bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of coffee on gastric emptying and oro‐caecal transit time
Authors: Boekema  , Lo  , Samsom  , Akkermans  , Smout  
Published: March 2003

BackgroundThe consumption of coffee allegedly induces or aggravates gastrointestinal symptoms. In order to investigate the effect of coffee on gastrointestinal motility we studied the effect of coffee on gastric emptying and oro‐caecal transit time.MethodsIn a randomised, controlled, cross‐over study gastric emptying and oro‐caecal transit time were studied in 12 healthy volunteers, using applied potential tomography and lactulose hydrogen breath test, respectively. After 1 day of coffee abstinence and an overnight fast, coffee or the control drink (water) was drunk and 10 min thereafter a liquid nutrient meal was ingested together with lactulose. During 150 min, recordings were made with applied potential tomography and breath samples were taken every 5 min. Lag‐phase duration and gastric half‐emptying time were determined by two blinded observers.ResultsThe lag‐phase duration after coffee (median 19.8 min, range 6–47 min) was not significantly different from that after water (median 19.3 min, range 11–37.5), nor was the gastric half‐emptying time (median 75.7 min, range 56–157.6 vs. median 83.4 min, range 64.6–148.4). Likewise, coffee had no significant effect on oro‐caecal transit time (median 135 min, range 60–270 vs. median 140 min, range 55–270). No significant correlation between any of these parameters and mean daily coffee intake was found.ConclusionsCoffee does not affect gastric emptying of a liquid meal or small bowel transit.
Fast, simple and highly sensitive double‐rounded polymerase chain reaction assay to detect medically relevant fungi in dermatological specimens
Authors: Turin  , Riva  , Galbiati  , Cainelli  
Published: March 2003

BackgroundEarly detection of fungal infection is essential for beginning of prompt and specific therapy. In this study we describe a rapid and sensitive procedure to detect, by polymerase chain reaction (PCR) assays, a wide range of medically important opportunistic and pathogenic fungi in dermal specimens from dermatomycoses‐affected patients.Materials and methodsThree primer pairs, amplifying fragments of the highly conserved gene coding for small ribosomal RNA (18S rDNA) and the adjacent internal transcribed spacer (ITS) rDNA, previously published by others, were probed on DNA from pure cultures of medically relevant human and animal fungal species. In order to evaluate the specificity of the assay, amplifications of control DNAs from other eukaryotes and prokaryotes were also carried out, and they gave negative results.ResultsThese primer sets, in single amplification or double‐rounded PCR assays, allowed specific amplification when applied to a wide number of fungal DNA from human and animal tissue specimens, including dermatophytes (genera Trichophyton, Microsporum), several yeast species (Candida, Saccharomyces, Cryptococcus, Malassezia) and moulds (Aspergillus, Penicillium). The PCR assay was able to detect as little as 10 pg of fungal DNA, corresponding to approximately 25 fungal genomes per sample specimen. A small‐scale DNA extraction method was also developed. This simple, time‐saving and sensitive procedure was successfully applied to 40 human and veterinary specimens, and the diagnosis was confirmed with cultural techniques, being shown to work even in the presence of other lesions or contaminating organisms.ConclusionsThis method allows early recognition of fungal pathogen cells in clinical samples as an alternative tool to conventional detection techniques.
Clinical importance of antibodies against platelet activating factor in antiphospholipid syndrome manifestations
Authors: Tektonidou  , Petrovas  , Ioannidis  , Vlachoyiannopoulos  , Moutsopoulos  
Published: March 2003

BackgroundWe assessed whether antibodies against platelet activating factor (PAF) are related to the presence of antiphospholipid syndrome (APS) clinical manifestations, in particular thrombosis, in patients with connective tissue diseases.Materials and methodsAnti‐PAF, anticardiolipin (aCL), antiβ2 glycoprotein I (antiβ2GPI) and antiphosphatidylcholine (anti‐PC) antibodies were determined in 52 patients with APS, 29 patients with systemic lupus erythematosus (SLE) aCL but without APS, 30 patients with SLE without aCL, and 30 patients with scleroderma. A new enzyme‐linked immunosorbent assay (ELISA) was developed for determining anti‐PAF antibodies in a bovine serum‐free fashion.ResultsThe ELISA showed high specificity. Homologous inhibition experiments showed 60–70% inhibition. Anti‐PAF antibodies were found in 18/52 APS patients, 10/29 SLE/aCL+ patients, 9/30 SLE/aCL− patients and 3/30 scleroderma patients. Anti‐PAF antibodies were significantly associated with anti‐PC antibodies (odds ratio [OR] 12.7, P < 0.01), and there was a modest association with immunoglobulin G (IgG) aCL (OR 3.1, P > 0.10), but not with IgM aCL or antiβ2GPI. Three SLE/aCL+ patients and five SLE/aCL− patients had clinical manifestations characteristic of APS. All these patients had anti‐PAF antibodies, while none had high titres of aCL or antiβ2GPI antibodies and only one had anti‐PC antibodies. Among the combined APS and SLE groups, the presence of anti‐PAF antibodies was significantly associated with clinical manifestations which are characteristic of APS (OR 2.6, P = 0.02). The effect was independent of IgG aCL and antiβ2GPI antibodies.ConclusionsAnti‐PAF antibodies are common in APS and SLE and comprise an independent factor for the development of thrombosis. Several patients experiencing thromboses have anti‐PAF antibodies without other antiphospholipid specificities.
Virological and immunological effects of antioxidant treatment in patients with HIV infection
Authors: Müller F. , Svardal A. M. , Nordøy I. , Berge R. K. , Aukrust P. , Frøland S. S. 
Published: March 2003

BackgroundIntracellular oxidative stress in CD4+ lymphocytes due to disturbed glutathione homeostasis may lead to impaired lymphocyte functions and enhanced HIV replication in patients with HIV infection, especially in those with advanced immunodeficiency. The aim of the present study was to assess whether short‐term, high‐dose antioxidant treatment might have effects on immunological and virological parameters in patients with HIV infection.Materials and methodsIn this pilot study, we examined virological and immunological effects of antioxidant combination treatment for 6 days with high doses of N‐acetylcysteine (NAC) and vitamin C in 8 patients with HIV infection. The following were assayed before, during and after antioxidant treatment: HIV RNA plasma levels; numbers of CD4+, CD8+, and CD14+ leukocytes in blood; plasma thiols; intracellular glutathione redox status in CD4+ lymphocytes and CD14+ monocytes; lymphocyte proliferation; lymphocyte apoptosis and plasma levels of tumour necrosis factor (TNF)α; soluble TNF receptors and neopterin in plasma.ResultsNo significant changes in HIV RNA plasma levels or CD4+ lymphocyte counts in blood were noted during antioxidant treatment in the patient group. However, in the 5 patients with the most advanced immunodeficiency (CD4+ lymphocyte counts < 200 × 106 L−1), a significant rise in CD4+ lymphocyte count, a reduction in HIV RNA plasma level of 0.8 log, an enhanced lymphocyte proliferation and an increased level of intracellular glutathione in CD4+ lymphocytes were found. No change in lymphocyte apoptosis was noted.ConclusionsShort‐term, high‐dose combination treatment with NAC and vitamin C in patients with HIV infection and advanced immunodeficiency lead to immunological and virological effects that might be of therapeutic value.
N‐acetylcysteine replenishes glutathione in HIV infection
Authors: De Rosa S.C. , Zaretsky M.D. , Dubs J.G. , Roederer M. , Anderson M. , Green A. , Mitra D. , Watanabe N. , Nakamura H. , Tjioe I. , Deresinski S.C. , Moore W.A. , Ela S.W. , Parks D. , Herzenberg L.A. , Herzenberg L.A. 
Published: March 2003

BackgroundGlutathione (GSH) deficiency is common in HIV‐infected individuals and is associated with impaired T cell function and impaired survival. N‐acetylcysteine (NAC) is used to replenish GSH that has been depleted by acetaminophen overdose. Studies here test oral administration of NAC for safe and effective GSH replenishment in HIV infection.DesignOral NAC administration in a randomized, 8‐week double‐blind, placebo‐controlled trial followed by optional open‐label drug for up to 24 weeks.SubjectsHIV‐infected, low GSH, CD4 T cells < 500 μL−1, no active opportunistic infections or other debilitation; n = 81. Study conducted prior to introduction of protease inhibitors.ResultsWhole blood GSH levels in NAC arm subjects significantly increased from 0.88 m m to 0.98 m
m, bringing GSH levels in NAC‐treated subjects to 89% of uninfected controls (P = 0.03). Baseline GSH levels in the placebo group (0.91) remained essentially the same during the 8 week placebo‐controlled trial. T cell GSH, adjusted for CD4 T cell count and β2‐microglobulin levels, also increased in the NAC‐treated subjects (P = 0.04). Adverse effects were minimal and not significantly associated with NAC ingestion.Conclusion.NAC treatment for 8 weeks safely replenishes whole blood GSH and T cell GSH in HIV‐infected individuals. Thus, NAC offers useful adjunct therapy to increase protection against oxidative stress, improve immune system function and increase detoxification of acetaminophen and other drugs. These findings suggest that NAC therapy could be valuable in other clinical situations in which GSH deficiency or oxidative stress plays a role in disease pathology, e.g. rheumatoid arthritis, Parkinson's disease, hepatitis, liver cirrhosis, septic shock and diabetes.
Smoking or its cessation does not alter the susceptibility to in vitro LDL oxidation
Authors: Van Den Berkmortel F. W. P. J. , Demacker P. N. M. , Wollersheim H. , Thien T. , Stalenhoef A. F. H. 
Published: March 2003

BackgroundEnhanced induction of low density lipoprotein (LDL) oxidation may play a role in the increased cardiovascular risk in smokers. We determined LDL oxidisability in vitro in non‐smokers, smokers and in subjects after smoking cessation.Patients and MethodsPlasma lipids and copper induced LDL oxidation in vitro were measured in 31 persistent smokers, 47 smokers who tried to stop smoking and 25 non‐smokers. In the smoking cessation group, blood was collected before then 1, 3, 6 and 12 months after smoking cessation, and in the persistent smoking and non‐smoking groups at baseline and after 12 months. Plasma thiobarbituric acid reactive substances (TBARS) were measured 3 times (at baseline then after 1 and 3 months) in all subjects who refrained from smoking (controlled by urinary cotinine concentrations) for at least 3 months.ResultsAt baseline, no differences in mean age, body mass index and lipid profiles between groups were present. Seventeen subjects of the smoking cessation group (36%) managed to quit during 12 months. Smoking cessation was associated with an increase in mean weight (P ≤ 0.001) and waist‐hip ratio (P ≤ 0.001). No major differences in LDL oxidisability were found between groups. A significant transient increase in high density lipoprotein (HDL) cholesterol was seen (from 1.20 ± 0.39 to 1.34 ± 0.42 mmol L−1) after 1 month of smoking cessation that disappeared after 3 months. However, after 1 month of smoking cessation, plasma TBARS decreased significantly (P < 0.05).ConclusionsNeither the previously observed increased cardiovascular risk in smokers nor the decreased risk in those who stopped smoking seem to be mediated by permanent changes in lipid profiles or by alterations in the susceptibility to in vitro oxidation of LDL.
The use of platelet density and volume measurements to estimate the severity of pre‐eclampsia
Authors: Järemo P. , Lindahl T. L. , Lennmarken C. , Forsgren H. 
Published: March 2003

This study evaluated whether it is possible to estimate the severity of pre‐eclampsia through in vitro measurements of platelet and granulocyte parameters.Eighteen pre‐eclamptic women in the third‐trimester of pregnancy and 11 women in the third‐trimester of normal pregnancies were included in the study. Three to 12 months after delivery, 15 patients with pre‐eclampsia and all the subjects with normal pregnancies were re‐examined. Before delivery, peak platelet density was determined using a specially designed apparatus. Before and 3–12 months after delivery the following were measured: platelet counts, mean platelet volume and neutrophil and monocyte counts. Furthermore, circulating P‐selectin, interleukin‐6 and myeloperoxidase were determined to estimate platelet, monocyte and granulocyte activities, respectively.Compared to their results after delivery, pre‐eclamptic females demonstrated lower platelet counts (P < 0·001) and raised mean platelet volumes (P < 0·01). Both pre‐eclamptic women (P < 0·01) and normal pregnancies (P < 0·05) demonstrated elevated soluble P‐selectin at pregnancy. Then pre‐eclamptic women had advanced neutrophil counts (P < 0·01) but normal pregnancies showed a similar phenomenon (P < 0·001). Interleukin‐6 remained normal during pregnancy. Plasma myeloperoxidase levels were lower both in pre‐eclampsia (P < 0·05) and in normal pregnancies (P < 0·001). In pre‐eclampsia elevated blood pressure was related to higher mean platelet volumes (P < 0·05). Furthermore, a group of pre‐eclamptic females whose platelets had disturbed density distribution displayed elevated mean platelet volumes (P < 0·01).The present work demonstrates considerable platelet alterations in pre‐eclampsia. We failed to show granulocyte involvement in the pathogenesis of the disease. Severe pre‐eclampsia is related to elevated mean platelet volumes. The latter parameter is associated with disturbed density distribution. It appears possible to estimate disease severity from measurements of platelet density and volume.
How hydrocortisone substitution influences the quality of life and the bone metabolism of patients with secondary hypocortisolism
Authors: Wichers M. , Springer W. , Bidlingmaier F. , Klingmüller D. 
Published: March 2003

BackgroundEven in the setting of chronic glucocorticoid substitution in hypocortisolaemic patients, severe side‐effects will eventually occur when the dosage is inappropriately high. This study evaluates the effect of usual hydrocortisone substitution dosages on the well‐being of the patients and on parameters of the bone metabolism to establish an optimum substitution dosage.DesignIn a double blind study nine patients with secondary hypocortisolism, being divided in three groups of three, received different doages of hydrocortisone (15, 20, 30 mg per day). Well‐being was assessed using three different, validated questionnaires. Markers of bone metabolism were measured in blood and urine.ResultsThe patients' quality of life was not impaired even at low dosages of hydrocortisone (15 or 20 mg per day). Of all laboratory parameters only osteocalcin significantly changed, decreasing at higher dosages.ConclusionsOur study shows that a risk of bone loss may be avoided with a substitution dosage of 20 mg or even 15 mg hydrocortisone per day, without influencing the well‐being of the patient.
Metabolism of glucocorticoids and mineralocorticoids in patients with adrenal incidentalomas
Authors: Maser‐Gluth C. , Reincke M. , Allolio B. , Schulze E. 
Published: March 2003

BackgroundAdrenal incidentalomas are mostly nonfunctioning adrenocortical adenomas (NFI). However, in 5%–12% of the patients a preclinical Cushing's syndrome (PCS) with autonomous cortisol production by the tumour is present. Since urinary free cortisol excretion is not sensitive enough to determine subclinical hypercortisolism, in the present study more sensitive indicators of daily cortisol production were measured.Design(1) Tetrahydrocortisol, tetrahydrocortisone, urinary free cortisone together with urinary free cortisol were measured in 35 patients with adrenal incidentalomas (29 NFI and six PCS) and in 35 healthy controls. (2) Since little is known about daily aldosterone production, aldosterone metabolite excretions were measured. (3) As recently reported, ACTH stimulation revealed an increased response of precursors of the glucocorticoid and mineralocorticoid pathway. To find out which steroidogenic enzymes have altered activities, a 1–24ACTH stimulation test (250 μg i.v.) was carried out in 25 patients and 18 healthy controls with determination of multiple steroids. (4) Finally, since it was assumed that 21‐hydroxylase deficiency or even 11b‐hydroxylase deficiency may be involved in adrenal tumourigenesis, the prevalence of germline CYP21B and CYP11B1 mutations were studied in the same patients, who had underwent the ACTH stimulation test.Results(1) Glucocorticoid metabolites were within the normal range in all but three patients with NFI. As a group, the patients had subtle alterations in cortisol metabolism. Tetrahydrocortisol excretion was elevated in NFI and PCS compared with normal subjects (2á1 ± 0á2 and 2á5 ± 0á5 vs. 1á5 ± 0á1 mg 24 h−1; P < 0á05). Accordingly, the twofold elevation of the tetrahydrocortisol/free cortisol ratio indicates an increased 5β‐reduction of cortisol in the liver. (2) Tetrahydroaldosterone and aldosterone‐18‐glucuronide excretions were not different to controls. (3) In patients with incidentalomas an increased response to ACTH was seen for 17‐hydroxyprogesterone (595 ± 133 vs. 160 ± 25 ng dL−1), 21‐desoxycortisol (105 ± 25 vs. 29 ± 9 ng dL−1) and 11‐desoxycortisol (401 ± 40 vs. 293 ± 17 ng dL−1). (4) In only one of 25 patients, a heterozygous deletion in exon 3 of the CYP21B gene was detected.Conclusions(1) In conclusion, even the excretion of the main glucocorticoid metabolites is not a marker sensitive enough to distinguish between NFI and PCS. However, it is also possible that alterations in cortisol secretion are qualitative rather than quantitative. (2) Zona glomerulosa function is not influenced. (3) The elevation of 21‐desoxycortisol argues against an impairment of 11β‐hydroxylase and favours a decreased activity of 21‐hydroxylase. All others had wild‐type sequences of both genes. (4) In conclusion, neither 21‐hydroxylase deficiency nor 11β‐hydroxylase deficiency are predisposing factors for adrenal tumourigenesis.
Pro‐inflammatory cytokines in patients with essential hypertension
Authors: Peeters A. C. T. M. , Netea M. G. , Janssen M. C. H. , Kullberg B. J. , Van der Meer J. W. M. , Thien T. 
Published: March 2003

BackgroundIt has been suggested that abnormalities in the immune response play a role in the pathogenesis of essential hypertension (EH). The aim of this study was to assess circulating concentrations and ex vivo production of the pro‐inflammatory cytokines tumour necrosis factor‐α(TNF‐α) and interleukin‐1β (IL‐1β), and of the anti‐inflammatory cytokines IL‐1 receptor antagonist (IL‐1ra) and IL‐6 , in patients with EH and compare them with healthy volunteers.Patients and methodsPlasma cytokine concentrations were measured in EH patients and control volunteers by specific radioimmunoassays and ELISA. Ex vivo cytokine production was assessed after stimulation of whole‐blood with lipopolysaccharide.ResultsCirculating concentrations of TNF, IL‐1 and IL‐6 did not differ between EH patients and controls. In contrast, IL‐1ra circulating levels were higher in EH patients. Hypertensive patients had an increased IL‐1 and IL‐6 production capacity when whole blood was stimulated ex vivo with lipopolysaccharide, while TNF production was lower. IL‐1ra production capacity did not differ between patients and controls.ConclusionsPatients with EH have an altered profile of pro‐and anti‐inflammatory cytokines, consistent with monocyte activation in the circulation. The importance of these changes for the pathogenesis of EH and/or its secondary complications remains to be elucidated.
The alpha‐amino group of l‐arginine mediates its antioxidant effect
Authors: Wallner S. , Hermetter A. , Mayer B. , Wascher T. C. 
Published: March 2003

Antioxidant effects may constitute part of the possible antiatherogenic effects of the amino acid l‐arginine. These antioxidant properties were further characterized in a model of lipoprotein oxidation.Oxidation of lipoproteins in unfractionated human serum was continuously monitored by a fluorescent probe. The antioxidant effects of l‐arginine, N‐α‐acetyl‐arginine and vitamin E in combination with l‐arginine were measured after initiation of free radical generation with either copper or 2,2′‐azobis(2‐amidinopropane) hydrochloride (AAPH). The half‐time of the fast propagation rate for copper‐induced lipoprotein oxidation increased after incubation with l‐arginine in a dose‐dependent manner (P < 0·01). N‐α‐acetyl‐arginine did not show such effects. Vitamin E and l‐arginine show different effects on copper‐induced oxidation, the former increasing only lag‐time, the latter increasing only propagation rate, and do not have reciprocal effects. In contrast to copper‐induced oxidation, l‐arginine increased the lag‐time of AAPH‐induced lipoprotein oxidation (P < 0·01), with no effect on the propagation rate at physiological concentrations. Again, N‐α‐acetyl‐arginine did not show any antioxidant effects.Our experiments provide further evidence that mechanisms other than serving as a substrate for the NO‐synthase could be involved in the antiatherosclerotic effect of l‐arginine. In addition, our experiments clearly show, that the antioxidant effect of l‐arginine is due to a chemical moiety different from that serving as the substrate for NO biosynthesis.
Effect of N‐acetylcysteine treatment on NO2‐impaired type II pneumocyte surfactant metabolism
Authors: Müller B. , Oske M. , Hochscheid R. , Seifart C. , Barth P. J. , Garn H. , Von Wichert P. 
Published: March 2003

Inhalation of nitrogen dioxide (NO2) is known to alter the composition of the bronchoalveolar lavage (BAL) and to impair the surfactant metabolism of type II pneumocytes. However, information is sparse as to whether application of the widely used antioxidant N‐acetylcysteine (NAC) is capable of preventing or reducing these alterations. The aim of the study was to investigate if in vivo administration of NAC to NO2‐inhaling rats protected BAL parameters and physiology of type II pneumocytes from impairment.For this purpose, rats were exposed to 720 p.p.m. h−1 NO2, that was applied continuously, intermittently or repeatedly. During inhalation one group of rats received saline and the other group received NAC antioxidant (200 mg kg−1, intraperitoneally) once a day.The BAL protein and phospholipid content increased most in the continuously and repeatedly NO2‐exposed rats when compared to the controls, while the intermittent exposure did not change these parameters. Application of NAC led to a marked decrease of the protein elevation for the continuously and intermittently exposed groups, but exhibited no influence on the BAL phospholipid. Surprisingly, all NO2 exposure modes elevated the glutathione content (reduced and oxidized) in the BAL. Application of NAC clearly decreased the content of both forms of glutathione in the continuously and the repeatedly NO2‐exposed groups. Phospholipid synthesis, measured by choline uptake into type II cells, was increased most after continuous NO2 inhalation. The NAC reduced this increase moderately. Whereas choline uptake by type II cells was obviously stimulated by NO2, the stimulated secretion of phosphatidylcholine from these cells was decreased by this oxidant. Only continuous exposure reduced this activity markedly. The NAC clearly restored the impaired secretion activity in the cells from the continuously NO2‐exposed animals.Since the efficacy of NAC in the prevention of NO2‐induced impairments in the surfactant system is striking mainly in the continuously exposed group, we suggest that administration of NAC to NO2‐induced lung injury partially restores altered BAL components and the impaired physiology of type II pneumocytes.