ABSTRACT
A 16-year-old patient presented with abdominal pain and sustained hypertension. Thorough evaluation including renography with and without captopril and renal vein renin sampling were normal. Duplex ultrasound, however, raised suspicion of a renal artery stenosis. This was confirmed by computed tomography angiography which showed a severe branch artery stenosis with post-stenotic dilatation consistent with focal fibromuscular dysplasia (FMD). As the hypertension was resistant to 3 classes of antihypertensive treatment, percutaneous transluminal renal angioplasty (PTRA) was offered. The procedure had immediate effect on the blood pressure. Without medication the patient remains normotensive 4 years after and the abdominal pain has only sporadically returned. The presented case illustrates the challenging process of diagnosing FMD-related renal branch artery stenosis as well as the potential benefits of PTRA in this patient group.
Subject(s)
Angioplasty, Balloon , Fibromuscular Dysplasia , Hypertension, Renovascular , Hypertension , Renal Artery Obstruction , Adolescent , Constriction, Pathologic , Fibromuscular Dysplasia/complications , Fibromuscular Dysplasia/diagnosis , Humans , Hypertension/diagnosis , Hypertension, Renovascular/diagnosis , Hypertension, Renovascular/etiology , Renal Artery , Renal Artery Obstruction/diagnosis , Renal Artery Obstruction/diagnostic imagingABSTRACT
INTRODUCTION: Intradialytic nutrition may improve nutritional status and reduce mortality in patients on maintenance hemodialysis (HD) but has been associated with adverse events, mainly hemodynamic instability. Some dialysis centers therefore restrict intradialytic meals. In 2 clinical studies, we investigated the effects of intradialytic glucose-insulin infusion (GII) and meal intake on blood pressure (BP), pulse wave velocity (PWV), pulse wave analysis (PWA), and cardiac output (CO). PWA yielded augmentation index standardized with heart rate 75 (AIx@HR75). METHODS: In the GII study, 12 nondiabetic HD patients had BP, PWV, PWA, and CO measured during 3 HD sessions: standard HD, HD with glucose infusion, and HD with GII. In the Meal study, 12 nondiabetic patients had BP and PWA measured on 3 study days: meal alone (non-HD), meal and HD, 2 meals and HD. Twelve matched healthy controls completed the non-HD day. FINDINGS: In the GII study, glucose or GII had no additional effects on hemodynamic parameters compared with standard HD. HD resulted in a decrease in systolic BP of 13%, in diastolic BP of 9%, in AIx@HR75 of 17%, and CO of 18%. PWV was reduced by only 5%. In the Meal study, a meal alone did not change BP, whereas the combined influence of HD and meal intake reduced systolic BP with 22% and diastolic BP with 19%. Furthermore, AIx@HR75 decreased by 37% on HD days and by 36% in controls, but was unaffected on non-HD days. DISCUSSION: In the GII study, HD significantly reduced BP, AIx@75, and CO, whereas PWV remained almost constant. No additional effects were observed by concomitant GII during HD. BP reductions seemed larger in the Meal study compared with the GII study. Taken together, HD per se appears as the main discriminant for intradialytic hypotension but in hemodynamically unstable patients the timing and route of nutrition provision should be considered carefully.
Subject(s)
Glucose/metabolism , Hemodynamics/physiology , Insulin/metabolism , Meals/physiology , Adult , Aged , Female , Humans , Male , Middle AgedABSTRACT
In this report, we present a challenging case of a 63-year-old Caucasian woman with an extreme stress response to blood pressure (BP) measurements. Office- and ambulatory BP measurements consistently found systolic BP above 200 mmHg. However, antihypertensive medication made her dizzy and extremely unwell, and she could barely tolerate treatment with a moderate dose of angiotensin-converting enzyme (ACE) inhibitor. Finger-cuff-based measurements (Finapres Finometer®) revealed extreme hypertension in relation to contact with medical professionals, but hypotension when the patient was seated alone unobserved. Months after, the patient suffered a hemorrhagic stroke possibly related to her extreme BP-fluctuations in stressful situations.
Subject(s)
White Coat Hypertension/physiopathology , Antihypertensive Agents/adverse effects , Antihypertensive Agents/therapeutic use , Blood Pressure Monitoring, Ambulatory , Dizziness/chemically induced , Female , Humans , Middle Aged , Stroke/etiology , White Coat Hypertension/complicationsABSTRACT
OBJECTIVE: Patients on maintenance hemodialysis (HD) are unable to compensate for an enlarged mineral load with increased excretion of calcium and phosphate in the urine. Hence, excess calcium and phosphate must be neutralized by other mechanisms to avoid toxicity. The present study examined the acute handling of a mineral load in HD patients as compared with healthy subjects. DESIGN: Controlled intervention study. SUBJECTS: Twelve HD patients and 12 matched healthy subjects. INTERVENTION: After a weight-adjusted standardized meal, blood samples were collected for the following 9 hours for ionized calcium, phosphate, parathyroid hormone (PTH), and fibroblast growth factor-23 (FGF23). The fractional excretion of calcium and phosphate was measured in controls. The patients were not allowed to take phosphate binders 24 hours before the experiment, and the study was performed on a non-HD day. RESULTS: In healthy subjects, plasma calcium and phosphate did not change significantly from baseline, whereas HD patients demonstrated a decrease in plasma phosphate from 60 to 120 minutes by maximum 10% ([6; 13%], mean [95% confidence interval], P < .001) below baseline. PTH increased in both HD patients and controls and peaked 300 minutes after the meal 11% ([4; 19%], P < .004) above baseline in both groups. No changes in FGF23 were observed in HD patients, whereas FGF23 steadily decreased in controls, reaching nadir values at the end of the study 16% ([10; 21%], P < .001) below baseline. Control subjects demonstrated an immediate postprandial increase in the fractional excretion of both calcium and phosphate CONCLUSIONS: In HD patients, the mineral load paradoxically induced a decrease in plasma phosphate, whereas ionized calcium remained unchanged although PTH increased. These findings suggest that excess calcium and phosphate may be disposed of by mineral deposition, which may include soft tissue and vascular calcification.
Subject(s)
Calcium/blood , Kidney Failure, Chronic/blood , Phosphates/blood , Postprandial Period , Renal Dialysis , Adult , Aged , Calcium/urine , Female , Fibroblast Growth Factor-23 , Fibroblast Growth Factors/blood , Humans , Male , Middle Aged , Parathyroid Hormone/blood , Phosphates/urineABSTRACT
OBJECTIVE: To investigate the response of serum fibroblast growth factor 21 (FGF21) to a meal and to insulin infusion in haemodialysis (HD) patients. DESIGN AND PATIENTS: Meal study: in a crossover design, 12 nondiabetic HD patients were randomly assigned to: (1) a non-HD day with one meal served, (2) a HD day with one meal served during HD and (3) a HD day with two meals served during and after HD, respectively. Twelve healthy controls participated in an experiment identical to the non-HD day. Insulin infusion study: in a crossover design, 11 nondiabetic HD patients were randomly assigned to receive a 4-h HD session with either: (1) no infusion, (2) glucose infusion or (3) glucose-insulin infusion. A meal was served 2 h before HD start. RESULTS: Meal study: serum FGF21 was 23-fold higher in HD patients than controls (P < 0·001). Postprandial FGF21 decreased on all four study days (P < 0·006), but the relative reductions from baseline were significantly greater in controls (P < 0·008). Postprandial changes in FGF21 were inversely related with triglycerides (P = 0·042) and positively related with insulin-like growth factor binding protein-1 (IGFBP-1) (P < 0·001). Serum FGF21 was only associated with changes in adiponectin (P = 0·001) and free fatty acids (P = 0·04) in the healthy controls. Insulin infusion study: as compared with no infusion, glucose and glucose-insulin infusion prevented the postprandial decrease in FGF21 and resulted in higher FGF21 concentrations by up to 25% (P = 0·003). CONCLUSIONS: Serum FGF21 was highly elevated in HD patients but the response of serum FGF21 to meal intake and insulin infusion seemed to be intact. Our results indicate that FGF21 may play an important role in short-term metabolic homoeostasis.
Subject(s)
Fibroblast Growth Factors/metabolism , Insulin/administration & dosage , Renal Dialysis , Adiponectin/metabolism , Adult , Aged , Blood Glucose/analysis , Case-Control Studies , Cross-Over Studies , Eating , Fatty Acids, Nonesterified/metabolism , Female , Glucose/analysis , Humans , Insulin Infusion Systems , Insulin-Like Growth Factor Binding Protein 1/blood , Male , Middle Aged , Postprandial Period , Triglycerides/blood , Triglycerides/metabolismABSTRACT
OBJECTIVE: Patients on maintenance haemodialysis (HD) have reduced circulating free and bioactive insulin-like growth factor I (IGF-I) due to increased IGF-binding proteins (IGFBPs). This study investigated the postprandial response of the IGF system in HD patients compared with matched healthy subjects. DESIGN AND PATIENTS: In a crossover study, twelve nondiabetic HD patients were assigned in a random order to three 10-h study days: (1) a non-HD day with one meal served at baseline (NHDM1), (2) an HD day with one meal served during HD (HDM1) and (3) an HD day with two meals served during and after HD, respectively (HDM2). Twelve healthy controls conducted session 1. RESULTS: After the baseline meal, insulin concentrations changed similarly in HD patients and controls, whereas hyperglycaemia was more prolonged in HD patients (P < 0·001). Postprandial IGFBP-1 showed greater reductions from baseline in controls (-76% [-81; -70%], mean [95% confidence intervals], P < 0·001) than in patients on non-HD days (-45% [-57; -30%], P < 0·001). In the latter group, the response was even more attenuated during HD (-22% [-38; -1%] and -24% [-40; -4%], P ≤ 0·041). After the second meal on HDM2 days, IGFBP-1 further decreased (-50% [-61; -37%], P < 0·001), whereas IGFBP-1 returned to baseline levels on the other study days. Consistently, at the end of the study days, bioactive IGF-I was significantly above baseline only on HDM2 days (+22% [+5; +43%], P = 0·012). CONCLUSIONS: HD patients were unable to suppress IGFBP-1 to the same extent as healthy controls, which may increase the risk of protein-energy wasting in maintenance HD. A second meal after HD, however, effectively suppressed IGFBP-1 and increased bioactive IGF-I.
Subject(s)
Insulin-Like Growth Factor Binding Proteins/metabolism , Insulin-Like Growth Factor I/metabolism , Renal Dialysis/methods , Adult , Aged , Biomarkers/metabolism , Blood Glucose/analysis , Case-Control Studies , Cross-Over Studies , Female , Humans , Insulin/blood , Insulin-Like Growth Factor Binding Protein 1/metabolism , Male , Middle Aged , Postprandial Period , Random AllocationABSTRACT
Fibromuscular dysplasia (FMD) is a disease of the musculature of arterial walls leading to stenoses, aneurysms, and dissections. The purpose of this report was to summarize the evidence for (1) one-time routine imaging from brain-to-pelvis and (2) lifelong antiplatelet therapy, for example, aspirin, for patients diagnosed with FMD as suggested by an international consensus report from 2019. PubMed was systematically searched, and the evidence providing a basis for the current consensus points, as well as articles published since, were reviewed. In four registries evaluating patients with FMD, the prevalence of multivessel involvement, aneurysms, and dissections was reported to be 43.5%-66.3%, 21.6%-30.6%, and 5.6%-28.1%, respectively. Any antiplatelet drug was used in 72.9% of patients, and aspirin was prescribed in up to 70.2% of patients. Based on the high prevalence of vascular manifestations, their associated morbidity, and the potential for endovascular or surgical intervention, the suggestion of one-time brain-to-pelvis screening with computed tomography angiography or magnetic resonance angiography is well supported. Contrarily, the evidence to support the consensus statement of lifelong antiplatelet therapy to all patients in the absence of contraindications is more uncertain since a beneficial effect has not been demonstrated specifically in patients with fibromuscular dysplasia. Therefore, until the efficacy and safety of primary thromboprophylaxis have been demonstrated in this patient group specifically, it may be equally appropriate to only use antiplatelet agents in patients with a clear indication after individual evaluation according to risk factors for thrombotic and thromboembolic complications.
Subject(s)
Fibromuscular Dysplasia , Platelet Aggregation Inhibitors , Humans , Fibromuscular Dysplasia/diagnosis , Fibromuscular Dysplasia/complications , Platelet Aggregation Inhibitors/therapeutic use , Computed Tomography Angiography/methods , Aspirin/therapeutic use , Aspirin/administration & dosage , Female , Magnetic Resonance Angiography/methods , Male , Middle Aged , Brain/diagnostic imaging , Brain/pathology , AdultABSTRACT
Ambulatory blood pressure monitoring (ABPM) may be stressful and associated with discomfort, possibly influenced by the number of cuff inflations. We compared a low frequency (LF-ABPM) regimen with one cuff inflation per hour, with a high frequency (HF-ABPM) regimen performed according to current guidelines using three cuff-inflations per hour during daytime and two cuff-inflations during night time. In a crossover study, patients underwent ABPMs with both frequencies, in a randomized order, within an interval of a few days. Patients reported pain (visual analogue scale from 0 to 10) and sleep disturbances after each ABPM. The primary endpoint was the difference in mean 24 h systolic BP (SBP) between HF-ABPM and LF-ABPM. A total of 171 patients were randomized, and data from 131 (age 58 ± 14 years, 47% females, 24% normotensive, 53% mildly hypertensive, and 22% moderately-severely hypertensive) completing both ABPMs were included in the analysis. Mean SBP was 137.5 mmHg (95% CI, 134.8;140.2) for HF-ABPM and 138.2 mmHg (95%CI, 135.2;141.1) for LF-ABPM. The 95% limits of agreement were -15.3 mmHg and +14.0 mmHg. Mean 24 h SBP difference between HF-ABPM and LF-ABPM was -0.7 mmHg (95%CI, -2.0;0.6). Coefficients of variation were similar for LF-ABPM and HF-ABPM. Pain scores (median with interquartile range), for HF-ABPM and LF-ABPM were 1.5 (0.6;3.0) and 1.3 (0.6;2.9) during daytime, and 1.3 (0.4:3.4) and 0.9 (0.4;2.0) during nighttime (P < 0.05 for both differences). We conclude that LF-ABPM and HF-ABPM values are in good agreement without any clinically relevant differences in BP. Furthermore, LF-ABPM causes a relatively modest reduction in procedure-related pain.
Subject(s)
Blood Pressure Monitoring, Ambulatory , Hypertension , Female , Humans , Adult , Middle Aged , Aged , Male , Cross-Over Studies , Blood Pressure/physiology , Pain/complicationsABSTRACT
BACKGROUND: Chronic kidney disease (CKD) is associated with accelerated vascular calcification and increased central systolic blood pressure when measured invasively (invCSBP) relative to cuff-based brachial systolic blood pressure (cuffSBP). The contribution of aortic wall calcification to this phenomenon has not been clarified. We, therefore, examined the effects of aortic calcification on cuffSBP and invCSBP in a cohort of patients representing all stages of CKD. METHODS: During elective coronary angiography, invCSBP was measured in the ascending aorta with a fluid-filled catheter with simultaneous recording of cuffSBP using an oscillometric device. Furthermore, participants underwent a non-contrast computed tomography scan of the entire aorta with observer-blinded calcification scoring of the aortic wall ad modum Agatston. RESULTS: We included 168 patients (mean age 67.0â ±â 10.5, 38 females) of whom 38 had normal kidney function, while 30, 40, 28, and 32 had CKD stages 3a, 3b, 4, and 5, respectively. Agatston scores adjusted for body surface area ranged from 48 to 40,165. We found that invCSBP increased 3.6 (95% confidence interval 1.4-5.7) mm Hg relative to cuffSBP for every 10,000-increment in aortic Agatston score. This association remained significant after adjustment for age, diabetes, antihypertensive treatment, smoking, eGFR, and BP level. No such association was found for diastolic BP. CONCLUSIONS: Patients with advanced aortic calcification have relatively higher invCSBP for the same cuffSBP as compared to patients with less calcification. Advanced aortic calcification in CKD may therefore result in hidden central hypertension despite apparently well-controlled cuffSBP. ClinicalTrials.gov identifier: NCT04114695.
Subject(s)
Blood Pressure Determination , Renal Insufficiency, Chronic , Vascular Calcification , Humans , Female , Male , Aged , Middle Aged , Renal Insufficiency, Chronic/physiopathology , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/diagnosis , Vascular Calcification/diagnostic imaging , Vascular Calcification/physiopathology , Blood Pressure Determination/methods , Aortic Diseases/physiopathology , Aortic Diseases/diagnostic imaging , Blood Pressure , Computed Tomography Angiography , Brachial Artery/physiopathology , Brachial Artery/diagnostic imaging , Coronary Angiography , Aortography , Predictive Value of TestsABSTRACT
BACKGROUND: A marked reduction in serum levels of bioactive insulin-like growth factor-I (IGF-I) has been observed in fasting hemodialysis (HD) patients during a 4-h HD session. The aim of the present study was to investigate the beneficial effect of hyperinsulinemia during HD on bioactive IGF-I and inflammatory biomarkers. METHODS: In a randomized cross-over study, 11 non-diabetic HD patients received a standardised HD session with either: 1) no treatment, 2) glucose infusion (10% glucose, 2.5 mL/kg/h), or 3) glucose-insulin infusion (10% glucose added 30 IU NovoRapid® per litre, 2.5 mL/kg/h). Each experiment consisted of three periods: pre-HD (-120 to 0 min), HD (0 to 240 min), and post-HD (240 to 360 min). A meal was served at baseline (-120 min); infusions were administered from baseline to 240 min. The primary outcome was change in bioactive IGF-I during the experiment. Secondary outcomes were changes in high-sensitivity C-reactive protein, interleukin-1ß, interleukin-6, and tumor necrosis factor α. Comparisons were performed using mixed-model analysis of variance for repeated measures. RESULTS: From baseline to the end of study, no significant differences were observed in the changes in either serum bioactive IGF-I or total IGF-I between study days. Overall, serum bioactive IGF-I levels rose above baseline at 120 to 300 min with a maximum increase of 20% at 120 min (95% confidence interval (CI), 9 to 31%; p < 0.001), whereas total IGF-I levels rose above baseline at 180 to 300 min with a maximum increase of 5% at 240 min (95% CI, 2 to 9%; p = 0.004). A significant difference was observed in the changes in serum IGF-binding protein-1 (IGFBP-1) between study days (p = 0.008), but differences were only significant in the post-HD period. From baseline to the end of HD, no significant difference was observed in the changes in serum IGFBP-1 levels between study days, and in this time period overall serum IGFBP-1 levels were below baseline at all time points with a maximum decrease of 51% at 180 min (95% CI, 45 to 57%; p < 0.001). None of the investigated inflammatory biomarkers showed any differences in the changes over time between study days. CONCLUSIONS: Postprandial insulin secretion stimulated the IGF-system during HD with no further effect of adding glucose or glucose-insulin infusion. Hyperinsulinemia during HD had no effect on biomarkers of inflammation. TRIAL REGISTRATION: ClinicalTrials.gov registry: NCT01209403.
Subject(s)
Hyperinsulinism/blood , Inflammation Mediators/blood , Insulin-Like Growth Factor I/metabolism , Renal Dialysis/trends , Adult , Aged , Biomarkers/blood , Blood Glucose/metabolism , Cross-Over Studies , Female , Glucose/administration & dosage , Humans , Hyperinsulinism/chemically induced , Insulin/administration & dosage , Insulin/blood , Male , Middle AgedABSTRACT
This review investigates patients with renovascular disease due to atherosclerotic renal artery stenosis. This group of patients has a very high risk of cardiovascular events. Randomised trials have failed to show that renal artery stenting is more effective than medical therapy alone in most patients but did not enroll patients with high-risk clinical syndromes. Recent cohort studies have observed a beneficial effect of renal artery stenting on blood pressure and kidney function in high-risk patients with atherosclerotic renovascular disease. Therefore, a Danish randomised trial has been initiated to explore these observations further.
Subject(s)
Atherosclerosis , Hypertension, Renovascular , Renal Artery Obstruction , Humans , Renal Artery Obstruction/complications , Renal Artery Obstruction/surgery , Atherosclerosis/therapy , Renal Artery , Blood Pressure , Hypertension, Renovascular/therapy , StentsABSTRACT
Background The aim of this study was to prospectively evaluate the effects of renal artery stenting in consecutive patients with severe atherosclerotic renal artery stenosis and high-risk clinical presentations as defined in a national protocol developed in 2015. Methods and Results Since the protocol was initiated, 102 patients have been referred for revascularization according to the following high-risk criteria: severe renal artery stenosis (≥70%) with true resistant hypertension, rapidly declining kidney function, or recurrent heart failure/sudden pulmonary edema. At baseline, the mean 24-hour ambulatory systolic blood pressure was 166.2 mm Hg (95% CI, 162.0-170.4), the defined daily dose of antihypertensive medication was 6.5 (95% CI, 5.8-7.3), and the estimated glomerular filtration rate was 41.1 mL/min per 1.73m2 (95% CI, 36.6-45.6). In 96 patients with available 3-month follow-up data, mean 24-hour ambulatory systolic blood pressure decreased by 19.6 mm Hg (95% CI, 15.4-23.8; P<0.001), the defined daily dose of antihypertensive medication was reduced by 52% (95% CI, 41%-62%; P<0.001), and estimated glomerular filtration rate increased by 7.8 mL/min per 1.73m2 (95% CI, 4.5-11.1; P<0.001). All changes persisted after 24 month follow-up. Among 17 patients with a history of hospitalization for acute decompensated heart failure, 14 patients had no new episodes after successful revascularization. Conclusions In this prospective cohort study, we observed a reduction in blood pressure and antihypertensive medication, an increase in estimated glomerular filtration rate, and a decrease in new hospital admissions attributable to heart failure/sudden pulmonary edema after renal artery stenting. Registration URL: https://clinicaltrials.gov. Identifier: NCT02770066.
Subject(s)
Angioplasty, Balloon , Renal Artery Obstruction , Angioplasty, Balloon/adverse effects , Antihypertensive Agents/pharmacology , Antihypertensive Agents/therapeutic use , Blood Pressure , Cohort Studies , Glomerular Filtration Rate , Humans , Prospective Studies , Renal Artery , Renal Artery Obstruction/complications , Renal Artery Obstruction/therapy , Stents , Treatment OutcomeABSTRACT
Repeated cuff-based blood pressure (BP) measurements may cause discomfort resulting in stress and erroneous recording values. SOMNOtouch NIBP is an alternative cuff-less BP measurement device that calculates changes in BP based on changes in pulse transit time (PTT) and a software algorithm. The device is calibrated with a single upper arm cuff-based BP measurement. We tested the device against a validated 24-h ambulatory BP monitoring (ABPM) device using both the previous (SomBP1) and the current software algorithm (SomBP2). In this study, 51 patients (mean age ± SD 61.5 ± 13.0 years) with essential hypertension underwent simultaneous 24-h ABPM with the SOMNOtouch NIBP on the left arm and a standard cuff-based oscillometric device on the right arm (OscBP). We found that mean daytime systolic BP (SBP) with OscBP was 140.8 ± 19.7 compared to 148.0 ± 25.2 (P = .008) and 146.9 ± 26.0 mmHg (P = .034) for SomBP1 and SomBP2, respectively. Nighttime SBP with OscBP was 129.5 ± 21.1 compared with 146.1 ± 25.8 (P < .0001) and 141.1 ± 27.4 mmHg (P = .001) for SomBP1 and SomBP2, respectively. Ninety-five% limits of agreement between OscBP and SomBP1 were ± 36.6 mmHg for daytime and ± 42.6 mmHg for nighttime SBP, respectively. Agreements were not improved with SomBP2. For SBP, a nocturnal dipping pattern was found in 33% of the study patients when measured with OscBP but only in 2% and 20% with SomBP1 and -2, respectively. This study demonstrates that BP values obtained with the cuff-less PTT-based SOMNOtouch device should be interpreted with caution as these may differ substantially from what would be obtained from a validated cuff-based BP device.
Subject(s)
Blood Pressure Monitoring, Ambulatory , Hypertension , Blood Pressure , Blood Pressure Determination , Humans , Hypertension/diagnosis , SphygmomanometersABSTRACT
OBJECTIVE: To evaluate the day-to-day biological variation of cystatin C in comparison with creatinine in healthy subjects and in patients with impaired renal function. MATERIAL AND METHODS: Eight weekly morning blood samples were taken from 20 healthy subjects (13 females and 7 males, median age 44 years, range 25-61) and 19 patients with impaired renal function (8 females and 11 males, median age 61 years, range 35-70). Serum cystatin C was measured using Dade Behring N Latex Cystatin C assay and serum creatinine by an enzymatic method (Roche). RESULTS: In the healthy subjects mean serum cystatin C was 0.70 mg/L (range 0.44-1.09) and mean serum creatinine 77 micromol/L (range 54-100). The analytical variance was 2.0% for cystatin C and 1.6% for creatinine. The intra-individual variance was greater for cystatin C than for creatinine (8.6% vs. 4.7%). The inter-individual variance was similar for both analytes (cystatin C 15.1% vs. creatinine 14.4%). In the patients with impaired renal function mean serum cystatin C was 1.86 mg/L (range 0.45-3.31) and mean serum creatinine 224 micromol/L (range 103-430). The analytical variance was 1.8% for cystatin C and 1.4% for creatinine. The intra-individual variance was greater for cystatin C than for creatinine (16.0% vs. 8.9%). CONCLUSION: In the present study, the intra-individual variance was greater for cystatin C than for creatinine in both healthy subjects and in patients with impaired renal function. Accordingly, serum creatinine is the preferred marker for serial monitoring of renal function in individuals with stable muscle mass.
Subject(s)
Creatinine/blood , Cystatin C/blood , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Reference Values , Young AdultABSTRACT
An experimental and simulation-based study was performed on a 12C ion minibeam radiation therapy (MBRT) field produced with a clinical broad beam and a brass multi-slit collimator (MSC). Silicon-on-insulator (SOI) microdosimeters developed at the Centre for Medical Radiation Physics (CMRP) with micron sized sensitive volumes were used to measure the microdosimetric spectra at varying positions throughout the MBRT field and the corresponding dose-mean lineal energies and RBE for 10% cell survival (RBE10) were calculated using the modified Microdosimetric Kinetic Model (MKM). An increase in the average RBE10 of â¼30% and 10% was observed in the plateau region compared to broad beam for experimental and simulation values, respectively. The experimental collimator misalignment was determined to be 0.7° by comparison between measured and simulated microdosimetric spectra at varying collimator angles. The simulated dose-mean lineal energies in the valley region between minibeams were found to be higher on average than in the minibeams due to higher LET particles being produced in these regions from the MSC. This work presents the first experimental microdosimetry measurements and characterisation of the local biological effectiveness in a MBRT field.
Subject(s)
Microtechnology/methods , Radiometry/methods , Relative Biological Effectiveness , Computer Simulation , Heavy Ion Radiotherapy , Linear Energy Transfer , SiliconABSTRACT
Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder with highly varying disease manifestations, many of which cause extensive morbidity. There are international consensus criteria for the diagnosis, monitoring and treatment of TSC, and approved medical treatment for some of the most serious disease manifestations. However, organisation of a rational and coordinated care of TSC patients involves many different medical specialities and is only sparsely described. This review describes the interdisciplinary care of TSC patients at Aarhus University Hospital, Denmark.
Subject(s)
Tuberous Sclerosis , Consensus , Denmark , Humans , Tuberous Sclerosis/diagnosis , Tuberous Sclerosis/therapyABSTRACT
BACKGROUND: The aim of this study was to measure the microdosimetric distributions of a carbon pencil beam scanning (PBS) and passive scattering system as well as to evaluate the relative biological effectiveness (RBE) of different ions, namely 12 C, 14 N, and 16 O, using a silicon-on-insulator (SOI) microdosimeter with well-defined 3D-sensitive volumes (SV). Geant4 simulations were performed with the same experimental setup and results were compared to the experimental results for benchmarking. METHOD: Two different silicon microdosimeters with rectangular parallelepiped and cylindrical shaped SVs, both 10 µm in thickness were used in this study. The microdosimeters were connected to low noise electronics which allowed for the detection of lineal energies as low as 0.15 keV/µm in tissue. The silicon microdosimeters provide extremely high spatial resolution and can be used for in-field and out-of-field measurements in both passive scattering and PBS deliveries. The response of the microdosimeters was studied in 290 MeV/u 12 C, 180 MeV/u 14 N, 400 MeV/u 16 O passive ion beams, and 290 MeV/u 12 C scanning carbon therapy beam at heavy ion medical accelerator in Chiba (HIMAC) and Gunma University Heavy Ion Medical Center (GHMC), Japan, respectively. The microdosimeters were placed at various depths in a water phantom along the central axis of the ion beam, and at the distal part of the Spread Out Bragg Peak (SOBP) in 0.5 mm increments. The RBE values of the pristine Bragg peak (BP) and SOBP were derived using the microdosimetric lineal energy spectra and the modified microdosimetric kinetic model (MKM), using MKM input parameters corresponding to human salivary gland (HSG) tumor cells. Geant4 simulations were performed in order to verify the calculated depth-dose distribution from the treatment planning system (TPS) and to compare the simulated dose-mean lineal energy to the experimental results. RESULTS: For a 180 MeV/u 14 N pristine BP, the dose-mean lineal energy yD¯ obtained with two types of silicon microdosimeters started from approximately 29 keV/µm at the entrance to 92 keV/µm at the BP, with a maximum value in the range of 412 to 438 keV/µm at the distal edge. For 400 MeV/u 16 O ions, the dose-mean lineal energy yD¯ started from about 24 keV/µm at the entrance to 106 keV/µm at the BP, with a maximum value of approximately 381 keV/µm at the distal edge. The maximum derived RBE10 values for 14 N and 16 O ions were found to be 3.10 ± 0.47 and 2.93 ± 0.45, respectively. Silicon microdosimetry measurements using pencilbeam scanning 12 C ions were also compared to the passive scattering beam. CONCLUSIONS: These SOI microdosimeters with well-defined three-dimensional (3D) SVs have applicability in characterizing heavy ion radiation fields and measuring lineal energy deposition with sub-millimeter spatial resolution. It has been shown that the dose-mean lineal energy increased significantly at the distal part of the BP and SOBP due to very high LET particles. Good agreement was observed for the experimental and simulation results obtained with silicon microdosimeters in 14 N and 16 O ion beams, confirming the potential application of SOI microdosimeter with 3D SV for quality assurance in charged particle therapy.
Subject(s)
Carbon/therapeutic use , Nitrogen/therapeutic use , Oxygen/therapeutic use , Radiometry/instrumentation , Silicon , Relative Biological EffectivenessABSTRACT
Traditional office blood pressure (OBP) measurement as performed in busy outpatient clinics agrees poorly with awake ambulatory BP, and generally BP is severely overestimated. Especially elderly patients may be overtreated with the risk of symptomatic hypotension and fall injuries. Furthermore, truly high OBP measurements are often ignored as white coat hypertension, which leads to undertreatment of hypertension in high-risk individuals. Traditional OBP is thus of limited use and may even be harmful. Better methods are available and should be implemented.
Subject(s)
Ambulatory Care Facilities/standards , Blood Pressure Determination/standards , Aged , Blood Pressure , Health Services Misuse , Humans , Hypertension/diagnosis , Nurses , Physicians , Practice Guidelines as TopicABSTRACT
PURPOSE: Microdosimetry is a vital tool for assessing the microscopic patterns of energy deposition by radiation, which ultimately govern biological effect. Solid-state, silicon-on-insulator microdosimeters offer an approach for making microdosimetric measurements with high spatial resolution (on the order of tens of micrometers). These high-resolution, solid-state microdosimeters may therefore play a useful role in characterizing proton radiotherapy fields, particularly for making highly resolved measurements within the Bragg peak region. In this work, we obtain microdosimetric measurements with a solid-state microdosimeter (MicroPlus probe) in a clinical, spot-scanning proton beam of small spot size. METHODS: The MicroPlus probe had a 3D single sensitive volume on top of silicon oxide. The sensitive volume had an active cross-sectional area of 250 µm × 10 µm and thickness of 10 µm. The proton facility was a synchrotron-based, spot-scanning system with small spot size (σ ≈ 2 mm). We performed measurements with the clinical beam current (≈1 nA) and had no detected pulse pile-up. Measurements were made in a water-equivalent phantom in water-equivalent depth (WED) increments of 0.25 mm or 1.0 mm along pristine Bragg peaks of energies 71.3 MeV and 159.9 MeV, respectively. For each depth, we measured lineal energy distributions and then calculated the dose-weighted mean lineal energy, y¯D. The measurements were repeated for two field sizes: 4 × 4 cm2 and 20 × 20 cm2 . RESULTS: For both 71.3 MeV and 159.9 MeV and for both field sizes, y¯D increased with depth toward the distal edge of the Bragg peak, a result consistent with Monte Carlo calculations and measurements performed elsewhere. For the 71.3 MeV, 4 × 4 cm2 beam (range at 80% distal falloff, R80 = 3.99 cm), we measured y¯D=1.96±0.08 keV/µm at WED = 2 cm, and y¯D=10.6±0.32 keV/µm at WED = 3.95 cm. For the 71.3 MeV, 20 × 20 cm2 beam, we measured y¯D=2.46±0.12 keV/µm at WED = 2.6 cm, and y¯D=11.0±0.24 keV/µm at WED = 3 cm. For the 159.9 MeV, 4 × 4 cm2 beam (R80 = 17.7 cm), y¯D=2.24±0.15 keV/µm at WED = 5 cm, and y¯D=8.99±0.71 keV/µm at WED = 17.6 cm. For the 159.9 MeV, 20 × 20 cm2 beam, y¯D=2.56±0.10 keV/µm at WED = 5 cm, and y¯D=9.24±0.73 keV/µm at WED = 17.6 cm. CONCLUSIONS: We performed microdosimetric measurements with a novel solid-state, silicon-on-insulator microdosimeter in a clinical spot-scanning proton beam of small spot size and unmodified beam current. For all of the proton field sizes and energies considered, the measurements of y¯D were in agreement with expected trends. Furthermore, we obtained measurements with a spatial resolution of 10 µm in the beam direction. This spatial resolution greatly exceeded that possible with a conventional gaseous tissue-equivalent proportional counter and allowed us to perform a high-resolution investigation within the Bragg peak region. The MicroPlus probe is therefore suitable for applications in proton radiotherapy.
Subject(s)
Microtechnology/methods , Protons , Radiometry/methods , Humans , Linear Energy Transfer , Radiation DosageABSTRACT
PURPOSE: This work aims to characterize a proton pencil beam scanning (PBS) and passive double scattering (DS) systems as well as to measure parameters relevant to the relative biological effectiveness (RBE) of the beam using a silicon on insulator (SOI) microdosimeter with well-defined 3D sensitive volumes (SV). The dose equivalent downstream and laterally outside of a clinical PBS treatment field was assessed and compared to that of a DS beam. METHODS: A novel silicon microdosimeter with well-defined 3D SVs was used in this study. It was connected to low noise electronics, allowing for detection of lineal energies as low as 0.15 keV/µm. The microdosimeter was placed at various depths in a water phantom along the central axis of the proton beam, and at the distal part of the spread-out Bragg peak (SOBP) in 0.5 mm increments. The RBE values of the pristine Bragg peak (BP) and SOBP were derived using the measured microdosimetric lineal energy spectra as inputs to the modified microdosimetric kinetic model (MKM). Geant4 simulations were performed in order to verify the calculated depth-dose distribution from the treatment planning system (TPS) and to compare the simulated dose-mean lineal energy to the experimental results. RESULTS: For a 131 MeV PBS spot (124.6 mm R90 range in water), the measured dose-mean lineal energy yD¯ increased from 2 keV/µm at the entrance to 8 keV/µm in the BP, with a maximum value of 10 keV/µm at the distal edge. The derived RBE distribution for the PBS beam slowly increased from 0.97 ± 0.14 at the entrance to 1.04 ± 0.09 proximal to the BP, then to 1.1 ± 0.08 in the BP, and steeply rose to 1.57 ± 0.19 at the distal part of the BP. The RBE distribution for the DS SOBP beam was approximately 0.96 ± 0.16 to 1.01 ± 0.16 at shallow depths, and 1.01 ± 0.16 to 1.28 ± 0.17 within the SOBP. The RBE significantly increased from 1.29 ± 0.17 to 1.43 ± 0.18 at the distal edge of the SOBP. CONCLUSIONS: The SOI microdosimeter with its well-defined 3D SV has applicability in characterizing proton radiation fields and can measure relevant physical parameters to model the RBE with submillimeter spatial resolution. It has been shown that for a physical dose of 1.82 Gy at the BP, the derived RBE based on the MKM model increased from 1.14 to 1.6 in the BP and its distal part. Good agreement was observed between the experimental and simulation results, confirming the potential application of SOI microdosimeter with 3D SV for quality assurance in proton therapy.