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PubMed1991

Beat-to-beat variation of heart rate in diabetic patients with autonomic neuropathy and in completely cardiac denervated patients following orthotopic heart transplantation.

Dysfunction of the vagal nerve, an early symptom in the development of autonomic neuropathy, can be assessed reliably by the beat-to-beat variation in heart rate. Patients after a cardiac transplantation are a unique model to investigate the beat-to-beat variation of a completely denervated heart. Heart rate and the beat-to-beat variation during normal and deep respiration were investigated in diabetic subjects with an autonomic neuropathy (n = 10), age and sex matched healthy controls (n = 10) and cardiac transplanted patients (n = 10). Further studies during pharmacological blockade of the parasympathetic nervous system with atropine were performed. In the denervated heart the coefficient of variation of the beat-to-beat interval was 0.38 +/- 0.02% during normal respiration, compared to 1.32 +/- 0.13% (P less than 0.0001) and 2.56 +/- 0.13% (P less than 0.0001) in the diabetic and control subjects, respectively. Administration of atropine (2 mg intravenously) decreased the coefficient of variation of the RR-interval to 0.73 +/- 0.09% in the diabetic patients (P less than 0.0005) and to 0.67 +/- 0.07% in the controls (P less than 0.0001), whereas the coefficient of variation remained unaffected in the cardiac denervated patients (0.39 +/- 0.02%). In the three groups an almost parallel increase of the RR-variation was observed during deep respiration at a rate of 6 breaths/min (from 0.38 +/- 0.02% to 1.99 +/- 0.38% in cardiac transplanted patients, P less than 0.0025; from 1.32 +/- 0.13% to 3.10 +/- 0.43% in diabetic patients, P less than 0.0025; from 2.56 +/- 0.13% to 5.42 +/- 0.94% in healthy controls, P less than 0.005). We conclude that a beat-to-beat variation of heart rate is present in the completely denervated heart. This RR-variation can not be influenced by a pharmacological blockade of the parasympathetic nervous system with atropine. The beat-to-beat variation increases during deep respiration not only in healthy controls but also in diabetic patients with autonomic neuropathy (partially denervated hearts) and cardiac transplanted patients (completely denervated hearts). This indicates an intracardiac mechanism in the modulation of heart rate.

Atropine↗

PubMed2005

Differences in circadian variations of tissue factor pathway inhibitor type 1 between able-bodied and spinal cord injured.

INTRODUCTION: Tissue factor pathway inhibitor type 1 (TFPI) is the physiological inhibitor of the tissue factor pathway of coagulation. TFPI is produced by endothelial cells, and most intravascular TFPI is composed of full-length TFPI associated with the endothelium. Circulating TFPI is mainly truncated and lipoprotein-associated, but a small fraction circulates in a free full-length form. Although hormonal state influences the plasma variation of TFPI between individuals, other factors like temporal variation may be important. Hence, in the current study we aimed at exploring the intra-individual variation with focus on the possible circadian variations of TFPI. MATERIALS AND METHODS: TFPI free and total antigen from 8 able-bodied and 6 tetraplegic men were measured at 12 time points during a 24 h period. RESULTS: TFPI free antigen in the able-bodied exhibited circadian variation with the highest levels (approximately 20% above mean) from 12:00 to 18:00 h and the lowest levels (approximately 15% below mean) at 09:00 and 02:00 h. In contrast, TFPI free antigen in the tetraplegic group showed no circadian variation. TFPI total antigen exhibited circadian variation in neither group, but mean TFPI total antigen was lower in the tetraplegic group compared with the able-bodied (80 versus 110 ng/mL, respectively). Notably, even if TFPI total antigen in both groups did not vary according to any specific circadian rhythm, the intra-individual variation was higher than the assay variation. CONCLUSION: TFPI free antigen exhibited circadian variations in able-bodied, but not in tetraplegic subjects and the able-bodied had higher levels of TFPI total antigen than the tetraplegic group.

Adult↗

PubMed2004

Finite element modeling and intravascular ultrasound elastography of vulnerable plaques: parameter variation.

BACKGROUND AND GOAL: More than 60% of all myocardial infarction is caused by rupture of a vulnerable plaque. A vulnerable plaque can be described as a large, soft lipid pool covered by a thin fibrous cap. Plaque material composition, geometry, and inflammation caused by infiltration of macrophages are considered as major determinants for plaque rupture. For diagnostic purposes, these determinants may be obtained from elastograms (i.e. radial strain images), which are derived from intravascular ultrasound (IVUS) measurements. IVUS elastograms, however, cannot be interpreted directly as tissue component images, because radial strain depends upon plaque geometry, plaque material properties, and used catheter position. To understand and quantify the influence of these parameters upon measured IVUS elastograms, they were varied in a finite element model (FEM) that simulates IVUS elastograms of vulnerable plaques. MATERIALS AND METHODS: IVUS elastography measurements were performed on a vessel mimicking phantom, with a soft plaque embedded in a hard wall, and an atherosclerotic human coronary artery containing a vulnerable plaque. Next, FEMs were created to simulate IVUS elastograms of the same objects. In these FEMs the following parameters were varied: Young's modulus (E), Poisson's ratio (nu) in range 0.49-0.4999, catheter position (translation of 0.8 mm), and cap thickness (t) in range 50-350 microm. Hereby the resulting peak radial strain (PRS) was determined and visualized. RESULTS: Measured static E for phantom was 4.2 kPa for plaque and 16.8 kPa for wall. Variation of E-wall in range 8.4-33.2 kPa and/or E-plaque in range 2.1-8.4 kPa using the phantom FEM, gave a PRS variation of 1.6%, i.e. from 1.7% up to almost 3.3%; for variation in nu this was only 0.07%, i.e. from 2.37% up to 2.44%. Variation of E-lipid in range 6.25-400 kPa and E-cap in range 700-2300 kPa using the artery FEM, gave a PRS variation of 3.1%, i.e. from 0.6% up to 3.7%. The PRS was higher for lower E-lipid and E-cap; it was located at a shoulder of the lipid pool. Variation of nu gave only a variation of 0.17%. Variation of t and E-cap resulted in a PRS variation of 1.4%, i.e. from 0.3% up to 1.7%; thinner and weaker caps gave higher PRS. Catheter position variation changed radial strain value. CONCLUSIONS: Measured IVUS elastograms of vulnerable plaques depend highly upon the Young's modulus of lipid and cap, but not upon the Poisson's ratio. Different catheter positions result in different IVUS elastograms, but the diagnostically important high strain regions at the lipid shoulders are often still detectable. PRS increases when cap weakens or cap thickness decreases.

Arteriosclerosis↗

PubMed2002

Intraindividual variation of PSA, free PSA and complexed PSA in a cohort of patients with prostate cancer managed with watchful observation.

OBJECTIVE: To determine the intraindividual variation of prostate-specific antigen (PSA) isoforms in prostate cancer patients managed conservatively with watchful observation. METHODS: Patients with favorable clinical parameters (stage T1b-T2b N0 M0, Gleason score </= 7, and PSA </= 15) were recruited to participate in a watchful observation program. Specimens were drawn for measurement of total (tPSA), free (fPSA) and complexed (cPSA) prostate-specific antigen isoforms. Total biologic variation and between-day analytical variation were used to calculate intraindividual variation. RESULTS: Total variation for each isoform and two ratios were not greatly affected by the time window for measurements in the interval 6 months to 2.7 yr. Analytical variation made only a small contribution to the total biologic variation. Intraindividual variation for a 1-yr time interval for tPSA, fPSA, cPSA and the ratios of fPSA and cPSA to tPSA was, respectively, 21.6, 19.3, 25.4, 20.0 and 13.1%. The amount of change required for a significant difference between two readings (with 95% confidence) was, respectively, 59.8, 53.4, 70.4, 55.3 and 36.2%. CONCLUSIONS: There is a significantly higher intraindividual variation of cPSA (25.4%), and a significantly lower intraindividual variation of the ratio cPSA to tPSA (13.1%) compared to the other individual PSA isoforms and to the ratio of fPSA to tPSA. The amount of change required for a significant difference between two concentrations is large for all variables studied, but the lowest is the ratio of cPSA to tPSA (36.2%). These results have significance for diagnosis and monitoring of patients with prostate cancer.

Cohort Studies↗

PubMed1998

Ethnicity and fetal heart rate variation.

OBJECTIVE: To determine the effect of ethnicity on fetal heart rate (FHR) variation. METHODS: A prospective study was conducted of 27 consecutive black women (of African or Caribbean ethnic origin) and 79 consecutive white women (of European ethnic origin) volunteers attending the antenatal clinic, with uncomplicated singleton pregnancies of at least 34 completed weeks' gestation. The participants had cardiotocography performed with an FHR monitor connected to a Sonicaid System 8002 computer. We studied the mean FHR, long-term FHR variation, short-term FHR variation, the number of accelerations, and the reactivity of the FHR. RESULTS: The long-term FHR variation in centiles corrected for gestational age, the duration in minutes of episodes of high FHR variation, the long-term FHR variation in beats per minute during episode of high FHR variation, and the number of accelerations were significantly reduced in fetuses of black women compared with those in fetuses of white women (P = .007, P = .005, P = .009, and P = .006, respectively, Mann-Whitney U test). The fetuses of black women had a significantly higher proportion of nonreactive traces (P = .009, Fisher exact test). However, there was no significant difference in the short-term FHR variation between the two groups (P = .101). CONCLUSION: There is an ethnic difference in FHR variation, with significantly reduced long-term variation in black fetuses.

Adult↗

PubMed2003

Practice variation and physician-specific effects.

This study provides estimates of practice variation for primary physician services in Norway. Nearly all previous studies on practice variation have encompassed mainly specialist and hospital services. Thus we provide evidence for treatment variation for a health care sector where information about treatment variation is relatively scarce. Our analyses were carried out on a large set of data from individual physician practices. We estimated the extent of practice variation according to type of diagnosis and type of treatment option. The main finding is that variation in clinical practice between physicians is an important determinant of expenditure for primary physician services. Depending on the type of diagnosis, physician-specific effects explained 47-66% of the variation in expenditure for laboratory tests, 59-66% of the variation in expenditure for consultations lasting over 20min and 49-61% of the variation in expenditure for specific procedures. The age and gender of the patients explained only about 1% of the variation in expenditure. This finding supports the results from previous studies, which have shown that patients' age and gender are inadequate when used as risk adjusters. We also identified physicians who moved their practice from one municipality to another, i.e. they changed their patient population completely. Our results showed that those physicians who moved did not change practice style after they moved, i.e. that physician's style of practice is stabile. This indicates that practice style reflects a deeply rooted behaviour with respect to how to practice medicine.

Contract Services↗

PubMed2001

The influence of interpatient and intrapatient rectum variation on external beam treatment of prostate cancer.

PURPOSE: The rectal dose/volume relationship and inherent variations thereof are fundamental parameters to guide dose escalation in prostate cancer treatment. This study evaluates the effect of rectal dose/volume variation on the risk of rectal complication for different planning target volume (PTV) constructions. METHODS AND MATERIALS: Thirty prostate patients with multiple daily CT scans obtained during the treatment course were included in this retrospective study. The dose distribution was calculated based on the pretreatment CT image alone. Treatment plans were generated by applying the four-field-box beam arrangement to each of three different PTVs: PTVs with 0.5-cm and 1.0-cm uniform margins, and a patient-specific PTV constructed using treatment imaging feedback. For each of the 30 patients, the rectal wall as manifested on each of multiple CT images was delineated after image bony registration to the pretreatment CT image, and applied to the corresponding treatment plan to obtain the rectal wall dose-volume histogram (DVH). Interpatient and intrapatient rectal dose/volume variations were quantified accordingly. The corresponding uncertainty and sensitivity of the risk of rectal complication to the variations were evaluated for each of the three PTVs. Finally, the efficacy of using multiple CT images to reduce uncertainty in planning evaluation was examined. RESULTS: Sensitivity of the risk of rectal complication to rectal dose/volume variation strongly depends on the clinical target volume (CTV)-to-PTV margin or prescription dose, or both. Compared to the conventional two-dimensional (2D) prostate cancer treatment, the sensitivity for a conformal treatment can be 3 times higher or more. Due to the interpatient rectal dose/volume variation, the individual normal tissue complication probability (NTCP) was distributed from 10% to 37% when a common prescription dose was applied for all patients. The intrapatient rectal dose/volume variation introduces at least +/- 25% uncertainty in the NTCP calculation for at least 10% or 25% of the patients treated with the PTV of 1.0- or 0.5-cm margin, respectively. These uncertainties were larger for the smaller PTV, with the standard deviation up to 20%. By applying multiple CT image feedback, the NTCP uncertainty could be reduced by a factor of 2. CONCLUSIONS: Shape and position variation of rectum has less influence on treatment planning in the conventional 2D treatment of prostate cancer. However, this influence is quickly growing with high treatment dose or small CTV-to-PTV margins. To reduce the variation and uncertainties in the treatment planning evaluation associated with the inter- and intrapatient rectal dose/volume variation, the iso-NTCP model and treatment image feedback technique can be applied in dose escalation trials of prostate cancer treatment.

Algorithms↗

PubMedDate not supplied

The variation of integrated backscatter in human hearts in differing ultrasonic transthoracic views.

It has been shown previously that in normal subjects the interventricular septum imaged in the long-axis view (LAX) and the left ventricular posterior wall imaged in both the LAX and the short-axis view (SAX) exhibit cyclic variation of integrated backscatter (IB) throughout the cardiac cycle, with maximum values occurring at end diastole (ED) and minimum at end systole (ES). The ability to demonstrate this cyclic variation within these myocardial regions in only two ultrasonic views has limited the potential clinical utility of an IB imaging system. To determine whether clinically useful information on the variation of IB is available from different myocardial regions in different ultrasonic views, we measured ED to ES variation of IB from the parasternal and apical views in normal subjects with a radiofrequency acquisition technique. Two independent clinical observers analyzed ED to ES variation of IB from 14 normal volunteers (mean age 32 +/- 6 years; range 21 to 45 years) in reconstructed two-dimensional ultrasonic images obtained from the parasternal LAX and SAX and apical two-chamber (2C) and four-chamber (4C) views. ED to ES variation of IB was measured from manually traced regions of interest (ROI) within the myocardium. These ROIs were chosen interactively and were located within the midposterior wall and the midanteroseptum in LAX views; within the midposterior wall, midanteroseptum, midseptum, and midlateral wall in SAX views; within the midseptum and the midlateral wall in 4C views; and within the midinferior wall and the midanterior wall 2C views. In all analyzed ROIs within the parasternal and apical views, ED to ES variation of IB was found. We have shown that the maximum magnitude of IB was at ES within the midseptum and in 10 out of 14 volunteers in the midanteroseptum measured from SAX views, the midanterior wall from 2C views, and the midlateral wall from 4C views. The rest of the ROIs analyzed exhibited the maximum value of IB cyclic variation at ED. We have confirmed that the ED to ES variation of IB is present not only when measured from the two standard parasternal views but also from the two apical views in all analyzed myocardial walls, and the minimum of this cyclic variation was not always coincident with ES nor the maximum with ED.

Adult↗

PubMed2004

Diurnal variation in microcirculation of ocular fundus and visual field change in normal-tension glaucoma.

PURPOSE: Diurnal variations in microcirculation of the ocular fundus in normal-tension glaucoma (NTG) were examined to compare with the normal control eyes. The correlation between progression of visual field impairment and diurnal variations in ocular circulation was also studied. METHODS: The subjects were 12 patients with NTG and 12 normal controls. Blood pressure (BP), intraocular pressure (IOP), ocular perfusion pressure (OPP), and square blur rate (SBR), an index of microcirculation acquired by the laser speckle method, were measured at 9 a.m. (morning), 3 p.m. (afternoon), and 9 p.m. (night). Diurnal variations in SBR were tested using the Friedman test and Wilcoxon signed ranks test. On the other hand, diurnal variations in BP, IOP, and OPP were tested by the analysis of variance. The visual field was evaluated at the same time as determining diurnal variation and again about 9 months later to calculate the change. The correlation between variation ratio in SBR and the change in visual field was examined by simple regression. RESULTS: A significant decrease (P=0.04) was found in SBR at night, as compared with the morning value, in the optic nerve head (ONH) of NTG, although no significant diurnal variations were found in SBR either in the choroid-retina or in normal control eyes. Other parameters showed no significant diurnal variations. The larger diurnal variation was in SBR of the ONH, and the more exacerbated visual field impairment was (r=0.59, P=0.04). CONCLUSION: These findings suggest that diurnal variations in the microcirculation of the ONH may play a role in the progression of NTG.

Aged↗

PubMed1992

Determinants of intra-individual variation in kidney function in normoalbuminuric insulin-dependent diabetic patients: importance of atrial natriuretic peptide and glycaemic control.

1. In order to investigate the modulation of kidney function in insulin-dependent diabetes mellitus, intraindividual variation in glomerular filtration rate, renal plasma flow, urinary albumin excretion rate and mean arterial blood pressure was assessed in 22 normoalbuminuric patients [age 31 +/- 8 years, duration of diabetes 9 +/- 5 years, mean arterial blood pressure 90 +/- 5 mmHg (means +/- SD), urinary albumin excretion rate 5.4 x/divided by 1.6 micrograms/min]. The variation in these parameters was calculated from the results of two clearance studies (continuous infusion of [125I]-iothalamate and 131I-hippuran as markers for glomerular filtration rate and renal plasma flow, respectively) and was subsequently analysed in relation to individual variation in plasma concentrations of atrial natriuretic peptide, arginine vasopressin, angiotensin II and aldosterone and measures of glycaemic control. 2. Simple correlation analysis showed a significant association between intra-individual variation in glomerular filtration rate and atrial natriuretic peptide (sigma = 0.66, P = 0.003). Besides variation in atrial natriuretic peptide, multiple regression analysis identified variation in glycated haemoglobin (P = 0.026) and arginine vasopressin (P = 0.057) as variables having independent association with variation in glomerular filtration rate [R2 with the three variables included (adjusted for degrees of freedom) = 0.50, analysis of variance: P = 0.002]. 3. With respect to variation in renal plasma flow, differences in fasting blood glucose concentration and mean arterial blood pressure were suggested as determinants (R2 = 0.36, analysis of variance: P = 0.009). 4. Variation in urinary albumin excretion rate (after log transformation) was statistically associated with variation in glycated haemoglobin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2006

Effect of pedal rate on diurnal variations in cardiorespiratory variables.

Recently, it was observed that the freely chosen pedal rate of elite cyclists was significantly lower at 06:00 than at 18:00 h, and that ankle kinematics during cycling exhibits diurnal variation. The modification of the pedaling technique and pedal rate observed throughout the day could be brought about to limit the effect of diurnal variation on physiological variables. Imposing a pedal rate should limit the subject's possibility of adaptation and clarify the influence of time of day on physiological variables. The purpose of this study was to determine whether diurnal variation in cardiorespiratory variables depends on pedal rate. Ten male cyclists performed a submaximal 15 min exercise on a cycle ergometer (50% Wmax). Five test sessions were performed at 06:00, 10:00, 14:00, 18:00, and 22:00 h. The exercise bout was divided into three equivalent 5 min periods during which different pedal rates were imposed (70 rev x min(-1), 90 rev x min(-1) and 120 rev x min(-1)). No significant diurnal variation was observed in heart rate and oxygen consumption, whatever the pedal rate. A significant diurnal variation was observed in minute ventilation (p=0.01). In addition, the amplitude of the diurnal variation in minute ventilation depended on pedal rate: the higher the pedal rate, the greater the amplitude of its diurnal variation (p=0.03). The increase of minute ventilation throughout the day is mainly due to variation in breath frequency (p=0.01)--the diurnal variation of tidal volume (all pedal rate conditions taken together) being non-significant--but the effect of pedal rate x time of day interaction on minute ventilation specific to the higher pedal rate conditions (p=0.03) can only be explained by the increase of tidal volume throughout the day. Even though an influence of pedal rate on diurnal rhythms in overall physiological variables was not also evidenced, high pedal rate should have been imposed when diurnal variations of physiological variables in cycling were studied.

Bicycling↗

PubMed2004

A single measurement is inadequate to estimate enterolactone levels in danish postmenopausal women due to large intraindividual variation.

Single measurements of enterolactone (ENL) used in epidemiologic studies are influenced by intraindividual variation. The objective of this controlled study was to investigate short-term intraindividual variations in serum and urine ENL. Based on these variations, the number of samples required to describe the basal ENL level was estimated. Healthy Danish postmenopausal women (n = 6) aged 54-67 y completed 3 study periods of 24 h within 2 mo. Blood samples were collected at 0, 4, 6, 8, 12, and 24 h and 24-h urine samples were collected. A low-lignan, standardized diet of 3 meals was served. ENL was measured by time-resolved fluoroimmunoassay. Intraindividual and interindividual variations were estimated using a mixed model with repeated measurements. Significant and systematic intraindividual within-day variations (CV) of 31% were observed in serum. Intraindividual day-to-day variations were 56% and overall intraindividual variation of samples collected at random times and on different days was estimated to be 64%. Describing this overall variation required 7 blood samples when estimated with a precision of 50% and 95% confidence. Day-to-day variations in 24-h urine samples were 49%. Large within-day and day-to-day variations suggest that a single measurement of ENL is inadequate to estimate the basal ENL level.

4-Butyrolactone↗

PubMed2001

Impact of underuse, overuse, and discretionary use on geographic variation in the use of coronary angiography after acute myocardial infarction.

BACKGROUND: Geographic variation in the use of medical procedures has been well documented. However, it is not known whether this variation is due to differences in use when procedures are indicated, discretionary, or contraindicated. OBJECTIVES: To examine whether use of coronary angiography after acute myocardial infarction (AMI) according to appropriateness criteria varied across geographic regions and whether underuse, overuse, or discretionary use accounted for variation in overall use. DESIGN: Retrospective cohort study using data from the Cooperative Cardiovascular Project. SETTING: Ninety-five hospital referral regions. PATIENTS: There were 44,294 Medicare patients hospitalized with AMI during 1994 or 1995, classified according to appropriateness for angiography. MAIN OUTCOME MEASURE: Variation in use of angiography, as measured by the difference between high and low rates of use across regions. RESULTS: Across regions, variation in the use of angiography was similar for indications judged necessary; appropriate, but not necessary; or uncertain. Variation was lowest for indications judged unsuitable (difference between high rate and low rate across regions = 16.3%; 95% CI = 12.6%; 20.6%). The primary cause of variation in the overall rate of angiography was due to use for indications judged appropriate, but not necessary or uncertain. When variation associated with these indications was accounted for, the difference between the resulting high and low overall rates was 10.8% (9.4%, 12.4%). In contrast, variation in the overall rate remained high when underuse in necessary situations or overuse in unsuitable situations was accounted for. CONCLUSIONS: Across regions, practice was more similar for patients categorized unsuitable for angiography than for patients with other indications. Variation in overall use of angiography appeared to be driven by utilization for discretionary indications rather than by underuse or overuse. If equivalent rates across geographic areas are judged desirable, then greater effort must be directed toward defining care for patients with discretionary indications.

Aged↗

PubMed2000

Variation of shell shape in the clonal snail Melanoides tuberculata and its consequences for the interpretation of fossil series.

Interpreting paleontological data is difficult because the genetic nature of observed morphological variation is generally unknown. Indeed, it is hardly possible to distinguish among several sources of morphological variation including phenotypic plasticity, sexual dimorphism, within-species genetic variation or differences among species. This can be addressed using fossil organisms with recent representatives. The freshwater snail Melanoides tuberculata ranks in this category. A fossil series of this and other species have been studied in the Turkana Basin (Kenya) and is presented as one of the best examples illustrating the punctuated pattern of evolution by the tenants of this theory. Melanoides tuberculata today occupies most of the tropics. We studied variation of shell shape in natural populations of this parthenogenetic snail using Raup's model of shell coiling. We considered different sources of variation on estimates of three relevant parameters of Raup's model: (1) variation in shell shape was detected among clones, and had both genetic and environmental bases; (2) sexual dimorphism, in those clones in which males occur, appeared as an additional source of shell variation; and (3) ecophenotypic variation was detected by comparing samples from different sites and years within two clones. We then tested the performance of discriminant function analyses, a classical tool in paleontological studies, using several datasets. Although the three sources of variation cited above contributed significantly to the observed morphological variance, they could not be detected without a priori knowledge of the biological entities studied. However, it was possible to distinguish between M. tuberculata and a related thiarid species using these analyses. Overall, this suggests that the tools classically used in paleontological studies are poorly efficient when distinguishing between important sources of within-species variation. Our study also gives some empirical bases to the doubts cast on the interpretation of the molluscan series of the Turkana Basin.

Animals↗

PubMed2006

Types and frequencies of biliary tract variations associated with a major portal venous anomaly: analysis with multi-detector row CT cholangiography.

PURPOSE: To retrospectively determine whether major portal venous variation was more frequently associated with biliary variants, with consideration of the types and frequencies of biliary tract variations in the right and left liver lobes. MATERIALS AND METHODS: Before undergoing computed tomographic (CT) cholangiography, patients gave informed consent. The retrospective research protocol was approved, and informed consent was waived by the ethics committee. Forty-four patients aged 29-80 years who underwent multi-detector row CT cholangiography had a major portal vein variation in which the main portal vein diverged into the common trunk of the left portal vein and right anterior sectorial portal vein. One hundred fifty-eight consecutive patients aged 26-89 years who did not have this variation served as the control group. Three radiologists retrospectively evaluated the confluence pattern of the bile duct, the relationship between this pattern and the portal vein, and the major branching pattern of the portal vein. Pearson chi2 and Fisher exact tests were performed to identify significant differences between the two patient groups. RESULTS: The classic hilar confluence pattern, where the right posterior sectorial duct connects supraportally with the right anterior sectorial duct, was less frequent in the patients with the portal vein variation than in the control subjects (32% vs 73%, P < .05). The following biliary tract variations were identified more frequently in the variation group than in the control group (P < .05): right posterior sectorial duct joining left hepatic duct with a supraportal course (34% vs 12%), right posterior sectorial duct joining right anterior sectorial duct with an infraportal course (13% vs 4%), right posterior sectorial duct following an infraportal course (23% vs 8%), and left lateral segmental ducts caudal to the umbilical portion of the portal vein (14% vs 3%). The right hepatic duct, which receives all biliary ducts from the right lobe, was significantly less frequently developed in the variation group (46% vs 79%, P < .05). In addition, retroportal bile ducts were seen in four patients with the portal vein variation (P < .05). CONCLUSION: Bile duct configurations in patients with portal vein variation were significantly different from those in control subjects.

Adult↗

PubMed1992

Endogenous nitric oxide protects against platelet aggregation and cyclic flow variations in stenosed and endothelium-injured arteries.

BACKGROUND: This study was designed to test the hypothesis that endogenously produced nitric oxide protects against platelet aggregation and cyclic flow variations in stenosed and endothelium-injured arteries of mongrel dogs. METHODS AND RESULTS: NG-Monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide formation, was administered at 5 mg/kg to 15 dogs after the left anterior descending coronary artery was mechanically injured and narrowed by external constrictors and to nine dogs before endothelial injury of the femoral artery and after injury and moderate arterial constriction. Treatment with L-NMMA resulted in cyclic flow variations (as detected by external Doppler flow probes) in the left anterior descending artery of seven of 15 dogs and in the femoral artery of four of nine dogs after endothelial injury. L-Arginine, the precursor for nitric oxide synthesis, was administered at 60 mg/kg and abolished cyclic flow variations in each of the 11 dogs. D-Arginine did not change the L-NMMA-induced cyclic flow variations. Saline infusion did not induce or change cyclic flow variations in any of the animals. Acetylcholine (1, 10, and 100 micrograms/min; n = 9) was administered in the femoral artery of nine additional dogs before and after endothelial injury in moderately stenosed femoral arteries. Acetylcholine did not induce cyclic flow variations in any animal; however, it did increase the severity of cyclic flow variations that developed in severely stenosed arteries. The diameter of the femoral artery was measured by intravascular ultrasound imaging. L-NMMA caused vasoconstriction of normal arteries, but no change was detected in endothelium-injured arteries. In contrast, L-arginine caused vasodilation of normal arteries, but, again, no change was noted in endothelium-injured arteries. Acetylcholine dilated normal femoral arteries but constricted arteries with endothelial injury. In both in vitro and ex vivo platelet studies, L-NMMA enhanced platelet aggregation, whereas L-arginine significantly reduced platelet aggregation. D-Arginine and acetylcholine showed no effect on platelet aggregation. CONCLUSIONS: Promotion of nitric oxide production decreases platelet aggregation and may eliminate cyclic flow variations, whereas a reduction in nitric oxide formation enhances platelet aggregation and may induce cyclic flow variations. Acetylcholine causes vasoconstriction at the femoral arterial site of endothelial injury and may increase the severity of cyclic flow variations.

Acetylcholine↗

PubMed2004

Long term changes in serum T4, T3, and TSH in benign thyroid disease: proof of a narrow individual variation.

AIM: The diagnosis of abnormalities of thyroid function is generally based on the measurement of thyroid hormones and TSH in blood. The recommended reference ranges for serum T4 and T3 as well as TSH are quite wide as the result of large differences in thyroid function tests in healthy persons. It has been proven that the individual variation within an individual is small, compared with the variation between individuals. We investigated long term variations of these parameters in patients with and without benign thyroid diseases. METHODS: We performed long term follow-up serum determinations of T3, T4, and TSH in a total of 150 patients for a time period of 3 to 13 years. The majority of patients had been put on L-thyroxine. Values of total T3, total T4, free T4 were measured with an almost unmodified test (RIA) over the years. RESULTS: The lowest relative coefficient of variation (<10%) was observed in the group of patients who had been treated with L-thyroxine only. Even for TSH, relatively low cofficients of variation were observed in this group. In the group of patients who had not received any medication, T3 and T4 showed also a variation of 10%. FT4 and TSH revealed a wider range of variation. Even after radioiodine therapy, T3 and T4 showed only a quite small variation, while TSH demonstrated a wide range with a variation of >30%. CONCLUSION: Our data demonstrate that there are only narrow variations of serum T4 and T3 within individuals with and without thyroid disorders.

Female↗

PubMed2005

Local regulatory variation in Saccharomyces cerevisiae.

Naturally occurring sequence variation that affects gene expression is an important source of phenotypic differences among individuals within a species. We and others have previously shown that such regulatory variation can occur both at the same locus as the gene whose expression it affects (local regulatory variation) and elsewhere in the genome at trans-acting factors. Here we present a detailed analysis of genome-wide local regulatory variation in Saccharomyces cerevisiae. We used genetic linkage analysis to show that nearly a quarter of all yeast genes contain local regulatory variation between two divergent strains. We measured allele-specific expression in a diploid hybrid of the two strains for 77 genes showing strong self-linkage and found that in 52%-78% of these genes, local regulatory variation acts directly in cis. We also experimentally confirmed one example in which local regulatory variation in the gene AMN1 acts in trans through a feedback loop. Genome-wide sequence analysis revealed that genes subject to local regulatory variation show increased polymorphism in the promoter regions, and that some but not all of this increase is due to polymorphisms in predicted transcription factor binding sites. Increased polymorphism was also found in the 3' untranslated regions of these genes. These findings point to the importance of cis-acting variation, but also suggest that there is a diverse set of mechanisms through which local variation can affect gene expression levels.

3' Untranslated Regions↗