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Biomedical subjects

M Popescu

Publications and source records attributed to M Popescu.

At least 19 recordsLinked to original sources

[Cytomegalovirus retinitis in AIDS. Effectiveness and complications of long-term therapy].

In a retrospective study of the records of 64 patients with AIDS and cytomegalovirus (CMV) retinitis, 47 patients were evaluated regarding the effectiveness of initial virustatic therapy, and 41 patients regarding the anatomical and functional long-term development (maintenance therapy, rate and intervals of recurrences, complications, adverse drug reactions, time of survival, and visual outcome). The average survival time of 45 treated patients was 226 days (31-717 days). More than 90% responded to initial therapy with ganciclovir or foscarnet. Forty-four percent remained free of recurrences until they died (for up to 15 months); 56% had 1 to 4 recurrences, altogether 35 episodes, of which 14 occurred after withdrawal of therapy. Recurrences were treated with high-dose reinduction therapy with good or partial response in more than 80% of cases. Nine patients showed "smouldering retinitis" at a late stage. Two out of 45 patients became blind shortly after diagnosis despite therapy; both showed a course mimicking acute retinal necrosis syndrome with histologically proven CMV disease. None of the 43 patients on maintenance therapy for up to 2 years became blind in both eyes. Only 2 out of 43 patients had a poor visual outcome < 40/100 in the better eye at a late disease stage. Of 60 affected eyes, 11 showed retinal detachment, 14 eyes developed optic atrophy and 12 eyes became blind. Our retrospective study shows that consistent maintenance therapy of patients with CMV retinitis prevents severe deterioration of visual acuity in most cases even in long disease courses and thus maintains quality of life.

AIDS-Related Opportunistic Infections

Chronobiology of pituitary-thyroid functions.

One hundred ninety four children, 11 +/- 1.5 years of age and 166 elderly men and women, 77 +/- 8 years of age were studied over one or (in the case of some of the elderly subjects) over several (up to 4) 24-hours spans. All subjects were diurnally active and rested at night and followed their regular three meal pattern. The subjects were studied in subgroups of 20-25 during all four seasons of the year. During each study, blood was collected at 4 hour intervals over one 24-hour span (6 samples). Circadian and circannual variations were found and described by cosinor analysis in the children as well as in the elderly subjects. The children with endemic goiter (134) as compared to those without endemic goiter (60) showed a slight circadian phase advance in plasma total and free T3, a lower circadian amplitude of total T4 concentrations and the absence of a detectable circadian rhythm in free T4. The children with goiter showed a phase delay in serum TBG. There was no difference between the children with and without goiter in the circadian MESOR of any thyroid parameter or of TSH. The children with endemic goiter in the region of Dimboviţa, Romania, are in clinical and biochemically euthyroid condition with some slight poral abnormalities of thyroid function. Seasonal variations in children and elderly patients showed the highest values of TSH during summer and fall, while the highest values in the plasma concentrations of thyroid hormones were found during the cold season of the years. Thyroglobulin in the children showed a circadian rhythm but no seasonal variation.

Aged

[Incidence of psychiatric syndromes and the psychosocial functional level of patients with HIV-1 infection].

There are not yet unselected studies on psychopathological syndromes in the course of HIV-infection in German-speaking countries. In a group of 55 patients in different stages of the infection two psychiatric explorations were done within an interval of about one year. The findings were analysed by the Brief Psychiatric Rating Scale (BPRS). The degree of psychosocial functioning was estimated using the GAF-scale (axis 5 of DSM-III-R). The diagnosis of dementia was based on DSM-III-R-criteria. Most of the patients (72%) showed normal or only slightly remarkable psychopathologic findings at both times. A significant increase in psychopathologic conspicuousness in the course of the disease was only found for the subscore BPRS 2 ("anergia"). Dementia was seen in five patients (9%) and only in the stage of manifest immune deficiency syndrome (WR 6). All-together there was only a slight decrease of psychosocial functioning detectable (median on the GAF-scale 75), which only in dementia showed a significant reduction.

AIDS Dementia Complex

[HIV-associated lymphomas].

Forty-one HIV-positive homosexual men (mean age 39.8 [23-72] years) with malignant lymphomas were examined with the object of exploring the clinical and pathological spectrum of HIV-associated lymphomas in Central Europe, and their therapeutic aspects. There were 33 patients with non-Hodgkin lymphoma of high malignancy and four with non-Hodgkin lymphoma of low malignancy; four further patients suffered from Hodgkin's disease. 27 patients died during the period of observation. The mean survival period after diagnosis was 5.5 months. It depended on the stage reached by the lymphoma at the time of diagnosis: 11.8 months in stage I, 10.6 months in stage II, 7 months in stage III, 3.3 months in stage IV and 1.3 months in patients with primary involvement of the central nervous system by the lymphoma. Eight out of nine patients with highly malignant non-Hodgkin lymphoma in stage I or II attained complete and lasting remissions after chemotherapy or irradiation. However, only minimal prolongation of life was achieved in the 16 patients with lymphomas in stages III or IV. The response rate among all patients treated (complete and partial remissions) was 75%; 45% achieved complete remission. Hodgkin's disease responded well to standard therapy, but the disease rapidly recurred in every case.

Adult

Circadian, weekly, and seasonal variations in cardiac mortality, blood pressure, and catecholamine excretion.

Time of occurrence of cardiac death due to arrhythmia, heart failure, or acute myocardial infarction was recorded in 86 elderly subjects, belonging to a group in whom circadian and circannual rhythms in blood pressure and urinary catecholamine excretion had been studied previously. All patients were retired, with no work responsibilities, and lived--closely-supervised in a home for the aged--on a routine that provided little differences between weekdays and weekends. Cardiac mortality showed a circadian variation, with a peak in the early morning hours, coinciding with the circadian peak in systolic and diastolic blood pressures. A weekly (circaseptan) variation in cardiac mortality was found, with the greatest number of patients dying on Mondays and the least on Thursdays. There were seasonal differences in cardiac mortality, with a peak in July and a broader peak during the cold season (December to February). The former coincides with the circannual peak in diastolic blood pressure, but is unrelated to the seasonal variation in norepinephrine excretion. Circadian, circaseptan, and circannual variations in cardiac mortality appear to be the expression of time-dependent, transient risk states for catastrophic cardiac events, which may lend themselves to preventive treatment.

Aged

Self-reported sleep quality in HIV infection: correlation to the stage of infection and zidovudine therapy.

We investigated self-reported sleep quality in a group of 50 patients in different stages of HIV-1 infection by using a standardized questionnaire (Pittsburgh Sleep Quality Index). Alterations of sleep were found to be significantly correlated with the most severe stage of infection in AIDS patients. Analysis of data failed to indicate a significant influence of zidovudine on self-reported sleep quality.

Adult

Comparison of serum and urine neopterin concentrations in patients with HIV-1 infection.

Urine and serum neopterin concentrations are now widely used to monitor patients with HIV-1 infection. However, there are no published studies comparing the levels in urine and serum, and relating both to the patients' immune status. Urine and serum neopterin concentrations correlated closely in our study population of 37 HIV-1 seropositive patients (34 homosexuals, 3 drug addicts) and 10 HIV-1 seronegative homosexuals. Our data further show that urine and serum neopterin concentrations correlate almost identically with the clinical and immunological presentation of HIV-1 infected individuals, as expressed by the Walter Reed Staging classification. In addition, there was no difference between the correlation of neopterin concentrations in either serum or urine with the Quetelet indices. It will depend on the clinical situation whether blood or urine sampling is preferred. Collection and handling of urine samples from HIV infected patients is less risky to health care personnel in HIV settings.

Adult

Immune activation markers to predict AIDS and survival in HIV-1 seropositives.

Neopterin concentrations in body fluids of HIV-1 seropositives provide predictive information. In 1986, we examined serum and urine neopterin concentrations in 29 HIV-1 seropositives. Serum levels of soluble IL-2 receptor (sIL2R), soluble CD8 (sCD8), tumour necrosis factor alpha (TNF-alpha) and circulating immune complexes (CIC) were retrospectively analysed in 1989. All individuals had increased serum and urine neopterin, sIL2R and CIC concentrations, 27/29 had increased sCD8 concentrations, whereas all had normal TNF-alpha levels. During a 3-year follow-up, high urine and serum neopterin concentrations were significantly associated with progression to AIDS and with the occurrence of AIDS-associated death. Both neopterin variables were of similar predictive value (p less than 0.001, generalized Wilcoxon test). sIL2R concentrations were of borderline significance in predicting the onset of AIDS (p = 0.05). All other parameters lacked predictive information in our study. We conclude, that chronic immune activation is detectable in almost all HIV-1 seropositives. Chronic immune activation may be associated with HIV-1 replication and may contribute to the immunopathology of HIV-1 infection.

Acquired Immunodeficiency Syndrome

Studies of water permeability and proteins of erythrocyte membranes in patients with Duchenne muscular dystrophy.

The characteristics of water permeability of erythrocytes from 54 Duchenne muscular dystrophy (DMD) patients and age-matched controls have been determined by a pulse nuclear magnetic resonance (NMR) technique. A decreased permeability of erythrocyte membrane in DMD was definitely found at all temperatures between 15 and 42 degrees C, with normal values for the activation energy of water diffusion. No differences between DMD and control subjects in the pattern of erythrocyte membrane polypeptides separated by two-dimensional electrophoresis could be detected. The findings are discussed in relation to the molecular mechanisms of water diffusion across erythrocyte membrane and the problem of erythrocyte membrane abnormalities in DMD. A new interpretation of erythrocyte membrane alterations is proposed based on the recent findings regarding the molecular pathology of DMD.

Adolescent

Phospholipase C contracts visceral smooth muscle.

Phospholipase C added into the muscle bath (0.2-1.5 units/ml) contracted the guinea-pig taenia coli in a concentration-dependent manner. The fully developed contraction appeared within second, like the contractile effect evoked by 5 microM acetylcholine. Pharmacochemical dissection (using phospholipase D, indomethacin, neomycin, Li+, phorbol ester and oleoyl-acetyl-glycerol) showed that the contractions induced by exogenous phospholipase C are mediated by inositol trisphosphate, not by diacylglycerol. Thus, direct evidence is provided for the key role of the phospholipase C/inositol-trisphosphate system in smooth muscle contraction.

Animals

Procedure for titration of interleukin-2 based on direct observation of factor-dependent growth of cells.

A semi-quantitative procedure for titration of interleukin-2 (IL-2) without the use of radioactive labeling of IL-2 target cells was developed. The procedure is based on the observation that those cells cultivated in round-bottom wells formed visible cultures and that the dimension of these cultures decreased at higher dilutions of IL-2 in the medium. The end-point of the titration can be easily established by observing the cultures with a concave mirror placed under the titration plate. The procedure has been used for the determination of IL-2 during its purification and characterization.

Animals

Multiplication of lymphocytic choriomeningitis virus in thymocytes during its persistence in mice.

Persistence of lymphocytic choriomeningitis (LCM) virus in mice infected in utero or neonatally is due to impairment of the specific subsets of thymus-dependent lymphocytes which, in the adult normal mouse, are involved in elimination of LCM virus. Virus-thymocyte interactions were studied since it was likely that this impairment takes place in the thymus. Using an infectious centre assay, we found that about 1% of the thymocytes from foetal and neonatal mice were productively infected by the virus while thymocytes from older mice were refractory to infection. The infected cells were Thy 1-positive and agglutinated by peanut lectin together with immature lymphocytes. Later, when virus persistence was established, the number of infected thymocytes declined to about 0.1% and these cells were not agglutinated by lectin. The results are compatible with the assumption that thymic precursor T-cells capable of elimination LCM virus are chronically infected by the virus and rendered non-functional.

Aging

Infectious lymphocytes in lymphocytic choriomeningitis virus carrier mice.

The infectivity of blood and lymphoid organs of mice persistently infected with lymphocytic choriomeningitis virus was found to be predominantly associated with lymphocytes and both T and B cells were infectious. A hypothesis is presented in which it is assumed that lymphocytes in carrier mice are infected via their LCM virus-specific antigen receptors, thereby leading to their antigen-triggered clonal expansion followed by infection and functional inactivation.

Animals

Diversity of lymphocytic choriomeningitis virus: variation due to replication of the virus in the mouse.

Depending on passage history, strain WE infectious LCM virus either damages L cells more or less severely or leaves them morphologically intact. Correspondingly, the plaques which are formed on L cell monolayers are of different appearance, ranging from intensely turbid to clear. Multiplication of LCM virus in certain mouse organs profoundly affects plaque characteristics. The brain, for instance, favours lytic variants while the spleen supports the replication of virus which forms turbid plaques. This statement holds if virus taken from organs of persistently infected mice or virus passaged from mouse to mouse is analysed and is true also if the initial preparation contains virus forming predominantly either clear or turbid plaques on L cell monolayers. Selection is not rapid and not absolute. It may take months of multiplication before a final state is reached, and even then the number of characteristic plaques is usually in great excess of the rest but never reaches 100%. Cloning procedures may alter the proportions, but with our experimental conditions no plaque has ever been isolated which would retain its characteristics upon passage. Differences of plaque type morphology were not reflected in differences of pathogenic properties, and both clear and turbid variants caused persistent infection if used to infect newborn mice and led to disease with signs of neurological involvement and death if inoculated intracerebrally into adult animals.

Animals