Brain choline-containing compounds are elevated in HIV-positive patients before the onset of AIDS dementia complex: A proton magnetic resonance spectroscopic study

The CNS is frequently involved in human immunodeficiency virus (HIV) infection. In recent studies using proton magnetic resonance spectroscopy, investigators found a significant reduction in N-acetyl aspartate, a metabolic marker of neurons, in late stages of dementia. To further understand the relationship between proton magnetic resonance spectroscopy changes and clinical disease and dementia, we compared 20 HIV-infected patients presenting at varying stages of acquired immunodeficiency syndrome (AIDS) dementia complex and infection to 10 age-matched controls. We found a significant reduction in N-acetyl aspartate/creatine only in patients who had advanced dementia and CD4 counts less that 200/microliter. By contrast, a significant elevation in compounds containing choline was present in patients in the early stages of HIV infection of who had CD4 counts greater than 200/microliter, in patients with normal MRI scans, and in all AIDS dementia complex groups, including subjects with no or minimal cognitive impairment. An elevated choline level also occurred in later stages of HIV infection (CD4 < 200/microliter). Our results suggest that an increase in choline occurs before N-acetyl aspartate decrements, MRI abnormalities, and the onset of dementia, and may therefore provide a useful marker for early detection of brain injury associated with HIV infection.     

Neurogenic bladder in patients with acquired immunodeficiency syndrome

We have performed a urodynamic study on 3 patients with acquired immunodeficiency syndrome (AIDS), presenting with a neurogenic bladder. The first patient had an ascending myelitis of probable herpetic origin, the second patient had a cerebral abscess caused by Toxoplasma gondii, and the third patient had an AIDS dementia complex. The urodynamic study showed an areflexic detrusor in the first 2 patients, and a hyperreflexic detrusor in the third patient.     

Acquired immunodeficiency syndrome dementia complex

Acquired immunodeficiency syndrome (AIDS) has become an epidemic in the United States. AIDS dementia complex (ADC) is a neurological dysfunction which has been indicated in 25-90% of AIDS patients, 30-40% of HIV-infected patients, and may be the only presenting manifestation of AIDS. Researchers have investigated many aspects of ADC including clinical features, etiology, epidemiology and prevalence, diagnosis (psychological parameters and laboratory investigations such as CSF, EEG, CT, MRI, PET, and ERP), assessment, neurological features (including neuropsychiatric and neuropsychological measures, and neuropathology), prognosis, and treatment. The research is controversial, complex, and contradictory. A discussion of the many areas of ADC and many hypotheses will be included.     

Effects of extracellular ATP on hair cells isolated from the guinea-pig semicircular canals

Using stereological methods, two cerebral cortical areas from AIDS brains were investigated. Neuronal density, profile area of neurons, and perikaryon volume fraction were measured and compared to age-matched control brains. In the fronto-orbital cortex (area 11) of AIDS brains, a significant loss of neurons was seen. The perikaryon volume fraction was likewise decreased. The size of neurons did not differ between control and AIDS brains. In patients with clinical signs of progressive dementia and in brains with human immunodeficiency virus (HIV)-specific neuropathology (HIV-leukoencephalopathy and/or HIV-encephalitis) as compared to patients lacking these features, a small decrease in neuronal density was noted but this difference did not reach the level of statistical significance (P = 0.16). In the superior parietal lobule (area 7) of AIDS brains, no loss of nerve cells was noted. AIDS patients with progressive dementia and brains with HIV-specific neuropathology showed no difference in neuronal densities as compared to those without such features. We conclude that the fronto-orbital cortex, in contrast to the parietal cortex, is mainly damaged in AIDS brains. Neuronal loss was not significantly correlated with development of dementing symptoms and of HIV-specific neuropathology.     

Envelope glycoprotein gp120 of human immunodeficiency virus type 1 alters ion transport in astrocytes: implications for AIDS dementia complex

Infection by human immunodeficiency virus type 1 (HIV-1) is often complicated by a variety of neurological abnormalities. The most common clinical syndrome, termed acquired immunodeficiency syndrome (AIDS) dementia complex, presents as a subcortical dementia with cognitive, motor, and behavioral disturbances and is unique to HIV-1 infection. The pathogenesis of this syndrome is poorly understood but is believed to involve interactions among virally infected macrophages/microglia, astrocytes, and neurons. In this study, we show that exposure of primary rat and human astrocytes to heat-activated HIV-1 virions, or to eukaryotically expressed HIV-1 and HIV-2 envelope glycoproteins (gp120) stimulates amiloride-sensitive Na+/H+ antiport, potassium conductance, and glutamate efflux. These effects are blocked specifically by amiloride, an inhibitor of Na+/H+ antiport and by the selective removal of gp120 with immobilized monoclonal antibody. As a result of modulation of astrocytic function by gp120, the ensuing neuronal depolarization and glutamate exposure could activate both voltage-gated and N-methyl-D-aspartate-regulated Ca2+ channels, leading to increases in intraneuronal Ca2+ and neuronal death. These findings implicate the astrocyte directly in the pathogenesis of AIDS dementia complex.     

Unique monocyte subset in patients with AIDS dementia

BACKGROUND: 15-30% of patients infected with HIV will develop a debilitating dementia. Whilst HIV enters the brain soon after infection, presumably within monocyte-derived macrophages, not all patients with HIV become demented. Blood monocytes probably cross the blood-brain barrier and give rise ultimately to parenchyma macrophages. We looked for a specific monocyte subset in AIDS patients with dementia. METHODS: Peripheral blood monocytes from three groups were compared: AIDS patients with (n = 12) and without (n = 11) dementia, and ten HIV seronegative healthy controls. We used flow cytometry to analyse monocytes, and cell lysis and apoptosis assays to examine monocyte effects on human brain cells in vitro. FINDINGS: We found a unique subset of monocytes in patients with AIDS dementia. These monocytes were more dense and granular and expressed CD14/CD16 and CD14/CD69. Means (SD) for CD14/CD16 in HIV-negative controls and in AIDS non-dementia and AIDS dementia patients were 6.5% (4), 16% (13), and 37% (21), respectively (p = 0.008 between the two groups of patients). The corresponding means for CD14/CD69 were 7% (6), 8% (10), and 69% (18) (p < 0.0001). INTERPRETATION: CD69 is a member of the natural-killer-cell gene complex that is expressed after activation. Supernatants from cultures containing these dense cells can trigger apoptosis of human brain cells in vitro. The monocyte subset we found in patients with AIDS dementia might enter the brain and expose neural cells to toxic factors.     

Human immunodeficiency virus-Type 1 (HIV-1) and the brain.

Infection with human immunodeficiency virus Type-1 (HIV-1), the causative agent of AIDS, can be associated with central nervous system as well as immune system disease. Advanced AIDS can be complicated by a dementia. Short of frank dementia, many AIDS patients manifest neuropsychological (NP) impairment including disturbance in speeded information processing, abstraction, learning, and recall. Data conflict on whether medically asymptomatic HIV-1 carriers have subtle NP deficits. Variations in tests chosen, criterion specification, and sample selection may all be contributing to disparate results. Longitudinal research is needed, and this should examine representative samples of HIV-1 seropositive individuals for whom approximate date of seroconversion is known and in whom sources of comorbidity (e.g., drug abuse, concurrent infections, CNS injuries) can be specified. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Slowed information processing as an early cognitive change associated with HIV infection.

Examined 18 human immunodeficiency virus (HIV)-infected male patients (mean age 32.6 yrs) with acquired immune deficiency syndrome (AIDS)-related complex without frank dementia and 12 sex- and age-matched seronegative controls on measures of information processing speed, vigilance, memory, cortical functioning, and emotional status. 10 Ss were receiving azidothymidine at the time of the study. Ss showed marginally significant slowed information processing relative to controls. Treated Ss performed better than untreated ones. An assessment of information processing speed may be useful in evaluating treatment effectiveness and clarifying illness course. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mycobacteremia in patients with the acquired immunodeficiency syndrome

BACKGROUND: Bacillemia is a key event in the pathogenesis of tuberculosis. Although current evidence indicates that Mycobacterium tuberculosis bacteremia is rare in patients seronegative for the human immunodeficiency virus, it has been increasingly reported in patients with the acquired immunodeficiency syndrome (AIDS). OBJECTIVE: To determine clinical and laboratory characteristics of patients with AIDS and tuberculosis with and without bacillemia. METHODS: Fifty patients with AIDS with clinical suspicion of disseminated mycobacterial disease were prospectively selected. Three consecutive blood samples were collected for culture using a standardized protocol. RESULTS: Mycobacterium was isolated from any body site in 42 patients (84%). Bacillemia was detected in 30 (71.4%) of these 42 patients: 11 (28.2%) caused by Mycobacterium avium-intracellulare complex and 19 (71.8%) caused by M tuberculosis. Blood culture was the only method used to confirm the diagnosis in 5 (15%) of the 33 tuberculosis cases. Tuberculosis in patients with AIDS developed with nonspecific insidious symptoms, a remarkable elevated alkaline phosphatase level, and without the classic miliary radiological pattern. We could demonstrate 2 previously unrevealed clinical characteristics of bacteremic tuberculosis in patients with AIDS: a shift to the left in the white blood cell count and abdominal lymph node enlargement. In patients with tuberculosis, the in-hospital mortality rate was higher among patients with bacillemia, although the posttreatment survival rate was comparable. CONCLUSIONS: Blood culture is a valuable tool to confirm the clinical diagnosis of disseminated tuberculosis in patients with AIDS and can distinguish patients with characteristic clinical findings and outcome. Abdominal ultrasonography may be an additional helpful tool to identify these patients.     

Therapeutical approaches to transmissible spongiform encephalopathies (TSE): the case of amphotericin-B

Within 1987-1995 the authors observed 16 cases of tuberculosis in HIV-infected patients which accounted for 26.7% of AIDS patients treated by them. 14 cases were diagnosed intravitally, 2 postmortem. Infiltrative, generalized, cavernous, intrathoracic lymph node, intraabdominal lymph node tuberculosis and tuberculous pleurisy were identified in 5, 6, 2, 1, 1 and 1 patients, respectively. 6 patients from the above are still alive and are receiving treatment (5 of them with infiltrative tuberculosis), 10 died. Tuberculosis course and outcomes in HIV-infected subjects depended on the stage of their immunodeficiency. In moderate immunodeficiency (CD4-lymphocyte > 200/mm3) tuberculosis ran, as a rule, as local and infiltrative, sensitive to specific therapy. In severe damage to immune system (CD4 < 100/mm3) tuberculosis acquired a generalized course, sometimes fulminant, resistant to treatment. It is inferred that HIV-infected subjects with immunodeficiency need tuberculosis prophylaxis with isoniazide or rifampicin.     

Risk of the development of dementia after interruption of zidovudine treatment

BACKGROUND: Epidemiologic data suggest that zidovudine (ZDV) could prevent the AIDS dementia complex (ADC), but this hypothesis has been specifically studied. PATIENTS AND METHODS: We have reviewed the medical records of all patients with human immunodeficiency virus (HIV) infection admitted to our section between January 1990 and December 1993 who were diagnosed with ADC, and we have compared them to those of a control group with regard to the interruption of ZDV at least 3 months before. Controls were selected from the remaining HIV-related admissions, matched by calendar year, CD4-cell count and previous HIV-disease stage. RESULTS: Thirty-nine cases and 39 controls were available for analysis; twenty-nine (74%) and 25 (64%) were male. The median age was similar for both groups: 30. Thirty-one patients (79%) in each group had a previous diagnosis of AIDS, six (15%) in each group had an AIDS-related complex and in two (5%) the ADC was the first complication of their HIV disease. The median CD4-cell counts were 79.6 and 79.4 x 10(6)/l. Twenty-three patients in each group had taken ZDV. Six of these from the ADC had withdrawn treatment, as compared to 2 from the control group (odds ratio [OR] 3.36; 95% confidence interval [CI]: 0.54-35.76). On the other hand, 16 patients with ADC were still on ZDV at the time of diagnosis, as compared to 21 controls (OR: 0.66; 95% CI: 0.22-1.60). CONCLUSION: In this case-control study, the interruption of treatment with ZDV was not found to be a risk factor for the development of ADC.     

Monokine products as predictors of AIDS dementia

OBJECTIVE: To determine whether or not soluble factors produced by peripheral blood mononuclear cells (PBMC) can predict AIDS dementia. DESIGN AND METHODS: PBMC were isolated from individuals with and without AIDS dementia complex (ADC) to determine if the levels of cytokines tumour necrosis factor (TNF)-alpha and interleukin (IL)-6, or the production of a neurotoxic substance, were significantly different. PBMC were studied after determining that the numbers of monocyte-derived macrophages isolated by adherence were highly variable from patients with ADC compared with individuals without ADC. We prospectively studied 16 AIDS dementia patients, 13 healthy HIV-seropositive individuals, and eight sero-negative controls. Supernatants from PBMC were assayed for TNF-alpha, IL-6 and alone for neurotoxicity on human neural cells in vitro. RESULTS: We observed a trend towards worse cognitive and motor performance in patients suffering from ADC but who had no opportunistic infections ('pure dementia'; n = 8). Levels of PBMC IL-6 were significantly higher in 'pure dementia' patients. There was a trend towards lower levels of PBMC TNF-alpha in the group of patients who had both dementia and opportunistic infections compared with "pure dementia' patients. Supernatant from PBMC of ADC patients was significantly more neurotoxic than that from healthy HIV-seropositive individuals. CONCLUSIONS: Macrophage isolation from PBMC of patients with ADC was altered. Soluble factors produced from PBMC were significantly more neurotoxic than soluble factors from PBMC of healthy HIV-seropositive individuals. PBMC production of TNF-alpha and IL-6 was not a significant predictor of ADC.     

The virology of AIDS.

In the short time since the cause of AIDS was identified, a considerable amount of knowledge has been gathered. The responsible agent, human immunodeficiency virus (HIV), is a retrovirus that changes the genetic composition of the cells it enters and subsequently destroys. Current knowledge about the virus suggests that it invades cells of the central nervous system, thus contributing to AIDS dementia complex. Vaccines are at present ineffective against the virus, in part because the molecular structure of the protein envelope is so changeable. Psychologists need to understand the virology and immunology of AIDS because components of the virus can alter central nervous system function in ways that have an impact on high-risk behavior. This may be a direct consequence of the virus or an indirect consequence of the production of immune system products in response to the virus. This article discusses the current state of knowledge of HIV and offers ways in which this knowledge may be used by psychologists to formulate a psychosocial and behavioral research agenda and strategies for improved, more effective patient care. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Nuclear matrix proteins distinguish normal diploid osteoblasts from osteosarcoma cells

We have recently discovered in Torino (Italy) a new pedigree with early-onset Alzheimer's disease. The index patient is a woman who, at the age of 43 years, showed progressive memory impairment and ideomotor apraxia. Several relatives of the patient have had a history of dementia. The ancestors of the patient were from Calabria (southern Italy) and members of the family emigrated to the north of Italy, to France, and to the United States. Up to now, the new kindred comprises 1950 members, distributed in eight generations. Thirty members affected with Alzheimer's disease have been identified. Neuropathologic confirmation of antemortem clinically diagnosed Alzheimer's disease has been achieved for one patient. The pedigree is consistent with autosomal dominant inheritance. The clinical course of the disease is fairly uniform: the first symptom is memory loss, beginning around age 40 years. Psychiatric symptoms like hallucinations and delusions follow. At a later stage of the disease, several patients developed myoclonus and generalized epileptic seizures and eventually died with profound dementia. The "Torino family" shows several genealogic and clinical similarities with other large multigenerational familial Alzheimer's disease pedigrees originating from the Calabria region.     

Diagnosis and management of esophageal disease in the acquired immunodeficiency syndrome

BACKGROUND: Esophageal disorders are common complications of human immunodeficiency virus (HIV)-infected patients. In a significant number of patients, the esophagus may be the site of the first acquired immunodeficiency syndrome (AIDS)-defining opportunistic illness. METHODS: We reviewed pertinent articles, obtained from a MEDLINE search, on the diagnosis and treatment of esophageal diseases in HIV disease. RESULTS: Infections are the most common cause of esophageal disease, and opportunistic disorders such as cytomegalovirus and idiopathic esophageal ulceration rarely present until the CD4 lymphocyte count falls below 100/mm3. Endoscopy is the most valuable tool for evaluating esophageal complaints in AIDS. CONCLUSIONS: Almost all esophageal infections in patients with AIDS are treatable; therefore, a thorough work-up is indicated. With the widespread use of more effective antiretroviral therapy including the protease inhibitors, there is a general consensus that the incidence of many opportunistic diseases appears to be decreasing.     

Nitric oxide synthase inhibition with N omega-nitro-L-arginine methyl ester affects blood pressure and cardiovascular structure in the genetically hypertensive rat strain

We examined an 18-year-old female and an 18-year-old male with mild mental retardation who suffered from the oscillatory form of sporadic essential myoclonus from an age of 3 years. Although the generalized oscillatory myoclonus resembled severe essential tremor, surface electromyography revealed small myoclonic jerks with frequencies of 6-8 Hz. As concomitant symptoms, the female case exhibited overanxious irritability from early childhood and generalized epileptic seizures occurred from the age of 4 years. In the male case, an obsessive-compulsive disorder and photosensitive convulsive seizures were persistently noted from early childhood. All their symptoms had been stable for at least the last 10 years. Thus, although non-progressive tremulous movements are rare in early childhood, sporadic essential myoclonus is causative. In contrast to hereditary essential myoclonus, sporadic essential myoclonus is considered to be more heterogeneous, especially in the various associated symptoms.     

AIDS-related dementia

Dementia is a common process in which there is gradual decrease in mental function due to disease of either cortical or subcortical structures. The numerous causes of dementia can be divided into those in which dementia is the primary manifestation, as in Alzheimer's disease, or secondary to chronic disease, neoplasms, endocrine and metabolic disorders and chronic infections. The dementia in AIDS is usually part of the syndrome of acquired immunodeficiency and may be its first manifestation.     

Circular forms of unintegrated human immunodeficiency virus type 1 DNA and high levels of viral protein expression: association with dementia and multinucleated giant cells in the brains of patients with AIDS

Thirty-one histologically abnormal brains from patients with AIDS were studied in order to establish the relationship between multinucleated giant cells, viral protein expression, the various forms of human immunodeficiency virus type 1 (HIV-1) DNA, and clinical evidence of dementia. Unintegrated HIV-1 DNA of 2 to 8 kb was found in 22 of the 31 brains. Multinucleated giant cells without any other pathology were found in 14 cases; unintegrated 1-long terminal repeat (1-LTR) circular forms of HIV-1 DNA and strongly positive immunohistochemistry for gp41 and p24 were found in most of these brains. Most of these patients had a clinical diagnosis of HIV-1-associated dementia and cerebral atrophy. In all the other brains studied, 1-LTR circles were absent and immunohistochemistry for gp41 and p24 was usually negative. Very few of these patients had a clinical diagnosis of dementia. Sequence comparison of the LTR region from integrated HIV-1 DNA with that from unintegrated 1-LTR circular forms of HIV-1 DNA in 12 cases showed no significant differences. A further comparison of these brain-derived LTR sequences with LTR sequences derived directly from lymphoid tissue also showed strong sequence conservation. The V3 loop of the virus from the brain was sequenced in 6 cases and had a non-syncytium inducing-macrophage-tropic genotype. Our results show that (i) although unintegrated HIV-1 DNA was present in most brains from patients with AIDS, molecular evidence of high levels of viral replication was associated with the presence of multinucleated giant cells and dementia, and that (ii) the HIV-1 LTR is not a determinant of neurotropism. These observations suggest that replication of HIV-1 and not just the presence of HIV-1 DNA within giant cells makes the important contribution to central nervous system damage.