Claudio Knüsli - Academia.edu (original) (raw)
Papers by Claudio Knüsli
PubMed, 1990
Local recurrences of intraperitoneal malignancies are mainly localized at the primary tumor site ... more Local recurrences of intraperitoneal malignancies are mainly localized at the primary tumor site and the peritoneal surface. Surgical procedures alone are neither able to further reduce the development of local recurrence nor to treat the already established recurrent disease. In this situation intraperitoneal chemotherapy as an "adjuvant" treatment modality could be thought helpful. Experimental and clinical trials have shown that high doses of cytotoxic agents can be applied to the abdominal cavity with less systemic side effects. While the recent published data are not promising for gastrointestinal malignancies, they seem to be more encouraging for ovarian cancer.
Antibiotics and Chemotherapy, Apr 16, 2015
PubMed, 1989
In a group of 31 patients a port-a-cath-system for intraperitoneal chemotherapy was installed. Fr... more In a group of 31 patients a port-a-cath-system for intraperitoneal chemotherapy was installed. From 23 evaluable patients 9 showed a tumor remission, but only 1 was a patient with gastrointestinal carcinoma. All others were patients with ovarial carcinoma. The median survival rate of all patients was 9 months after implantation of the intraperitoneal catheter. 50% of all patients with gastrointestinal carcinoma died within the first 6 months, only 1 of 11 patients with ovarial carcinoma died in this period.
PubMed, Dec 1, 1983
Morphology, frequency and significance of capillary sclerosis (CS) in the ureter and electron mic... more Morphology, frequency and significance of capillary sclerosis (CS) in the ureter and electron microscopic findings in early papillary necrosis are described. CS of the urinary tract is characterized by a thickening of the basement membrane of capillaries lying just underneath the urothelium. The basement membrane changes can be demonstrated by PAS, Sudan stain and autofluorescence with equal reliability. By electron microscopy the thickened basement membranes exhibit a tree ring like pattern permeated by lipid vacuoles. CS is most often present in the renal pelvis and the ureter and only in particularly severe cases also in the urinary bladder. The most severe CS is found in the proximal and middle third of the ureter. In a prospective autopsy study CS was found in 3.5% of autopsies of adults and in 83% of clinically recognized phenacetin abusers. Since there is no association with other renal or metabolic diseases, CS can be considered as specific for phenacetin abuse. This finding is further substantiated by a significant correlation between the degree of severity of capillary sclerosis and the daily dose of phenacetin in grams. In about half of the patients with known analgesic abuse but without CS, possible causes for the lack of CS can be identified, of which the most important is regression of CS after stopping the abuse. Electron microscopic studies of early papillary necrosis show the same BM changes as in the ureter in peritubular capillaries, loops of Henle and similar BM alterations in the collecting ducts. The morphologic findings in the ureter and in the renal papilla suggest that CS in papillary necrosis are the consequence of a toxic damage of endothelial and in the kidney of endothelial and epithelial cells.
Routledge eBooks, Jun 9, 2020
Forum médical suisse =, Jul 23, 2008
PubMed, Feb 16, 1980
In 442 inhabitants of Basel 451 malignant tumors of the lower urinary tract were found at autopsy... more In 442 inhabitants of Basel 451 malignant tumors of the lower urinary tract were found at autopsy or biopsy from 1963 to 1977. 69/442 patients were abusers of phenacetin containing analgesics. Carcinomas and sarcomas of the lower urinary tract were nearly 13 times as frequent in abusers as in non-abusers. Carcinomas of the renal pelvis were 77 times, carcinomas of the ureter 89 times and those of the urinary bladder 7 times as frequent among abusers. The differences in incidence of malignant tumors are statistically highly significant for all localizations and for multiple carcinomas as well, even if smokers are excluded. "Phenacetin tumors" occurred in younger patients and were more common in women than in non-abusers. They were ofen, though not always, accompanied by analgesic nephropathy. Comparison with other etiological factors such as aromatic amines or thorotrast demonstrated that phenacetin abuse is of greatest importance. The significance of smoking cannot be established unequivocally. Because of the occurrence of a large number of malignant tumors in phenacetin abusers it is very important to prohibit by legislation the use of phenacetin or paracetamol containing analgesics without medical prescription. In addition, these drugs should be replaced by other analgesic compounds.
Annals of Oncology, 2012
Objectives: This prospective, phase 2 study evaluated the efficacy and safety of dovitinib in pat... more Objectives: This prospective, phase 2 study evaluated the efficacy and safety of dovitinib in patients (pts) with advanced gastrointestinal stromal tumors (GISTs) who failed previous standard tyrosine kinase inhibitors (TKI). Methods: Thirty pts with pathologically proven metastatic or unresectable GIST who failed a minimum of both imatinib and sunitinib were accrued between Sep 2011 and Apr 2012. Dovitinib was administered orally at 500 mg qd for 5 consecutive days followed by a 2 day rest period. Results: The median age was 57.5 years (range, 35-76). All had metastatic disease in the peritoneum (n = 22), liver (n = 20), lung (n = 4), or bone (n = 4). Thirteen pts (43%) also failed nilotinib (n = 8), regorafenib (n = 2) or both nilotinib and regorafenib (n = 3) after failure of imatinib and sunitinib. By RECIST criteria, there were no objective responses, 19 (63.3%) had stable disease (SD), 5 (16.7%) progressive disease (PD), and 6 (20.0%) were not evaluable. By EORTC PET criteria (at 4 weeks), 3 pts (10.0%) achieved a partial response, 15 (50.0%) had SD, 10 (33.3) showed PD, and 2 were not evaluable. With a median follow-up of 4.8 months (range, 0.8-7.5), the medi an progression-free survival (PFS) and overall survival were 3.6 months (95% CI, 2.7-4.4) and 6.2 months (95% CI, 4.9-7.5), respectively. PFS could be predicted by PET response (PD vs no PD) at 4 weeks (p = 0.003). Grade 3 or 4 adverse events of dovitinib with frequency > 5% pts included asthenia (16.7%), leucopenia (6.7%), thrombocytopenia (6.7%), and hypertension (6.7%). Those toxicities were manageable with dose modification, and there were no treatment-related deaths. Conclusions: Dovitinib showed antitumor activity with manageable toxicities in this heavily pretreated cohort of GIST patients.
Schweizerische Rundschau für Medizin Praxis = Revue suisse de médecine Praxis, Jan 2, 1989
The costs chemotherapy for eight patients with different diagnoses treated between 1983 and 1985 ... more The costs chemotherapy for eight patients with different diagnoses treated between 1983 and 1985 were analyzed, based on case histories and invoices submitted to medical insurance companies. Total monthly costs of therapy included drug costs, diagnostic costs, fees and hospital charges. The total monthly chemotherapy costs ranged between SFr. 379.- and SFr. 6065.- and between SFr. 874.- and SFr. 3476.- for 5 outpatients and two inpatients respectively. Total monthly drug costs ranged between SFr. 103.- (Fluorouracil) and SFr. 1744.- (Adriamycin) for palliative therapies, and between SFr. 620.- (MOPP-ABVD) and SFr. 2490.- (Cis-Platin, Velbe, Bleomycin) for curative therapies. The drug costs (Methotrexate) of a third inpatient exceeded the flat rate paid by insurance, the remaining costs being covered by the state. About 50% of cancer chemotherapy costs are due to drug costs. Drug costs of curative therapies seem to be higher than those of palliative therapies. A reduction of total co...
Journal of Interferon Research, 1992
ABSTRACT This study reports on biological response modification induced by prolonged continuous s... more ABSTRACT This study reports on biological response modification induced by prolonged continuous subcutaneous (s.c.) infusion of recombinant interferon-gamma (rIFN-gamma) with particular attention to changes of soluble CD14. This glycoprotein with an unknown function is derived from myeloid cells carrying membrane CD14, which is the receptor for lipopolysaccharide (LPS)-LPS-binding protein (LBP) complexes. Fifteen metastatic cancer patients received weekly escalating doses of rIFN-gamma starting at either 50 or 100 micrograms/24 h and increasing up to 400 micrograms/24 h for a median duration of 6 weeks. The maximum tolerated dose was higher (200 micrograms/24 h) with the lower (50 micrograms/24 h) starting dose. Biological activity of rIFN-gamma was evaluated by weekly measurements of CD14, neopterin, and beta 2-microglobulin concentrations in serum as well as monocyte HLA class I and II antigen expression and tumor cytotoxicity. Serum IFN-gamma concentrations increased 20-fold within 4 weeks of therapy. The levels were correlated to the mean dose (r = 0.95, p less than 0.05). Among the biological markers, two patterns were observed. First, serum CD14 concentration and expression of monocyte HLA class II antigens increased significantly during the first week, and marker expression correlated with serum IFN-gamma levels (p less than 0.05); CD14 and HLA class II antigens thereafter returned to pretreatment levels within 4 weeks of therapy despite persistently elevated serum IFN-gamma concentrations. Second, serum neopterin and beta 2-microglobulin concentrations as well as monocyte HLA class I expression also increased significantly within the first week, but remained elevated thereafter without any further dose relationship.(ABSTRACT TRUNCATED AT 250 WORDS)
Cancer Immunology, Immunotherapy, 1990
ABSTRACT The expression of the monocyte membrane glycoprotein CD14 was measured and related to th... more ABSTRACT The expression of the monocyte membrane glycoprotein CD14 was measured and related to the serum interferon gamma (IFN gamma) concentration in thirteen patients with disseminated cancer during treatment with human recombinant interferon gamma (rIFN gamma). The drug was administered by continuous subcutaneous infusion using an escalating dose schedule, starting at 50 micrograms/day or 100 micrograms/day and increasing weekly up to 600 micrograms/day, if tolerated. Treatment was continued at a mean maximal tolerated dose of 200 micrograms/day for a median duration of 43 days. Serum IFN gamma concentration and monocyte CD14 antigen expression (immunofluorescence with the monoclonal antibody LeuM3 and fluorescence-activated cell sorting analysis) were determined weekly. The serum IFN gamma concentration was positively correlated with the rIFN gamma dose (P less than 0.05). Therapy induced a dose-dependent enhancement of CD14 antigen expression. The increase in mean CD14 fluorescence intensity was on average 60% after 3 weeks of treatment at a mean dose of 220 micrograms rIFN gamma/day and was reversed after withdrawal of therapy. Patients with a rapidly rising serum IFN gamma concentration (starting dose 100 micrograms/day) showed a smaller increment in CD14 fluorescence intensity than those with slowly rising serum IFN gamma levels (starting dose 50 micrograms/day). Since rIFN gamma is known to down-regulate CD14 antigen expression in vitro, monocytes from patients off therapy and from healthy volunteers were cultured with this cytokine. A similar decrease of CD14 fluorescence was observed in both groups. In patients several factors, such as IFN gamma concentration, duration of drug effect and type of serum, were evaluated and could not explain the discrepant in vivo and in vitro findings. In conclusion, the monocyte marker CD14 was found to be differentially regulated by rIFN gamma in vivo and in vitro. In vivo, secondary mediators, induced by rIFN gamma and acting on a constantly renewed cell population, may contribute to the enhanced CD14 expression.
Journal of Molecular Medicine, Nov 1, 1982
SummaryThe findings presented in this study are based on 29.226 autopsies performed (between 1953... more SummaryThe findings presented in this study are based on 29.226 autopsies performed (between 1953 and 1977) at Basel University on adult inhabitants of Basel, from which 409 urinary tract tumors (UTT) and 513 phenacetin abusers (PA) were discovered. There were 44 (8.6%) PA with UTT which, when compared with the control group (1.27%), represents a statistically significant increased incidence. Of the 50 UTT in PA, 52% occurred in the bladder, 6% in the ureter, and 42% in the renal pelvis. The induction time for tumors of the urinary bladder was about 27 years, and for tumors of the renal pelvis about 20 years. The commonest tumors arising in PA were invasive solid and non-invasive papillary urothelial carcinomas. PA with UTT died earlier than nonabusers but had metastases as frequently as nonabusers. Analgesic nephropathy was not always an accompanying disease. The daily dose of g/phenacetin in tumor patients in general, and in patients with tumors of the urinary bladder in particular, was about 1 g lower than in patients with analgesic nephropathy (without tumors) and in those with tumors of the renal pelvis. Thus, for the localization of the tumors, the daily dose seems to be more important than the total dose. Our investigation proved that not only tumors of the renal pelvis, but also of the ureter and the urinary bladder, are significantly more frequent in PA than in nonabusers. It is suspected that despite restriction of the over-the-counter sale of phenacetin-containing analgesics and even after stopping any analgesic abuse, UTT will further increase due to the longer induction time. Routine cytological screening tests of the urine are recommended for all known PA. A prescription for all phenacetin- and paracetamol-containing analgesics is necessary.
Bulletin des Médecins Suisses, 2019
Schweizerische Ärztezeitung, 2019
Einleitung: Die abdominothorakale Ösopagusresektion (Ivor Lewis Operation) ist ein Standardeingri... more Einleitung: Die abdominothorakale Ösopagusresektion (Ivor Lewis Operation) ist ein Standardeingriff in der Behandlung des Ösophaguskarzinoms. Eine Erweiterung des Hiatus ist oft notwendig, damit der Magenschlauch spannungsfrei in den Thorax zu liegen kommt. Dadurch besteht das Risiko einer[for full text, please go to the a.m. URL]
The present study discusses the probability of a major accident in a nuclear power plant and, by ... more The present study discusses the probability of a major accident in a nuclear power plant and, by simulation of such an accident, it evaluates the harm to people. It aims at characterizing the health effects of ionizing radiation, and it assesses the number of people impacted by a radioactive cloud, and by the deposition of radioactive material on the ground. It further evaluates the number of people in need of a resettlement. It also analyses the size of the area lost for agriculture due to radio-contamination. More specifically, the Western European nuclear power plants (NPPs) under scrutiny are Beznau, Gosgen, Leibstadt and Muhleberg in Switzerland and Bugey in France. The study models a major nuclear accident using meteorological files, one for each day during the year 2017 with help of the trajectory and dispersion model Hysplit. The source terms of the simulated accidents are specific to each of the five NPPs. They represent an amount situated between the Fukushima and Chernoby...
Bulletin des Médecins Suisses, May 30, 2018
pour le comité PSR/IPPNW Schweiz a Médecine interne / oncologie, FMH; b Médecine interne, FMH; c ... more pour le comité PSR/IPPNW Schweiz a Médecine interne / oncologie, FMH; b Médecine interne, FMH; c Prof. émérite de radiologie, FMH; d Médecine interne, FMH; e médecine générale, FMH; f PD chirurgie/recherche clinique, FMH L'élévation massive de la valeur limite d'exposition prévue dans la révision des ordonnances relatives à la radioprotection [1] échauffe les esprits à propos de la protection de la population vivant à proximité de la plus ancienne centrale nucléaire au monde, Beznau en Argovie. Au centre, les risques pour la santé humaine d'une exposition, en cas d'accident, à un rayonnement ionisant faible. Effets sanitaires induits par les rayonnements-données scientifiques Les connaissances actuelles sur les maladies induites par les rayonnements ionisants résultent d'études systématiques faites au Japon sur les survivants des bombes atomiques. Elles servent de base pour évaluer les risques en matière de radioprotection [2]. Huit études épidémiologiques ont été publiées ces dernières années, démontrant que l'évaluation des risques s'applique de la même manière pour des doses situées entre 1 et 100 mSv (tab. 1). Plusieurs groupes travaillant indépendamment les uns des autres ont reproduit les mêmes observations sur les rapports doses-effets. Ce sont des critères parmi les plus certains en faveur de la causalité: le risque de cancer augmente de manière linéaire avec la dose d'exposition. Ces études confirment ainsi le modèle «Linear no Threshold» (LNT) [3]. Dans sa communication aux médias du 2 mars 2018 [4a, b], le Conseil fédéral partage l'idée que les faibles doses de rayonnement doivent être prises en considération.
Schweizerische Ärztezeitung
Medicine, Conflict and Survival
The civilian and military nuclear technologies have been compared by many to the ‘so called’ nucl... more The civilian and military nuclear technologies have been compared by many to the ‘so called’ nuclear ‘Siamese twins’ since they are so closely connected one can hardly separate them. Knowledge of the civilian nuclear technology allows creating materials and technology that can also be used for military nuclear projects. Comprehensive nuclear programs – even if they are purely civilian in nature – therefore often provoke concern that the real intention is the desire to possess nuclear weapons. Most importantly, the inherent quality of ionizing radiation of nuclear energy processes leads to identical severe health effects both by military and civilian utilization. The proliferation of nuclear weapons is a risk that must be taken very seriously. Given the longevity of environmental contamination due to nuclear tests, nuclear accidents and uranium mining, in the interest of future generations human rights aspects must be increasingly taken into consideration. This is presently a focus of PSR/IPPNW Switzerland.
Schweizerische Ärztezeitung
Nach dem Willen des Bundesrats spätestens ab 2050 in der Schweiz nicht mehr am Netz: Atomkraftwerke.
PubMed, 1990
Local recurrences of intraperitoneal malignancies are mainly localized at the primary tumor site ... more Local recurrences of intraperitoneal malignancies are mainly localized at the primary tumor site and the peritoneal surface. Surgical procedures alone are neither able to further reduce the development of local recurrence nor to treat the already established recurrent disease. In this situation intraperitoneal chemotherapy as an "adjuvant" treatment modality could be thought helpful. Experimental and clinical trials have shown that high doses of cytotoxic agents can be applied to the abdominal cavity with less systemic side effects. While the recent published data are not promising for gastrointestinal malignancies, they seem to be more encouraging for ovarian cancer.
Antibiotics and Chemotherapy, Apr 16, 2015
PubMed, 1989
In a group of 31 patients a port-a-cath-system for intraperitoneal chemotherapy was installed. Fr... more In a group of 31 patients a port-a-cath-system for intraperitoneal chemotherapy was installed. From 23 evaluable patients 9 showed a tumor remission, but only 1 was a patient with gastrointestinal carcinoma. All others were patients with ovarial carcinoma. The median survival rate of all patients was 9 months after implantation of the intraperitoneal catheter. 50% of all patients with gastrointestinal carcinoma died within the first 6 months, only 1 of 11 patients with ovarial carcinoma died in this period.
PubMed, Dec 1, 1983
Morphology, frequency and significance of capillary sclerosis (CS) in the ureter and electron mic... more Morphology, frequency and significance of capillary sclerosis (CS) in the ureter and electron microscopic findings in early papillary necrosis are described. CS of the urinary tract is characterized by a thickening of the basement membrane of capillaries lying just underneath the urothelium. The basement membrane changes can be demonstrated by PAS, Sudan stain and autofluorescence with equal reliability. By electron microscopy the thickened basement membranes exhibit a tree ring like pattern permeated by lipid vacuoles. CS is most often present in the renal pelvis and the ureter and only in particularly severe cases also in the urinary bladder. The most severe CS is found in the proximal and middle third of the ureter. In a prospective autopsy study CS was found in 3.5% of autopsies of adults and in 83% of clinically recognized phenacetin abusers. Since there is no association with other renal or metabolic diseases, CS can be considered as specific for phenacetin abuse. This finding is further substantiated by a significant correlation between the degree of severity of capillary sclerosis and the daily dose of phenacetin in grams. In about half of the patients with known analgesic abuse but without CS, possible causes for the lack of CS can be identified, of which the most important is regression of CS after stopping the abuse. Electron microscopic studies of early papillary necrosis show the same BM changes as in the ureter in peritubular capillaries, loops of Henle and similar BM alterations in the collecting ducts. The morphologic findings in the ureter and in the renal papilla suggest that CS in papillary necrosis are the consequence of a toxic damage of endothelial and in the kidney of endothelial and epithelial cells.
Routledge eBooks, Jun 9, 2020
Forum médical suisse =, Jul 23, 2008
PubMed, Feb 16, 1980
In 442 inhabitants of Basel 451 malignant tumors of the lower urinary tract were found at autopsy... more In 442 inhabitants of Basel 451 malignant tumors of the lower urinary tract were found at autopsy or biopsy from 1963 to 1977. 69/442 patients were abusers of phenacetin containing analgesics. Carcinomas and sarcomas of the lower urinary tract were nearly 13 times as frequent in abusers as in non-abusers. Carcinomas of the renal pelvis were 77 times, carcinomas of the ureter 89 times and those of the urinary bladder 7 times as frequent among abusers. The differences in incidence of malignant tumors are statistically highly significant for all localizations and for multiple carcinomas as well, even if smokers are excluded. "Phenacetin tumors" occurred in younger patients and were more common in women than in non-abusers. They were ofen, though not always, accompanied by analgesic nephropathy. Comparison with other etiological factors such as aromatic amines or thorotrast demonstrated that phenacetin abuse is of greatest importance. The significance of smoking cannot be established unequivocally. Because of the occurrence of a large number of malignant tumors in phenacetin abusers it is very important to prohibit by legislation the use of phenacetin or paracetamol containing analgesics without medical prescription. In addition, these drugs should be replaced by other analgesic compounds.
Annals of Oncology, 2012
Objectives: This prospective, phase 2 study evaluated the efficacy and safety of dovitinib in pat... more Objectives: This prospective, phase 2 study evaluated the efficacy and safety of dovitinib in patients (pts) with advanced gastrointestinal stromal tumors (GISTs) who failed previous standard tyrosine kinase inhibitors (TKI). Methods: Thirty pts with pathologically proven metastatic or unresectable GIST who failed a minimum of both imatinib and sunitinib were accrued between Sep 2011 and Apr 2012. Dovitinib was administered orally at 500 mg qd for 5 consecutive days followed by a 2 day rest period. Results: The median age was 57.5 years (range, 35-76). All had metastatic disease in the peritoneum (n = 22), liver (n = 20), lung (n = 4), or bone (n = 4). Thirteen pts (43%) also failed nilotinib (n = 8), regorafenib (n = 2) or both nilotinib and regorafenib (n = 3) after failure of imatinib and sunitinib. By RECIST criteria, there were no objective responses, 19 (63.3%) had stable disease (SD), 5 (16.7%) progressive disease (PD), and 6 (20.0%) were not evaluable. By EORTC PET criteria (at 4 weeks), 3 pts (10.0%) achieved a partial response, 15 (50.0%) had SD, 10 (33.3) showed PD, and 2 were not evaluable. With a median follow-up of 4.8 months (range, 0.8-7.5), the medi an progression-free survival (PFS) and overall survival were 3.6 months (95% CI, 2.7-4.4) and 6.2 months (95% CI, 4.9-7.5), respectively. PFS could be predicted by PET response (PD vs no PD) at 4 weeks (p = 0.003). Grade 3 or 4 adverse events of dovitinib with frequency > 5% pts included asthenia (16.7%), leucopenia (6.7%), thrombocytopenia (6.7%), and hypertension (6.7%). Those toxicities were manageable with dose modification, and there were no treatment-related deaths. Conclusions: Dovitinib showed antitumor activity with manageable toxicities in this heavily pretreated cohort of GIST patients.
Schweizerische Rundschau für Medizin Praxis = Revue suisse de médecine Praxis, Jan 2, 1989
The costs chemotherapy for eight patients with different diagnoses treated between 1983 and 1985 ... more The costs chemotherapy for eight patients with different diagnoses treated between 1983 and 1985 were analyzed, based on case histories and invoices submitted to medical insurance companies. Total monthly costs of therapy included drug costs, diagnostic costs, fees and hospital charges. The total monthly chemotherapy costs ranged between SFr. 379.- and SFr. 6065.- and between SFr. 874.- and SFr. 3476.- for 5 outpatients and two inpatients respectively. Total monthly drug costs ranged between SFr. 103.- (Fluorouracil) and SFr. 1744.- (Adriamycin) for palliative therapies, and between SFr. 620.- (MOPP-ABVD) and SFr. 2490.- (Cis-Platin, Velbe, Bleomycin) for curative therapies. The drug costs (Methotrexate) of a third inpatient exceeded the flat rate paid by insurance, the remaining costs being covered by the state. About 50% of cancer chemotherapy costs are due to drug costs. Drug costs of curative therapies seem to be higher than those of palliative therapies. A reduction of total co...
Journal of Interferon Research, 1992
ABSTRACT This study reports on biological response modification induced by prolonged continuous s... more ABSTRACT This study reports on biological response modification induced by prolonged continuous subcutaneous (s.c.) infusion of recombinant interferon-gamma (rIFN-gamma) with particular attention to changes of soluble CD14. This glycoprotein with an unknown function is derived from myeloid cells carrying membrane CD14, which is the receptor for lipopolysaccharide (LPS)-LPS-binding protein (LBP) complexes. Fifteen metastatic cancer patients received weekly escalating doses of rIFN-gamma starting at either 50 or 100 micrograms/24 h and increasing up to 400 micrograms/24 h for a median duration of 6 weeks. The maximum tolerated dose was higher (200 micrograms/24 h) with the lower (50 micrograms/24 h) starting dose. Biological activity of rIFN-gamma was evaluated by weekly measurements of CD14, neopterin, and beta 2-microglobulin concentrations in serum as well as monocyte HLA class I and II antigen expression and tumor cytotoxicity. Serum IFN-gamma concentrations increased 20-fold within 4 weeks of therapy. The levels were correlated to the mean dose (r = 0.95, p less than 0.05). Among the biological markers, two patterns were observed. First, serum CD14 concentration and expression of monocyte HLA class II antigens increased significantly during the first week, and marker expression correlated with serum IFN-gamma levels (p less than 0.05); CD14 and HLA class II antigens thereafter returned to pretreatment levels within 4 weeks of therapy despite persistently elevated serum IFN-gamma concentrations. Second, serum neopterin and beta 2-microglobulin concentrations as well as monocyte HLA class I expression also increased significantly within the first week, but remained elevated thereafter without any further dose relationship.(ABSTRACT TRUNCATED AT 250 WORDS)
Cancer Immunology, Immunotherapy, 1990
ABSTRACT The expression of the monocyte membrane glycoprotein CD14 was measured and related to th... more ABSTRACT The expression of the monocyte membrane glycoprotein CD14 was measured and related to the serum interferon gamma (IFN gamma) concentration in thirteen patients with disseminated cancer during treatment with human recombinant interferon gamma (rIFN gamma). The drug was administered by continuous subcutaneous infusion using an escalating dose schedule, starting at 50 micrograms/day or 100 micrograms/day and increasing weekly up to 600 micrograms/day, if tolerated. Treatment was continued at a mean maximal tolerated dose of 200 micrograms/day for a median duration of 43 days. Serum IFN gamma concentration and monocyte CD14 antigen expression (immunofluorescence with the monoclonal antibody LeuM3 and fluorescence-activated cell sorting analysis) were determined weekly. The serum IFN gamma concentration was positively correlated with the rIFN gamma dose (P less than 0.05). Therapy induced a dose-dependent enhancement of CD14 antigen expression. The increase in mean CD14 fluorescence intensity was on average 60% after 3 weeks of treatment at a mean dose of 220 micrograms rIFN gamma/day and was reversed after withdrawal of therapy. Patients with a rapidly rising serum IFN gamma concentration (starting dose 100 micrograms/day) showed a smaller increment in CD14 fluorescence intensity than those with slowly rising serum IFN gamma levels (starting dose 50 micrograms/day). Since rIFN gamma is known to down-regulate CD14 antigen expression in vitro, monocytes from patients off therapy and from healthy volunteers were cultured with this cytokine. A similar decrease of CD14 fluorescence was observed in both groups. In patients several factors, such as IFN gamma concentration, duration of drug effect and type of serum, were evaluated and could not explain the discrepant in vivo and in vitro findings. In conclusion, the monocyte marker CD14 was found to be differentially regulated by rIFN gamma in vivo and in vitro. In vivo, secondary mediators, induced by rIFN gamma and acting on a constantly renewed cell population, may contribute to the enhanced CD14 expression.
Journal of Molecular Medicine, Nov 1, 1982
SummaryThe findings presented in this study are based on 29.226 autopsies performed (between 1953... more SummaryThe findings presented in this study are based on 29.226 autopsies performed (between 1953 and 1977) at Basel University on adult inhabitants of Basel, from which 409 urinary tract tumors (UTT) and 513 phenacetin abusers (PA) were discovered. There were 44 (8.6%) PA with UTT which, when compared with the control group (1.27%), represents a statistically significant increased incidence. Of the 50 UTT in PA, 52% occurred in the bladder, 6% in the ureter, and 42% in the renal pelvis. The induction time for tumors of the urinary bladder was about 27 years, and for tumors of the renal pelvis about 20 years. The commonest tumors arising in PA were invasive solid and non-invasive papillary urothelial carcinomas. PA with UTT died earlier than nonabusers but had metastases as frequently as nonabusers. Analgesic nephropathy was not always an accompanying disease. The daily dose of g/phenacetin in tumor patients in general, and in patients with tumors of the urinary bladder in particular, was about 1 g lower than in patients with analgesic nephropathy (without tumors) and in those with tumors of the renal pelvis. Thus, for the localization of the tumors, the daily dose seems to be more important than the total dose. Our investigation proved that not only tumors of the renal pelvis, but also of the ureter and the urinary bladder, are significantly more frequent in PA than in nonabusers. It is suspected that despite restriction of the over-the-counter sale of phenacetin-containing analgesics and even after stopping any analgesic abuse, UTT will further increase due to the longer induction time. Routine cytological screening tests of the urine are recommended for all known PA. A prescription for all phenacetin- and paracetamol-containing analgesics is necessary.
Bulletin des Médecins Suisses, 2019
Schweizerische Ärztezeitung, 2019
Einleitung: Die abdominothorakale Ösopagusresektion (Ivor Lewis Operation) ist ein Standardeingri... more Einleitung: Die abdominothorakale Ösopagusresektion (Ivor Lewis Operation) ist ein Standardeingriff in der Behandlung des Ösophaguskarzinoms. Eine Erweiterung des Hiatus ist oft notwendig, damit der Magenschlauch spannungsfrei in den Thorax zu liegen kommt. Dadurch besteht das Risiko einer[for full text, please go to the a.m. URL]
The present study discusses the probability of a major accident in a nuclear power plant and, by ... more The present study discusses the probability of a major accident in a nuclear power plant and, by simulation of such an accident, it evaluates the harm to people. It aims at characterizing the health effects of ionizing radiation, and it assesses the number of people impacted by a radioactive cloud, and by the deposition of radioactive material on the ground. It further evaluates the number of people in need of a resettlement. It also analyses the size of the area lost for agriculture due to radio-contamination. More specifically, the Western European nuclear power plants (NPPs) under scrutiny are Beznau, Gosgen, Leibstadt and Muhleberg in Switzerland and Bugey in France. The study models a major nuclear accident using meteorological files, one for each day during the year 2017 with help of the trajectory and dispersion model Hysplit. The source terms of the simulated accidents are specific to each of the five NPPs. They represent an amount situated between the Fukushima and Chernoby...
Bulletin des Médecins Suisses, May 30, 2018
pour le comité PSR/IPPNW Schweiz a Médecine interne / oncologie, FMH; b Médecine interne, FMH; c ... more pour le comité PSR/IPPNW Schweiz a Médecine interne / oncologie, FMH; b Médecine interne, FMH; c Prof. émérite de radiologie, FMH; d Médecine interne, FMH; e médecine générale, FMH; f PD chirurgie/recherche clinique, FMH L'élévation massive de la valeur limite d'exposition prévue dans la révision des ordonnances relatives à la radioprotection [1] échauffe les esprits à propos de la protection de la population vivant à proximité de la plus ancienne centrale nucléaire au monde, Beznau en Argovie. Au centre, les risques pour la santé humaine d'une exposition, en cas d'accident, à un rayonnement ionisant faible. Effets sanitaires induits par les rayonnements-données scientifiques Les connaissances actuelles sur les maladies induites par les rayonnements ionisants résultent d'études systématiques faites au Japon sur les survivants des bombes atomiques. Elles servent de base pour évaluer les risques en matière de radioprotection [2]. Huit études épidémiologiques ont été publiées ces dernières années, démontrant que l'évaluation des risques s'applique de la même manière pour des doses situées entre 1 et 100 mSv (tab. 1). Plusieurs groupes travaillant indépendamment les uns des autres ont reproduit les mêmes observations sur les rapports doses-effets. Ce sont des critères parmi les plus certains en faveur de la causalité: le risque de cancer augmente de manière linéaire avec la dose d'exposition. Ces études confirment ainsi le modèle «Linear no Threshold» (LNT) [3]. Dans sa communication aux médias du 2 mars 2018 [4a, b], le Conseil fédéral partage l'idée que les faibles doses de rayonnement doivent être prises en considération.
Schweizerische Ärztezeitung
Medicine, Conflict and Survival
The civilian and military nuclear technologies have been compared by many to the ‘so called’ nucl... more The civilian and military nuclear technologies have been compared by many to the ‘so called’ nuclear ‘Siamese twins’ since they are so closely connected one can hardly separate them. Knowledge of the civilian nuclear technology allows creating materials and technology that can also be used for military nuclear projects. Comprehensive nuclear programs – even if they are purely civilian in nature – therefore often provoke concern that the real intention is the desire to possess nuclear weapons. Most importantly, the inherent quality of ionizing radiation of nuclear energy processes leads to identical severe health effects both by military and civilian utilization. The proliferation of nuclear weapons is a risk that must be taken very seriously. Given the longevity of environmental contamination due to nuclear tests, nuclear accidents and uranium mining, in the interest of future generations human rights aspects must be increasingly taken into consideration. This is presently a focus of PSR/IPPNW Switzerland.
Schweizerische Ärztezeitung
Nach dem Willen des Bundesrats spätestens ab 2050 in der Schweiz nicht mehr am Netz: Atomkraftwerke.