of circulating eosinophil cationic protein. Serum-soluble CD23, usually increased in atopic conditions and hyper-IgE, was similar to that of normal control subjects in the HIV-positive patients with hyper-IgE. On the basis of our findings, we conclude that a hyper-IgE-like syndrome represents a distinct aspect of the clinical manifestations associated with HIV infection and that the immunologic mechanisms in this condition seem to differ from those known in primary hyper-IgE syndrome, because CD4+ TH2 type cells, which are currently believed to have a role in IgE production, are severely depleted in HIV-positive patients.

Purpose: We measured the perimetric performance in patients with either acquired immunodeficiency syndrome (AIDS) or human immunodeficiency virus (HIV) disease but without AIDS., Methods: Light-difference sensitivity in the central field was measured in 74 eyes of 37 patients. The Humphrey Field Analyzer 640, program 30-2 was used. Additionally, 143 eyes of 143 normal control subjects were studied., Results: Mean deviation was significantly reduced in patients with HIV disease compared with control subjects (mean +/- S.E.M., -4.30 +/- 0.52 vs -0.77 +/- 0.15, respectively; P < .0001). Analysis of subgroups demonstrated that patients with lymphadenopathy syndrome or AIDS-related complex (N = 40 eyes; -3.52 +/- 0.41; P < .0001) as well as patients with AIDS (N = 34 eyes; -5.23 +/- 0.97; P < .0001) had a reduced mean deviation. Those comparisons remained significant (P < .0001) when data were analyzed independently for the right eyes and for the left eyes. Corrected pattern standard deviation (3.15 +/- 0.30 vs 1.39 +/- 0.09; P < .0001) was higher in patients with HIV disease compared with control subjects. Again, analysis of subgroups disclosed a significant increase in patients with lymphadenopathy syndrome or AIDS-related complex (2.55 +/- 0.36; P < .0001) as well as in patients with AIDS (3.85 +/- 0.51; P < .0001). Both comparisons remained significant when data were analyzed independently for the right and left eyes., Conclusions: This study demonstrates visual dysfunction despite normal visual acuity in patients with HIV disease. Our results are consistent with the hypothesis of damage at the neuroretinal level.

The Czech Republic is characterized here as both a low HIV prevalence area (1.64 registered positivity per 10(5) population and 45 AIDS patients notified in the 1986-93 period) and a low tuberculosis prevalence area (mortality rate 0.8, incidence of bacillary pulmonary cases 11.3 per 10(5) population and risk of infection 0.04 in 1990). From 1986 to 1993 a total of 10 cases of mycobacterial infections complicating AIDS or ARC disease were registered in the Czech Republic in 9 male patients aged from 29 to 55, 8 homosexuals, and one woman aged 48. Classical pulmonary tuberculosis caused by M. tuberculosis was diagnosed in one male patient and was controlled by antituberculosis chemotherapy. The remaining mycobacterial infections were caused by the following opportunistic mycobacterial pathogens. (a) M. avium in five individuals, four of them died of a disseminated disease; (b) M. kansasii--in two patients, one died of a disseminated infection; (c) M. xenopi--involved in a fatal generalized CMV, and cryptococcal and mycobacterial infection; (d) M. fortuitum caused a generalized disease in a case of exhaustive multifocal encephalopathy. Authors conclude that under conditions of low prevalence of both HIV and tuberculosis infection the risk to AIDS patients of contracting classical tuberculosis is low. A relatively frequent occurrence of non-tuberculosis mycobacterial disease in AIDS patients afflicted with the impaired immunity is explained by transmission of opportunistic mycobacteria from the environment.

Objectives: This study evaluated prospectively the frequency, clinical outcome and pathologic findings of acute global left ventricular dysfunction in human immunodeficiency virus (HIV) infection during the various stages of the disease., Background: Acute global left ventricular dysfunction in the course of HIV infection is still a poorly defined clinical entity, and little is known about the outcome after the acute onset., Methods: Between January 1988 and June 1992, 136 HIV-positive (HIV+) patients without clinical, electrocardiographic or echocardiographic evidence of cardiovascular dysfunction on admission were prospectively studied with serial echocardiograms. Patients were assigned to three groups: 1) anti-HIV+ asymptomatic (17 patients, 12.5%); 2) acquired immunodeficiency syndrome (AIDS)-related complex (26 patients, 19.1%); 3) AIDS (93 patients, 68.4%)., Results: During a mean follow-up period of 415 +/- 220 days, seven patients, all in the AIDS subgroup, developed clinical and echocardiographic findings of acute global left ventricular dysfunction; of these, six (85%) died of congestive heart failure. Mean survival time from symptom onset was 41 +/- 13 days. Necropsy findings in five patients revealed acute lymphocytic myocarditis in three, cryptococcal myocarditis in one and interstitial edema and fibrosis in one. In only one patient was left ventricular dysfunction reversible with treatment., Conclusions: Although infrequent, acute global left ventricular dysfunction is not rare in the course of HIV infection. It seems to occur exclusively during the AIDS stage. Acute global left ventricular dysfunction is often fatal but may be reversible and is mainly associated with the pathologic findings of acute myocarditis.

AIDS in children is a multisystem disease. The various infections, degenerative, proliferative and vascular lesions can be classified into three categories based on the known, presumed or undetermined pathogenesis. The primary lesions are due to HIV infection. The associated lesions are related to direct or indirect sequelae of HIV infection or its treatment. The third category is of lesions of undetermined pathogenesis. The pediatric pathologist plays an important role in the study and management of AIDS by demonstrating new pathologic lesions, by making the etiologic diagnosis of infection in children with AIDS, and by providing clinicopathologic correlation which leads to better understanding of the disease process and its natural history. Diagnosis of neoplastic disorders is also made by the pathologist. There is a dearth of systematic pathologic study of AIDS in children in developing countries. Although no basic differences between pathologic lesions in pediatric AIDS in Western countries, and in developing countries is expected, such a study would lead to better understanding and better management of the disorder as it affects children from the developing countries.

We developed and evaluated an automated screening test for antibody to human immunodeficiency virus type 1 (HIV-1) using EDTA-2Na-treated whole blood and an extract of paper disk-absorbed dried whole blood from 60 hemophiliacs infected with HIV-1 and 210 diseased and healthy controls. The specificity and the sensitivity of this system were judged to be 100% with both the whole blood and the extract. This test allows measurement of HIV-1 antibody in whole blood and dried whole blood on a small paper disk and gives a result within 13 minutes; the system can process 150 samples per hour. Therefore, it may be useful at many testing sites, such as emergency departments, intensive care units, blood banks, and commercial laboratories, as well as for mail-order testing from remote areas and developing countries.

Complex and bidirectional relationships operate between the hypothalamic-pituitary-adrenal (HPA) axis and the immune system (IS) and either in vivo or in vitro evidence supports a physiological role of the HPA axis-IS network. A part of the well-known pharmacological effects of glucocorticoid hormones (GC) as immunodepressive agents, the direct effects of many HPA axis hormones on IS functions are actually documented also in physiologic conditions. Conversely, numerous IS soluble mediators are reported to affect the HPA axis functions at various steps of HPA axis regulation, in both physiologic and pathologic conditions. Stress and aging may represent two paradigmatic conditions to show the relevance of the bidirectional network between HPA axis and IS, as in both HPA activation and IS impairment are frequently coexistent. Finally, in the context of the wide spectrum of HIV-related HPA axis abnormalities, a case of a Cushing's syndrome associated to an acquired immunodeficiency syndrome (AIDS-related complex) in a 24-year-old homosexual drug abuser is reported.

Objective: To assess the appropriateness of narcotic-prescribing practices in an ambulatory clinic for patients infected with HIV., Design, Setting, and Patients: The medical records of 220 (190 HIV-positive) patients, seen in a clinic primarily designed for the long-term follow-up of ambulatory HIV-infected patients and located in an inner-city, public teaching hospital, were retrospectively reviewed to determine the prevalence and appropriateness of prescribing Drug Enforcement Administration schedule 2 narcotics. Appropriateness was based on published guidelines for the use of narcotics in the treatment of cancer patients., Measurements and Main Results: The prevalence of narcotic use among the HIV-positive patients was 15%. Narcotics were prescribed for 38% of the patients who died, 33% of those with AIDS [Centers for Disease Control and Prevention (CDC) clinical class C], 4% of those with AIDS-related complex (ARC) (CDC clinical class B), and 5% of asymptomatic HIV-positive patients (CDC clinical class A). None of the HIV-negative patients seen in the clinic received narcotics. Narcotics were more likely to be prescribed for patients with AIDS than for patients with ARC (p < 0.001) or for HIV-positive patients (p < 0.001). For the three CDC clinical classes, there was no significant difference among the proportions of patients receiving narcotics inappropriately (p = 0.108). Among the risk groups, intravenous drug abusers were more likely to be prescribed narcotics inappropriately than were men who were homosexual (p < 0.001) or individuals who were heterosexual (p = 0.013); transfusion recipients were also more likely to be prescribed narcotics inappropriately than were homosexual men (p = 0.026) or heterosexual men or women (p = 0.032). Narcotics were more likely to be prescribed for patients with disseminated histoplasmosis (p = 0.022), Pneumocystis carinii pneumonia (p = 0.001), candidal esophagitis (p = 0.020), Kaposi's sarcoma (p < 0.001), or wasted appearance (p = 0.043). Inappropriate prescriptions were more likely to be given to patients with dementia (p = 0.005) or wasted appearance (p = 0.019)., Conclusions: Physicians tend to prescribe narcotics inappropriately to patients known to have previously abused drugs and to those who appear wasted or have dementia. Physicians have a duty to prescribe narcotics appropriately as guided by recognized medical indications and the patients' views concerning their current medical needs.

Phase I dose-escalating trials of didanosine revealed dose-limiting toxicities, including pancreatitis, and established a total daily dose of 12.5 mg/kg/day as the maximum tolerated dose. Clinical and pharmacokinetic data of 61 patients from two trials were analyzed to further evaluate the risk of pancreatitis: 1 (6.3%) of 16 patients who received < 500 mg/day didanosine, 2 (13.3%) of 15 who received 500-750 mg/day, and 15 (50%) of 30 who received > 750 mg/day developed pancreatitis (P < .001). A relationship between risk of pancreatitis and steady-state plasma concentrations of didanosine and age was also observed, suggesting that knowledge of didanosine pharmacokinetics provided additional information regarding risk of toxicity. Further confirmation of these findings will be necessary to determine if the risk factors for pancreatitis remain the same at lower doses currently used.

Incidence, type and clinical significance of cardiac involvement in advanced HIV infection was determined in 32 patients (30 men, two women; mean age 34.2 [21-52] years; mean CD4-cell number 52.2 [0-192]/microliters) over a period of 31 months. Any cardiac involvement was assessed diagnostically by one- and two-dimensional and Doppler echocardiography, complemented by other examinations and results of treatment. 14 patients (43.8%) had abnormal cardiac findings, presumably AIDS-associated. This included left ventricular pump dysfunction of various degrees of severity (n = 11), left ventricular dilatation (n = 2), pericardial effusion (n = 11), as well as cor pulmonale in primary pulmonary arterial hypertension (n = 2). In one patient the first manifestation of AIDS was tubercular pericarditis; in two patients there was a likely connection to disseminated pneumocystis infection and toxoplasmosis, respectively. In 11 patients no specific cause was found for the cardiac involvement. Nine of the 14 patients (64%) had symptoms due to the cardiac involvement. These findings indicate that the incidence and clinical significance of cardiac involvement must be taken into account in any treatment concept for AIDS.

Selective tropism of human immunodeficiency virus (HIV) for cells with CD4 receptors and especially for TH lymphocytes--key cells in hematopoiesis--has from the clinico-biologic point of view a great many hematologic manifestations of which knowledge is essential for a good diagnosis and treatment as well as for a judicious estimation of prognosis. Thus the study presents the hematologic entities specifically associated with HIV infection (such as ITP, NHML) as well as the hematologic entities associated with HIV infection without presenting a causal relationship with the latter. The study also discusses the quantitative and morphologic changes of peripheral blood and of bone marrow often enlightening for the disease and its complications. An important chapter in the study is devoted to the hematologic changes induced by the HIV infection therapy as well as by the manners of therapeutic approach to the complex hematologic problems raised by the disease.

Background: Although the cause of Kaposi's sarcoma (KS) is unknown, its unique epidemiology suggests that an infectious, sexually transmitted agent or agents may contribute to its pathogenesis., Methods: To assess the natural history of KS associated with the acquired immunodeficiency syndrome and to identify factors associated with its development, data were analyzed from a multicenter, observational cohort study of 1044 persons with the acquired immunodeficiency syndrome or the acquired immunodeficiency syndrome-related complex and a total CD4 cell count of less than 0.25 x 10(9)/L who were treated with zidovudine between April 1987 and April 1988. Records were reviewed bi-monthly. Follow-up continued for 2 years or until death., Results: One hundred thirty-one patients (13%) had KS a study enrollment, and 143 developed KS (14%) during follow-up, with a 2-year actuarial risk of 21%. The probability of KS at 2 years for patients with initial CD4 cell counts of less than 0.1 x 10(9)/L was 25%, compared with 15% for those with counts of 0.1 x 10(9)/L or more. By logistic regression, a baseline CD4 cell count of less than 0.1 x 10(9)/L (relative odds, 1.43; 95% confidence interval, 1.04 to 1.95), homosexuality (relative odds, 3.71; 95% confidence interval, 1.82 to 7.56), cytomegalovirus disease (relative odds, 1.56; 95% confidence interval, 1.01 to 2.41), and white race (relative odds, 1.64; 95% confidence interval, 1.11 to 2.43) were independently associated with KS. Median survival after KS was 408 days, and KS was an independent predictor of death (relative hazard, 1.78; 95% confidence interval, 1.26 to 2.52)., Conclusions: Kaposi's sarcoma contributes to human immunodeficiency virus-related morbidity and mortality, especially among male homosexuals. This large cohort study provides further evidence for an association between risk for cytomegalovirus infection and KS.

Several infectious, neoplastic or inflammatory skin diseases, may be early manifestations of HIV infection. We reviewed the clinical data of 226 HIV seropositive male patients with cutaneous disease, from a total of 337 inpatients at the Infectious Diseases Unit--Department of Medicine 1--Curry Cabral Hospital, from 1985 to 1991. Some considerations are made about the most common dermatological disorders: oral candidiasis, seborrheic dermatitis, Kaposi's sarcoma, herpes simplex infection, drug-related skin disorders, herpes zoster and dermatophytosis. The high prevalence of cutaneous manifestations in HIV infection, the uncommon clinical findings and their occasional therapeutic problems, makes an early diagnosis essential.

We examined lymph nodes from multiple sites in 50 individuals infected with human immunodeficiency virus (HIV-1) who died accidentally of drug overdoses and in whom there was no evidence of opportunistic infection. The size, histologic pattern, presence of Warthin-Finkeldey-type giant cells, and estimation of CD4 cell count of these lymph nodes were compared with those of 13 seronegative drug addicts (controls). Lymph nodes from seropositive individuals were slightly but significantly larger than those of controls. Lymph nodes from seropositive cases were much more likely to contain secondary follicles (90%) than were those from controls (20%). Unlike follicles in control nodes, most secondary follicles in the seropositive cases were in various stages of fragmentation and involution. As follicular changes progressed, there was a decrease in CD4 cells and an increase in intrafollicular and paracortical plasma cells. Plasmacytosis was much more prevalent in lymph nodes from seropositive individuals than in controls. Warthin-Finkeldey-type giant cells were present in at least one node in 29 of 50 seropositive cases, were most numerous in those showing follicular hyperplasia with fragmentation (45% of cases), and were especially numerous in Peyer's patches (61% of cases). There was generally good concordance of HIV-1-associated follicular morphology among diverse lymph node groups. There is prolonged generalized, mild hyperplastic lymphadenopathy with frequent syncytial cells in intravenous drug addicts with asymptomatic HIV-1 infection.

A 46-year-old man was admitted because of hypotension and consciousness disturbance. He was a patient with hemophilia B, and diagnosed as having an AIDS-related complex 2 years prior to admission. On admission he had severe hyponatremia. Hormonal studies revealed that he had Addison's disease. Serum cytomegalovirus (CMV) antibody titers were high, and a CMV antigen was detected in his urine, which suggested CMV adrenalitis caused by an active CMV infection. After the administration of hydrocortisone and ganciclovir, his general clinical condition and biochemical test results were back to normal. However, the adrenal dysfunction was irreversible, despite the treatment with ganciclovir. With an increase in the number of AIDS patients, we have to consider adrenal insufficiency due to a CMV infection in patients with AIDS.

Elevated plasma levels of vasoactive intestinal polypeptide (VIP) (as assessed by a radio-immunoassay), were found in 7/11 patients with AIDS or AIDS-related Complex (ARC), evaluated because of prolonged intractable diarrhea with either an infectious (6 cases) or a non-infectious (5 cases) etiology. Six subjects have been treated with the somatostatin analogue octreotide, which gave both a favourable clinical response and a significant reduction in plasma VIP concentrations. Evaluation of plasma VIP levels may provide a pathophysiological basis for explaining the efficacy of octreotide therapy in HIV-infected patients suffering from both infectious and non-infectious refractory diarrhea.

We reported recently that anti-Fab autoantibodies of the IgG isotype are associated with the decrease of helper/inducer (CD4+) lymphocytes in human immunodeficiency virus-infected (HIV+) hemophilia patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC). In the present study we investigated the subclass distribution of IgG-anti-Fab autoantibodies, and whether anti-Fab antibodies of the IgA and IgM isotypes also are associated with the development of AIDS. Sera of HIV+ patients with AIDS had significantly higher IgA-anti-Fab activity than HIV+ patients with ARC (p < 0.02), HIV+ patients without AIDS/ARC (p < 0.0001), HIV-negative (HIV-) patients (p < 0.001), or healthy controls (p < 0.0001). An inverse association was found between IgA-anti-Fab activity and CD4+ cell counts (r = -0.396, p < 10(-6)). In contrast, no association of CD4+ cell counts was observed with IgM-anti-Fab. However, IgM-anti-Fab was significantly increased in patients with thrombocytopenia. We found a significant association between IgA-anti-Fab activity and serum neopterin concentrations (r = 0.310, p < 10(-5)). IgG-anti-Fab activity was detected mainly in the IgG3 fraction, although in HIV+ patients with AIDS/ARC various IgG subclasses were present. Affinity-purified anti-Fab antibodies isolated from sera of AIDS patients bound to rgp120-preincubated CD4+ cells of a healthy individual, supporting our hypothesis that anti-Fab antibodies and free circulating gp120 molecules are involved in the elimination of uninfected CD4+ cells. Removal of anti-Fab autoantibodies from the circulation by immune adsorbance might be a useful approach in the treatment of AIDS.

HIV-infected patients commonly experience haematological disturbances including anemia, neutropenia or thrombocytopenia. Bone marrow failure may be caused by HIV itself, or by secondary involvement by opportunistic pathogens and malignancy. The need for multiple concomitant suppressive treatments may increase the risk of cytopenias. Strategy to reduce both anemia and neutropenia as well as to improve the haematological tolerance to myelotoxic agents have been developed by using haematological growth factors. So far, erythropoietin and granulocyte(macrophage) colony-stimulating factors have been successfully used in clinical trials including HIV-patients with either zidovudine-associated anemia or severe HIV or drug-induced neutropenia. However, according to the cost of these palliative approaches, there is a need for more reliable data showing that these growth factors could really have a major impact on the patient's compliance to therapy, reduction of hospitalization and infection rate and improvement of the overall survival.

Objective: The pathogenesis of neurologic and neuropsychologic dysfunction in HIV-1 infection is unclear. The purpose of the study was to determine an association between cerebral perfusion and HIV-1-related ocular microangiopathic syndrome., Methods: We studied 28 HIV-1-infected patients, seven of whom presented with asymptomatic HIV infection, nine with lymphadenopathy syndrome or AIDS-related complex, and 12 with AIDS. Cerebral perfusion was semi-quantitatively measured by single photon emission computed tomography of the brain using technetium-99 hexamethyl-propylenamine oxime (HMPAO-SPECT). The conjunctival manifestation of HIV-1-related microangiopathic syndrome was measured by a rating scale determining blood-flow sludging and, retinal cotton-wool spots were counted. CD4 count, neopterin, beta 2-microglobulin (beta 2M), haemoglobin, and age were determined as putative confounding variables., Results: Mean conjunctival sludge in patients with normal HMPAO-SPECT findings was 1.3 +/- 0.5 (mean +/- s.e.m.); no cotton-wool spots were present. In patients with slightly impaired HMPAO-SPECT, it was 2.1 +/- 0.6 and mean cotton-wool spot count was 1.1 +/- 0.4. In patients with severely impaired HMPAO-SPECT, mean conjunctival sludge was 4.5 +/- 0.3 and mean cotton-wool spot count was 4.9 +/- 1.1 HMPAO-SPECT findings were closely associated with conjunctival sludge (r = 0.72; P < 0.001) and number of cotton-wool spots (r = 0.78; P < 0.001), whereas only a slight association with staging of HIV disease was found (P = 0.052). Analysis of covariance controlling for CD4 count neopterin, beta 2M, age, and haemoglobin demonstrated a significant difference between the three HMPAO-SPECT groups for both the number of cotton-wool spots (P < 0.001) and the conjunctival sludge rating (P < 0.001)., Conclusion: There was a close association between severity of HIV-1-related ocular microangiopathic syndrome and severity of cerebral hypoperfusion. Microvascular alterations might contribute to the pathogenesis of neurological and neuropsychological symptoms in patients with HIV-1 disease. Furthermore, the conjunctival sludge rating and the number of cotton-wool spots might be appropriate indicators for severity of microvascular changes of the central nervous system [corrected].

We prospectively studied the utility of fine needle aspiration (FNA) to diagnose non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) in patients with human immunodeficiency virus (HIV) infection and lymphadenopathy. Twenty-one patients with a clinical evidence of lymphoma underwent 24 FNA and site-specific tissue biopsies. Twenty-two of the 24 biopsy results were consistent with a malignant lymphoproliferative neoplasm: NHL (19 cases), HD (two cases), and T-cell lymphoma (one case). Two biopsies showed reactive lymphoid hyperplasia consistent with a clinical diagnosis of persistent generalized lymphadenopathy. There was an 87% correlation (21 of 24) between FNA and biopsy diagnoses. Eighteen of the 19 biopsy-confirmed NHL cases were diagnosed with FNA. Both cases of HD and the one T-cell lymphoma were also diagnosed with aspirate material. In conclusion, the FNA in HIV-infected individuals with suspected malignant lymphadenopathy is highly sensitive (95%). The FNA, when used in conjunction with the clinical appearance, is a useful tool in the management of HIV infection and lymphadenopathy.

The Authors have carried out a study on the therapeutic effect of thymostimulin in HIV-positive subjects with lymphoadenopathy syndrome. Of the 140 selected patients, 70 were subjected to a treatment with thymostimulin (50 mg/die i.m. for 30 days + 50 mg/3 times a week i.m. in the second, third and fourth month + 50 mg/once a week i.m. in the fifth and sixth month) and of these patients, 60 completed the treatment and the estimated follow-up of twelve months. At the end of this period the following observations were made about the group treated: 1) improvement of the skin reaction to the Multitest (CMI) antigens in 66.7% of the cases, no changes in 30% of the cases and deterioration in 3.3% of the cases; 2) the total T-lymphocytes show an increase in the 6th month, remaining stable for the check-ups of the 9th and 12th months; 3) a significant increase of the CD4 lymphocytes in the 6th month with CD4/CD8 ratio close to the normal values, remaining the same even at the end of the follow-up; 4) during the study none of the treated patients developed opportunistic infections or HIV-related neoplasms. The results were also subjected by the Authors to statistical analyses between the two groups and therefore testify to a favourable effect of thymostimulin with an improvement in the laboratory indications taken into consideration and, above all, the quality of life.

To determine the prevalence, incidence, and effects on disease progression and survival of herpes zoster in patients with advanced human immunodeficiency virus (HIV) disease, data from a multicenter observational cohort study of 1044 patients with AIDS or AIDS-related complex (ARC) and CD4 cell count < or = 0.25 x 10(9)/L treated with zidovudine were analyzed. Of 163 patients (16%) with a history of herpes zoster at enrollment, 22 (13%) had a recurrence during the 2-year follow-up. For those without prior herpes zoster, the probability of its development was 6.3% at 1 and 8.8% at 2 years. Progression to AIDS was not associated with herpes zoster. By proportional hazards analysis, an initial occurrence of herpes zoster was associated with prolonged survival independent of baseline CD4 cell count and disease stage; however, recurrence tended to be associated with death. Thus, herpes zoster is relatively common in advanced HIV infection and its initial occurrence late in disease may indicate improved prognosis.

We report a case of a 33-year-old man, intravenous drugs abuser, HIV-positive, with peripheral lymphadenopathy, hepato-splenomegaly and fever, in which a ganglionic biopsy showed a histology with morphologic features of multicentric Castleman's-like disease, and minute foci of Kaposi's sarcoma ganglion, without cutaneous lesions. Given the interrelationships between this morphology of angiofollicular lymph node hyperplasia, the development of Kaposi's Sarcoma, and the aggressive clinical course seen in our patient and those in the literature, the use of lymph node biopsy may be an important prognostic tool for the patients with the acquired immunodeficiency syndrome.