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Biomedical subjects

I Elovaara

Publications and source records attributed to I Elovaara.

At least 55 records · Page 3Linked to original sources
PubMed1993

HIV-1 specificity of cerebrospinal fluid and serum IgG, IgM, and IgG1-G4 antibodies in relation to clinical disease.

The reactivities of intrathecal and serum IgG and IgM, and IgG1-4 subclass antibodies to various HIV-1 proteins were assessed by immunoblotting at various stages of HIV-1 infection. All patients were examined neurologically including CT and/or MRI, and with HIV-1-specific and nonspecific tests of the cerebrospinal fluid (CSF). In early infection, the occurrence of anti-gag antibodies in both CSF and serum was higher than that of anti-pol antibodies among all IgG subclasses (P < 0.05). Also in late infection, anti-gag IgG1 response was most frequent (P < 0.04), while anti-gag IgG3 and IgG4 reactivities predominated over similar anti-pol antibodies (P < 0.05, respectively). Of anti-pol reactivities, in the CSF of subjects at early infection anti-p32 IgG and IgG1 antibodies were more frequent than in patients at late stages (P < 0.015). In late infection, however, the occurrence of anti-p64 IgM and IgG2-4 antibodies of both CSF and serum was higher than at early stages (P = 0.014). Regarding anti-env response, in patients with advanced infection, the CSF and serum IgG subclass reactivity against gp120 was restricted to IgG1. The CSF of individual patients with HIV encephalopathy showed a higher or similar occurrence of polyisotypic anti-gag and anti-pol IgG3 antibodies than corresponding serum. These results indicate association between declining frequency of anti-pol p32 and anti-env gp120 antibodies and severity of HIV-1 disease.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS Dementia Complex↗
PubMed1993

Cytoimmunological abnormalities in cerebrospinal fluid in early stages of HIV-1 infection often precede changes in blood.

We determined the proportions of CD2+, CD4+ and CD8+ lymphocytes in the cerebrospinal fluid (CSF) and paired blood samples of 19 neurologically examined subjects with CDC II/III stage HIV-1 infection and 21 controls. Using a three-layer indirect immunoperoxidase technique, we found that 16 HIV-1-infected subjects had an abnormally low CD4+/CD8+ ratio of the CSF due to a decrease in the proportion of CD4+ T cells and/or an increase in that of CD8+ lymphocytes. Compared to controls, in the HIV-1-infected group this ratio appeared to be lower in both CSF and blood (P < 0.001). The changes of lymphocyte subpopulations were more marked in the CSF than in blood, and no clear associations were found between the findings of paired CSF and blood samples. Cytological examination of the CSF revealed that 12 of 14 patients had an elevated total cell count and an abnormal differential count with a predominance of mononuclear phagocytes. An elevated number and/or proportion of enlarged lymphoid cells was found in most cases. The total cell counts, and total numbers of mononuclear phagocytes and lymphocytes of the patients were higher than in controls (P < 0.001). Our study shows that the changes in CSF lymphocyte subsets often precede those in blood and that immunological events in the central nervous system (CNS) are not directly reflected in peripheral blood. Cytoimmunological abnormalities in the CSF of individuals with early stages of HIV-1 infection indicate subclinical CNS involvement, and may be of importance for therapeutic considerations.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Cognitive performance in HIV-1 infection: relationship to severity of disease and brain atrophy.

We examined cognitive performance in 72 HIV-1 infected patients and 34 controls. None of the patients had opportunistic infections or unusual neoplasms of the central nervous system (CNS). Factors other than HIV-1 known to cause cognitive decline were excluded from both groups. Cognitive functioning analysed with special emphasis on the severity of HIV infection was related to neuroradiological and immunological findings. In patients with AIDS-related complex (CDC IVa) or AIDS (CDC IVc,d), a deterioration of memory as well as cognitive speed and flexibility was detected. Furthermore, memory deficits were associated with central cerebral and infratentorial atrophy in those patients, while no association was found between cognitive deficits and immunological abnormalities. Patients at CDC stages II or III showed slight association between altered cognitive speed and flexibility and elevated leukocyte count, suggesting a subclinical CNS disease already at early stages of HIV infection.

AIDS Dementia Complex↗
PubMed1993

CSF follow-up in HIV-1 infection: intrathecal production of HIV-specific and unspecific IGG, and beta-2-microglobulin increase with duration of HIV-1 infection.

Ninety-nine sequential cerebrospinal fluid (CSF) samples from 28 human immunodeficiency virus-1 (HIV-1)-infected patients were analyzed during the follow-up of 9 months to 4 years. Intrathecal synthesis of HIV-antibodies and IgG (p < 0.01), and the levels of beta-2-microglobulin (beta 2m) in the CSF (p < 0.05) and serum (p < 0.01) increased with duration of HIV-1 infection. No effect of duration of HIV-1 infection was observed on the individual CSF white cell counts and the levels of blood-brain-barrier (BBB) permeability. In 13 patients with HIV-1-associated central nervous system (CNS) disease, the effect of duration was seen as an increase of the individual beta 2m levels in serum (p < 0.01). Moreover, 7 of 9 patients who developed neurological disease or showed its progression during the study increased the level of beta 2m in the CSF. All of them increased the level of beta 2m in serum. In 15 neurologically healthy subjects, the effect of duration was expressed as an increase of the level of individual beta 2m in CSF (p < 0.05) and intrathecal IgG synthesis (p < 0.01). In the AIDS group, the level of beta 2m in the CSF increased, but in less severe stages the dependency of the individual CSF parameters on disease duration was not found. Our results indicate that elevated levels of beta 2m in CSF and serum appear to predict progression of neurological and systemic diseases, respectively. Elevated beta 2m in the CSF of clinically intact individuals may indicate subclinical neurological disease caused by HIV-1.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS Dementia Complex↗
PubMed1992

Radiological study of the brain at various stages of human immunodeficiency virus infection: early development of brain atrophy.

One hundred and one persons infected with human immunodeficiency virus (HIV-1), in whom other central nervous system infections or diseases were excluded, underwent brain CT and/or MRI at various stages of HIV-1 infection: 29 were asymptomatic (ASX), 35 had lymphadenopathy syndrome (LAS), 17 had AIDS-related complex (ARC), and 20 had AIDS. A control group of 32 HIV-1-seronegative healthy persons underwent brain MRI. The most common finding was brain atrophy, found in 9% of controls, and 31% of ASX cases, 29% of LAS, 59% of ARC and 70% of AIDS. Even the difference between the ASX or LAS groups and controls was significant. The changes were bilateral and symmetrical, and they were more severe at later stages of infection. Infratentorial atrophy was seen in the early stages; supratentorial atrophy became more pronounced at ARC, and generalized atrophy was typical of AIDS. Non-specific small hyperintense foci were found on MRI in 13% of controls and 6-15% of the infected groups. Larger, diffuse, bilateral white matter infiltrates were detected in 4 demented patients with AIDS. Four patients with AIDS and 1 with LAS had focal hyperintense lesions in the internal capsules, lentiform nuclei or thalamus, often bilateral on MRI. One patient with AIDS, examined with CT only, had low density in the lentiform nucleus. Loss of brain parenchyma can occur at an early stage of HIV-1 infection, and the atrophic process becomes more intense at later stages (ARC and AIDS). Parenchymal infiltration, seen as hyperintense areas on MRI, is most often associated with severe clinical symptoms, in the later stages of the disease.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Increased occurrence of free immunoglobulin light chains in cerebrospinal fluid and serum in human immunodeficiency virus-1 infection.

The presence of free immunoglobulin light chains (FLCs) in the cerebrospinal fluid (CSF) and sera of patients with human immunodeficiency virus-1 (HIV-1) infection, multiple sclerosis (MS), and neurologically healthy control individuals was investigated by paying special attention to ensure that only truly free light chains would be detected. The FLCs were extracted by specifically binding them to Sepharose-coupled anti-FLC monoclonal antibodies, and thereafter they were electrophoresed and immunoblotted with monoclonal antibodies to both light chain (LC) isotypes. A frequent occurrence of kappa and lambda FLCs was found in both CSF and sera of HIV-1 infected patients. In HIV-1 infection and in MS, the frequency of FLCs of the CSF was equal. In healthy controls, only occasional weak FLCs were observed in either CSF or serum. FLC bands of the CSF from patients with HIV-1 infection tended to be more intensive than those of the appropriately diluted sera. Both intrathecal synthesis of FLCs and their transudation from sera through the impaired blood-brain barrier (BBB) may contribute to this. Increasing severity of general HIV-1 infection was accompanied by an increase of FLC intensity in sera. A qualitative demonstration of FLC in the CSF may be meaningful only in the absence of altered BBB function.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Dementia associated with human immunodeficiency virus: subcortical or cortical?

Two different types of dementia and corresponding neuropathological findings of patients with human immunodeficiency virus (HIV) infection are presented. In one case, "subcortical" dementia with slow movements and mental processes as well as problems in active recall but without focal defects corresponded to diffuse leukoencephalopathy. In another case, "cortical" dementia with impaired abstraction and memory as well as several focal defects corresponded to microglial nodules in cortical and in deep grey matter, with only a mild diffuse leukoencephalopathy. Thus, in contrast to earlier interpretations, subcortical dementia does not appear to be the only form of dementia in HIV-infected patients, and cortical dysfunction may also occur.

AIDS Dementia Complex↗
PubMed1991

EEG in early HIV-1 infection is characterized by anterior dysrhythmicity of low maximal amplitude.

We analyzed the EEGs of 67 HIV-1-infected patients at various stages of the disease and of 35 HIV-1-seronegative controls. The most common EEG abnormality in HIV-1 infection was an increased amount of generalized episodic or persistent, predominantly anterior slow activity, associated with a low level of maximal amplitude. When compared to the controls, a lower maximal amplitude of dominant background activity (p less than 0.001), and more marked generalized (p less than 0.01) and anterior (p less than 0.001) disturbances were already seen in early stages of HIV-1 infection. EEG abnormalities were more severe in patients with advanced HIV-1 infection than in those at early infection (p less than 0.001 to p less than 0.05). The presence of a more marked, posteriorly (p less than 0.01) accentuated, generalized slow activity (p = 0.02) was found more often in patients with T-helper cell counts lower than 0.4 x 10(9) (p = 0.05) than in those with higher numbers of T-helper cells. No clear associations were found between the severity of EEG abnormalities and the duration of HIV-1 infection. Our results suggest that EEG is a sensitive method in detecting subclinical functional cerebral disturbances caused by HIV-1.

AIDS Dementia Complex↗
PubMed1990

Mild brain atrophy in early HIV infection: the lack of association with cognitive deficits and HIV-specific intrathecal immune response.

Brain MRI and/or CT were performed on 72 HIV-infected patients at various stages of the disease, and on 34 controls. The neuroradiological findings were related to duration of the infection, neurological symptoms, and cognitive abnormalities as well as to immunological findings in the CSF and blood. All types of brain atrophy were more severe and more frequent in HIV-infected subjects than in controls. Patients with neurological symptoms, those with advanced HIV infection, and patients with a duration of HIV infection of more than 4 years showed the most severe and most frequent neuroradiological abnormalities, including central and cortical atrophy, brain stem atrophy, and cerebellar atrophy. Subjects with cognitive defects exhibited more severe central atrophy than cognitively intact patients. However, slight brain atrophy and/or parenchymal lesions were found in 57% of cognitively intact HIV-seropositive individuals. Patients with brain atrophy and those with radiologically normal brain, both showed increased intrathecal synthesis of total IgG, and intrathecal HIV-antibody synthesis. However, a declined general immune response and a lowered CSF leukocyte count were seen predominantly in patients with brain atrophy. The results suggest that subcortical, neurologically "silent" areas of brain white matter are an early target of HIV infection.

AIDS Dementia Complex↗
PubMed1989

CSF and serum beta-2-microglobulin in HIV infection related to neurological dysfunction.

Elevated (greater than 2.2 mg/l) CSF beta-2-microglobulin (beta 2m) level was found in 9 of 16 neurologically symptomatic patients but in only 4 of 21 who were neurologically symptom-free (P less than 0.01). Serum beta 2m concentration was elevated (greater than 2.5 mg/l) in 12 of 16 neurologically symptomatic patients but in only 8 of 21 symptom-free patients (P less than 0.01). When the CSF and serum beta 2m levels were related to various stages of HIV infection, the highest mean values for both CSF and serum were found in patients with acquired immunodeficiency syndrome (AIDS), followed by lower values in AIDS-related complex (ARC), lymphadenopathy syndrome (LAS), and asymptomatic seropositive individuals (ASX), in decreasing order of preference. Our results suggest that elevated beta 2m in CSF and serum is related to the stage of general HIV infection and that elevated CSF beta 2m in the presence of intact BBB may be useful in evaluating CNS involvement in HIV-infected patients.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Cognitive changes as early signs of HIV infection.

Neuropsychological examination was performed on 13 patients and 10 matched controls to assess the brain involvement of patients with human immunodeficiency virus (HIV) infection. HIV-infected patients showed a significant decline in visuomotor, visuoconstructive and practical abilities as well as in motor-free visuospatial performance and repeating a long sentence. These findings could not be explained by the concomitant mental depression of these patients. Neither were they associated with any particular stage of HIV infection. The results suggest that mild cognitive changes may be detected even in the early stages of HIV infection, when examined by appropriate neuropsychological methods.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Oligoclonal immunoglobulin bands in cerebrospinal fluid of patients with Alzheimer's disease and vascular dementia.

We examined serum and cerebrospinal fluid (CSF) of 16 patients with Alzheimer's disease (AD), 28 patients with vascular dementia (VD), their age-matched controls and multiple sclerosis (MS) patients in order to evaluate the humoral immune response within the central nervous system both quantitatively and qualitatively. Intra-blood-brain barrier (BBB) protein synthesis was calculated by CSF IgG index. The presence of oligoclonal banding (OCB) was investigated with agarose isoelectric focusing (IEF) followed by immunoblotting with antihuman IgG. No patient with AD and only 4 patients with VD had slightly elevated IgG indexes, and no statistically significant differences in the indexes were found between the two groups. No bands were found in the CSF of AD patients but 3 VD patients had OCB in both serum and CSF. One VD patient had bands in serum but no bands in CSF. No kappa or lambda free light chains were found in those demented patients with demonstrable bands in the CSF and serum. No OCB were found in control sera and CSF. For comparison, the majority of patients with MS had OCB in CSF. Thus, no consistent increase of intrathecal protein synthesis was found in patients with AD and VD. Methodological differences explain at least part of the conflicting results published earlier.

Aged↗
PubMed1988

Intrathecal humoral immunologic response in neurologically symptomatic and asymptomatic patients with human immunodeficiency virus infection.

We analyzed the intrathecal humoral immunologic response in 42 human immunodeficiency virus (HIV)-infected patients. Eighteen patients had clinical neurologic abnormalities, while the remaining 24 patients were neurologically symptom-free. Nine of the neurologically symptomatic patients at early infection had slight neurologic dysfunction; in nine other subjects at late infection, the neurologic impairment was moderate or severe. When compared with symptom-free patients, neurologically symptomatic patients had increased intra-blood-brain barrier (BBB) HIV-specific IgG (p less than 0.001) and total IgG synthesis (p less than 0.01) with oligoclonal bands (OCBs) in the CSF and/or serum (11/18 versus 3/24). At early stages of the infection, neurologically symptomatic patients showed increased total intrathecal IgG synthesis (9/9) coincident with OCBs in the CSF and serum (7/9) and slight mononuclear pleocytosis (7/9), but less frequent HIV-specific IgG production within the CNS (6/9). In advanced infection, the number of neurologically symptomatic patients with intrathecal HIV-specific IgG synthesis (8/9) was higher, while the number of those with increased total intra-BBB IgG synthesis (5/9; p less than 0.01), OCBs (4/9), and increased CSF leukocyte count (1/9; p less than 0.001) was lower than at early infection. Our data suggest humoral intra-BBB immunoactivation at early stages of HIV infection followed by declining B cell response within the CNS at advanced infection.

Acquired Immunodeficiency Syndrome↗
PubMed1987

CSF protein and cellular profiles in various stages of HIV infection related to neurological manifestations.

CSF protein and cellular profiles were studied in 28 HIV-infected patients. Twenty of them had neurological complaints, but only 6 patients had objective neurological deficits such as dementia, ocular motility disorders or polyneuropathy. The serum/CSF HIV antibody ratio was on average lowest in acquired immunodeficiency syndrome (AIDS) (4 patients) and highest or almost normal in lymphadenopathy syndrome (LAS) (11) and asymptomatic seropositivity (ASX) (7), while it varied between these extremes in AIDS-related complex (ARC) (6). However, low values of the ratio were also found in the HIV-infected patients free of neurological symptoms and even in one ASX patient. The CSF IgG index was elevated in all these 4 general stages of HIV infection without any significant differences between them. The CSF/serum albumin ratio was slightly increased in patients with neurological deficits, but this ratio showed no association with any other clinical factor analysed. CSF leucocytes were increased in the early stages of the disease, but later the cellular reaction subsided. HIV was isolated from post mortem brain tissue of two AIDS patients and from the CSF of one of them. The results suggest increased intrathecal virus-specific IgG synthesis, not only in patients with neurological deficits and at advanced stages of infection, but also in neurologically symptom-free subjects and at early infection. The lack of correlation between the increased virus-specific IgG synthesis within the CNS and the presence of neurological symptoms suggests that neurologically "silent" areas of brain white matter are often affected in HIV infection.

AIDS-Related Complex↗
PubMed1987

Serum and cerebrospinal fluid proteins and the blood-brain barrier in Alzheimer's disease and multi-infarct dementia.

Serum concentrations of IgG, IgA, IgM, haptoglobin, transferrin, prealbumin and albumin quantitated nephelometrically in 22 patients with Alzheimer's disease (AD), 29 patients with multi-infarct dementia (MID) and their age-matched controls were normal. Cerebrospinal fluid (CSF) albumin and CSF/serum ratio for albumin were higher in AD and MID patients compared to controls, but no significant differences were found between AD and MID. Patients with MID had elevated CSF IgG, IgA, IgM and prealbumin levels compared to controls and to AD. An increased CSF IgG index was found in 5 MID patients but none of the AD patients. Thus, the blood-brain barrier permeability is often increased in MID as well as in AD. There is no increased intrathecal IgG synthesis in AD but it may occur in MID.

Aged↗