[Exanthema in multiple therapy in HIV infection].
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Biomedical subjects
Publications and source records attributed to M Weisser.
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The question whether the natural history of HIV infection in women is affected by pregnancy has not so far been convincingly answered. We used prospective cohort data to compare pregnant and nonpregnant HIV-infected women during follow-up within the Swiss HIV Cohort Study (SHCS) and the Swiss Collaborative HIV and Pregnancy Study (SCHPS). Pregnant women were eligible if a CD4 cell count had been made before conception had taken place. Additional inclusion criteria were a pregnancy completed to delivery during follow-up and an observation period of at least 6 months after delivery. Thirty-two women who fulfilled these criteria were compared with 416 controls, matched for age and CD4 cell count at entry, who had not been pregnant during follow-up. Mean follow-up time was 4.8 years for pregnant women and 3.6 years for controls. The rate of any AIDS-defining event was higher in pregnant women (rate ratio [RR] from Cox regression, 1.92; 95% confidence interval [CI], 0.80-4.64) but this did not reach statistical significance (p = .15). A statistically significant difference (p = .008) emerged only for one AIDS-defining event, recurrent bacterial pneumonia (RR, 7.98; 95% CI, 1.73-36.8). The rate of death was similar in the two groups (RR, 1.14; 95% CI, 0.48-2.72; p = .8). Our results thus indicate that, after taking CD4 cell counts before conception into account, acceleration of disease progression is inconsistent among HIV-infected women who become pregnant during follow-up.
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Apoptosis is characterized by chromatin condensation and DNA fragmentation in the absence of release of cytosolic enzymes such as lactate dehydrogenase (LDH). In contrast, necrosis is characterized by cell swelling, membrane disintegration with cytosolic enzyme release, and absence of chromatin condensation. Staining of cells with Hoechst H33342 dye is a routine method for identifying apoptotic nuclei. However, this process is tedious and prone to individual bias. Therefore, we investigated the suitability of an artificial neural network (ANN) to recognize and distinguish between apoptosis and necrosis. Using a human endothelial cell line (ECV304), we trained an ANN with DNA-stained apoptotic and necrotic nuclei obtained from cells exposed for 8 h to cycloheximide (Chx; 100 microM)/tumour necrosis factor-alpha (TNF; 50 ng/ml) or tert-butylhydroperoxide (t-BH; 2 mM), respectively. After this training step, the ANN correctly assigned necrosis induced by t-BH and apoptosis induced via Chx/TNF, Chx/CD95 activation, Pseudomonas exotoxin A/TNF, or X-rays. In all cases, apoptosis and necrosis as assigned by the ANN correlated with DNA fragmentation and LDH release.
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The aim of this study was to characterize early ultrastructural, biochemical, and functional alterations of the pulmonary surfactant system induced by Salmonella minnesota lipopolysaccharide (LPS) in rat lungs. Experimental groups were: (1) control in vitro, 150 min perfusion; (2) LPS in vitro, 150 min perfusion, infusion of 50 microg/ml LPS after 40 min; (3) control ex vivo, 10 min perfusion; (4) LPS ex vivo, lungs perfused for 10 min from rats treated for 110 min with 20 mg/kg LPS intraperitoneally. Morphometry of type II pneumocytes showed that LPS increased stored surfactant. Lamellar bodies were increased in size, but decreased in numerical density, suggesting that giant lamellar bodies observed in LPS-treated lungs may result from fusion of normal bodies. Structural analysis of alveolar surfactant composition showed that LPS elicited an increase in lamellar body-like and multilamellar forms. Bronchoalveolar lavage (BAL) material from LPS-treated lungs was decreased in phospholipids. BAL bubble surfactometer analysis showed a reduction in hysteresis area caused by LPS. We conclude that LPS leads to alterations of intracellular and alveolar surfactant within 2 h: fusion of lamellar bodies, reduction in surfactant secretion, and changes in alveolar surfactant transformation, composition, and function, which may contribute to the development of respiratory distress.
In recent years the availability of highly active antiretroviral therapies and prophylaxis and treatment of opportunistic infections in patients with HIV-disease have reduced morbidity and mortality. Many different drugs may be prescribed in a patient simultaneously. Therefore, the potential for interactions between different substances is increased. The possible mechanisms of drug interaction concern pharmakokinetics (absorption, metabolism, elimination) and pharmakodynamics. They can lead to significant changes in plasma concentrations and may affect efficacy and toxicity of a drug. One of the most important mechanisms of interaction is the inhibition or induction of the hepatic cytochrome P-450 enzyme system. All protease-inhibitors are metabolized by CYP450, mostly by the subunit 3A4. Proteinase-inhibitors are themselves very potent inhibitors of CYP4503A4 and increase the concentration of drugs metabolized this way. This article summarises the most important mechanisms of drug interactions and demonstrates the most frequent and clinical significant consequences.
Plasmalogens-substantial compounds of brain tissue--suffer degradation either by hydrolysis under production of aldehydes or by oxidation with lipid peroxylradicals by generation of plasmalogen epoxides. The latter react by addition of pentafluorobenzylhydroxylamine HCl (PFBHA HCL) under hydrolysis to alpha-hydroxyaldehydes which are immediately transformed to pentafluorobenzyloximes (PFBO). Likewise, free aldehydes are transformed to PFBO-derivatives. PFBO-derivatives of free aldehydes and PFBO-derivatives of alpha-hydroxyaldehydes were extracted and after trimethylsilylation quantified by GC/FID and by GC/MSD. The remaining aqueous phase, containing plasmalogens besides other lipids, was hydrolyzed by treatment with acid. The hydrolysis products of plasmalogens, long chain aldehydes, react with PFBHA HCl to produce PFBO-derivatives. These were also quantified by GC/FID. This method allows the quantification of plasmalogens, free aldehydes and plasmalogenepoxides in human brain samples to study changes in the relation of these compounds with increasing age. While the ratio of plasmalogens in respect to derived aldehydes seems to remain constant during life time, the quotient of plasmalogenepoxides to plasmalogens increases with age, indicating that lipid peroxidation processes are involved in the damage of plasmalogens in the brain of aged individuals, starting at an age of about 70 years.
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The content of plasmalogens in bovine brain was investigated with respect to age. No difference between the plasmalogen content in brain of young and old individuals was detected. In old individuals, plasmalogens suffer much easier hydrolysis to corresponding aldehydes than in young ones. In addition, the brain of old animals contain an approx. 30-fold higher amount of free aldehydes and plasmalogen epoxides compared to young ones. Aldehydes, as well as derived alpha-hydroxyaldehydes, were trapped by addition of pentafluorobenzylaminehydrochloride. The resulting pentafluorobenzyloxime derivatives were enriched by thin-layer chromatography, transferred to trimethylsilyl derivatives and further investigated by GC/MS. Quantification was achieved by GC/FID as well as by GC/ECD.
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The combination of interstitial radiotherapy and interstitial hyperthermia is more promising in the treatment of tumors than one of these methods alone. The unit developed by us uses the afterloading needles for heating up the tumor tissue with ohm current and for controlling the distribution of temperature in the target volume. Up to twelve needles are provided by one commutator with the R.F. current controlled by the computer. The temperature is measured by three thermistors per needle which are arranged at an axial distance of 2 cm each. The linearization of the thermistor characteristics and the control of cummutator and R.F. generator is performed by the computer over an interface constructed by us. In order to achieve a homogeneous distribution of temperature in the target volume and to avoid hot spots, we have examined several needle configurations by measuring in an homogeneous phantom.
The study was supposed to develop a method allowing to combine interstitial hyperthermia with high dose rate afterloading therapy. For hyperthermia, metallic hollow needles, which are also used in brachytherapy, are connected with the RF source by a computer-controlled relay switch. The temperature is measured by thermistors incorporated into the needles. Several heating methods are investigated in a homogenous phantom and compared by means of the experimentally determined temperature/time evolutions and isotherms (in a stationary state).
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Two newborns with cogestive heart failure due to a congenital arterio-venous fistula involving the great vein of Galen are described. The main diagnostic criteria of this anomaly are a hyperactive heart, bounding carotid artery pulses, and a continuous murmur over the skull. The anomaly was visualized by cerebral angiography. In view of the frequent complications such as the development of hydrocephalus, operative treatment seems indicated.
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