A single dose of theophylline improves hypoglycemia unawareness in type 1 diabetic patients. Prol... more A single dose of theophylline improves hypoglycemia unawareness in type 1 diabetic patients. Prolonged theophylline use is, however, associated with emergence of tolerance. This study investigated whether prolonged use of theophylline retains efficacy for counterregulatory defects in patients with type 1 diabetes and hypoglycemia unawareness. Experiments were performed with 12 subjects with type 1 diabetes and hypoglycemia unawareness. All subjects participated in a crossover study of 2 randomly scheduled 15-day study periods during which 250 mg theophylline twice daily or matching placebo was used. On the final day of each period, hyperinsulinemic (360 pmol x m(-2) x min(-1)) hypoglycemic (5.0, 3.5, 2.5 mmol x L(-1)) glucose clamps were used to assess counterregulatory and cardiovascular responses. Under normoglycemic conditions, there were no differences between theophylline and placebo. Under hypoglycemic conditions, theophylline enhanced responses of growth hormone, symptoms, he...
We retrospectively assessed the diagnostic utility of dedicated positron emission tomography (PET... more We retrospectively assessed the diagnostic utility of dedicated positron emission tomography (PET) and hybrid PET-computed tomography (CT) scans with [F-18]fluorodeoxyglucose (FDG) in the imaging evaluation of patients with known or suspected recurrent and metastatic cholangiocarcinoma. The study group included 24 patients (13 males and 11 females; age range, 34-75 years) with known or suspected recurrent and metastatic cholangiocarcinoma. We performed 8 dedicated PET scans (Siemens 953/A, Knoxville, Tenn) in 8 patients and 24 hybrid PET-CT scans (Siemens Biograph, Knoxville, Tenn) in 16 patients. Four patients underwent both pretreatment and posttreatment scans. Nonenhanced CT transmission scans were obtained for attenuation correction after administration of oral contrast material. PET images were obtained 60 minutes after the intravenous administration of 15 mCi (555 MBq) FDG. Prior treatments included surgery alone in 12 patients, surgery and chemotherapy in 6 patients, and surgery and combined chemoradiation therapy in 6 patients. Diagnostic validation was conducted through clinical and radiologic follow-up (2 months to 8 years). PET and CT were concordant in 18 patients. PET-CT correctly localized a hypermetabolic metastatic lesion in the anterior subdiaphragmatic fat instead of within the liver and was falsely negative in intrahepatic infiltrating type cholangiocarcinoma. PET was discordant with CT in 6 patients. PET was negative in an enlarged right cardiophrenic lymph node on CT, which remained stable for 1 year. In 1 patient, PET-CT scan showed hypermetabolic peritoneal disease in the right paracolic gutter without definite corresponding structural abnormalities, which was subsequently confirmed on a follow-up PET-CT scan performed 6 months after the initial study, at which time peritoneal nodular thickening was evident on concurrent CT. PET-CT documented the progression of locally recurrent and metastatic disease in another patient based on interval appearance of several new hypermetabolic lesions and significant increase in the standardized uptake values of the known lesions despite little interval change in the size and morphologic character of lesions on concurrent CT. It was also helpful in excluding metabolically active disease in patients with contrast enhancement at either surgical margin of hepatic resection site or focally within hepatic parenchyma and in an osseous lesion. Overall, based on the clinically relevant patient basis for detection of recurrent and metastatic cholangiocarcinoma, the sensitivity and specificity of PET (alone and combined with CT) were 94% and 100% and, for CT alone, were 82% and 43%, respectively. FDG PET and PET-CT are useful in the imaging evaluation of patients with cholangiocarcinoma (except for infiltrating type) for detection of recurrent and metastatic disease and for assessment of treatment response. In particular, the combined structural and metabolic information of PET-CT enhances the diagnostic confidence in lesion characterization.
Renal vascular responses to pregnancy have frequently been studied, by investigating renal vascul... more Renal vascular responses to pregnancy have frequently been studied, by investigating renal vascular resistance (RVR), renal flow, glomerular filtration rate (GFR), and renal artery responses to stimuli. Nonetheless, several questions remain: 1. Which vasodilator pathways are activated and to what extent do they affect RVR, renal flow and GFR across species, strains and gestational ages, 2. Are these changes dependent on renal artery adaptation, 3. At which cellular level does pregnancy affect the involved pathways? In an attempt to answer the questions raised, we performed a systematic review and meta-analysis on animal data. We included 37 studies (116 responses). At mid-gestation, RVR and GFR change to a similar degree across species and strains, accompanied by variable change in renal flow. At least in rats, changes depend on NO activation. At late gestation, changes in RVR, renal flow and GFR vary between species and strains. In rats, these changes are effectuated by sympathetic...
Working and participating in society are important for one's health and wellbeing. This also ... more Working and participating in society are important for one's health and wellbeing. This also works the other way around: in order to work or participate, one has to be healthy. Every doctor should learn about this reciprocal relationship during their medical training. In a survey undertaken by the Netherlands Society of Occupational Medicine, the amount of time spent on occupational medicine in the curriculum of eight Dutch medical faculties was examined. The study showed vast differences between faculties in the amount of time spent on occupational medicine, in the learning methods employed and also in the number of students who participate in internships. The situation in the Netherlands compares favourably with that in other European countries. Sufficient specific attention to subjects related to health and work during undergraduate education is important for all doctors and a prerequisite to increase the number of medical students who subsequently choose a career in occupati...
Thiazolidinediones (TZDs) are associated with fluid retention that has been suggested to be resis... more Thiazolidinediones (TZDs) are associated with fluid retention that has been suggested to be resistant to treatment with loop diuretics. This resistance is thought to be caused by upregulation of renal epithelial sodium channels (ENaCs). In this study, we tested whether these mechanisms are of clinical significance. We conducted a well-controlled study in 12 insulin-resistant nondiabetic participants, who received treatment for 9 weeks with either rosiglitazone at a dosage of 4 mg b.i.d. or placebo. The aim of the study was to investigate whether upregulation of ENaCs by rosiglitazone reduces furosemide's natriuretic response and enhances the response to the ENaC inhibitor amiloride. The natriuretic response to furosemide and amiloride and the amount of α-ENaC in urinary exosomes were quantified. Rosiglitazone neither reduced furosemide-induced natriuresis nor changed furosemide's concentration-effect curve. Furthermore, rosiglitazone did not change either amiloride-induced n...
In the concentration range that is normally achieved in humans, e.g., after the drinking of coffe... more In the concentration range that is normally achieved in humans, e.g., after the drinking of coffee or in patients treated with theophylline, the cardiovascular effects of methylxanthines are primarily due to antagonism of adenosine A(1) and A(2) receptors. Inhibition of phosphodiesterases or mobilization of intracellular calcium requires much higher concentrations. In conscious humans, acute exposure to caffeine results in an increase in blood pressure by an increased total peripheral resistance, and a slight decrease in heart rate. This overall hemodynamic response is composed of direct effects of caffeine on vascular tone, on myocardial contractility and conduction, and on the sympathetic nervous system. Caffeine is the most widely consumed methylxanthine, mainly derived from coffee intake. Regular coffee consumption can affect various traditional cardiovascular risk factors, including a slight increase in blood pressure, an increase in plasma cholesterol and homocysteine levels, ...
Septic shock is associated with increased microvascular permeability. As a model for study of the... more Septic shock is associated with increased microvascular permeability. As a model for study of the pathophysiology of sepsis, endotoxin administration to humans has facilitated research into inflammation, coagulation and cardiovascular effects. The present study was undertaken to determine whether endotoxin administration to human volunteers can be used as a model to study the sepsis-associated increase in microvascular permeability. In an open intervention study conducted in a university medical centre, 16 healthy volunteers were evaluated in the research unit of the intensive care unit. Eight were administered endotoxin intravenously (2 ng/kg Escherichia coli O113) and eight served as control individuals. Microvascular permeability was assessed before and 5 hours after the administration of endotoxin (n = 8) or placebo (n = 8) by three different methods: transcapillary escape rate of I(125)-albumin; venous occlusion strain-gauge plethysmography to determine the filtration capacity;...
TBV – Tijdschrift voor Bedrijfs- en Verzekeringsgeneeskunde, 2013
ABSTRACT Het signaleren van beroepsziekten is een belangrijke reden om preventie op het werk op g... more ABSTRACT Het signaleren van beroepsziekten is een belangrijke reden om preventie op het werk op gang te brengen. De bedrijfsarts kan dit alleen bereiken samen met de werknemer en de werkgever. Deze kwalitatieve studie heeft als doel om in kaart te brengen wat werknemer en werkgever kunnen bijdragen om preventie bij de bedrijfsarts te stimuleren. Twee focusgroepen zijn georganiseerd voor vijftien bedrijfsartsen die deelnemen aan het Peilstation Intensief Melden en werden geleid door medewerkers van het Nederlands Centrum voor Beroepsziekten. De vraag luidde: Wat hebt u als bedrijfsarts van de werknemer of de werkgever nodig om preventie op het werk op gang te brengen na het constateren van een beroepsziekte? De antwoorden van de bedrijfsartsen zijn door de leiders van de focusgroepen gecategoriseerd in thema’s. De beide focusgroepen gaven een gemiddeld cijfer van 8 voor de mate van tevredenheid over de mogelijkheid om de eigen ideeën aan bod te laten komen. De bedrijfsartsen noemden als bevorderende factoren persoonskenmerken van de werknemer zoals zelfverzekerd zijn, kenmerken van de beroepsziekte zoals een ongunstige prognose voor herstel, en het werk van de werknemer zoals goed identificeerbare gezondheidsrisico’s. Ondersteuning van de werknemer door zijn werkgever en collega’s, en een zichtbare bedrijfsarts werken ook bevorderend. Voor de werkgever zijn bevorderende factoren betrokken en proactief zijn. Daarnaast is de relatie van de werkgever met de branche van belang, bijvoorbeeld door een branchebenadering voor signalering en preventie. Ook actieve handhaving door de Inspectie SZW en de Inspectie voor de Gezondheidszorg bevordert preventie. Een andere bevorderende factor is een contract met een preventieparagraaf, waarbij expliciet wordt vermeld welke acties de bedrijfsarts neemt bij het signaleren van een beroepsziekte om werknemer en werkgever te stimuleren de gezondheidsrisico’s aan te pakken.
In vitro studies suggest that the vasodilator mechanism of action of calcitonin gene-related pept... more In vitro studies suggest that the vasodilator mechanism of action of calcitonin gene-related peptide (CGRP) involves various endothelium-dependent and endothelium-independent mechanisms. An in vivo analysis of the contribution of nitric oxide, prostaglandins, calcium-sensitive potassium channels (K(+)(Ca) channels), and adenosine triphosphate (ATP)-sensitive potassium channels (K(+)(ATP) channels) to CGRP-induced vasodilation in humans was performed. CGRP (3, 10, and 30 ng x min(-1) x dL(-1) forearm) was infused into the brachial artery of 40 healthy subjects. Forearm vascular responses were measured by venous occlusion plethysmography. First, dose-response curves were constructed during coinfusion of CGRP with placebo (sodium chloride, 0.9%). After washout, in 5 subgroups (n = 8 each), the infusions of CGRP were repeated with placebo (time-control experiments), N(G)-monomethyl-L-arginine (L-NMMA, a nitric oxide-synthase inhibitor), indomethacin (a cyclooxygenase inhibitor), tetraet...
In the present prospective study, five blood tests for detection of human cytomegalovirus (HCMV),... more In the present prospective study, five blood tests for detection of human cytomegalovirus (HCMV), nucleic acid sequence-based amplification (NASBA) for detection of early (immediate-early antigen) and late (pp67) mRNA, PCR for detection of HCMV DNA (DNA PCR), culture, and pp65 antigenemia assay, and culture and DNA PCR of urine and throat swab specimens were compared for their abilities to predict the development of disease caused by HCMV (HCMV disease). Of 101 human immunodeficiency virus (HIV)-infected patients with </=100 CD4(+) lymphocytes per mm(3), 25 patients developed HCMV disease. The pp65 antigenemia assay (sensitivity, 50%; specificity, 89%) and DNA PCR of blood (sensitivity, 69%; specificity, 75%) were most accurate in predicting the development of HCMV disease within the next 12 months. Both blood culture and late pp67 mRNA NASBA had high specificities (91 and 90%, respectively) but low sensitivities (25 and 13%, respectively). The sensitivities of urine culture, DNA...
Flosequinan (BTS 49465, 7-fluoro-1-methyl-3-methyl-sulphinyl-4-quinolone), a recently direct-acti... more Flosequinan (BTS 49465, 7-fluoro-1-methyl-3-methyl-sulphinyl-4-quinolone), a recently direct-acting vasodilator that should cause relatively less reflex tachycardia, was given in a single oral dose of 200 mg to 10 untreated patients with moderate to severe hypertension. Flosequinan caused a fall in blood pressure (BP) from 181/116 +/- 7/4 to 161/102 +/- 5/4 mm Hg (P < 0.05). The proportional decrease of mean arterial pressure (MAP) was 14.6% (P < 0.01). Together with the decrease of BP an increase of heart rate from 79 +/- 5 to 96 +/- 5 beats/min occurred (31 +/- 4%, P < 0.01). Forearm blood flow increased insignificantly (NS) from 3.7 +/- 0.6 to 5.5 +/- 1.5 ml/100 ml/min together with a small decrease in forearm vascular resistance from 47 +/- 7 to 39 +/- 7 arbitrary units (NS). Forearm venous distensibility remained stable around 0.03% mm Hg (NS). Neurohormonal parameters showed the consequences of systemic vasodilation: noradrenaline rose from 1.25 +/- 0.10 to 2.88 +/- 0...
Objective To examine the effects of short-term cyclic stretch on apoptosis in alveolar type II ce... more Objective To examine the effects of short-term cyclic stretch on apoptosis in alveolar type II cells (A549). To study in vitro the direct influence of alveolar type II cells on mechanical stretch. Methods A549 were treated with different doses of lipopolysaccharide (LPS), 0 ng/ml, 1 ng/ml, 10 ng/ml, 100 ng/ml, 1000 ng/ml, and then A549 were lengthened 5%, 15%, 30% using a FLEXCELL tension unit 4000, a vacuum-driven device that applies strain to cells, which were cultured in six-well plates coated with collagen-I, and 12 cycles/min for 4 hours. Apoptosis was measured using the flow cytometry method that measures annexin V and propidium iodide (PI) staining. The morphological changes of apoptotic cells were observed by transmission electron microscope. Results Apoptosis could be induced in alveolar type II cells (A549) by mechanical stretch. The percentage of annexin V + PI cells increased after being treated with cyclic stretch for 4 hours by 5%, 15%, 30% in all groups. The morphological features of apoptotic cells demonstrated by transmission electron microscope were as follows: shrinkage of the cell, chromatin condensation and aggregation under the nuclear membrane as a crescent or lump, membrane-encapsulated nuclear fragment or cell organ formed by invagination of the cell membrane, and apoptotic body formation followed by vacuolization. Conclusion Apoptosis induced by mechanical stretch and LPS is dose dependent. Mechanical stretch aggravates apoptosis especially in cells treated with LPS. Annexin V and PI double staining is a specific, sensitive, and quantitative method for analyzing apoptotic cells. It is also helpful to clarify the protective mechanism of low-volume ventilation in ARDS. PaO 2 /FiO 2 430 [421; 440] # 380 [349; 397] 165 [68; 289] # C (ml/cmH 2 O) 28 [24; 32]* 18 [16; 21]* 12 [8; 17]* R i (cmH 2 O/l/s) 4.1 [3.9; 4.5] 4.5 [4.3; 5.1] 5.1 [3.7; 7.9] # P < 0.05 control vs 24-hour peritonitis, *P < 0.05 control vs 12-hour and 24-hour peritonitis.
Introduction Community-acquired pneumonia remains a common condition worldwide. It is associated ... more Introduction Community-acquired pneumonia remains a common condition worldwide. It is associated with significant morbidity and mortality. The aim of this study was to evaluate conditions that could predict a poor outcome. Design Retrospective analyse of 69 patients admitted to the ICU from 1996 to 2003. Demographic data included age, sex and medical history. Etiologic agents, multiorgan dysfunction, nosocomial infections, SAPS II and PORT scores were recorded for each patient. For statistical analysis we used a t test, chi-square test and Mann-Whitney U test on SPSS ® . A value of P less than 0.05 was considered significant. Results Forty-seven patients were male and 22 patients were female. Mean age was 52 years. Sixty-seven percent had serious pre-morbid conditions including pulmonary disease (34.8%), cardiac problems (36.2%), diabetes (13%) and chronic liver disease (5.8%); 40.6% were smokers, drug abusers or alcohol dependents. Sixtyeight patients required invasive mechanical ventilation. The average length of ventilation was 13.5 days, median 8 days. The mean SAPS II score was 40.14 and the mean PORT score was 141. The mortality rate was 27.5% (SAPS II estimated mortality, 35%). Complications reported were ARDS (40.6%), septic shock (34.8%), acute renal failure (2.9%), cardiac arrest (8.7%) and nosocomial infeccions (46.4%). Mortality rates were higher for previous hepatic (75%) and metabolic (33%) diseases. We found a close association between crude mortality and SAPS II score (P = 0.003) and development of complications (P = 0.0028). Respiratory dysfunction (P = 0.006) and septic shock (P = 0.022) were most significantly related to mortality. No significant differences were founded regarding age, comorbidities, PORT score, etiologic agents, nosocomial infections and length of invasive mechanical ventilation. Conclusions Previous hepatic chronic disease was strictly related to higher mortality as well as isolation of MRSA. ARDS and septic shock predicted a poor outcome. SAPS II score was the best severity indicator of mortality.
Introduction Septic shock is associated with increased microvascular permeability. As a model for... more Introduction Septic shock is associated with increased microvascular permeability. As a model for study of the pathophysiology of sepsis, endotoxin administration to humans has facilitated research into inflammation, coagulation and cardiovascular effects. The present study was undertaken to determine whether endotoxin administration to human volunteers can be used as a model to study the sepsisassociated increase in microvascular permeability.
Clinical experience suggests that the administration of fluids in human endotoxemia reduces sympt... more Clinical experience suggests that the administration of fluids in human endotoxemia reduces symptoms. In the present study, the effects of a standardised fluid protocol on symptoms, inflammatory and hemodynamic parameters in human endotoxemia are determined. With approval of the local ethics committee, 16 healthy volunteers received 2 ng/kg of Escherichia coli endotoxin (O:113). After an overnight fast, nine subjects received 1.5 l of 2.5% glucose/0.45% NaCl the hour prior to the endotoxin administration and 150 ml/h during the course of the experiment (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;prehydrated group&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;). Seven subjects only received a continuous infusion of 75 ml/h during the experiment (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;non-prehydrated group&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;). The course of inflammatory parameters and symptoms were determined and mean arterial pressure, heart rate and forearm blood flow were measured. In the prehydrated group, TNF-alpha increased to 522 +/- 63 pg/ml (mean +/- SEM) while the maximum in the non-prehydrated group was 927 +/- 187 pg/ml (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.04). IL-10 increased similarly in both groups (non-prehydrated 117 +/- 18 pg/ml and prehydrated 99 +/- 18 pg/ml; P = NS). The prehydrated group had a significantly lower (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.004) symptom score and recovered sooner (P = 0.004). Endotoxin-induced changes in hemodynamics revealed no significant differences between groups. We demonstrate that prehydration in experimental human endotoxemia significantly shifts the cytokine balance towards a more anti-inflammatory pattern. This effect is associated with a reduction in symptoms, whereas the changes in hemodynamic parameters are not influenced by prehydration.
TBV - Tijdschrift voor Bedrijfs- en Verzekeringsgeneeskunde, 2009
ABSTRACT ‘Het diagnosticeren en melden van werkgerelateerde aandoeningen behoort tot de expertise... more ABSTRACT ‘Het diagnosticeren en melden van werkgerelateerde aandoeningen behoort tot de expertise van de bedrijfsarts, daarover is weinig verschil van mening.’1 Dat dit in de beroepsgroep wordt ondersteund, blijkt uit de grote deelname van bedrijfsartsen aan het Peilstation Intensief Melden (PIM). Vanaf 1 januari 2009 doen 181 bedrijfsartsen mee aan het project. Onderdeel van dit project is een scholingsprogramma. De scholing wil van bedrijfsartsen beroepsziekteexperts maken. Naar verwachting melden zij meer beroepsziekten en zijn de meldingen van betere kwaliteit.2 In dit artikel beschrijven we de doelen van het PIM-scholingsprogramma en hoe het is opgezet. Daarnaast bespreken we gegevens van een vragenlijstonderzoek onder de deelnemers bij de start van PIM.
A single dose of theophylline improves hypoglycemia unawareness in type 1 diabetic patients. Prol... more A single dose of theophylline improves hypoglycemia unawareness in type 1 diabetic patients. Prolonged theophylline use is, however, associated with emergence of tolerance. This study investigated whether prolonged use of theophylline retains efficacy for counterregulatory defects in patients with type 1 diabetes and hypoglycemia unawareness. Experiments were performed with 12 subjects with type 1 diabetes and hypoglycemia unawareness. All subjects participated in a crossover study of 2 randomly scheduled 15-day study periods during which 250 mg theophylline twice daily or matching placebo was used. On the final day of each period, hyperinsulinemic (360 pmol x m(-2) x min(-1)) hypoglycemic (5.0, 3.5, 2.5 mmol x L(-1)) glucose clamps were used to assess counterregulatory and cardiovascular responses. Under normoglycemic conditions, there were no differences between theophylline and placebo. Under hypoglycemic conditions, theophylline enhanced responses of growth hormone, symptoms, he...
We retrospectively assessed the diagnostic utility of dedicated positron emission tomography (PET... more We retrospectively assessed the diagnostic utility of dedicated positron emission tomography (PET) and hybrid PET-computed tomography (CT) scans with [F-18]fluorodeoxyglucose (FDG) in the imaging evaluation of patients with known or suspected recurrent and metastatic cholangiocarcinoma. The study group included 24 patients (13 males and 11 females; age range, 34-75 years) with known or suspected recurrent and metastatic cholangiocarcinoma. We performed 8 dedicated PET scans (Siemens 953/A, Knoxville, Tenn) in 8 patients and 24 hybrid PET-CT scans (Siemens Biograph, Knoxville, Tenn) in 16 patients. Four patients underwent both pretreatment and posttreatment scans. Nonenhanced CT transmission scans were obtained for attenuation correction after administration of oral contrast material. PET images were obtained 60 minutes after the intravenous administration of 15 mCi (555 MBq) FDG. Prior treatments included surgery alone in 12 patients, surgery and chemotherapy in 6 patients, and surgery and combined chemoradiation therapy in 6 patients. Diagnostic validation was conducted through clinical and radiologic follow-up (2 months to 8 years). PET and CT were concordant in 18 patients. PET-CT correctly localized a hypermetabolic metastatic lesion in the anterior subdiaphragmatic fat instead of within the liver and was falsely negative in intrahepatic infiltrating type cholangiocarcinoma. PET was discordant with CT in 6 patients. PET was negative in an enlarged right cardiophrenic lymph node on CT, which remained stable for 1 year. In 1 patient, PET-CT scan showed hypermetabolic peritoneal disease in the right paracolic gutter without definite corresponding structural abnormalities, which was subsequently confirmed on a follow-up PET-CT scan performed 6 months after the initial study, at which time peritoneal nodular thickening was evident on concurrent CT. PET-CT documented the progression of locally recurrent and metastatic disease in another patient based on interval appearance of several new hypermetabolic lesions and significant increase in the standardized uptake values of the known lesions despite little interval change in the size and morphologic character of lesions on concurrent CT. It was also helpful in excluding metabolically active disease in patients with contrast enhancement at either surgical margin of hepatic resection site or focally within hepatic parenchyma and in an osseous lesion. Overall, based on the clinically relevant patient basis for detection of recurrent and metastatic cholangiocarcinoma, the sensitivity and specificity of PET (alone and combined with CT) were 94% and 100% and, for CT alone, were 82% and 43%, respectively. FDG PET and PET-CT are useful in the imaging evaluation of patients with cholangiocarcinoma (except for infiltrating type) for detection of recurrent and metastatic disease and for assessment of treatment response. In particular, the combined structural and metabolic information of PET-CT enhances the diagnostic confidence in lesion characterization.
Renal vascular responses to pregnancy have frequently been studied, by investigating renal vascul... more Renal vascular responses to pregnancy have frequently been studied, by investigating renal vascular resistance (RVR), renal flow, glomerular filtration rate (GFR), and renal artery responses to stimuli. Nonetheless, several questions remain: 1. Which vasodilator pathways are activated and to what extent do they affect RVR, renal flow and GFR across species, strains and gestational ages, 2. Are these changes dependent on renal artery adaptation, 3. At which cellular level does pregnancy affect the involved pathways? In an attempt to answer the questions raised, we performed a systematic review and meta-analysis on animal data. We included 37 studies (116 responses). At mid-gestation, RVR and GFR change to a similar degree across species and strains, accompanied by variable change in renal flow. At least in rats, changes depend on NO activation. At late gestation, changes in RVR, renal flow and GFR vary between species and strains. In rats, these changes are effectuated by sympathetic...
Working and participating in society are important for one's health and wellbeing. This also ... more Working and participating in society are important for one's health and wellbeing. This also works the other way around: in order to work or participate, one has to be healthy. Every doctor should learn about this reciprocal relationship during their medical training. In a survey undertaken by the Netherlands Society of Occupational Medicine, the amount of time spent on occupational medicine in the curriculum of eight Dutch medical faculties was examined. The study showed vast differences between faculties in the amount of time spent on occupational medicine, in the learning methods employed and also in the number of students who participate in internships. The situation in the Netherlands compares favourably with that in other European countries. Sufficient specific attention to subjects related to health and work during undergraduate education is important for all doctors and a prerequisite to increase the number of medical students who subsequently choose a career in occupati...
Thiazolidinediones (TZDs) are associated with fluid retention that has been suggested to be resis... more Thiazolidinediones (TZDs) are associated with fluid retention that has been suggested to be resistant to treatment with loop diuretics. This resistance is thought to be caused by upregulation of renal epithelial sodium channels (ENaCs). In this study, we tested whether these mechanisms are of clinical significance. We conducted a well-controlled study in 12 insulin-resistant nondiabetic participants, who received treatment for 9 weeks with either rosiglitazone at a dosage of 4 mg b.i.d. or placebo. The aim of the study was to investigate whether upregulation of ENaCs by rosiglitazone reduces furosemide's natriuretic response and enhances the response to the ENaC inhibitor amiloride. The natriuretic response to furosemide and amiloride and the amount of α-ENaC in urinary exosomes were quantified. Rosiglitazone neither reduced furosemide-induced natriuresis nor changed furosemide's concentration-effect curve. Furthermore, rosiglitazone did not change either amiloride-induced n...
In the concentration range that is normally achieved in humans, e.g., after the drinking of coffe... more In the concentration range that is normally achieved in humans, e.g., after the drinking of coffee or in patients treated with theophylline, the cardiovascular effects of methylxanthines are primarily due to antagonism of adenosine A(1) and A(2) receptors. Inhibition of phosphodiesterases or mobilization of intracellular calcium requires much higher concentrations. In conscious humans, acute exposure to caffeine results in an increase in blood pressure by an increased total peripheral resistance, and a slight decrease in heart rate. This overall hemodynamic response is composed of direct effects of caffeine on vascular tone, on myocardial contractility and conduction, and on the sympathetic nervous system. Caffeine is the most widely consumed methylxanthine, mainly derived from coffee intake. Regular coffee consumption can affect various traditional cardiovascular risk factors, including a slight increase in blood pressure, an increase in plasma cholesterol and homocysteine levels, ...
Septic shock is associated with increased microvascular permeability. As a model for study of the... more Septic shock is associated with increased microvascular permeability. As a model for study of the pathophysiology of sepsis, endotoxin administration to humans has facilitated research into inflammation, coagulation and cardiovascular effects. The present study was undertaken to determine whether endotoxin administration to human volunteers can be used as a model to study the sepsis-associated increase in microvascular permeability. In an open intervention study conducted in a university medical centre, 16 healthy volunteers were evaluated in the research unit of the intensive care unit. Eight were administered endotoxin intravenously (2 ng/kg Escherichia coli O113) and eight served as control individuals. Microvascular permeability was assessed before and 5 hours after the administration of endotoxin (n = 8) or placebo (n = 8) by three different methods: transcapillary escape rate of I(125)-albumin; venous occlusion strain-gauge plethysmography to determine the filtration capacity;...
TBV – Tijdschrift voor Bedrijfs- en Verzekeringsgeneeskunde, 2013
ABSTRACT Het signaleren van beroepsziekten is een belangrijke reden om preventie op het werk op g... more ABSTRACT Het signaleren van beroepsziekten is een belangrijke reden om preventie op het werk op gang te brengen. De bedrijfsarts kan dit alleen bereiken samen met de werknemer en de werkgever. Deze kwalitatieve studie heeft als doel om in kaart te brengen wat werknemer en werkgever kunnen bijdragen om preventie bij de bedrijfsarts te stimuleren. Twee focusgroepen zijn georganiseerd voor vijftien bedrijfsartsen die deelnemen aan het Peilstation Intensief Melden en werden geleid door medewerkers van het Nederlands Centrum voor Beroepsziekten. De vraag luidde: Wat hebt u als bedrijfsarts van de werknemer of de werkgever nodig om preventie op het werk op gang te brengen na het constateren van een beroepsziekte? De antwoorden van de bedrijfsartsen zijn door de leiders van de focusgroepen gecategoriseerd in thema’s. De beide focusgroepen gaven een gemiddeld cijfer van 8 voor de mate van tevredenheid over de mogelijkheid om de eigen ideeën aan bod te laten komen. De bedrijfsartsen noemden als bevorderende factoren persoonskenmerken van de werknemer zoals zelfverzekerd zijn, kenmerken van de beroepsziekte zoals een ongunstige prognose voor herstel, en het werk van de werknemer zoals goed identificeerbare gezondheidsrisico’s. Ondersteuning van de werknemer door zijn werkgever en collega’s, en een zichtbare bedrijfsarts werken ook bevorderend. Voor de werkgever zijn bevorderende factoren betrokken en proactief zijn. Daarnaast is de relatie van de werkgever met de branche van belang, bijvoorbeeld door een branchebenadering voor signalering en preventie. Ook actieve handhaving door de Inspectie SZW en de Inspectie voor de Gezondheidszorg bevordert preventie. Een andere bevorderende factor is een contract met een preventieparagraaf, waarbij expliciet wordt vermeld welke acties de bedrijfsarts neemt bij het signaleren van een beroepsziekte om werknemer en werkgever te stimuleren de gezondheidsrisico’s aan te pakken.
In vitro studies suggest that the vasodilator mechanism of action of calcitonin gene-related pept... more In vitro studies suggest that the vasodilator mechanism of action of calcitonin gene-related peptide (CGRP) involves various endothelium-dependent and endothelium-independent mechanisms. An in vivo analysis of the contribution of nitric oxide, prostaglandins, calcium-sensitive potassium channels (K(+)(Ca) channels), and adenosine triphosphate (ATP)-sensitive potassium channels (K(+)(ATP) channels) to CGRP-induced vasodilation in humans was performed. CGRP (3, 10, and 30 ng x min(-1) x dL(-1) forearm) was infused into the brachial artery of 40 healthy subjects. Forearm vascular responses were measured by venous occlusion plethysmography. First, dose-response curves were constructed during coinfusion of CGRP with placebo (sodium chloride, 0.9%). After washout, in 5 subgroups (n = 8 each), the infusions of CGRP were repeated with placebo (time-control experiments), N(G)-monomethyl-L-arginine (L-NMMA, a nitric oxide-synthase inhibitor), indomethacin (a cyclooxygenase inhibitor), tetraet...
In the present prospective study, five blood tests for detection of human cytomegalovirus (HCMV),... more In the present prospective study, five blood tests for detection of human cytomegalovirus (HCMV), nucleic acid sequence-based amplification (NASBA) for detection of early (immediate-early antigen) and late (pp67) mRNA, PCR for detection of HCMV DNA (DNA PCR), culture, and pp65 antigenemia assay, and culture and DNA PCR of urine and throat swab specimens were compared for their abilities to predict the development of disease caused by HCMV (HCMV disease). Of 101 human immunodeficiency virus (HIV)-infected patients with </=100 CD4(+) lymphocytes per mm(3), 25 patients developed HCMV disease. The pp65 antigenemia assay (sensitivity, 50%; specificity, 89%) and DNA PCR of blood (sensitivity, 69%; specificity, 75%) were most accurate in predicting the development of HCMV disease within the next 12 months. Both blood culture and late pp67 mRNA NASBA had high specificities (91 and 90%, respectively) but low sensitivities (25 and 13%, respectively). The sensitivities of urine culture, DNA...
Flosequinan (BTS 49465, 7-fluoro-1-methyl-3-methyl-sulphinyl-4-quinolone), a recently direct-acti... more Flosequinan (BTS 49465, 7-fluoro-1-methyl-3-methyl-sulphinyl-4-quinolone), a recently direct-acting vasodilator that should cause relatively less reflex tachycardia, was given in a single oral dose of 200 mg to 10 untreated patients with moderate to severe hypertension. Flosequinan caused a fall in blood pressure (BP) from 181/116 +/- 7/4 to 161/102 +/- 5/4 mm Hg (P < 0.05). The proportional decrease of mean arterial pressure (MAP) was 14.6% (P < 0.01). Together with the decrease of BP an increase of heart rate from 79 +/- 5 to 96 +/- 5 beats/min occurred (31 +/- 4%, P < 0.01). Forearm blood flow increased insignificantly (NS) from 3.7 +/- 0.6 to 5.5 +/- 1.5 ml/100 ml/min together with a small decrease in forearm vascular resistance from 47 +/- 7 to 39 +/- 7 arbitrary units (NS). Forearm venous distensibility remained stable around 0.03% mm Hg (NS). Neurohormonal parameters showed the consequences of systemic vasodilation: noradrenaline rose from 1.25 +/- 0.10 to 2.88 +/- 0...
Objective To examine the effects of short-term cyclic stretch on apoptosis in alveolar type II ce... more Objective To examine the effects of short-term cyclic stretch on apoptosis in alveolar type II cells (A549). To study in vitro the direct influence of alveolar type II cells on mechanical stretch. Methods A549 were treated with different doses of lipopolysaccharide (LPS), 0 ng/ml, 1 ng/ml, 10 ng/ml, 100 ng/ml, 1000 ng/ml, and then A549 were lengthened 5%, 15%, 30% using a FLEXCELL tension unit 4000, a vacuum-driven device that applies strain to cells, which were cultured in six-well plates coated with collagen-I, and 12 cycles/min for 4 hours. Apoptosis was measured using the flow cytometry method that measures annexin V and propidium iodide (PI) staining. The morphological changes of apoptotic cells were observed by transmission electron microscope. Results Apoptosis could be induced in alveolar type II cells (A549) by mechanical stretch. The percentage of annexin V + PI cells increased after being treated with cyclic stretch for 4 hours by 5%, 15%, 30% in all groups. The morphological features of apoptotic cells demonstrated by transmission electron microscope were as follows: shrinkage of the cell, chromatin condensation and aggregation under the nuclear membrane as a crescent or lump, membrane-encapsulated nuclear fragment or cell organ formed by invagination of the cell membrane, and apoptotic body formation followed by vacuolization. Conclusion Apoptosis induced by mechanical stretch and LPS is dose dependent. Mechanical stretch aggravates apoptosis especially in cells treated with LPS. Annexin V and PI double staining is a specific, sensitive, and quantitative method for analyzing apoptotic cells. It is also helpful to clarify the protective mechanism of low-volume ventilation in ARDS. PaO 2 /FiO 2 430 [421; 440] # 380 [349; 397] 165 [68; 289] # C (ml/cmH 2 O) 28 [24; 32]* 18 [16; 21]* 12 [8; 17]* R i (cmH 2 O/l/s) 4.1 [3.9; 4.5] 4.5 [4.3; 5.1] 5.1 [3.7; 7.9] # P < 0.05 control vs 24-hour peritonitis, *P < 0.05 control vs 12-hour and 24-hour peritonitis.
Introduction Community-acquired pneumonia remains a common condition worldwide. It is associated ... more Introduction Community-acquired pneumonia remains a common condition worldwide. It is associated with significant morbidity and mortality. The aim of this study was to evaluate conditions that could predict a poor outcome. Design Retrospective analyse of 69 patients admitted to the ICU from 1996 to 2003. Demographic data included age, sex and medical history. Etiologic agents, multiorgan dysfunction, nosocomial infections, SAPS II and PORT scores were recorded for each patient. For statistical analysis we used a t test, chi-square test and Mann-Whitney U test on SPSS ® . A value of P less than 0.05 was considered significant. Results Forty-seven patients were male and 22 patients were female. Mean age was 52 years. Sixty-seven percent had serious pre-morbid conditions including pulmonary disease (34.8%), cardiac problems (36.2%), diabetes (13%) and chronic liver disease (5.8%); 40.6% were smokers, drug abusers or alcohol dependents. Sixtyeight patients required invasive mechanical ventilation. The average length of ventilation was 13.5 days, median 8 days. The mean SAPS II score was 40.14 and the mean PORT score was 141. The mortality rate was 27.5% (SAPS II estimated mortality, 35%). Complications reported were ARDS (40.6%), septic shock (34.8%), acute renal failure (2.9%), cardiac arrest (8.7%) and nosocomial infeccions (46.4%). Mortality rates were higher for previous hepatic (75%) and metabolic (33%) diseases. We found a close association between crude mortality and SAPS II score (P = 0.003) and development of complications (P = 0.0028). Respiratory dysfunction (P = 0.006) and septic shock (P = 0.022) were most significantly related to mortality. No significant differences were founded regarding age, comorbidities, PORT score, etiologic agents, nosocomial infections and length of invasive mechanical ventilation. Conclusions Previous hepatic chronic disease was strictly related to higher mortality as well as isolation of MRSA. ARDS and septic shock predicted a poor outcome. SAPS II score was the best severity indicator of mortality.
Introduction Septic shock is associated with increased microvascular permeability. As a model for... more Introduction Septic shock is associated with increased microvascular permeability. As a model for study of the pathophysiology of sepsis, endotoxin administration to humans has facilitated research into inflammation, coagulation and cardiovascular effects. The present study was undertaken to determine whether endotoxin administration to human volunteers can be used as a model to study the sepsisassociated increase in microvascular permeability.
Clinical experience suggests that the administration of fluids in human endotoxemia reduces sympt... more Clinical experience suggests that the administration of fluids in human endotoxemia reduces symptoms. In the present study, the effects of a standardised fluid protocol on symptoms, inflammatory and hemodynamic parameters in human endotoxemia are determined. With approval of the local ethics committee, 16 healthy volunteers received 2 ng/kg of Escherichia coli endotoxin (O:113). After an overnight fast, nine subjects received 1.5 l of 2.5% glucose/0.45% NaCl the hour prior to the endotoxin administration and 150 ml/h during the course of the experiment (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;prehydrated group&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;). Seven subjects only received a continuous infusion of 75 ml/h during the experiment (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;non-prehydrated group&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;). The course of inflammatory parameters and symptoms were determined and mean arterial pressure, heart rate and forearm blood flow were measured. In the prehydrated group, TNF-alpha increased to 522 +/- 63 pg/ml (mean +/- SEM) while the maximum in the non-prehydrated group was 927 +/- 187 pg/ml (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.04). IL-10 increased similarly in both groups (non-prehydrated 117 +/- 18 pg/ml and prehydrated 99 +/- 18 pg/ml; P = NS). The prehydrated group had a significantly lower (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.004) symptom score and recovered sooner (P = 0.004). Endotoxin-induced changes in hemodynamics revealed no significant differences between groups. We demonstrate that prehydration in experimental human endotoxemia significantly shifts the cytokine balance towards a more anti-inflammatory pattern. This effect is associated with a reduction in symptoms, whereas the changes in hemodynamic parameters are not influenced by prehydration.
TBV - Tijdschrift voor Bedrijfs- en Verzekeringsgeneeskunde, 2009
ABSTRACT ‘Het diagnosticeren en melden van werkgerelateerde aandoeningen behoort tot de expertise... more ABSTRACT ‘Het diagnosticeren en melden van werkgerelateerde aandoeningen behoort tot de expertise van de bedrijfsarts, daarover is weinig verschil van mening.’1 Dat dit in de beroepsgroep wordt ondersteund, blijkt uit de grote deelname van bedrijfsartsen aan het Peilstation Intensief Melden (PIM). Vanaf 1 januari 2009 doen 181 bedrijfsartsen mee aan het project. Onderdeel van dit project is een scholingsprogramma. De scholing wil van bedrijfsartsen beroepsziekteexperts maken. Naar verwachting melden zij meer beroepsziekten en zijn de meldingen van betere kwaliteit.2 In dit artikel beschrijven we de doelen van het PIM-scholingsprogramma en hoe het is opgezet. Daarnaast bespreken we gegevens van een vragenlijstonderzoek onder de deelnemers bij de start van PIM.
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