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PubMed2002

A comparative analysis of bone and cartilage metabolism in two strains of guinea-pig with varying degrees of naturally occurring osteoarthritis.

OBJECTIVE: To evaluate the interaction of bone and cartilage in knee osteoarthritis (OA) pathogenesis in two guinea-pig strains with appreciable differences in bone metabolism. DESIGN: Two guinea-pig strains were evaluated for their susceptibilities to OA using semi-quantitative histological grading of knee joints and quantification of biomarkers including urinary excretion of hydroxylysyl-pyridinoline (HP) and lysyl-pyridinoline (LP) collagen cross-links, serum osteocalcin (OC), and synovial fluid levels of keratan sulfate (KS). RESULTS: At 12 months of age, Strain 13 guinea-pigs had minimal to mild histological evidence of OA compared to the Hartley strain guinea-pigs. The Hartley strain, with more severe OA, had a higher rate of bone formation (serum osteocalcin) and bone resorption (HP and LP) evident at a young age with persistence of a greater rate of bone formation at 12 months of age. The Strain 13 possessed much thicker subchondral bone at the outset (2 months) compared to the Hartley; however, the Hartley strain showed the greatest increase in subchondral bone thickness coincident with the development of cartilage degeneration. Thus, the process of subchondral bone thickening, in contrast to the absolute initial subchondral bone thickness, was a hallmark of OA in the guinea-pig. Moreover, Strain 13 had lower intraarticular proteoglycan turnover. Levels of synovial fluid keratan sulfate were positively correlated with the severity of histological OA. CONCLUSIONS: This pilot study represents the first evidence of differential susceptibility to OA in guinea-pigs. Comparison of these two strains of guinea-pig has revealed that increased metabolism within the affected tissues, cartilage and bone, is associated with the development and progression of OA. This work demonstrates that the Strain 13 is a viable age-matched control to the Hartley strain and merits a more in depth evaluation of the contribution of bone and bone metabolism to OA.

Amino Acids↗

PubMed1994

Parameters influencing SPET regional brain uptake of technetium-99m hexamethylpropylene amine oxine measured by calibrated point sources as an external standard.

Using calibrated point sources as an external standard to convert single-photon emission tomography (SPET) brain counts into absolute values of regional brain uptake (rBU) of technetium-99m hexamethylpropylene amine oxime (HMPAO), the relative contribution of different parameters to interindividual variability of cerebellar rBU was examined in 33 healthy volunteers. Stepwise regression analysis identified body surface as the most important factor underlying interindividual variability (P < 0.001), when compared with brain volume. In the normal volunteer population presented, age decrement of rBU corrected for body surface and brain volume equalled 60.5-0.20 x age. Based on the data of eight normal volunteers, including four test-retest studies with heart rate (HR) differences greater than 5 units and four test-stress studies with doubling of heart rate after bicycle exercise, influence of heart rate may be expressed by the equation delta rBU = 0.35 delta HR. Clinically, estimation of the relative influence of different factors allows normalization and extension of the applicability of the rBU quantification method used from longitudinal studies to group comparisons. Interestingly, results of the Daily Stress Inventory Scale and a subjective rating scale suggest the absence of a significant influence of minor stress on rBU. When using one vial per patient, chromatography may be omitted in clinical routine practice and lipophilicity may be estimated as 90% of the injected dose, if administered within 10 min after preparation. Finally, sensitivity of the quantification method was tested in eight volunteers using acetazolamide brain activation and showed a mean increase in cerebellar rBU of 30.2%, varying between 14.1% and 75.9%.

Acetazolamide↗

PubMed1984

Quantification of individual serum bile acids in patients with liver diseases using high-performance liquid chromatography.

Using high-performance liquid chromatography combined with a column of immobilized 3 alpha-hydroxysteroid dehydrogenase, 15 bile acids, i.e., cholate, chenodeoxycholate, deoxycholate, lithocholate, ursodeoxycholate, and their five taurine conjugates and five glycine conjugates, were clearly separated and quantified in 38 patients with various hepatobiliary diseases and 9 normal controls. The serum levels of bile acids, both primary and total, were elevated in patients with liver disease, but did not differentiate between parenchymal disease and cholestasis. The ratio of cholate/chenodeoxycholate was significantly increased in cholestasis as compared with parenchymal liver injury. In primary biliary cirrhosis, the ratio of total glycine/taurine conjugates was decreased, with a marked increase of taurochenodeoxycholate. The bile acid pattern was distinctly different between extrahepatic cholestasis and primary biliary cirrhosis, which mainly reflects intrahepatic cholestasis. In acute hepatitis, there was a quick normalization of major taurine and glycine conjugates in the convalescent stage. Most of the major taurine and glycine conjugated bile salts were significantly elevated in cirrhosis, and the elevation of taurochenodeoxycholate was particularly marked in the decompensated state. Furthermore, the quantitative relationship between taurocholate and taurochenodeoxycholate in cirrhosis was reversed from that in acute hepatitis. These changes in absolute and relative concentrations of bile acids in various liver diseases perhaps reflect differing pathology and metabolism, and may prove diagnostic. Measurement of individual bile salts is easily and quickly done with this method, and may lend itself clinical application.

Adolescent↗

PubMed2000

Modified microelectrodes and multivariate calibration for flow injection amperometric simultaneous determination of ascorbic acid, dopamine, epinephrine and dipyrone.

Flow injection amperometric quantification of ascorbic acid (AA), dopamine (DA), epinephrine (EP) and dipyrone (DI) in mixtures (in the microgram g-1 range) was successfully performed by using an array of microelectrodes with units modified by the electrodeposition of different noble metals, together with multivariate calibration analysis. The four groups of microelectrodes utilized included a pure gold electrode and electrodes modified by electrodeposition of platinum, palladium or a mixture of platinum + palladium. The array of microelectrodes was inserted in a flow cell and the amperometric data acquisition was performed with a four-channel potentiostat. The analysis of the resulting signals was carried out by a multivariate calibration method, using a group of 16 standard mixtures selected by a two-level factorial design. The analysis of synthetic samples and pharmaceutical compounds containing AA and DI led to very similar values to those obtained by the classical iodimetric analysis. The average absolute errors (in microgram g-1) calculated for each analyte were 0.3, 0.2, 0.4 and 0.4 for AA, DA, EP and DI, respectively.

Ascorbic Acid↗

PubMed1996

Evidence of structural and material adaptation to specific strain features in cortical bone.

BACKGROUND: Functionally induced strains provide epigenetic signaling for bone modeling and remodeling activities. Strain gauge documentation of the equine third metacarpal reveals a neutral axis passing through the craniolateral cortex, resulting in a narrow band of cortex loaded predominantly in tension, with the remainder of the cortex experiencing a wide range of compression strain magnitudes that are maximal in the caudomedial cortex. This predictable strain pattern provides a model for examining the hypothesis that strain mode, magnitude, and strain energy density are potential correlates of compact bone structural and material organization. METHODS: Structural and material variables were quantified in nine equine (standard breeds) third metacarpals for comparison with the in vivo strain milieu that was evaluated in thoroughbred horses. The variables quantified included secondary osteon population density (OPD), fractional area of secondary bone (FASB), fractional area of porous spaces, collagen fiber orientation, mineral content (% ash), and cortical thickness. Each bone was sectioned transversely at 50% of length, with subsequent quantification of eight radial sectors and three intracortical regions (periosteal, middle, endosteal). Linear regression analysis compared these variables to magnitudes of corresponding regional in vivo longitudinal strain, shear strain, and strain energy density values reported in the literature. RESULTS: The craniolateral ("tension") cortex of this bone is distinguished by its 30% lower FASB and with the lateral cortex exhibits 20% darker gray level (more longitudinal collagen) compared with the average of all other locations. Conversely, the remaining ("compression") cortices as a group have a high OPD, are more extensively remodeled, and contain more oblique-to-transverse collagen. The caudal cortices (caudomedial, caudal, caudolateral) are significantly thinner (P < 0.01) and have 4% lower mineral content (P < 0.05) than all other locations. Moderately strong correlations exist between collagen fiber orientation and normal strain (r = 0.752) and shear strain (r = 0.555). When normal and shear strains were transformed to their respective absolute values, thus eliminating the effects of strain mode (tension vs. compression), these correlation coefficients decreased markedly. CONCLUSIONS: Collagen fiber orientation is related to strain mode and may function to accentuate rather than attenuate bending. These differences may represent adaptations that function synergistically with bone geometry to promote a beneficial strain distribution and loading predictability during functional loading.

Adaptation, Physiological↗

PubMed2004

Habituation to galvanic vestibular stimulation for analysis of susceptibility to carsickness.

OBJECTIVE: In a previous study we developed a standardized procedure for a reproducible quantification of galvanic-induced body sway (GBS). In line with other reports, GBS shows short-term (fast) habituation upon stimulus repetition. The aim of this study was to evaluate whether the degree of short-term habituation to galvanic vestibular stimulation (GVS) is correlated with susceptibility to carsickness. MATERIAL AND METHODS: A total of 24 female subjects underwent computer-controlled GVS as part of a prospective experimental study conducted in a tertiary referral center. A binaural 1-cosinusoidal stimulus of 0.5 Hz and 1 mA was repeated five times. Binaural stimulation was chosen to obtain maximum responses, making possible habituation to repetitive GVS obvious. The groups consisted of 12 subjects suffering from carsickness and 12 healthy subjects. RESULTS: Analysis of the repeated measurements test showed that the GBS-gain curve for the carsickness group was always superimposed on that for the healthy subjects. However, the (absolute) first to fifth GBS gains showed no significant differences (p = 0.134 - 0.995). When comparing short-term habituation in subjects suffering from carsickness versus healthy subjects, the results showed no differences in the mean values of the first (30.534% vs 27.024%), final (42.637% vs 38.544%) and average (35.544% vs 33.644%) habituations (p = 0.875, 0.991 and 0.951, respectively). CONCLUSION: We did not observe any significant differences in sensitivity or habituation of the GBS in carsick subjects compared to healthy subjects. This implies that carsick subjects show a similar ability to discard an irrelevant, non-motion sickness-inducing galvanic stimulus as healthy subjects.

Adult↗

PubMed2004

A general technique to rank protein-ligand binding affinities and determine allosteric versus direct binding site competition in compound mixtures.

To realize the full potential of combinatorial chemistry-based drug discovery, generic and efficient tools must be developed that apply the strengths of diversity-oriented chemical synthesis to the identification and optimization of lead compounds for disease-associated protein targets. We report an affinity selection-mass spectrometry (AS-MS) method for protein-ligand affinity ranking and the classification of ligands by binding site. The method incorporates the following steps: (1) an affinity selection stage, where protein-binding compounds are selected from pools of ligands in the presence of varying concentrations of a competitor ligand, (2) a first chromatography stage to separate unbound ligands from protein-ligand complexes, and (3) a second chromatography stage to dissociate the ligands from the complexes for identification and quantification by MS. The ability of the competitor ligand to displace a target-bound library member, as measured by MS, reveals the binding site classification and affinity ranking of the mixture components. The technique requires no radiolabel incorporation or direct biochemical assay, no modification or immobilization of the compounds or target protein, and all reaction components, including any buffers or cofactors required for protein stability, are free in solution. We demonstrate the method for several compounds of wide structural variety against representatives of the most important protein classes in contemporary drug discovery, including novel ATP-competitive and allosteric inhibitors of the Akt-1 (PKB) and Zap-70 kinases, and previously undisclosed antagonists of the M(2) muscarinic acetylcholine receptor, a G-protein coupled receptor (GPCR). The theoretical basis of the technique is analyzed mathematically, allowing quantitative estimation of binding affinities and, in the case of allosteric interaction, absolute determination of binding cooperativity. The method is readily applicable to high-throughput screening hit triage, combinatorial library-based affinity optimization, and developing structure-activity relationships among multiple ligands to a given receptor.

Binding Sites↗

PubMed2001

[Progression of coronary calcium].

BACKGROUND: The progression of coronary atherosclerosis is determined by risk factor exposure. It is also an important predictor of future cardiac events in its own right. Coronary calcium represents an integral part of coronary atherosclerosis. Accurate measurements can be obtained by using electron-beam computed tomography (EBT) or recently developed multidetector spiral CT scanners which are in the state of evaluation. The variability of EBT-derived quantification of coronary calcium is < 10% and thus suitable for determining the progression of coronary calcium. PROGRESSION OF CORONARY CALCIUM: In the healthy general population, the annual progression measures approximately 24%, whereas in untreated, asymptomatic high-risk patients, it is 40-50%. Similar values are observed in symptomatic patients with modern pharmacological therapy. There is a considerable amount of inter-individual variability in the progression of coronary calcium, probably as a result of the complex interplay of numerous factors which influence the process. Progression of coronary calcium is observed at typical predilection sites of atherosclerosis in the coronary tree. Changes in overall coronary calcium result from uniform changes at these sites. This uniform pattern of change suggests that the development of calcified plaque disease is a coronary systemic process. The baseline amount of coronary calcium is significantly associated with its progression. In patients with a high baseline calcium score, absolute progression is enhanced. LDL-cholesterol is the most important risk factor influencing progression. Indeed, the effect of medical therapy on coronary atherosclerosis can be assessed. Preliminary data indicate that clear-cut progression of coronary calcium is associated with an increased risk of cardiac events. CONCLUSION: For the first time, EBT-derived measurements of the progression of coronary calcium enable direct assessment of the activity of coronary calcified atherosclerosis. The interaction between therapeutic measures, progression of anatomical disease, and clinical course can be appreciated.

Adult↗

PubMed2003

Precise gas chromatography with retention time locking in comprehensive toxicological screening for drugs in blood.

The long-term precision of three retention parameters, the absolute retention time (RT), the relative retention time related to dibenzepin (RRT), and the internal retention index based on the alkylfluoroaniline series (RI), were studied with 14 basic drugs on HP-5 and DB-17 columns with and without the use of the retention time locking option (RTL). Using the constant flow mode in all experiments, the RTL method was found to produce superior precision with all three retention parameters compared to the non-RTL method on each column. The results showed that RTL offers a significant advantage within a single instrument method, not only between methods, with CV<0.1% by RRT. Consequently, a dual-column gas chromatographic procedure with nitrogen-phosphorus detection was described for comprehensive screening for basic drugs in 1-ml whole blood samples. The method consisted of one-step liquid-liquid extraction with butyl acetate, identification using RRT in the RTL mode, and quantification based on single point calibration. The method allowed reliable screening and quantification of 124 basic drugs at therapeutic and toxic concentration levels in autopsy blood.

Chromatography, Gas↗

PubMed2005

The effects of urethritis on seminal plasma HIV-1 RNA loads in homosexual men not receiving antiretroviral therapy.

OBJECTIVES: To examine the effects of urethritis and its treatment on semen plasma HIV-1 RNA load in HIV-1 infected men not receiving antiretroviral therapy (ART), in a developed world setting. METHODS: Prospective case-control study. HIV-1 infected homosexual men, not receiving ART for at least 3 months, with (cases) and without (controls) symptomatic urethritis, were recruited. Blood and semen were collected for HIV-1 RNA quantification at presentation, before antibiotic therapy, and at 1 and 2 weeks. RESULTS: 20 cases (13 gonococcal urethritis and/or chlamydial urethritis (GU/CU) and seven non-specific urethritis (NSU)) and 35 controls were recruited. Baseline characteristics and blood plasma viral load were similar in cases and controls. Mean log semen plasma viral loads were higher among those with GU/CU compared with controls (4.27 log versus 3.55 log respectively; p = 0.01) but not in those with NSU (3.48 log; p = 0.82). Following antibiotics, semen plasma viral loads fell by a mean of 0.25 log (95% CI: 0.03 to 0.47) in those with GU/CU. Semen plasma viral loads did not fall in those with NSU. CONCLUSIONS: In this study of 55 homosexual men not on ART, semen plasma viral loads were approximately fivefold higher in those with GU/CU, but not NSU, compared with controls. Treatment of GU/CU resulted in reduction in semen plasma viral loads. Although absolute effects were considerably lower when compared to patients from a similar study from sub-Saharan Africa, our data demonstrate the potential for sexually transmitted infections to enhance HIV infectivity of men not receiving ART in the developed world.

Adult↗

PubMed1994

A randomized, placebo-controlled trial of recombinant human granulocyte colony-stimulating factor administration in newborn infants with presumed sepsis: significant induction of peripheral and bone marrow neutrophilia.

Host defenses in the human neonate are limited by immaturity in phagocytic immunity. Such limitations seem to predispose infected newborns to neutropenia from an exhaustion of the neutrophil reserve. Among the critical defects thus far identified in neonatal phagocytic immunity is a specific reduction in the capacity of mononuclear cells to express granulocyte colony-stimulating factor (G-CSF) after stimulation. However, the safety, pharmacokinetics, and biological efficacy of administration of recombinant human (rh)G-CSF to infected human newborns to compensate for this deficiency is unknown. Forty-two newborn infants (26 to 40 weeks of age) with presumed bacterial sepsis within the first 3 days of life were randomized to receive either placebo or varying doses of rhG-CSF (1.0, 5.0 or 10.0 micrograms/kg every 24 hours [36 patients] or 5.0 or 10.0 micrograms/kg every 12 hours [6 patients]) on days 1, 2, and 3. Complete blood counts with differential and platelet counts were obtained at hours 0, 2, 6, 24, 48, 72, and 96. Circulating G-CSF concentrations were determined at hours 0, 2, 6, 12, 14, 16, 18, 24, and 36. Tibial bone marrow aspirates were obtained after 72 hours for quantification of the bone marrow neutrophil storage pool (NSP), neutrophil proliferative pool, granulocyte progenitors, and pluripotent progenitors. Functional activation of neutrophils (C3bi expression) was determined 24 hours after rhG-CSF or placebo administration. Intravenous rhG-CSF was not associated with any recognized acute toxicity. RhG-CSF induced a significant increase in the blood neutrophil concentration 24 hours after the 5 and 10 micrograms/kg doses every 12 and 24 hours and it was sustained as long as 96 hours. A dose-dependent increase in the NSP was seen following rhG-CSF. Neutrophil C3bi expression was significantly increased at 24 hours after 10 micrograms/kg every 24-hour dose of rhG-CSF. The half-life of rhG-CSF was 4.4 +/- 0.4 hours. The rhG-CSF was well tolerated at all gestational ages treated. The rhG-CSF induced a significant increase in the peripheral blood and bone marrow absolute neutrophil concentration and in C3bi expression. Future clinical trials aimed at improving the outcome of overwhelming bacterial sepsis and neutropenia in newborn infants might include the use of rhG-CSF.

Bone Marrow↗

PubMedDate not supplied

Prediction of equilibrated urea in children on chronic hemodialysis.

Urea rebound (UR) after hemodialysis (HD) requires the use of equilibrated urea (Ceq) instead of immediate end-dialysis urea (Ct) for correct quantification of HD, which is impractical. A new formula for predicting Ceq in children is suggested in our study. Thirty eight standard pediatric HD sessions (single pool Kt/V = 1.70 +/- 0.35, K = 4.65 +/- 1.14 ml/min/kg, UF coeff. = 3.2-6.2 ml/h/mm Hg, t = 3.80 +/- 0.46 h) in 15 children (M: 6, F: 9), ages 14.5 +/- 3.28 years were analyzed. Blood samples were taken: before, 70 min from the start, at the end, and 60 min after the end of HD sessions. After correlating UR (20.32 +/- 7.74%) to various HD parameters, we found that it was mainly determined by HD efficiency parameters. Therefore we correlated Ceq to HD efficiency parameters (Ct, urea reduction ratio, Kt/V, and K/V) and found a very high correlation between Ct and Ceq (r = 0.973). Linear regression analysis was used to further investigate this relationship, and a new formula to predict Ceq from Ct was obtained (Ceq = 1.085 Ct + 0.729, R2 = 0.946, SE = 0.49, absolute residuals = 0.38 +/- 0.29 mmol/L). In a validation study (10 HD sessions with new set of urea blood samples) the results obtained by the new formula were compared with measured values of Ceq and those obtained by the Smye formulae. Values predicted by the new formula (9.91 +/- 2.92 mmol/L) were not significantly different from the measured values (10.33 +/- 3.44 mmol/L). Absolute error of the new formula was 0.78 +/- 0.73 mmol/L, median 0.65; ie., 6.93 +/- 5.3%, median 7.7%. Ceq predicted by the Smye formulae (10.95 +/- 4.18 mmol/L) also did not significantly differ from the measured values, but absolute error of predicted values was markedly higher (1.21 +/- 0.90 mmol/L, median 0.89; 11.73 +/- 7.72%, median 10.11%; p < 0.05). When predicted Ceq was used for calculating equilibrated Kt/V (eKt/V), the new formula resulted in lower absolute error (0.09 +/- 0.07, median 0.08) than the Smye method (0.14 +/- 0.08, median 0.12). We conclude that our simple formula is sufficiently accurate in predicting Ceq in standard pediatric HD and that it is more accurate than the existing Smye formulae, while requiring only pre- and post-HD urea samples. We suggest the use of the new formula for predicting Ceq, which can then be used instead of Ct for a more accurate estimation of double pool Kt/V, URR, V, and PCR.

Adolescent↗

PubMed2000

A fractional dialysate collection method to estimate solute removal in continuous venovenous hemodialysis.

BACKGROUND: Fractional direct dialysis quantification (fDDQ), whereby a known proportion of dialysate effluent is sampled, can reliably estimate total solute removal in intermittent hemodialysis (IHD). Our study aimed to develop and test the technique in continuous venovenous hemodialysis (CVVHD). METHODS: Twenty dialysate collections (mean duration 23.5 hours, range 17.25 to 26.6) were performed in 12 patients on CVVHD. An infusion pump diverted 10% of the total effluent volume to the fractional collection (fc), the remainder being channeled into the bulk collection (bc). Both fc and bc were collected on ice and assayed for urea nitrogen (UN) and creatinine (Cr). Actual solute removal (ASR) was calculated from the measured effluent volume and solute concentrations of the fc and bc. Estimated solute removal (ESR) was calculated from the product of the fc solute concentration and effluent volume. All fc/bc samples in 15 out of 20 collections underwent gram stain and aerobic/anaerobic culture. RESULTS: Bland-Altman analyses suggested good agreement between ASR and ESR [absolute values of percentage differences: 95% CI = 1.73, 5.17% (UN); 1.88, 4.31% (Cr)]. Favorable concordance correlation coefficients confirmed this [rc = 0.995 (UN), 0.997 (Cr)] and were apparently unaffected by heavy pseudomonal growths in 4 out of 7 culture positive collections [rc = 0.997 (UN), 0.997 (Cr); culture negative (N = 8), rc = 0.996 (UN), 0.997 Cr)]. CONCLUSION: fDDQ, using 24-hour, pump-assisted, cooled fractional dialysate sampling reliably estimates total solute removal and provides a practical alternative to total dialysate collection in assessing delivered dialysis dose.

Creatinine↗

PubMed1998

Normal values for left ventricular volumes obtained using gated PET.

BACKGROUND: Accurate assessment of left ventricular (LV) volumes provides important insights into myocardial function, being particularly important for diseases of the heart in which there is progressive dilatation of the LV, such as remodeling after myocardial infarction. We have recently validated a method for measuring LV volumes using gated positron emission tomography (PET) with oxygen-15 labeled carbon monoxide (C15O). The present study was performed to establish normal values for LV volumes, in absolute units, using this technique. METHODS: Forty subjects [21 males and 19 females; age 49 +/- 13 years (mean +/- SD), range 24-80; body surface area (BSA) range 1.50-2.18 m2] were studied. End diastolic (EDV) and end systolic volumes (ESV) were calculated by determining the edge of the end diastolic and end systolic blood pool images (obtained using PET with C15O) and summing the volume of the voxels comprising the blood pool. RESULTS: For the overall study population, EDV was 109 +/- 20 ml and ESV 37 +/- 12 ml. When stratified according to gender, these values were: in males, EDV was 117 +/- 18 ml and ESV 42 +/- 18 ml; in females, EDV was 100 +/- 19 ml and ESV 32 +/- 8 ml. The differences between gender groups (EDV: p = 0.0027, ESV: p = 0.0029) were eliminated when volumes were corrected for BSA. CONCLUSIONS: These data will form a database of normal values for comparison with pathological conditions of the heart. PET quantification of LV volumes offers a means of measurement of function using an imaging modality that can also assess regional myocardial perfusion and metabolism during the same study session.

Adult↗

PubMed2000

Radiation-induced regional cerebral blood volume (rCBV) changes in normal brain and low-grade astrocytomas: quantification and time and dose-dependent occurrence.

PURPOSE: New tumor-conformal radiation-treatment modalities have been established with the intention to spare normal tissue while maintaining or improving local tumor control. To document radiation-induced changes in normal brain and low-grade astrocytoma we measured regional cerebral blood volumes (rCBV) using a dynamic susceptibility-weighted contrast-enhanced MR technique (DSC-MRI). We attempted to assess pretherapeutic rCBV values and time- and dose-dependent changes following radiotherapy. METHODS AND MATERIALS: For prospective and longitudinal assessment of rCBV in normal brain and low-grade astrocytoma, 25 patients with histologically proven fibrillary astrocytoma (WHO Grade II) were examined before radiotherapy and during follow-up. Based on CT- and MR-data sets in a stereotactic setup, three-dimensional (3D) treatment planning was done. Radiotherapy was delivered using fractionated stereotactic radiotherapy (FSRT) to mean and median total doses of 60.9 and 60 Gy, respectively (range, 55.8-66 Gy). During MR imaging for treatment planning and follow-up examinations, 55 T2-weighted gradient echo images were acquired before, during, and after intravenous contrast bolus injection. The acquired signal-time curves were converted into concentration-time curves. The area under the tissue concentration-time curve was calculated and normalized to an integrated arterial input function. Thus, absolute rCBV values could be calculated. RESULTS: Pretherapeutic mean rCBV for normal gray (GM) and white brain matter (WM) were 7.2 +/- 2.7 and 3.6 +/- 1.5 mL/100 g tissue, respectively. Mean rCBV for astrocytoma was 6.5 +/- 3.7 mL/100 g tissue. After radiotherapy, rCBV for GM and WM was significantly reduced (p < 0.01) in high-dose areas (40-100% of total dose). A nonsignificant reduction was measured in low-dose areas (up to 40% of total dose). Reduction of rCBV in astrocytomas to a plateau level of 4.6 +/- 0.4 mL/100 g tissue was measured at 6 months after radiotherapy and remained stable in locally controlled tumors. CONCLUSION: Monitoring of rCBV changes in normal brain and low-grade astrocytoma was feasible using a DSC-MRI technique. The method was able to document radiation effects in low-grade astrocytoma, even if the majority of tumors showed no change in diagnostic MR-imaging. Radiation induced decrease of rCBV in GM and WM was correlated to total dose delivered to a tissue area, with high doses causing a significant decrease. Minor decline of rCBV in GM and WM outside high-dose areas after stereotactic radiotherapy confirms the efficacy to spare normal brain tissue by the use of modern conformal radiotherapy techniques. Nonetheless, a critical minimal dose initiating rCBV changes is yet unknown.

Adult↗

PubMed1989

[Relationship between flushing response and drinking behavior].

Shipyard employees and their spouses in Kawasaki were surveyed twice as subjects on the relationship between flushing response and drinking behavior. Data obtained from 1,463 respondents of the two surveys, are used for the analysis. Flushing responses were classified into five types according to the amount of absolute alcohol which induced flushing; fast flushing (FF), medium flushing (MF), slow flushing (SF), no flushing (NF) and unknown. A distribution of the flushing types in males did not show statistical differences among native places and age groups, but among jobs. The distribution in females was not statistically different among native places and jobs, but among age groups. A large number of drinkers who frequently drank belonged to NF and SF. Those who belonged to NF and SF drank every day during the surveyed period (for 1 week). Most of drinkers who drank two kinds and more alcoholic beverages at a chance of drinking belonged to SF and NF. The alcohol consumption during the surveyed period ranged in due to order among males as: FF less than MF less than unknown less than SF less than NF, and among females as: unknown less than FF less than MF less than SF and NF. The results analyzed by "Hayashi's quantification scaling type I" showed that the drinking frequency and the most favorite alcoholic beverage much contributed to the alcohol consumption, but the flushing type didn't so much. However, it made the fact clear that NF contributed to increase alcohol consumption, and unknown and FF did to decrease alcohol consumption.

Adult↗

PubMed1999

Measurement of plasma renin activity with use of HPLC-electrospray-tandem mass spectrometry.

BACKGROUND: The measurement of renin activity is complicated by difficulties in the quantification of angiotensin 1 (Ang1), the product of the renin-catalyzed reaction. We report an HPLC-electrospray-tandem mass spectrometry (HPLC-ESI-MS/MS) method for the quantification of Ang1 as a measure of plasma renin activity (PRA). METHODS: After incubation (37 degrees C for 3 or 18 h), samples were prepared using C18 solid-phase extraction. [Val]5Ang1 was used as the internal standard (IS). Chromatography was performed on a C18 column, using 200 mL/L ammonium acetate buffer-800 mL/L methanol as the mobile phase. The flow rate was 150 microL/min, with a chromatographic run time of 5 min/sample. Mass spectrometric detection was in the positive ionization mode with selected reaction monitoring (Ang1 m/z 649.0-->784.0; IS m/z 641.9-->770.4). RESULTS: The assay was linear over the range 2.5-500 ng Ang1/mL, which corresponded to a limit of detection (signal-to-noise ratio of 3:1) of PRA of 0.14 ng Ang1. mL-1. h-1. The imprecision (CV) of the assay at PRA values of 26.1, 13.5, 3.2, and 0.78 ng Ang1. mL-1. h-1 was 7.0%, 7.0%, 15%, and 11%, respectively. Absolute recoveries were 92.3% (Ang1) and 87.4% (IS). Incubation times of 3 h vs 18 h in the PRA assay gave good agreement at PRA <2 ng Ang1. mL-1. h-1, but samples with a PRA of 2-5 ng Ang1. mL-1. h-1 gave lower PRA results after incubation for 18 h than after 3 h. We compared the HPLC-ESI-MS/MS assay and an RIA for the determination of PRA, with PRA incubation times of 3 h and 1.5 h, respectively. The mean PRA based on RIA of Ang1 was higher than that obtained using HPLC-ESI-MS/MS. CONCLUSION: The HPLC-ESI-MS/MS method allows sensitive and specific measurement of PRA. The higher activities measured with the RIA method highlight its potential for overestimation of PRA.

Chromatography, High Pressure Liquid↗

PubMed1998

Colour-coded duplex sonography of preocclusive carotid stenoses.

OBJECTIVE: The accuracy of colour-coded duplex sonography (CCDS) for differentiating preocclusive stenoses from occlusions of the internal carotid artery (ICA) is a crucial point in non-invasive quantification of atherosclerotic lesions prior to carotid endarterectomy. METHODS: A total of 401 consecutive patients with CCDS followed by ICA arteriographies as gold standard was available for comparison. The entire number was divided into groups of <90%, 90-94%, preocclusive (95-99%) stenoses and occlusions. Sensitivity, specificity, and predictive value for distinguishing these groups were calculated using a contingency table. RESULTS: With CCDS we found a sensitivity of 88% and a specificity of 99% in 43 preocclusive ?95% stenoses. Similar findings were seen in 31 occlusions of the ICA (SE 87%, SP 99%). CCDS accurately differentiates the subgroups of severe carotid obstructions (90-94%, ?95% and occluded) shown by a predictive accuracy of 97, 96 and 93%. Carotid endarterectomies were performed in two of three angiographically occluded but sonographically preocclusive arteries. Intraoperatively preocclusive ICAs were seen in both cases. CONCLUSION: CCDS showed a high accuracy for differentiating preocclusive stenoses and occlusion of the ICA. Intraoperative findings indicated that angiography is not the absolute gold standard for preocclusive carotid disease in every case. Irregularities of the stenosis channel make it impossible to estimate the true area reduction in stenoses ?90%. The hemodynamic estimation of degree of stenosis by Doppler ultrasound may be closer to reality than angiographic measurement.

Carotid Artery, Internal↗