Symptom-free Individuals Research Articles

Striatal dysfunction during failed motor inhibition in children at risk for bipolar disorder

A better understanding of the neural underpinnings of bipolar disorder (BD) can be obtained by examining brain activity in symptom-free individuals at risk for BD. This study examined the neural correlates of motor inhibition in a sample of symptom-free youths at familial risk for BD. 19 euthymic youths with BD, 13 asymptomatic youths with a first-degree relative with BD, and 21 healthy comparison children completed the stop signal task in a 3 T scanner. Children at familial risk for BD exhibited increased putamen activation during unsuccessful inhibition that distinguished them from both healthy and BD children. Youths with BD exhibited reduced activation of the right nucleus accumbens during unsuccessful inhibition as compared to the other participant groups. Striatal activation patterns differ between youths at risk for BD and healthy comparison children during a motor inhibition task.

Noninvasive estimation of the ocular elastic modulus for age-related macular degeneration in the human eye using sequential ultrasound imaging

Introduction Elastic modulus estimation may be an important clinical criterion, as it seems to affect such eye parameters as intraocular pressure, ocular pulsation, blood flow, effect of topical medications, and post-refractive surgery complications. The purpose of this study was to examine the differences in elasticity in the ocular axial length, posterior wall thickness (posterior pole), and retina–choroid thickness under normal and aged-related macular degeneration (AMD) conditions in the human eye by directly estimating the elastic modulus with sequential and noninvasive ultrasound image processing. Materials and Methods In this study, 25 healthy subjects and 20 patients with non-neovascular AMD participated in the experiment. The deformation of the ocular axial length, posterior wall thickness and retina–choroid complex thickness was captured using high-resolution ultrasonography before and after loading. The B-mode (20 MHz) and A-mode (8 MHz) frames were obtained and processed with an echo tracking technique. The elastic modulus was estimated using changes in ocular axial length, posterior wall thickness and retina–choroid complex thickness and with applied stress measurements. Results There was a significant difference ( p < 0.05) in the ocular axial length elastic modulus between the AMD and healthy subjects (AMD patients: 95.165 ± 26.431 kPa, vs. healthy subjects: 49.539 ± 25.867 kPa). Moreover, there was a statistically significant difference ( p < 0.05) in the posterior wall thickness elastic modulus between AMD patients and healthy subjects (AMD patients: 50.519 ± 12.295 kPa, vs. healthy subjects: 20.519 ± 11.827 kPa). However, no statistically significant difference ( p-value > 0.05) was found in the retina–choroid complex elastic modulus between the two groups (AMD patients: 20.134 ± 3.898 kPa, vs. healthy subjects: 15.630 ± 4.250 kPa). Conclusion Although the results were obtained examining a relatively low number of patients, it would appear that noninvasive ultrasound estimation of the local elastic moduli of ocular axial length and posterior wall thickness is suited to aid in detection of the non-exudative AMD thus manifesting its potential as a screening tool in symptom-free individuals.

Striatal dopamine synthesis capacity in twins discordant for schizophrenia

Elevated striatal dopamine synthesis capacity is thought to be fundamental to the pathophysiology of schizophrenia and has also been reported in people at risk of psychosis. It is therefore unclear if striatal hyperdopaminergia is a vulnerability marker for schizophrenia, or a state feature related to the psychosis itself. Relatives of patients with schizophrenia are themselves at increased risk of developing the condition. In this study we examined striatal dopamine synthesis capacity in both members of twin pairs discordant for schizophrenia. In vivo striatal dopamine synthesis capacity was examined using fluorine-18-l-dihydroxyphenylalanine (18F-DOPA) positron emission tomography (PET) scans in seven twin pairs discordant for schizophrenia and in a control sample of 10 healthy control twin pairs. Striatal 18F-DOPA uptake was not elevated in the unaffected co-twins of patients with schizophrenia (p=0.65) or indeed in the twins with schizophrenia (p=0.89) compared to the control group. Levels of psychotic symptoms were low in the patients with schizophrenia who were in general stable [mean (s.d.) Positive and Negative Syndrome Scale (PANSS) total=56.8 (25.5)] whereas the unaffected co-twins were largely asymptomatic. Striatal dopamine synthesis capacity is not elevated in symptom-free individuals at genetic risk of schizophrenia, or in well-treated stable patients with chronic schizophrenia. These findings suggest that striatal hyperdopaminergia is not a vulnerability marker for schizophrenia.

Chirurgie du rachis du sujet âgé : radiculalgie, canal rétréci : particularités, enjeux, résultats ?

Lumbar spinal stenosis is a common condition in elderly patients and also one of the most common reasons to perform spinal surgery at an advanced age. Disc degeneration, facet degeneration and hypertrophy, and ligamentum flavum hypertrophy and calcification will usually participate in the genesis of a stenotic condition in the elderly. Those changes can lead to symptoms by themselves or decompensate a preexisting narrow spinal canal. Even though some lesions are more central or more lateral, this classic dichotomy is less present in the elderly patient in whom the degenerative process usually encroaches both central and lateral pathways. However, it must be stressed that so-called stenotic images (sometimes severe) are present on imaging studies in a great number of symptom-free individuals and that the relationship between degenerative lesions, importance of abnormal images and complaints is still unclear. Differential diagnosis with vascular disorders, also common in the elderly, can be challenging. This is of utmost importance, especially if a surgical procedure is considered in order to avoid disappointing results. Lumbar stenosis is a very common reason for decompressive surgery and/or fusion. Several studies have showed that surgical treatment gives better results than a conservative one, at mid and longer follow-up. Such a surgery has to be indicated and planified with great care given the complications due to the numerous comorbidities often present in aging patients. A fusion performed with the laminectomy increases complication rate. Classical, wide laminectomies have to be avoided as much as possible as they can trigger postoperative instability. More conservative and structure sparing procedures, such as laminarthrectomy, are preferred. Recently, new techniques, such as interspinous implants, have been proposed. Good initial results need to be confirmed by further studies.

Circulating microparticles may influence early carotid artery remodeling

To test associations of circulating microparticles with large artery remodeling before atherosclerosis is detectable. In 232 untreated symptom-free individuals, we measured microparticles of various cellular origins (platelet, endothelial and leukocyte) by specific anti-GPIb (glycoprotein Ib), anti-cluster of differentiation (CD) 105 and anti-CD11a antibodies, and common carotid artery intima-media thickness (IMT), internal and external diameters by ultrasound. Except for CD105 microparticles with IMT to lumen ratio (IMT/D, P < 0.05), microparticles correlated with no carotid dimensions. Significant interactions existed between each microparticle type and IMT on internal and external diameters (GPIb, P < 0.01; CD105 and CD11a microparticles P < 0.001) consisting of lower trend in increased diameter with increasing IMT in individuals with high than in those with low microparticle level (according to the median) of each origin. As a result, individuals within the third IMT tertile had lower internal diameter in the presence of high than in the presence of low level of GPIb, CD105 or CD11a microparticles (P = 0.001, <0.05 or 0.01, respectively), and lower external diameter in the presence of high than in the presence of low level of GPIb and CD11a microparticles (P = 0.001 and 0.01). Also, individuals within third IMT tertile exhibited positive correlations of IMT with CD105 and CD11a microparticles (P < 0.05), negative correlations of internal diameter with GPIb (P < 0.05), CD105 (P < 0.05) and CD11a microparticles (P < 0.01) and of external diameter with GPIb and CD11a microparticles (P < 0.05), and positive correlations of IMT/D with CD105 and CD11a microparticles (P < 0.001). Increased levels of leukocyte and endothelial-derived microparticles are associated with carotid inward remodeling in individuals with the greatest IMT before atherosclerosis is detectable.

Comparison of Results of Detection of Rhinovirus by PCR and Viral Culture in Human Nasal Wash Specimens from Subjects with and without Clinical Symptoms of Respiratory Illness

Human rhinoviruses (HRV) cause acute upper respiratory illness. The frequency of HRV-associated illnesses appears greater when PCR assays are used to detect rhinoviruses. The present study performed PCR-based detection of HRV upon entry of subjects into respiratory syncytial virus and parainfluenza type 3 vaccine trials when subjects were symptom-free and upon subsequent development of clinical symptoms of respiratory illness during the trial. The background of HRV PCR positivity in symptom-free individuals (30/139 [22%]) was only slightly lower than in those with respiratory illness (28/77 [36%]). For subjects with multiple samples, it was estimated that HRV was detectable by PCR for approximately 100 days before, during, and after clinical symptoms were documented. PCR is a remarkably more sensitive method of detecting HRV than is tissue culture. The presence of HRV RNA may not always reflect an association with infectious virus production. The limited association of HRV RNA with illness suggests caution in assigning causality of HRV PCR positivity to clinical symptoms of respiratory illness.

Incidence and outcomes of mental disorders in a regional population: the Northern Rivers Mental Health Study

To estimate the incidence of mental disorders in a cohort of previously symptom-free individuals who are representatives of a regional Australian population. To map changing patterns of diagnosis and comorbidity within the cohort over a 2 year period.Two year follow-up of a community-based cohort drawn from a telephone screening of 9191 randomly selected adults. Subjects were administered a comprehensive face-to-face interview which included the Composite International Diagnostic Interview. A total of 1407 subjects were interviewed at baseline, and 968 subjects were reinterviewed (a 68.8% follow-up rate).There was considerable change in disorder status over the study period, and analysis of the Composite International Diagnostic Interview scoring suggests that these changes reflected real changes in symptomatology. Of subjects interviewed at both baseline and follow-up, 638 were classified as disorder-free at their entry to the study. After 2 years, 98 of these met criteria for a mental disorder during the preceding 12 months. After adjusting for sampling and gender, the 12 month incidence of any mental disorder among subjects who had been disorder-free 2 years previously was 9.95 per hundred person-years at risk. At baseline, a further 330 subjects met ICD-10 criteria for a mental disorder during the previous 12 months. Two years later, 167 of these subjects (50.6%) were disorder-free, and 163 still met the criteria for a mental disorder, although there had often been considerable change in their diagnosis. Subjects with a mental disorder at the commencement of the study were significantly more likely than those without a disorder to have a positive diagnosis 2 years later (p < 0.001). The number of diagnoses at baseline was a strong predictor of the number of diagnoses at follow-up (p < 0.001), and each additional comorbid diagnosis at baseline also increased the probability of a persisting disorder at follow-up (p < 0.001).Over a 2 year period, the majority of subjects with a mental disorder will become disorder-free, while a significant number of previously disorder-free individuals will develop a positive diagnosis. Health services need to be designed to meet this labile demand.

Incidence and Outcomes of Mental Disorders in a Regional Population: The Northern Rivers Mental Health Study

To estimate the incidence of mental disorders in a cohort of previously symptom-free individuals who are representatives of a regional Australian population. To map changing patterns of diagnosis and comorbidity within the cohort over a 2 year period. Two year follow-up of a community-based cohort drawn from a telephone screening of 9191 randomly selected adults. Subjects were administered a comprehensive face-to-face interview which included the Composite International Diagnostic Interview. A total of 1407 subjects were interviewed at baseline, and 968 subjects were reinterviewed (a 68.8% follow-up rate). There was considerable change in disorder status over the study period, and analysis of the Composite International Diagnostic Interview scoring suggests that these changes reflected real changes in symptomatology. Of subjects interviewed at both baseline and follow-up, 638 were classified as disorder-free at their entry to the study. After 2 years, 98 of these met criteria for a mental disorder during the preceding 12 months. After adjusting for sampling and gender, the 12 month incidence of any mental disorder among subjects who had been disorder-free 2 years previously was 9.95 per hundred person-years at risk. At baseline, a further 330 subjects met ICD-10 criteria for a mental disorder during the previous 12 months. Two years later, 167 of these subjects (50.6%) were disorder-free, and 163 still met the criteria for a mental disorder, although there had often been considerable change in their diagnosis. Subjects with a mental disorder at the commencement of the study were significantly more likely than those without a disorder to have a positive diagnosis 2 years later (p < 0.001). The number of diagnoses at baseline was a strong predictor of the number of diagnoses at follow-up (p < 0.001), and each additional comorbid diagnosis at baseline also increased the probability of a persisting disorder at follow-up (p < 0.001). Over a 2 year period, the majority of subjects with a mental disorder will become disorder-free, while a significant number of previously disorder-free individuals will develop a positive diagnosis. Health services need to be designed to meet this labile demand.

Bronchial Reactivity in Healthy Individuals Undergoing Long-term Topical Treatment With β-Blockers

To assess the impact of long-term treatment with topical timolol on bronchial reactivity in healthy individuals. Twenty-one otherwise healthy individuals with high-pressure primary open-angle glaucoma were enrolled in a randomized controlled clinical trial. Eleven patients underwent 3 years of topical 0.5% timolol treatment followed by a 1-year washout period; 10 patients underwent primary argon laser trabeculoplasty. Functional variables and bronchial reactivity (forced expiratory volume in 1 second and metacholine challenge test results) were assessed in both groups at enrollment and after 3 and 4 years of follow-up. After 3 years, a measurable response to metacholine challenge was recorded in 6 of 11 otherwise symptom-free individuals treated with 0.5% timolol twice daily. A detectable response to metacholine challenge was still present in half of these individuals (3 of 6) when further washed out for 1 year from the topical beta-blocker. No significant variation in bronchial reactivity was measured in the laser-treated group during 4 years of follow-up. Healthy individuals who undergo long-term topical application of a nonselective beta-blocker (0.5% timolol) can develop a subclinical increase in bronchial reactivity. This phenomenon may not be completely reversible on withdrawal of the beta-blocker.

Lumbar spinal stenosis in the elderly: an overview.

Lumbar spinal stenosis is a common condition in elderly patients and also one of the most common reasons to perform spinal surgery at an advanced age. Disc degeneration, facet degeneration and hypertrophy, and ligamentum flavum hypertrophy and calcification usually participate in the genesis of a stenotic condition in the elderly. These changes can lead to symptoms by themselves or decompensate a preexisting narrow canal. Although some lesions are more central or more lateral, this classic dichotomy is less present in the elderly patient, in whom the degenerative process usually encroaches both central and lateral pathways. Some less common causes of lumbar spinal stenosis are found in the aging subject, such as Paget's disease. However, it must be stressed that so-called stenotic images (sometimes severe) are present on imaging studies in a great number of symptom-free individuals, and that the relationship between degenerative lesions, importance of abnormal images, and complaints is still unclear. Lumbar stenosis is a very common reason for decompressive surgery and/or fusion. Various conditions can lead to a narrowing of the neural pathways and differential diagnosis with vascular troubles, also common in the elderly, can be challenging. The investigation of stenotic symptoms should be extremely careful and thorough and include a choice of technical examinations including vascular investigations. This is of utmost importance, especially if a surgical sanction is considered to avoid disappointing results.

Myth: fluids, bed rest, and caffeine are effective in preventing and treating patients with post-lumbar puncture headache.

Myth: fluids, bed rest, and caffeine are effective in preventing and treating patients with post-lumbar puncture headache.

Imaging of onset and progression of Alzheimer's disease with voxel-compression mapping of serial magnetic resonance images

Early diagnosis and monitoring of the progression of Alzheimer's disease is important for the development of therapeutic strategies. To detect the earliest structural brain changes, individuals need to be studied before symptom onset. We used an imaging technique known as voxel-compression mapping to localise progressive atrophy in patients with preclinical Alzheimer's disease. Four symptom-free individuals from families with early-onset Alzheimer's disease with known autosomal dominant mutations underwent serial magnetic resonance imaging (MRI) over 5-8 years. All four became symptomatic during follow-up. 20 individuals with a clinical diagnosis of probable Alzheimer's disease and 20 control participants also underwent serial MR imaging. A non-linear fluid matching algorithm was applied to register repeat scans onto baseline imaging. Jacobian determinants were used to create the voxel-compression maps. Progressive atrophy was revealed in presymptomatic individuals, with posterior cingulate and neocortical temporoparietal cortical losses, and medial temporal-lobe atrophy. In patients with known Alzheimer's disease, atrophy was widespread apart from in the primary motor and sensory cortices and cerebellum, reflecting the clinical phenomenology. Voxel-compression maps confirmed early involvement of the medial temporal lobes, but also showed posterior cingulate and temporoparietal cortical losses at presymptomatic stage. This technique could be applied diagnostically and used to monitor the effects of therapeutic intervention.

Enhanced contact tracing and spatial tracking of Mycobacterium tuberculosis infection by enumeration of antigen-specific T cells

Identification of individuals latently infected with Mycobacterium tuberculosis is an important part of tuberculosis control. The current method, the tuberculin skin test (TST), has poor specificity because of the antigenic cross-reactivity of purified protein derivative (PPD) with M bovis BCG vaccine and environmental mycobacteria. ESAT-6 is a secreted antigen that is highly specific for M tuberculosis complex, but is absent from M bovis BCG. With an enzyme-linked immunospot (ELISPOT) assay for interferon gamma, we have identified ESAT-6-specific T cells as an accurate marker of M tuberculosis infection. We did a prospective, masked study of 50 healthy contacts, with varying but well defined degrees of exposure to M tuberculosis, who attended an urban contact-tracing clinic. We assessed and compared the efficacy of our assay and TST for detection of symptomless infected individuals by correlation of test results with the degree of exposure to an infectious index case. The ESAT-6 ELISPOT assay results had a strong positive relation with increasing intensity of exposure (odds ratio=9.0 per unit increase in level of exposure [95% CI 2.6--31.6], p=0.001), whereas TST results had a weaker relation with exposure (1.9 [1.0--3.5], p=0.05). By contrast, ELISPOT results were not correlated with BCG vaccination status (p=0.7), whereas TST results were significantly more likely to be positive in BCG-vaccinated contacts (12.1 [1.3--115.7], p=0.03). This new antigen-specific T cell-based assay could allow more accurate identification of symptom-free individuals recently exposed to M tuberculosis, and thereby help to improve tuberculosis control.

Prevalence of celiac antibodies in children with neurologic disorders

Neurologic complications are a recognized but unusual manifestation of celiac disease (CD) in adults and children. The use of antigliadin and antiendomysial antibodies in screening has revealed the frequency of CD among symptom-free individuals to be high. Recently, a high frequency (57%) of antigliadin antibodies was demonstrated in adult patients with neurologic dysfunctions of unknown cause. We investigated the yield of screening for CD in children with common neurologic disorders. One hundred sixty-seven children, 1-16 years of age, were included in the study: 41 with migraine headaches, 39 with attention-deficit disorder with or without hyperactivity, 36 with epileptic disorders, and 51 with hypotonia and motor abnormalities. Positive IgG antigliadin antibodies were evident in 22 children (13%) in the study group compared with three children (9%) in the control group. However, in all children, negative IgA and endomysial antibodies were observed; thus duodenal biopsies were not performed. Contrary to studies performed in adults, these results did not demonstrate any relationship between common neurologic disorders without a specific diagnosis during childhood and CD. Thus screening for CD does not need to be routinely included in the diagnostic evaluation of children with these disorders.

The Dilemma of Antenatal HIV Testing: What Goes on in the European Community?

The aura of therapeutic nihilism that embraced the diagnosis of HIV seropositivity in symptom-free individuals at the beginning of the 1990s has largely been dispersed, so that official advice is that on balance it is better to know than not to knowl2. Nowhere is this more true than in the sphere of maternity care. In addition to the basic benefits to the woman herself, there is the important issue of mother-tochild transmission3. Not only has a serious and usually lethal infection of infants and children been recognized, but also we have now learned that transmission of this disorder from mother to child can largely be prevented by measures taken during late pregnancy, during labour and in the early neonatal period. These include prophylactic anti-retroviral therapy given to the mother4, avoidance of breastfeeding5 and caesarean section6. If we wish to achieve a substantial reduction in HIV transmission from mother to child, a fundamental requirement is to know the sero-status of the mother in time for appropriate interventions. This requirement has provoked a maelstrom of ethical, legal, special-interest, professional and economic arguments in an area already made tempestuous by issues of confidentiality, insurance loading, discrimination and minority rights, together with the move towards 'demedicalization'7.

Hereditary cerebral cavernous angiomas: clinical and genetic features in 57 French families

Cavernous angiomas, which are vascular malformations mostly located in the central nervous system, may be inherited as an autosomal dominant disorder known as familial cerebral cavernoma (FCC). FCC has been studied in Hispanoamerican families, in which a strong founder effect was shown. We studied the families of 57 non-Hispanic patients with cavernous angiomas. All 28 neurosurgery centres in France collaborated in the study. Inclusion criteria were: families of index patients known to have at least one clinically affected relative, and families of index patients with multiple cavernous angiomas who initially presented as sporadic cases. Clinical and cerebral magnetic resonance imaging (MRI) investigations were done in all patients and in other at-risk individuals who consented to take part. On MRI, 16 of 22 sporadic index patients had relatives with cavernous angiomas. 51 multiple-case families, including 100 patients with symptoms and 164 symptom-free individuals had MRI lesions. Most FCC patients had multiple lesions and there was a strong correlation between number of lesions and age (p<0.01). The sensitivity of gradient-echo sequences was higher than that of standard MRI for detection of small cavernous angiomas. Pattern of inheritance was autosomal dominant, with incomplete clinical penetrance. The occurrence of de-novo mutations was strongly suggested in some families. Neuroimaging penetrance of FCC is much higher than clinical penetrance. 75% of sporadic cases with multiple lesions are in fact familial cases. The proportion of patients developing clinical symptoms is higher in the hereditary form than in the sporadic form of the disorder.

HIV-1 suppression by early treatment with hydroxyurea, didanosine, and a protease inhibitor

Most HIV-1 production occurs in dividing (activated) Tlymphocytes. Non-dividing resting lymphocytes and macrophages, however, might be long-term reservoirs for HIV-1. We wanted to increase the antiviral efficacy of combination therapies by targeting simultaneously reservoir cells and the virus. Hydroxyurea blocks cellular activation necessary for viral replication in CD4 Tlymphocytes, protease-inhibitors inhibit HIV-1 replication in dividing cells, and hydroxyurea with didanosine is effective in non-dividing cells. 1,2 Eleven individuals were treated within 2 months after the onset of symptoms of primary HIV-1 infection and before complete serconversion, with a combination of hydroxyurea, didanosine, and indinavir. No greater than grade 2 toxicity was found, except for grade 3 episodes of nephrolithiasis in two patients; toxic events were resolved by switching from indinavir to nelfinavir. CD4 counts increased significantly by an average of 207 whereas CD8 counts decreased by an average of 399. CD4/CD8 ratio returned to normal in nine of eleven treated patients. This increase of CD4 counts was unexpected because the combination of hydroxyurea with didanosine, despite synergistic HIV-1 inhibition, in symptom-free individuals with CD4 counts between 200 and 500/mL, had not resulted in a significant increase of CD4 T-lymphocytes. 3

Does malarial tolerance, through nitric oxide, explain the low incidence of autoimmune disease in tropical Africa?

Autoimmune disease is generally rare in tropical rural populations. Plasma concentrations of nitrite plus nitrate (reactive nitrogen intermediates), reflecting high nitric-oxide production somewhere in the body, can be high in patients who have cerebral malaria, but even higher in symptom-free parasitised individuals, who are termed malaria-tolerant. We propose that the nitric oxide causing high serum levels of reactive nitrogen intermediates in malaria-tolerant individuals is generated in macrophages during the establishment and maintenance of malarial tolerance, and makes autoimmune disease rare in many tropical rural populations by minimising proliferation of autoreactive T cells. Conversely, innately low levels of nitric-oxide generation in these populations, selected by malarial disease in tropical areas, could rationalise their high frequency of autoimmune disease and hypertension when living in western societies.

Frequent infection of peripheral blood CD8-positive T-lymphocytes with HIV-1

Although lymphocytes expressing the CD4 surface receptor for HIV-1 have been identified as the principal target of the virus, the extent to which infection of other cell types of the immune system contributes to immunodeficiency is unknown. We investigated the cell types in peripheral blood infected with HIV and the relation of viral load in different subsets to disease progression. The study group consisted of 16 HIV-infected individuals, eight of whom had clinically defined AIDS with CD4 cell counts less than 200/microL blood. The main component subsets of peripheral blood mononuclear cells were purified by magnetic bead separation, and included CD4 and CD8 lymphocytes, B lymphocytes, monocytes, and dendritic cells. HIV proviral sequences within these separate populations were quantified by limiting-dilution nested polymerase chain reaction. HIV-1 proviral sequences were detected in T-helper cells, cytotoxic T cells, dendritic cells, and monocytes. CD4 T lymphocytes constituted the main reservoir of HIV in all but one of the symptom-free individuals studied (those with CD4 count > 200/microL). However, in all the individuals with CD4 counts of less than 200/microL, most infected cells within the peripheral blood mononuclear cell fraction were either dendritic cells or CD8 lymphocytes. Infection of CD8 cells accounted for between 66% and 97% of total proviral load in five of the eight AIDS patients. A strong inverse relation between total CD8 count and the frequency of CD8 T-lymphocyte infection was found. This study provides evidence for widespread infection of lymphocytes of the CD8 phenotype, indicating that HIV-1 has a broader tropism for different cell types in vivo than described for cultured virus. Infection of CD8 cells may contribute to the decline of this subset upon disease progression in HIV-infected individuals. Infection of CD8 cells may or may not occur by a non-CD4-dependent mechanism of virus entry.

Circulating HCV-RNA, HCV genotype, and liver histology in asymptomatic individuals reactive for anti-HCV antibody and their follow-up study.

The present study was aimed to clarify the virologic status, liver histologies, and the results of follow-up liver tests in symptom-free individuals with anti-HCV antibodies and normal liver tests. Forty-nine individuals with normal liver tests and positive second generation anti-HCV antibody assay were entered into this study. Cases with hepatitis C viremia were evaluated for HCV genotype, amount of circulating HCV-RNA, and liver histology and were followed-up for more than one year. Of the forty-nine individuals, 36 had hepatitis C viremia, indicated by polymerase chain reaction (PCR) assay. Liver histology was as follows: 3 had non-specific changes, 25 had chronic persistent hepatitis (CPH), and 8 had chronic active hepatitis (CAH). Twenty-four cases with CPH and CAH developed an elevated AST and/or ALT concentration (> 30 IU/l) between 12 and 32 months of follow-up. The amount of circulating HCV-RNA ranged from 10(2) to 10(7) copies/50 microliters serum. The distribution of HCV genotypes was nearly the same as that for symptomatic CAH. These data suggest that the histological examination and follow-up examination are very important for following symptom-free individuals with hepatitis C viremia because there are some candidates for interferon therapy among them. There are few individuals who will remain healthy among asymptomatic HCV carriers.