[Psychiatrists who took shelter in French-speaking Switzerland from 1933-1945].
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History, 20th Century↗
Biomedical subjects
C Müller
Publications and source records attributed to C Müller.
[Experiences with alkaline filter elution for the detection of DNA damage by genotoxic compounds].
In biological effect monitoring the alkaline filter elution is a suitable method to detect DNA strand breakage and cross-linking in peripheral blood lymphocytes. We applied this method to three groups of workers occupationally exposed to carcinogens: n = 39 welders with exposure to chromium and nickel, n = 20 female shoemakers with exposure to benzene and n = 25 disinfectors in hospitals with exposure to ethylene oxide. In comparison to standardised control groups our results must be interpreted as indicating an increased rate of DNA cross-linking in welders and disinfectors whereas the female shoemakers showed an increased rate of DNA strand breakage. The differences between the results of the exposed groups and the stratified control groups were significant in most cases. We could reexamine 6 shoemakers 4 months after cessation of exposure to benzene; at this moment the results were indicating a clear decrease of the DNA strand breakage. Therefore the method of alkaline filter elution seems to be a valuable tool in biological effect monitoring of groups occupationally or environmentally exposed to carcinogens, especially if the exposure is low, but persistent over a long period.
Benzene↗
Variables associated with the assessment of systemic tumor necrosis factor alpha levels during hemodialysis.
Conflicting results have been published concerning the systemic induction of the cytokine tumor necrosis factor alpha (TNF alpha) during hemodialysis (HD). We therefore evaluated in vitro TNF alpha production in whole blood as well as in vivo variability of TNF alpha levels in patients on long-term HD. Whole blood was incubated at room temperature (RT) with or without exogenously added endotoxin (ET), and plasma-TNF alpha was measured after 5, 30, 120, 240, and 960 min by specific enzyme immunoassay. Additionally, plasma-TNF alpha before and after 120 and 240 min HD was studied longitudinally once a week over a period of 4 weeks in 36 patients on Cuprophan (CU, n = 23) or polysulfone-F60 (PSu, n = 13) HD. Mean plasma TNF alpha levels in vitro rose from (mean) 8 pg/ml after 5 min to 12 pg/ml (120') and 32 pg/ml (960') even without ET addition, and to 18 pg/ml (after 120') and 88 pg/ml (after 960') when 0.1 microgram/ml ET were added. Pre-dialytic as well as intra-dialytic TNF alpha levels in patients showed high intra-individual variability. A substantial (> 100%) increase in plasma TNF alpha was observed during only 14 out of 84 treatments with CU and 20 out of 47 with PSu, however, the increase in TNF alpha was not statistically significant in either group. We conclude that the sampling procedure, if not carefully standardized, is a potential source of artifacts with regard to "systemic" TNF alpha levels. The high intra and inter-individual variability of plasma TNF alpha suggests that results of cross-sectional studies are questionable.
Cellulose↗
[Immunohistochemical findings in otosclerotic lesions].
Despite numerous scientific efforts, the etiology of otosclerosis still remains unknown. Pathogenically, there are several signs of a chronic inflammatory process of the bony otic capsule. In this study, we tried to characterize the components of chronic inflammation by immunohistochemical techniques. Within otosclerotic lesions a mixed cellular infiltrate can be observed, consisting of lymphocytes, macrophages and plasma cells. Macrophages which are capable of presenting antigen in association with major histocompatibility antigens (MHC) class I and class II to CD8(+)-, and CD4(+)-T cells, respectively, were found in otosclerotic lesions based on their expression of the MAC387 antigen. Furthermore, HLA-DR positive cells and complement C3 have been found in resorption lacunae of otosclerotic lesions. Several osteoblasts and chondrocytes in active otosclerotic lesions reveal a strong surface expression of beta-2-microglobulin, indicating an increased MHC class I antigen expression in active otosclerotic lesions. In agreement with recently published data we found that a large fraction of the lymphoid cells are antigen-primed T-cells expressing an alpha/beta T-cell receptor in association with CD3 molecules on their surfaces. CD4+ lymphocytes which functionally represent lymphokine-secreting cells are activated through the specific recognition of antigen, presented in context with MHC class II molecules such as HLA-DR. Therefore, the presence of MHC class II positive cells are crucial for the initiation of a local immune response. Thus, our observation of HLA-DR positive cells in otosclerotic lesions is of particular interest.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[The effect of halothane, alfentanil and propofol on blood flow velocity, blood vessel cross section and blood volume flow in the middle cerebral artery].
Transcranial Doppler sonography (TCD) has gained in relevance for noninvasive monitoring of the cerebral circulation during the perioperative period. As long as the diameters of the investigated vessels remain unknown, however, flow velocities alone are not really informative. Exact vessel diameter determination in humans under the influence of different anesthetic drugs has not yet been performed due to ethical and methodological restrictions. A new modification of TCD allows analysis of the reflected "Doppler power", which is proportional to the cross-sectional area of the insonated vessel. METHODS. Three groups of 15-16 patients each (ASA I) were investigated after informed consent. Anesthesia was induced with droperidol, alfentanil, thiopental, and vecuronium bromide. After intubation patients were normoventilated with N2O:O2 = 3:2 and additional doses of alfentanil were injected until the transcranial ultrasound probe was fixed to the temporal bone and focused on the middle cerebral artery. Baseline values of heart rate (HR), mean arterial pressure (MAP), expiratory minute volume (EMV), end-expiratory CO2 (FeCO2), and TCD were measured. Then 1.5 vol% halothane, 25-50 micrograms/kg alfentanil, or propofol (1.5 mg/kg iv., 10 mg/kg.min) was administered. Further measurements (HR, MAP, EMV, FeCO2 and TCD) were performed at 3, 6, 10, and 20 min after the start in the halothane and propofol groups and after 3 and 6 min in the alfentanil group. The following transcranial parameters were derived from the TCD device: mean maximal flow velocity (vmmax), pulsatility index, time-averaged mean velocity (vmmen), "vessel area (VA)", and "volume flow (VF)". The mean +/- standard deviation of each parameter was calculated. Statistical evaluation was performed by paired t-tests (level of significance P less than 0.05). RESULTS. HR showed a tendency to increase after halothane and to decline after alfentanil. Alfentanil induced a short-term decline in MAP. End-expiratory minute volume and FeCO2 showed only minor alterations in all three groups. The vmmax was nearly doubled by halothane. Alfentanil induced a transitory decline in vmmax while Propofol decreased it markedly. The pulsatility index showed a decrease after halothane; alfentanil caused a short-term increase. Propofol induced a strong increase after 3 min; in the following period a return to baseline values was observed. The vmmean was increased by halothane and reduced by 32% propofol. VA was found to be unaltered by alfentanil and propofol but was more than doubled by halothane. Accordingly, the relative value for VF increased by 148% under halothane. VF appeared to decline after propofol. DISCUSSION. The described method allows only the determination of relative values: it is not possible to quantify exactly how much the VA changed. Halothane caused significant increases of VA measured in the middle cerebral artery, whereas alfentanil and propofol did not influence this parameter. This is in accordance with previous experiments in dogs in which halothane decreased the resistance of large basal cerebral arteries (LAR). LAR remained unaltered after alfentanil administration. The site of action of some anesthetic agents on cerebral vessels does not seem to be restricted to cerebral arterioles: at least for halothane, a vasodilating effect on large cerebral arteries could be demonstrated. This should be kept in mind when transcranial Doppler is applied during the perioperative period.
Alfentanil↗
[Dermatoglyphic diagnosis in patients with atopic eczema].
The purpose of this investigation was to find out whether the new Dermalog system could be used in conjunction with dermatoglyphics in patients with atopic dermatitis. For this purpose, 92 patients with atopic eczema (58 women and 34 men) were examined and were compared with two different control groups. The first control group, representing the normal population, consisted of 100 female and 100 male randomly selected subjects. The second control group (55 women and 24 men) excluded any persons with a history of atopic syndrome. First of all, hand and fingerprints were taken. The data were stored in a computer and were statistically analysed with the aid of significance and discrimination tests. Evaluation of the patients' data showed no significant difference from the first control group. Results in the second, selected, control group were better. For example, in this group, in which the probability was 93.1%, 76.4% of the women examined were found to have atopic dermatitis. The probability among the male patients examined was 99.9% and the corresponding sensitivity, 77.0%.
Adolescent↗
Cellular immunodeficiency in protein-losing enteropathy. Predominant reduction of CD3+ and CD4+ lymphocytes.
Cellular immunological abnormalities were studied in a patient with protein-losing enteropathy associated with constrictive pericarditis. Analysis of lymphocyte subpopulations in peripheral blood showed lymphopenia with a decrease of CD3+ and CD4+ T cells, whereas CD8+ lymphocytes, B cells and NK cells were within the normal range. Fecal loss of lymphocytes as a cause of lymphopenia was evidenced by a marked excretion of 111-indium-labeled peripheral blood mononuclear cells via stool. Proliferative responses against several mitogens were severely reduced as was in vitro IgG production. Delayed-type hypersensitivity reaction against a variety of antigens was absent. Vaccination with tick-borne encephalitis virus, used for primary immunization, and with the recall antigen tetanus toxoid resulted in a blunted antibody response. After pericardectomy, the severity of enteric protein loss declined, serum immunoglobulin levels returned to the normal range, and total lymphocytes and CD3+ and CD4+ counts increased but remained low even 12 months after surgery. Fecal loss of lymphocytes was found to be reduced after pericardectomy, but was higher than that seen in a disease control patient with active inflammatory bowel disease. In vitro immunoglobulin production returned to normal, DTH could be demonstrated against purified protein derivative and proteus antigen, but mitogen-driven blastogenic response of lymphocytes remained low. Revaccination with tick-borne encephalitis and tetanus toxoid antigens seven months after surgery resulted in a dramatic increase of serum levels of antibodies against both antigens, comparable to that seen in healthy control individuals.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Total denervation of the pancreas does not alter the pancreatic polypeptide-induced inhibition of pancreatic exocrine secretion in dogs.
Pancreatic polypeptide (PP) is a potent inhibitor of pancreatic exocrine secretion in vivo. The mechanism of pancreatic inhibition by PP is unknown, but the absence of PP receptors on pancreatic exocrine cells makes a direct effect of this hormone on the gland unlikely. In this study, we investigated the hypothesis that PP exerts its inhibitory effect via extrinsic neural pathways. Ten dogs with gastric and pancreatic fistulas were given an intravenous infusion of 250 ng/kg-1 h-1 secretin and 50 ng/kg-1 h-1 caerulein over 3 h. One hour after starting the infusion, 400 pmol kg-1 h-1 porcine PP were administered over 1 h. Pancreatic bicarbonate and protein secretions were measured. Later, the pancreas was extrinsically denervated. PP infusion decreased bicarbonate secretion in the intact gland by 47% and in the denervated pancreas by 57%. Protein secretion was diminished by exogenous PP by 31% in the intact and by 44% in the denervated pancreas. Despite pancreatic denervation, PP still exerted a significant inhibitory effect. Atropine infusion completely blocked the inhibitory effect of PP on caerulein-stimulated pancreatic protein secretion both in the intact and denervated pancreas and of secretion-evoked bicarbonate output in the denervated gland. We conclude that the inhibitory action of the hormone is not mediated via extrinsic neural pathways of the pancreas, but PP may exert its effect via intrinsic atropine-sensitive mechanisms.
Animals↗
Serum osteocalcin levels are decreased in patients with acute viral hepatitis.
In 16 patients with acute viral hepatitis and 32 sex- and age-matched control subjects the serum levels of osteocalcin, a biochemical parameter of bone formation, as well as the serum levels of parathyroid hormone, 25-hydroxyvitamin D, calcium and phosphorus were measured. The serum levels of osteocalcin (P less than 0.0001) and parathyroid hormone (P less than 0.0001) were significantly lower when measured at the time of maximal aminotransferase levels in the patients with hepatitis than in the control subjects. In contrast, the serum levels of calcium and 25-hydroxyvitamin D were similar in the patients and the controls. In nine patients with acute hepatitis measurements of the biochemical bone metabolism parameters were performed after normalization of the liver enzymes. In these patients a significant increase of serum osteocalcin levels towards normal values (P less than 0.0005) was found, parathyroid hormone levels tended to increase. Our data suggest an alteration of bone metabolism in patients with acute viral hepatitis. Bone formation as reflected by serum osteocalcin levels seems to be decreased in acute hepatitis and returns to normal after recovery from hepatitis.
Acute Disease↗
X-linked centronuclear myopathy: mapping the gene to Xq28.
The X-linked recessive centronuclear/myotubular myopathy (XLR-CNM/MTM1), a severe neonatal disorder characterized by generalized hypotonia, muscle weakness and primary asphyxia, has recently been mapped to Xq28. This report presents linkage analysis data of eight families with X-linked centronuclear myopathy. Four probes from the region Xq26-27 and five Xq28 probes were used to get more precise gene localization and marker order. St14 (DXS52), fully informative in all families, shows significant linkage to the CNM gene (z = 3.60; theta = 0.05), followed by DX13 (DXS15) (z = 2.03; theta = 0.06) and F8 (z = 1.86; theta = 0.00). Combination of the physical map derived by Kenwrick and Gitschier (1989) and our linkage data lead to the most probable order R/GCP-G6PD-(XLR-CNM-F8)-p767-St14-cpX67-++ +DX13 placing the CNM gene close to F8. The results of this study confirm strong linkage of the CNM gene to the region Xq28 and will permit carrier testing and prenatal diagnosis in CNM families. We conclude that the precise localization of this devastating disorder may be of great importance for genetic counselling in families at risk. The lack of information about gene frequency and mutation rate as well as the severity and burden of the disease point to the inevitable need for accurate clinical diagnosis.
Chromosome Mapping↗
Dopamine D2 receptor imaging with SPECT: studies in different neuropsychiatric disorders.
The purpose of the present study is to visualize and quantify dopamine D2 receptors in the living human brain using an 123I-labeled ligand and the single photon emission computerized tomography (SPECT) technique. S-(-)-Iodobenzamide [S-(-)-IBZM] has been shown to be a highly selective ligand with high affinity for D2 receptors in experimental studies. Five millicuries (185 MBq) of 123I-labeled S-(-)-IBZM was administered intravenously to 12 control subjects, 22 parkinsonian patients under L-Dopa therapy, 12 parkinsonian patients without L-Dopa, 10 unmedicated patients with Huntington's disease, and 12 patients under different neuroleptics. Data collection with a rotating double-head scintillation camera started 1 h after injection and lasted for 50 min. In a semiquantitative approach, a ratio was calculated between mean counts per pixel in the striatum and a region in the lateral frontal cortex, which was 1.74 +/- 0.10 in the control group. A marked reduction of this ratio was found in patients with Huntington's disease (1.38 +/- 0.12; p = 0.0001), no significant changes in untreated parkinsonian patients (1.67 +/- 0.14), but a reduction in L-Dopa-treated cases (1.59 +/- 0.13; p = 0.0014). A curvilinear relationship was found between total daily dose of neuroleptics and the reduction of this ratio. Estimated receptor blockade under full neuroleptic treatment was 75-80%. S-(-)-IBZM binding was reduced with increasing age (p less than 0.01). Specific binding was reduced markedly when the racemic mixture of IBZM was used, and no specific binding was seen with the R-(+)-isomer, demonstrating the stereoselectivity of IBZM binding.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[A new instrument for measuring eyelid strength].
Former investigations concerning muscular eyelid strength with dynamic registration revealed great inter- and intraindividual variations. We tried to minimize these influences by using an electronic power register with isometric registration. This is important because lid closing is a complex mechanism of horizontal and vertical movements with continuously changing power vectors. Our new apparatus reduces false results. A normal collective of 114 persons was examined. The results show no statistically significant age- or sex-related differences in lid strength.
Eyelid Diseases↗
The monoclonal antibody 11G7 recognizes a novel differentiation antigen expressed on hemopoietic precursor cells.
A monoclonal antibody (11G7) detecting a novel antigen on human hemopoietic progenitor cells (named 11G7R = 11G7 receptor) was raised by immunization of a Balb/c mouse with the leukemic blasts of a patient suffering from chronic myelogenous leukemia blast crisis (CML-BC). The antigen is expressed on most of MHC class II bearing peripheral blood leucocytes (PBL) and on a subpopulation of bone marrow mononuclear cells (BMMNC). By FACS-sorting and colony assays, it could be demonstrated that 11G7R is expressed on myelo-monocytic and myelo-granulocytic bone marrow precursor cells (GM-CFC, G-CFC, M-CFC) but is absent from erythroid precursor cells (BFU-E) and on cells exhibiting the capacity to form mixed colonies (GEMM-CFC). Double-fluorescence analysis on BMMNC revealed that 11G7R is expressed on a subset of B-cells, myeloid cells and cells carrying the HPCA-1 antigen (CD34). It has a similar distribution pattern to the myeloid antigens CD13 and CD33. However, in contrast to these antigens, 11G7R is also expressed on the blasts of several lymphoid leukemias (4/9 B-ALL, 1/2 T-ALL) and therefore it is not restricted to the myeloid lineage.
Animals↗
Constrictive pericarditis without typical haemodynamic changes as a cause of oedema formation due to protein-losing enteropathy.
A 41-year-old man presented with physical signs of leg oedema and a laboratory value of decreased serum albumin of 2.4 g.dl-1. Loss of protein via the gastrointestinal tract was demonstrated by an increased faecal excretion of 51-chromium-labelled-albumin and by elevated stool clearance of alpha 1-antitrypsin. No anatomical lesions or intestinal disease were found to explain this protein loss. Constrictive pericarditis was suspected as the cause of protein-losing enteropathy but could not be confirmed by right heart catheterization, in which normal filling pressures and no sign of 'dip and plateau' pressure pattern were found. However, magnetic resonance imaging clearly demonstrated a thickening of the pericardium over the right heart and a tubular-shaped right ventricle as signs of constrictive pericarditis. Peripheral oedema disappeared and serum protein concentration returned to normal after pericardectomy. This demonstrates that moderate pericardial constriction not resulting in discernible pressure abnormalities in the right heart can be associated with protein-losing enteropathy and thus result in hypoproteinaemic peripheral oedema. In this condition a morphological investigation by magnetic resonance imaging is of importance in order not to miss the diagnosis of a potentially treatable disease.
Adult↗
Functional liver imaging with 99Tcm-galactosyl-neoglycoalbumin (NGA) in alcoholic liver cirrhosis and liver fibrosis.
Synthesis of 99Tcm-galactosyl-neoglycoalbumin (99Tcm-NGA), a recently described new radioligand with high specificity for hepatic binding protein (HBP), a galactose-residue specific receptor on hepatocytes, was carried out by covalent coupling of 2-imino-2-methoxyethyl-1-thio-beta-D-galactopyranoside to the primary amino groups of human serum albumin. NGA was purified by ultrafiltration and size exclusion high-pressure liquid chromatography (HPLC). Using a computer-based simulation program, time-activity data for the liver and precordium, blood radioactivity 2 min after i.v. injection of the radioligand, the association constant of 99Tcm-NGA-binding to HBP measured on human liver biopsies in vitro, and other patient-related parameters were put into a five-state non-linear model describing the pharmacokinetics of 99Tcm-NGA. By fitting the parameters of the model iteratively to the experimental data, an estimate of HBP concentration in the liver and of total liver blood flow was obtained. Using this model we studied 32 patients (53 +/- 11 years) with different clinical stages of alcoholic liver cirrhosis. Child B and Child C stage cirrhotic patients had a lower HBP concentration in the liver compared to control individuals (0.96 +/- 0.21 mumol l-1). The group with the most advanced cirrhosis (Child C stage) had a significantly lower HBP concentration (0.27 +/- 0.15 mumol l-1) than Child A patients (0.66 +/- 0.21 mumol l-1; P less than 0.01) and Child B patients (0.53 +/- 0.18 mumol l-1; P less than 0.05). In four patients with biopsy-proven liver fibrosis (0.84 +/- 0.20 mumol l-1) no difference in receptor concentration from normal individuals was estimated. Changes in liver blood flow were not significant between the groups. A direct comparison of HBP concentration estimated in vivo by 99Tcm-NGA functional imaging and HBP concentration measured in vitro on a surgically removed liver biopsy specimen from the same patient with a normal liver and liver cirrhosis showed good matching of these two values. The results suggest that in vivo estimation of HBP concentration in the liver by 99Tcm-NGA functional imaging might be a suitable method for determining liver cell mass.
Adult↗
Performance of fluorescence polarisation immunoassay reagents for carbamazepine, phenytoin, phenobarbitone, primidone, and valproic acid on a Cobas Fara II analyser.
Reagents are now available for the measurement of a range of antiepileptic drugs by fluorescence polarisation immunoassay using the Roche Cobas Fara II analyser. Evaluation data are presented that demonstrate that these assays represent a convenient, cost-effective, and analytically reliable alternative to other commercially available systems for the measurement of drugs during therapeutic drug monitoring. The use of a general-purpose analyser, the opportunity to perform different drug assays simultaneously, and long calibration stability confer significant benefits on these methods. These are especially applicable for the laboratory that undertakes only small or moderate numbers of such investigations during therapeutic drug monitoring.
Anticonvulsants↗
Lack of association between the frequencies of HLA-DR or HLA-DP alleles and the occurrence of chronic graft-versus-host disease.
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Alleles↗
Upper keratinocytes of psoriatic skin lesions express high levels of NAP-1/IL-8 mRNA in situ.
In order to better understand the factors regulating disease promotion and activity in psoriasis (PS), we searched for the in situ expression of mRNA for various cytokines in long-standing PS skin lesions. Specific hybridization with a NAP-1/IL-8 anti-sense RNA probe was keratinocyte associated and yielded strong and specific signals exclusively in the upper layers of the lesional epidermis, but not in uninvolved skin from psoriatic patients or normal skin from non-psoriatics. Interestingly, NAP-1/IL-8 transcripts were focally clustered in a spotty pattern predominantly between the tips of elongated papillae, but were absent in the lower epidermal region and the dermal compartment. We consistently failed to detect appreciable numbers of TNF-alpha and/or IL-6 mRNA-containing cells in psoriatic lesions. These results support the notion that IL-8, rather than IL-6, is an important disease-promoting cytokine in PS. In view of the known in vitro and in vivo effects of IL-8, it is conceivable that this substance greatly contributes to the major pathologic changes seen in psoriatic skin, i.e., keratinocyte hyperproliferation and leucocyte infiltration. In this case, local pharmacologic down-regulation of NAP-1/IL-8 activity could be a promising therapeutic strategy in PS.
Cell Adhesion Molecules↗