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Biomedical subjects

S Vogel

Publications and source records attributed to S Vogel.

At least 55 records · Page 3Linked to original sources

[Low dosage, fractionated, percutaneous teletherapy of subfoveal choroid neovascularization].

AIM: The effect of low-dose fractionated percutaneous teletherapy on visual acuity and the changes in subfoveal neovascular membranes (SNM) in age-related macular degeneration (ARMD) were studied. PATIENTS AND METHODS: Forty-four patients (aged from 56 to 86 years) were treated. Best distant and near visual acuity was assessed before (initial visual acuity; IVA) and 5 weeks, 3, 6 and 12 months after teletherapy. Fluorescein angiography was done before and 3 and 12 months after radiation. Patients were divided into different groups by IVA for analysis. Mean follow-up was 9 months. Teletherapy was done by a 9 MeV linear accelerator through a lateral port in the half-beam technique with a single dose of 2 Gy to a total dose of 20 Gy within 20 days. RESULTS: No severe negative side effects have been observed. Four patients reported epiphora. Visual acuity decreased one line in the group with an IVA of 0.05-0.2. The group with IVA 0.3-0.5 remained unchanged during the observation period. We found a tendency for increased visual acuity in group IVA > or = 0.6. CONCLUSIONS: Teletherapy seems to have an influence on visual acuity, SNM, and metamorphopsia. IVA and duration of thillness play important roles. We cannot say if there is a persistent effect, as these are preliminary results. The longest follow-up so far has been 12 months. In order to better evaluate the potential of radiotherapy, this study must be pursued and coupled with further studies analyzing the effect on SNM in ARMD.

Aged↗

Pharmacokinetic modeling of recombinant interleukin-2 in patients with human immunodeficiency virus infection.

A novel model was developed to characterize the time-varying clearance of recombinant interleukin-2 (IL-2). Sixty-eight patients with human immunodeficiency virus infection received 83 cycles of IL-2 either by continuous infusion or by subcutaneous injection for 5 days. IL-2 concentrations after intravenous infusions peaked at 24 hours and then declined by 55% to 78% during the remainder of the infusion. Soluble IL-2 receptors increased greater than 10-fold before gradually returning to baseline. Subcutaneous administration showed a dose-dependent decrease in area under the concentration-time curve (AUC) between days 1 and 5. A model was developed in 9 patients who had IL-2 concentrations and soluble IL-2 receptors determined by ELISA. Concentrations were fitted by an indirect stimulatory pharmacodynamic model. An additional 59 patients with only IL-2 concentrations were fitted to a simplified empiric model. Both models provided an overall r2 of 0.99 for the plot of observed versus fitted concentrations. The time-dependent increase in IL-2 clearance, likely receptor-mediated, was well described with use of an indirect-effects pharmacokinetic-pharmacodynamic model.

Adult↗

Varying dietary fat type of reduced-fat diets has little effect on the susceptibility of LDL to oxidative modification in moderately hypercholesterolemic subjects.

The effect of the fatty acid composition of reduced-fat diets on the in vitro oxidation of LDL was examined in 14 moderately hypercholesterolemic [low density lipoprotein (LDL) > 3.36 mmol/L] postmenopausal female and male subjects (age 44-78 y). Each subject consumed each of five reduced-fat diets [30 energy percent (E%) fat, 17 E% protein and 53 E% carbohydrate] enriched in beef tallow, canola oil, corn oil, olive oil or rice bran oil (20 E%) for 32-d periods. In vitro oxidation of LDL was assessed by incubating LDL with hemin and hydrogen peroxide, and measuring the time required for the reaction to reach maximum velocity (lag time). LDL lag times were 93.2 +/- 25.8, 95.9 +/- 26.4, 104.2 +/- 32.7, 108.0 +/- 26.6 and 113.1 +/- 24.0 min for corn oil, beef tallow, rice bran oil, canola oil and olive oil periods, respectively. When the data from all dietary phases were pooled, LDL alpha-tocopherol level (r = 0.30, P = 0.01) and plasma 18:1/18:2 ratio (r = 0.22, P = 0.08) were positively related to resistance of LDL to oxidation. Differences induced by the dietary perturbations in LDL content of beta-cryptoxanthin, lutein/zeaxanthin, lycopene, alpha-carotene or beta-carotene, and LDL particle size were not related to resistance of LDL to oxidation. In conclusion, in middle-aged and elderly moderately hypercholesterolemic subjects, the consumption of reduced-fat diets enriched in animal fat or vegetable oils with a relatively wide range of fatty acid profiles did not alter the in vitro susceptibility of LDL to oxidation. The advantages of reducing the saturated fat content of the diet were reflected in lower total and LDL cholesterol levels.

Adult↗

Prospective sonographic evaluation of interleukin-2-induced changes in the gallbladder.

PURPOSE: To describe the changes in the gallbladder induced by interleukin-2 (IL-2) therapy and to correlate the findings with the clinical course. MATERIALS AND METHODS: Twenty-five men with human immunodeficiency virus (HIV) infection were examined prospectively with right upper quadrant ultrasonography (US) before and after receiving IL-2 therapy. Four patients also underwent US after a second course of IL-2. The gallbladder was evaluated for wall thickening, echotexture, and intramural and pericholecystic fluid. Correlation was made between the clinical signs and symptoms, IL-2 dose, CD4 cell count, and the US appearance of the gallbladder. RESULTS: There was significant correlation between symptoms of right upper quadrant pain during IL-2 therapy and US abnormalities of the gallbladder, including an increase in wall thickening (P = .012) and the development of intramural (P = .015) and pericholecystic (P = .006) fluid. More severe abnormalities were seen with higher IL-2 doses. All symptoms resolved with cessation of IL-2 therapy. In patients who underwent repeat US, the gallbladder reverted to a normal appearance. No correlation was found between the CD4 cell count and the development of symptoms or the US appearance of the gallbladder. CONCLUSION: IL-2-induced changes resolve rapidly with cessation of therapy, and no surgical intervention is needed. These changes can be avoided or reduced by decreasing the IL-2 dose during subsequent cycles.

Abdominal Pain↗

Murine epidermal lipoxygenase (Aloxe) encodes a 12-lipoxygenase isoform.

Using a combination of conventional screening procedures and polymerase chain reaction cloning, we have isolated a cDNA encoding an epidermis-type 12-lipoxygenase (e12-lipoxygenase) from mouse epidermis. The open reading frame corresponds to a protein of 662 amino acids and was found to be 99.8% identical to the ORF of an epidermal lipoxygenase gene Aloxe, described recently [Van Dijk et al. (1995) Biochim. Biophys. Acta 1259, 4-8]. When expressed in human embryonic kidney cells the recombinant protein could be shown to synthesize 12(S)-HETE from arachidonic acid. By fluorescence in situ hybridization the e12-lipoxygenase gene was localized to chromosome band 11 B1-B3.

Amino Acid Sequence↗

Numerical aberrations of chromosomes 1, 2, and 7 in astrocytomas studied by interphase cytogenetics.

For both juvenile astrocytomas and astrocytomas of adults, numerical and structural aberrations of chromosomes 1 and 7 have been described. To study the frequency of those aberrations in more detail and to exclude in vitro artifacts, we investigated directly prepared material from 18 juvenile and 26 astrocytomas of adults by fluorescence in situ hybridization with DNA probes specific for chromosome regions 1p36, 1q12, 2cen, and 7cen. Chromosome 2 was used as control in the hybridization with chromosome 7. To exclude tissue-specific alterations, we tested cerebral and cerebellar paraffin-embedded material from persons who had died from other diseases. In 13 of the juvenile astrocytomas, we found a loss of 1p36 in relation to 1q12 in 16 astrocytomas of adults, a gain of signals from 1p36 or both probes for chromosome 1 was seen. Gain of chromosome 7 was found in 25 cases. Unexpectedly, gain of chromosome 2 occurred in 32 cases. For both probes, there was no difference between astrocytomas of children and those of adults. Our data suggest that loss of 1p is an early event in the development of juvenile astrocytomas and that trisomy 7 is frequent in malignant tumors and tumors containing a potential of growing malignantly.

Adolescent↗

Different release of cytokines into the cerebrospinal fluid following surgery for intra- and extra-axial brain tumours.

To elucidate the role of cytokines in brain repair processes and in local inflammation after neurosurgical procedures, cerebrospinal fluid (CSF) samples from 8 patients with intra-axial tumours and 8 patients with extra-axial tumours were analysed for interleukin (IL)-1 beta, IL-1 receptor antagonist (IL-1 ra), IL-6, IL-8, IL-10, and tumour necrosis factor (TNF)-alpha at the beginning and after surgery. Levels of IL-6 and IL-8 increased dramatically in all patients just hours after surgery and fell during subsequent days. IL-1 beta was found only in low amounts in the CSF of both patient groups. Other cytokines demonstrated different courses. In patients with intra-axial tumours IL-1 ra peaked two to four hours after surgery with a subsequent decrease. In patients with extra-axial tumours there was a continuous low-level IL-1 ra release into the CSF without a peak. TNF-alpha was not present in detectable levels in the CSF after surgery for extra-axial tumours but was found to peak two to four hours after surgery for intra-axial tumours. IL-10 was detected in the CSF of both patient groups, but a higher peak was seen after surgery for extra-axial tumours. These results suggest different requirements for the cytokine response and an involvement of different cell types in cytokine release. However, the analysis of the CSF from both patient groups showed no differences in cell counts and populations, with a mild pleocytosis being present in both patient groups after surgery. Therefore, we conclude that after surgery for extra-axial tumours cytokines were predominately produced by non-immune cells stimulated through hypoxia or mechanical irritation. After surgery for intra-axial tumours with a significant brain injury immune cells-activated by necrotic material-seen to be involved in the process of cytokine synthesis. In these cases an additional IL-1ra and TNF-alpha peak was found and these cytokines may be markers for cerebral injury.

Adult↗

Women with insulin-dependent diabetes mellitus (IDDM) complicated by eating disorders are at risk for exacerbated alterations in lipid metabolism.

OBJECTIVE: To examine lipid parameters that are affected in women with insulin-dependent diabetes mellitus (IDDM) who engaged in disordered eating behaviours. DESIGN: Randomized, unmatched. SETTING: Tertiary care. SUBJECTS: Ninety women (18-46 y) with IDDM. INTERVENTIONS: Classification of subjects based on severity of eating disorder: clinical (n = 14), subclinical (n = 13) and control (n = 63). Blood was analysed for glycosylated haemoglobin (HbA1c) and serum for triglycerides and cholesterol. Carotenoid and tocopherol concentrations were analysed by high performance liquid chromatography (HPLC). Dietary intake was assessed by the National Cancer Institute food frequency questionnaire. RESULTS: HbA1c was significantly increased im women demonstrating clinical and subclinical symptoms compared to control (10.4 +/- 2.6, 10.0 +/- 1.5 and 8.3 +/- 1.6%, respectively, P < 0.05). Triglycerides concentrations were significantly increased in women with subclinical eating disorders compared to controls. In women who intentionally omitted or reduced insulin, triglyceride cholesterol and HbA1c were significantly increased compared to controls. Women with IDDM and eating disorders who exhibited bulimic behaviours consumed significantly more energy, total fat and cholesterol compared to controls and women with eating disorders who were restrained eaters. CONCLUSION: While IDDM is known to perturb lipid metabolism, these data demonstrate that eating disorders, in combination with IDDM, results in additional alterations in lipid metabolism.

Adolescent↗

Comparison between esophageal Wallstent and Ultraflex stents in the treatment of malignant stenoses of the esophagus and cardia.

BACKGROUND AND STUDY AIMS: Several published studies have examined various self-expanding metal esophageal stents for use in the palliative treatment of esophageal or cardiac neoplasia, but few have compared different self-expanding metal stents. The aim of this study was to evaluate non-covered Wallstent and Ultraflex prostheses in the treatment of malignancies in the esophagus and the cardiac region. MATERIALS AND METHODS: In a retrospective study, the effectiveness of non-covered Wallstents (46 patients) and Ultraflex stents (36 patients) was compared in the treatment of malignancies in the esophageal and cardiac regions. RESULTS: Reintervention procedures were necessary in 16 of the 46 Wallstent patients (six patients during an early phase) and in 22 of the 36 Ultraflex patients (13 during an early phase) (overall P = 0.022; early P = 0.018). The major complication in the Wallstent group was tumor ingrowth (12 of 35 complications), while in the Ultraflex group, it was incomplete deployment (18 of 49 complications). Incomplete stent deployment occurred more often in patients treated with Ultraflex (P = 0.01), and food impaction was more often observed in the Wallstent group (P = 0.001). In addition, in patients with Ultraflex stents, more complex reinterventions were necessary than those required with Wallstents (four vs. 13 complex reinterventions, P = 0.0046). Wallstents tended to improve dysphagia better than Ultraflex stents. CONCLUSION: Compared to Ultraflex stents, Wallstents have several significant short-term and long-term advantages in the palliative treatment of malignancy of the esophagus and cardia.

Adult↗

Plasma retinol and plasma and lipoprotein tocopherol and carotenoid concentrations in healthy elderly participants of the Framingham Heart Study.

Data on plasma concentrations of tocopherols and the major carotenoids in adults aged > or = 65 y, particularly in those > 80 y, are sparse. In the current study retinol, tocopherol (alpha- and gamma-tocopherols), and carotenoid (lutein/zeaxanthin, cryptoxanthins, lycopene, and alpha- and beta-carotene) concentrations were determined in 638 subjects, 230 men (aged 75 +/- 5 y) and 408 women (76 +/- 6 y), of the Framingham Heart Study. All subjects were free of clinical evidence of cardiovascular disease and cancer. Percentile ranges were comparable with those established in younger cohorts. Moreover, women had significantly higher plasma alpha-tocopherol and plasma and lipoprotein concentrations of beta-cryptoxanthin and alpha- and beta-carotene than did men. Lycopene concentrations were inversely correlated with age and lowest among subjects > or = 80 y. Total intakes (diet+supplements) of vitamin C and vitamin E, but not dietary intakes alone, were positively associated with plasma alpha-tocopherol and inversely associated with gamma-tocopherol concentrations. In multivariate analyses, plasma cholesterol and triacylglycerol concentrations and total intake of vitamins E and C predicted 64% and 55% of the plasma alpha-tocopherol concentrations in men and women, respectively. Important predictors for the majority of carotenoids included plasma cholesterol concentration, body mass index (negative effect), and smoking status (negative effect); for lycopene concentration they included cholesterol concentration and age (negative effect). In summary, percentile ranges and lipoprotein distributions were comparable with those established in younger cohorts, suggesting that overall antioxidant status is not altered in people between the ages of 67 and 96 y.

Aged↗

The lipid peroxidation end product 4-hydroxy-2,3-nonenal up-regulates transforming growth factor beta1 expression in the macrophage lineage: a link between oxidative injury and fibrosclerosis.

An increasing number of reports underscore the frequent association of fibrosclerotic diseases of lung, liver, arterial wall, brain, etc., with the accumulation of oxidatively modified lipids and proteins. A cause-and-effect relationship has been proposed between cellular oxidative damage and increased fibrogenesis based on the fact that experimental treatment with antioxidants either prevents or quenches the fibrotic process. With some peculiarities in the different organs, fibrosclerosis is essentially the result of the interaction of macrophages and extracellular matrix-producing cells. The cross-talk is mediated by fibrogenic cytokines, among which the most important appears to be transforming growth factor beta1 (TGF-beta1). This report describes treatment of different types of macrophage, of both human and murine origin, with 4-hydroxy-2,3-nonenal (HNE) a major aldehyde end product of membrane lipid oxidation found consistently to induce both mRNA expression and synthesis of TGF-beta1. Since increased HNE levels have been demostrated in the cirrhotic liver and in the oxidatively modified low-density human lipoproteins associated with atherosclerosis, the up-regulation of macrophage TGF-beta1 by HNE appears to be involved in the pathogenesis of these and similar diseases characterized by fibrosclerosis.

Aldehydes↗

Management of swallowing disorders and chronic aspiration by glottic closure procedure.

We report an 18-year-old man with a posterior fossa tumor who had to undergo a partial resection of the tumor and supportive radiation therapy. Functional deficits of the lower cranial nerves, particularly the glossopharyngeal and vagal nerves, associated with severe swallowing disorders and refractory aspiration pneumonia were seen postoperatively. The admission to the intensive care unit (ICU) resulted from increasing respiratory failure accompanied by recurrent septic episodes. Nutritional support via nasogastric tube and later percutaneous endoscopic gastrostomy (PEG) were hampered by complications such as persistent sinusitis, local dermatitis surrounding the entrance of the PEG tube, and the development of duodenal ulcers. Furthermore, the use of continuous subglottic aspiration failed to prevent pulmonary infections. After a 9-week stay in the ICU due to inadequate antimicrobial therapy of aspiration pneumonia and the patient's persistent sepsis, a temporary surgical separation of airway and food passages was performed by glottic closure. Subsequently chronic aspiration stopped, and 3 months after admission to the ICU, the patient had stable vital organ function and was transferred to a surgical ward free of infections. Glottic closure was reversed successfully 7 months later. When compared with laryngeal function on admission, there was no more impairment. Thus, temporary glottic closure seems to be an efficacious treatment to prevent life-threatening septic complications in patients with refractory aspiration pneumonia.

Adolescent↗

Factors associated with multiple admissions to a public psychiatric hospital.

The purpose of this study was to identify the psychiatric and social factors associated with multiple admissions, especially for psychotic patients. Demographic and diagnostic information (based on the DSM-III-R) was collected on a computerized database for all patients admitted to the only psychiatric hospital in Geneva, Switzerland. Patients who had had at least three admissions over a period of 1 year were compared with a control group drawn from the total clinic population. In 1994, a total of 1575 patients were hospitalized, and 18% of these patients were readmitted for the third or more time. The principal diagnoses were psychotic disorders (25%), affective disorders (35%) and substance-related disorders (24%). The predictors of multiple admissions for psychotic patients were a comorbidity of substance-related disorder, longer duration of illness, female sex, younger age and poorer psychosocial adjustment during the past year. These results highlight the usefulness of a computerized psychiatric database. Indeed, early identification of the types of psychiatric patient who are likely to be readmitted is necessary to enable the planning and implementation of specific programmes of ambulatory care to prevent rehospitalization.

Adult↗

Clarithromycin lowers plasma zidovudine levels in persons with human immunodeficiency virus infection.

The use of antiretroviral agents and drugs for the treatment and prophylaxis of opportunistic infections has lengthened the survival of persons with AIDS. In the era of multidrug therapy, drug interactions are important considerations in designing effective and tolerable regimens. Clarithromycin has had a significant impact on the treatment of disseminated Mycobacterium avium complex infection, and zidovudine is the best-studied and one of the most widely used antiretroviral agents in this population. We conducted a study to determine the maximally tolerated dose of clarithromycin and the pharmacokinetics of clarithromycin and zidovudine individually and in combination. Mixing studies were conducted to simulate potential interaction in the gastric environment. The simultaneous administration of zidovudine and clarithromycin had little impact on the pharmacokinetics of clarithromycin or of its major metabolite. However, coadministration of zidovudine and clarithromycin at three doses (500 mg orally [p.o.] twice daily [b.i.d.], 1,000 mg p.o. b.i.d., and 2,000 mg p.o. b.i.d.) reduced the maximum concentration of zidovudine by 41% (P < 0.005) and the area under the concentration-time curve from 0 to 4 h for zidovudine by 25% (P < 0.05) and increased the time to maximum concentration of zidovudine by 84% (P < 0.05), compared with zidovudine administered alone. Mixing studies did not detect the formation of insoluble complexes due to chelation, suggesting that the decrease in zidovudine concentrations results from some other mechanism. Simultaneous administration of zidovudine and clarithromycin appears to decrease the levels of zidovudine in serum, and it may be advisable that these drugs not be given at the same time. Drug interactions should be carefully evaluated in persons with advanced human immunodeficiency virus infection who are receiving multiple pharmacologic agents.

Adult↗

Neuropsychological and neurophysiological consequences of partial callosotomy.

Sixty-five patients with lesions affecting the third ventricle (54 patients) or the corpus callosum itself (11 patients) underwent partial callosotomy or a circumscribed callosal resection. Before the surgery 20 patients were studied using the battery of cognitive, affective and behavioural tests which was repeated 10 and 100 days after surgery. No disconnection syndrome was over observed after the partial commissurotomy. Transcranial magnetic stimulation over the sensorimotor cortex was performed in 10 patients to determine conduction time of callosal fibres by measuring inhibition of tonic voluntary electromyographic activity in muscle's ipsilateral to the activated hemisphere. It was found that this inhibition was absent in patients with lesions of the trunk of the corpus callosum and present in patients with lesions of the genu or splenium. In addition magnetic resonance imaging measurements of the corpus callosum were performed in 40 normal subjects to establish a classification system for corpus callosal area. The results showed a wide variability of the cross-sectional area of the corpus callosum. The comparison of the shape of the corpus callosum lead to a categorisation according to the presence and location of depressions on its surface.

Brain Neoplasms↗