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Biomedical subjects

J Catalan

Publications and source records attributed to J Catalan.

At least 19 recordsLinked to original sources

Risk of HIV dementia and opportunistic brain disease in AIDS and zidovudine therapy.

OBJECTIVE: To determine the incidence of HIV dementia and opportunistic brain disease in AIDS relative to the use of licensed antiretoviral medication (zidovudine, zalcitabine, didanosine, and stavudine). METHOD: Medical records were evaluated retrospectively in a longitudinal cohort of 1109 patients with AIDS during the period 1991-4. Treatment groups were defined by start and duration of zidovudine treatment, the drugs used most often during this period were: (a) no zidovudine, (b) zidovudine before AIDS, (c) zidovudine before and after AIDS, and (d) zidovudine used in AIDS. Main outcome measures were cumulative incidence and survival from AIDS to onset of HIV dementia, progressive multifocal leukoencephalopathy (PML), cerebral toxoplasmosis, and primary CNS lymphoma. RESULTS: Risk of brain disease including HIV dementia and opportunistic brain disease was reduced in patients who started zidovudine before AIDS and continued in AIDS (relative risk (RR) 0.55, 95% confidence interval (95% CI) 0.36-0.84) as well as zidovudine initiated in AIDS (RR 0.27, 95% CI 0.17-0.45) compared with untreated subjects. Treatment effects were not constant over time, decreasing by 14%-32% for each six months of follow up. This was supported by unadjusted incidences across groups stratified by duration of zidovudine use, indicating reduced risk with treatment for up to 18 months but not with longer duration of use of zidovudine. Other antiretroviral drugs had no significant effect, although these were used by only 14% of patients in this cohort. CONCLUSION: The time limited but effective neuroprotection offered by zidovudine monotherapy for <18 months suggests that non-specific mechanisms of cerebral immunological defence may benefit from antiretroviral treatment. Due to the limitations of a retrospective study these findings require confirmation and further investigation in the context of current combination drug treatments.

AIDS Dementia Complex

Neurophysiological changes associated with psychiatric symptoms in HIV-infected individuals without AIDS.

HIV-1 infection may be complicated by a number of psychopathological conditions. While organic mental disorders, such as HIV-related psychosis and dementia, are late manifestations, mood disorders may occur during both asymptomatic and symptomatic stages of infection. The possible impact of brain involvement due to neurotropism of HIV-1 has not been investigated systematically in these latter conditions. The psychiatric caseness of HIV-seropositive individuals without AIDS and seronegative controls was assessed using a standardized clinical interview (Present State Examination). A comparison was made between individuals with and without psychiatric caseness using clinical, neuropsychological, and neurophysiological assessments. An increased prevalence of current psychiatric illness was found in subjects with early symptomatic HIV infection compared to those with asymptomatic infection and controls. This could not be attributed to psychiatric history, as well as to clinical and immunological markers of HIV infection, however, psychiatric caseness in early symptomatic infection was associated with marked neurophysiological changes, detectable by quantitative electroencephalography. Altogether, this study provided preliminary evidence that psychiatric symptoms in symptomatic but not asymptomatic HIV infection may be associated with subtle brain involvement preceding the immunological and neurocognitive impairment characteristic for AIDS.

Adult

Treatment of HIV-related psychotic disorders with risperidone: a series of 21 cases.

We describe a consecutive series of 21 patients with HIV or AIDS who received risperidone for psychotic disorders. Of these, 13 became symptom-free, 7 showed substantial improvement, and 1 had no response. Most responded to low doses of risperidone (mean maximum dose 3.3 mg) and needed only a short course of treatment (mean 6.4 weeks). The 12 manic patients did particularly well: 9 became symptom-free and the mean Young mania rating scale fell from 28.36 to 3.91. No serious adverse effects were reported. Three patients became drowsy and two experienced drooling, but these resolved after dose reductions or at the end of treatment. No adverse hematological effects were observed. We suggest that risperidone may be the treatment of choice for patients with HIV-related psychotic disorders.

Acquired Immunodeficiency Syndrome

Reasons given by patients for "non-progression' in HIV infection.

Identification of the reasons for long-term survival in HIV infection is an area of current intense research. The objective of this study was to determine the perceptions among patients with different rates of disease progression as to the reasons for a good outcome with HIV. In a case-control study of 134 long-term (> or = 8 years) HIV-infected participants, 62 were defined as non-progressors; current CD4 cell count > or = 500 x 10(6)/L and asymptomatic or only mildly symptomatic. Two groups of control patients were identified: intermediate progressors who also had been HIV-infected for > or = 8 years, but whose current CD4 cell count was < 500 x 10(6)/L (n = 61), and a group of rapid progressors who had developed AIDS within 5 years of HIV infection (n = 11). Non-progressors were asked 'what do you feel are the reasons for your good outcome with HIV-infection?' and intermediate and rapid progressors were asked 'what do you feel are the reasons for a good outcome with HIV infection?'. Mental attitude, and in particular a positive outlook was the reason most frequently given for a good outcome among both non-progressors (NP) 42%, and progressors (P) 40%, followed by lifestyle measures and personal action (NP 31%, P 35%). Medical treatments such as anti-retroviral drugs were rarely suggested (< 3%). No significant differences were observed in the frequency of the different reasons given by non-progressors and progressors. The belief among our long-term HIV-infected individuals, that a positive outlook, lifestyle and personal action are important determinants of a good prognosis, is in sharp contrast to the biomedical model of disease progression that prevails among the medical and scientific research community.

Acquired Immunodeficiency Syndrome

Cerebral proton magnetic resonance spectroscopy in asymptomatic HIV infection.

OBJECTIVE: To determine whether proton magnetic resonance spectroscopy (MRS) demonstrates central nervous system abnormalities in asymptomatic HIV-1-infected individuals. DESIGN: Both prospective and retrospective cross-sectional analyses of MRS in asymptomatic HIV-infected individuals. SETTING: Two specialists HIV/AIDS outpatient facilities in London. PARTICIPANTS: Eighty-four HIV-1 seropositive asymptomatic men; 29 HIV-1 antibody-negative homosexual men at high-risk for HIV infection and 48 HIV-1 antibody-negative men at low-risk for HIV infection as controls. MAIN OUTCOME MEASURES: Single voxel, gradient-localized proton MRS performed at 1.5 T with 135 msec echo-time and 1,600 msec repeat-time in an 8 ml volume of interest positioned in the parieto-occipital white matter. Spectroscopic results were expressed as ratios between the areas under the N-acetyl (NA), creatine (Cr) and choline (Cho) resonance peaks. RESULTS: There were no differences between those controls at high and those at low-risk for HIV infection. Comparing the combined control groups with the asymptomatic seropositive patients there were statistically significant differences in NA/Cho, NA/Cr (both P < 0.05) and NA/(NA + Cho + Cr) (P < 0.01). CONCLUSION: Abnormalities in cerebral biochemistry may be demonstrated by proton MRS during asymptomatic HIV-1 infection.

Brain

The psychological impact on staff of caring for people with serious diseases: the case of HIV infection and oncology.

Psychological stress and work-related burnout in staff working with AIDS and with cancer patients were compared using a self-report method of assessment. Measures included the General Health Questionnaire (GHQ), Maslach Burnout Inventory (MBI), and the Social Adjustment Scale (SAS-M). More than 80% of those staff who were approached responded to the questionnaire, including 70 doctors and nurses working with people with AIDS and 41 doctors and nurses working in oncology. More than a third of staff had substantial levels of psychological morbidity, and about a fifth had significant levels of work-related stress. Factors associated with the presence of high levels of psychological morbidity and with abnormal levels of emotional exhaustion, depersonalization, and concerns about personal accomplishment were identified. Staff described the work situations with which they had difficulty dealing and some of the coping strategies they used. The findings confirm that staff working with people with cancer or AIDS experience psychological difficulties of the kind likely to respond to interventions aimed at improving their ability to cope with work-related stresses. The mental health services could play an important role in carrying out research in this field and in providing practical help to deal with staff's difficulties.

Acquired Immunodeficiency Syndrome

Women and HIV infection: investigation of its psychosocial consequences.

HIV infection is associated with substantial psychological and social morbidity, although there is a dearth of studies of women with the infection. In recent years, developed countries have reported an increase in the prevalence of HIV infection in women, a fact that makes it all the more important to address the study of their psychological and social status. The study is a controlled investigation of HIV seropositive (n = 49) and seronegative women (n = 43), including study of psychological status and history, social functioning and perceived supports, coping style, life events, and sexual difficulties. The results show that about a third of women were psychiatric cases, regardless of HIV status, although more than half of symptomatic women were psychiatric cases. Seropositive women were less likely to use instrumental social supports and more likely to use mental disengagement as ways of coping. Regarding perceived social supports, positive women had lower scores on social integration and guidance. Positive women were more likely to experience sexual difficulties and not to be in a relationship. Negative women reported more adverse life events in the last 6 months. Psychiatric morbidity was associated with poorer social adjustment and more adverse life events, but not with serostatus. HIV positive women and those at risk of HIV infection have substantial levels of psychological and social morbidity that require recognition by those involved in their care and provision of adequate mental health intervention.

Adaptation, Psychological

Cloning, expression and functional activities of a single chain antibody fragment directed to fusion protein of respiratory syncytial virus.

BACKGROUND: HNK20 is a murine IgA which is currently being investigated in clinical trials against respiratory syncytial virus (RSV) infections in infants and young children. OBJECTIVE: To produce a single chain antibody fragment (scFv) from HNK20 hybridoma cells and assess its functional activities in vitro and in vivo (mouse model). STUDY DESIGN: The V regions of heavy and light chains were cloned and linked by a sequence encoding for (Gly4 Ser)3 and expressed in Escherichia coli. RESULTS: Over 100 mg/l of the HNK20-scFv was produced in shake flasks after induction with isopropyl (beta-D-thiogalactopyranoside (IPTG). ScFv was purified under native conditions on a Ni2+ affinity column and migrated as a single band of 34 kDa on sodium dodecyl sulfate (SDS)-gels. ScFv demonstrated similar affinity as its parent IgA molecule, neutralized RSV in vitro and significantly reduced RSV titers in lungs of mice when administered intranasally shortly before or a day after RSV challenge. CONCLUSION: It is possible that this scFv or its derivatives, when applied by intranasal or pulmonary route, will be useful for treatment of RSV infections in infants and young children.

Animals

Prospective associations between lateralised brain function and immune status in HIV infection: analysis of EEG, cognition and mood over 30 months.

Prospective relations between individual differences in both lateralised neuro-psychophysiological functions and mood ratings with immune status (CD4 and CD8 counts) were examined in asymptomatic HIV-positive men (n = 27) over thirty months. They participated in a controlled study of zidovudine versus placebo (results published elsewhere). Measures included EEG spectra, neuropsychological tests and mood ratings. A model of reciprocal lateralised influences on the immune system was tested whereby patients with left superior to right hemispheric functions were predicted to show a less deleterious outcome than those with the opposite asymmetry pattern. Prospective relations with immune status were found in the EEG with lateralised theta, alpha and beta activity; among cognitive measures with word fluency, semantic processing, and lateralised motor and recognition memory (word/face) processes; with mood ratings including depression, confusion and the total mood score. The nature of the effects supported the laterality predictions. These unique data, showing that neuro-psychophysiological factors in HIV+ but otherwise healthy subjects predict immune competence and compromise present 2-3 years later, warrant replication in a larger cohort.

Adult

Genomic incompatibilities in the hybrid zone between house mice in Denmark: evidence from steep and non-coincident chromosomal clines for Robertsonian fusions.

The pattern of chromosomal variation is investigated in house mice from the Danish hybrid zone between the translocation-prone Mus musculus domesticus and the chromosomally conservative M. m. musculus. The cytogenetic analysis confirmed the non-introgression of three pairs of Robertsonian (Rb) fusions from M. m. domesticus into the M. m. musculus genome. The geographic distribution of two of these Rb fusions was shown to follow staggered chromosomal clines which increased in steepness the closer they were to the centre of the hybrid zone as defined by allozymes. Analysis of alternate hypotheses suggests that chromosomal differentiation of the Danish domesticus occurred after contact was established with musculus. The staggering of the clines would reflect the order of arrival of the Rb fusions into the hybrid zone. Several models with different processes of underdominance of the chromosomal heterozygotes are discussed to account for the difference in width between clines. A selective model with increasing levels of genomic underdominance due to interaction with a progressively enriched musculus genome provides the best fit for the observed pattern. Selection against Rb fusions with little effect on the recombination of linked allozyme markers supports the view that no reduction in gene flow due to chromosomal heterozygosity is yet apparent through the hybrid zone and that only the centromeric segments of the Rb fusions are incompatible with the musculus genome.

Animals

Unconventional organization of amplified esterase B gene in insecticide-resistant mosquitoes of the Culex pipiens complex.

The amplified esterase B gene responsible for resistance to organophosphorus insecticides in Culex mosquitoes is shown to form a DNA "puff" in salivary gland polytene chromosomes. This "puff" is absent in susceptible mosquitoes lacking the amplified gene, and unlike all puffs known today, it is neither related to development nor involved in protein synthesis. The "puff" therefore corresponds to a special arrangement of the very large number of copies (possibly up to 250,000) of the 25-30-kb DNA fragment encompassing the esterase B structural gene in polytene chromosomes. In addition, the amplified and nonamplified esterase B gene(s) were found to be localized on chromosome 2L, and flanked by identical banding patterns, indicating the absence of an important chromosome rearrangement before, during, or after gene amplification.

Animals

Neurophysiological evaluation of zidovudine in asymptomatic HIV-1 infection: a longitudinal placebo-controlled study.

The effect of early antiretroviral medication with zidovudine on neurophysiological functions was evaluated in subjects with asymptomatic HIV-1 infection. Patients were recruited participants of a larger double-blind randomised placebo-controlled treatment trial with zidovudine (Concorde). The main outcome measures included: quantitative electroencephalography (QEEG), auditory event-related potentials (AEP) and pattern-reversal visual evoked potentials (PRVEP), as well as standard clinical, virological and immunological markers. No significant impairment and no difference between treatment groups was found in visual P100 latency and auditory long-latency P3 responses which is in agreement with the absence of neurological and neuropsychological impairment over the study period. Significant treatment effects were revealed by quantitative electroencephalography (QEEG). While the placebo group showed a significant increase in delta and theta slow frequency QEEG activity over the study period, slow wave amplitude remained unchanged in the zidovudine group after a mean follow-up period of 28 months. In summary, the data provide evidence for a low level neuropathological process in asymptomatic HIV-1 infection which can be effectively suppressed by antiretroviral medication.

Adult

Sister-chromatid exchanges in cattle: breed, sex and BrdU dose effects.

The spontaneous incidence of sister-chromatid exchanges (SCE) was investigated in a group of cattle, composed of 21 animals of both sexes and from two different breeds (Fleckvieh and Pirenaica). Peripheral lymphocytes of these animals were cultured in three different bromodeoxyuridine (BrdU) concentrations: 5, 15 and 30 micrograms/ml. The work was carried out following a randomized block design. Among the analyzed sources of variability, group, breed and BrdU dose factors had significant effects on the SCE frequency. No differences between sexes were found. Comparisons of the BdrU doses showed that the 5 micrograms/ml dose differed from both the 15 and 30 micrograms/ml doses, whereas the 15 and 30 micrograms/ml doses did not differ from each other. The results indicate that the breed of cattle as well as the BrdU dose chosen for the analysis must be considered when the SCE test is used for the biomonitoring of environmental mutagens.

Analysis of Variance

Suicidal behaviour and HIV infection--is there a link?

The association between suicidal behaviour and HIV infection has been the subject of much attention in recent years. In this paper we review the evidence about the prevalence of suicide, suicidal ideation and deliberate self-harm in individuals with HIV infection. Finally we discuss the significance of the findings, in particular some of the methodological problems encountered in this field.

Acquired Immunodeficiency Syndrome

Psychological distress among gay men supporting a lover or partner with AIDS: a pilot study.

To date, there has been little research to examine how much psychological distress is caused to people providing care and support to a lover or partner with AIDS. This study aimed to determine the level of psychological distress experienced by a sample of gay men providing care and support to a lover or partner with AIDS. It was conducted as a cross-sectional questionnaire survey. A control group was not enlisted, thus the study was descriptive in nature. The experimental hypothesis proposed that providing care and support would result in a high level of psychological distress. Thirty-eight gay men, some of whom themselves were infected with HIV, who were the primary carer of a lover or partner with an AIDS diagnosis were assessed using a self-report questionnaire. The 28-item General Health Questionnaire was used as a measure of global psychological distress. In addition, Martin's (1988) Traumatic Stress Response Scale was used as a measure of psychological distress arising specifically from AIDS. The sample reported high levels of global and AIDS-specific psychological distress. The levels of distress reported were of such a degree to indicate that the majority of the sample were probably suffering from significant psychiatric problems. The results strongly suggest that providing care and support to a lover or partner with AIDS may have an adverse affect on the carer's own psychological health: however, because of the design of the study it is impossible to state this conclusively.

Acquired Immunodeficiency Syndrome