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The authors examined the effect of tamoxifen (TAM), a multiple-drug resistance modulator, on the pharmacokinetics of doxorubicin (DOX) in patients with non-Hodgkin's lymphoma treated according to the CHOP-protocol which included DOX, cyclophosphamide, vincristine, and prednisone. The dose of DOX was 50 mg/m2, but was reduced 25% if the patient was older than 60 years. Of these, 10 randomly-selected patients received a daily dose of 480 mg of TAM (Group-1) and 10 others did not (Group-2). Blood samples were collected at different time intervals, and DOX was measured in plasma by liquid chromatography. The concentration-time data of DOX exhibited the characteristics of the two-compartment open model well. The mean (SEM) values of alpha, beta, k12, k21, k10, Vc, Vss, AUC, total clearance, and mean residence time observed in Group-1 were 4.06 (0.96) hr(-1), 0.0395 (0.0068) hr(-1), 3.13 (0.79) hr(-1), 0.264 (0.052) hr(-1), 0.708 (0.19) hr(-1), 525 (156) l/m2, 1060 (163) l/m2, 1145 (234) microg x hr/l, 49.3 (8.5) l/hr x m2, and 26.8 (6.6) hours, respectively. Those in Group-2 were 4.99 (1.13) hr(-1), 0.0432 (0.0073) hr(-1), 2.46 (0.63) hr(-1), 0.111 (0.026) hr(-1), 2.46 (0.86) hr(-1), 231 (53) l/m2, 812 (149) l/m2, 1690 (276) microg x hr/l, 30.3 (4.1) l/hr x m2, and 29.7 (5.1) hours, respectively. Of these parameters, the difference between the two groups was significant (p < or = 0.0169) only in k21. Thus, the coadministration of TAM at the earlier-mentioned dose appears generally to have no significant influence on the pharmacokinetics of doxorubicin when used in the CHOP-protocol.
Ther Drug Monit 1997 Dec
PMID:Effect of tamoxifen on the pharmacokinetics of doxorubicin in patients with non-Hodgkin's lymphoma. 942 Nov 3

The excretion of marijuana metabolites occurs over an extended period of time, yet few studies have been designed for accurate estimation of excretion half-lives. The authors monitored excretion of the primary urinary metabolite of marijuana, 11-nor-9-carboxy-delta9-tetrahydrocannabinol (THCCOOH), by gas chromatography-mass spectrometry in a controlled clinical study of marijuana smoking that included measurement of the drug in each urine void collected during the 3-week study. Terminal excretion half-lives of THCCOOH were determined in six healthy male subjects with histories of marijuana smoking; the study was conducted on the clinical research unit of a major medical institution. Subjects smoked a single marijuana cigarette (placebo, 1.75% or 3.55% THC) each week. Urine specimens (N=953) were analyzed under blind conditions for THCCOOH by gas chromatography-mass spectrometry. Mean+/-SEM half-lives calculated by the amount remaining to be excreted method after the low and high doses were 31.5+/-1.0 hours (range, 28.4 to 35.3 hours) and 28.6+/-1.5 hours (range, 24.9 to 34.5 hours), respectively, when a 7-day monitoring period was used. The amounts of THCCOOH excreted over a 7-day period were 93.9 +/-24.5 microg (range, 34.6 to 171.6 microg) and 197.4+/-33.6 microg after the low- and high-dose sessions. Longer half-lives, 44.3 to 59.9 hours, were obtained with a 14-day sample collection. This study documents the prolonged excretion of THCCOOH in urine and emphasizes the importance of study design in the precise estimation of terminal excretion half-lives. A sensitive analytical method and a prolonged specimen collection period are important study considerations in the monitoring of marijuana excretion.
Ther Drug Monit 1998 Oct
PMID:Urinary excretion half-life of 11-nor-9-carboxy-delta9-tetrahydrocannabinol in humans. 978 Jan 37

OBJECTIVE: To analyze various factors influencing season variations in blood pressure under ordinary circumstances. METHODS: We examined home and office blood pressures in 315 outpatients with essential hypertension. The majority (88%) were being administered antihypertensived drugs. Their office and home blood pressures were recorded in 1993. The patients were 156 men and 159 women, aged 60.8 +/- 0.6 years (mean +/- SEM). The office blood pressure was measured monthly by the same physicians. The home blood pressure was measured every day by the patients, in the morning and evening. RESULTS: The home blood pressures both in men and in women exhibited significant seasonal variations, to a similar extent. The winter-summer difference in home blood pressure was 3.9 +/- 0.5 mmHg systolic and 1.7 +/- 0.3 mmHg diastolic for the men and 4.6 +/-0.5 mmHg systolic and 2.4 +/- 0.3 mmHg diastolic for the women. The office blood pressure of the men also exhibited significant seasonal variation. There was no seasonal variation in office systolic blood pressure in the women. The levels of home blood pressure in the men and women were similar during each season, whereas the office systolic blood pressure of the women was significantly higher than that of men throughout the year. For the total group of patients, the winter-summer differences in home systolic blood pressure was positively correlated to age. The seasonal variations in blood pressure were not affected by body mass index, smoking status, and administration of antihypertensive medication.CONCLUSIONS: Seasonal variations in blood pressure existed both for male and for female hypertensive patients and occurred even for subjects being treated with antihypertensive drugs. However, there was no seasonal variation in the office systolic blood pressure of women, suggesting that the differences between the office and home blood pressures and between thermoregulatory mechanisms for the sexes may have obscured it.
Blood Press Monit 1998 Apr
PMID:Seasonal variations in office and home blood pressures in hypertensive patients treated with antihypertensive drugs. 1021 38

BACKGROUND: There is no useful oscillometric device to measure the systemic arterial pressure in small experimental animals except rats. Therefore we evaluated a recently developed automatic oscillometric device for the indirect blood pressure measurement in guinea pigs.METHODS: Twenty male Hartley guinea pigs were used. We found that unanaesthetized guinea pigs stayed comfortably in a guinea pig-holder without training. A pneumatic cuff was placed snugly around the crus of the left limb. Cuff size was selected according to previous recommendations (cuff width = limb circumference x 0.4). Systolic blood pressure corresponded to the point at which oscillations began to increase; mean arterial pressure corresponded to the point at which the oscillations peaked. Diastolic blood pressure was calculated from the values of systolic and mean blood pressures. To test the accuracy of this device, the direct and indirect values were arbitrarily collected from simultaneous recordings of six anaesthetized guinea pigs with various levels of blood pressure induced by intravenous noradrenaline infusions. RESULTS: The oscillometric device for indirect blood pressure measurements allows the measurement of blood pressure easily and quickly. Twenty unanaesthetized guinea pigs had a heart rate of 280.0 +/- 6.7 beats/min (mean +/- SEM) and systolic, mean and diastolic blood pressures of 94.0 +/- 2.2, 63.6 +/- 1.7 and 48.4 +/- 1.6 mmHg, respectively. These values are almost the same as those found in earlier studies. Correlation coefficients between direct and indirect values were > 0.9 for all blood pressures. CONCLUSIONS: These results suggest that this device may be valuable for monitoring systemic arterial blood pressure in guinea pigs.
Blood Press Monit 1996 Oct
PMID:Non-invasive measurement of systemic arterial pressure in guinea pigs by an automatic oscillometric device. 1022 71

OBJECTIVES: Syst-China is the ongoing placebo-controlled double-blind outcome trial in older (aged 60 years or more) Chinese patients with isolated systolic hypertension (systolic blood pressure 160-219 mmHg and diastolic blood pressure < 95 mmHg). This article is based on the data accumulated until 31 August 1992. Its purpose is to investigate the extent to which the variability in the clinic blood pressure readings at baseline could predict the blood pressure changes observed in the placebo arm of the trial. METHODS: From 2379 patients recruited into the trial, 728 [455 men and 273 women, aged 66.7+/-5.5 years (mean +/- SD)] were selected, because their blood pressure readings for the three run-in visits as well as 3, 6 and 12 months after random allocation were available. Overall and between-visit blood pressure variabilities at baseline were estimated from the two readings obtained with the subject seated during the first and second run-in visits. The baseline blood pressure used to calculate the blood pressure changes during follow-up was the average of the two readings during the third run-in visit. RESULTS: The blood pressure variability at baseline was larger for women than it was for men. For all of the subjects combined, the blood pressure had decreased by 4.1+/-14.4 mmHg (P < 0.001) systolic and 0.5+/-6.7 mmHg (P < 0.06) diastolic by the 3-month follow-up visit, by 8.5+/- 15.2 and 1.4+/-7.5 mmHg, respectively, after 6 months and by 10.3+/-15.7 and 1.9+/-7.9 mmHg, respectively, after 1 year (p < 0.001 for all). Stepwise multiple regression analysis showed that sex, age, alcohol intake and the blood pressure at baseline were significant determinants of the long-term (1 year) blood pressure changes. Aftger adjustment for the aforementioned covariates, the between-visit variability was a significant predictor of the changes in the diastolic blood pressure after 1 year of placebo treatment for the men (partial r+/-SEM -0.36+/-0.12, P < 0.01) and for all of the subjects (-0.19+/-0.09, P < 0.05). For men, the partial regression coefficient between the overall variability and the changes in the diastolic blood pressure also attained statistical significance (-0.39+/- 0.14, P < 0.01). CONCLUSION: For older Chinese patients with isolated systolic hypertension, in particular for men, a higher blood pressure variability at baseline was associated with a larger decrease in diastolic blood pressure during 1-year follow-up on placebo, explaining up to 2% of the variance of the observed changes. Similar associations were not observed for systolic blood pressure.
Blood Press Monit 1997 Dec
PMID:Predictive value of clinic blood pressure variability for pressure changes during placebo in elderly hypertensives. 1023 85

A high-performance liquid chromatography (HPLC) method was developed for the simultaneous analysis of trimethoprim (TMP), sulphamethoxazole (SMX), and acetylsulphamethoxazole (AcSMX) in small amounts of blood. The method involved precipitation with 50 microL trichloracetic acid (1M) to 125 microL plasma or serum sample. 60 microL supernatant was added to 60 microL mobile phase, modified with 50microL 1 M sodium hydroxide/mL. The mobile phase consisted of 20% acetonitrile and 80% phosphate buffer adjusted to pH 6.15. Using 125 microL of the sample, limits of quantitation were 0.1 microg/mL for TMP, 1.0 microg/mL for SMX, and 1.0 microg/mL for AcSMX. The precision of the method was 2% to 11% over the range of concentrations tested, 0.5-30 microg/mL for TMP, 5-300 microg/mL for SMX, and 2.5-150 microg/mL for AcSMX, respectively. No interference with other commonly used drugs was observed. The method is rapid, simple, specific, and sensitive enough for pharmacokinetic studies. The small amount of blood required makes it suitable for pediatric patients. The method was used to analyze samples from Tanzanian children aged 6-59 months participating in a cotrimoxazole (TMP/SMX)/chloroquine randomized trial for the treatment of uncomplicated malaria. Venous blood samples from 68 children were collected 2 hours after the first dose of TMP/SMX (4 mg/kg TMP/20 mg/kg SMX at two divided doses for 5 days) and again at treatment day 4. Individual variations in plasma concentrations of TMP, SMX, and AcSMX were considerable. The mean and SEM plasma concentrations (g/mL) of TMP, SMX, and AcSMX 2 hours after the first treatment dose were 2.0 +/- 1.0 (range 0.5-6), 53 +/- 22 (range 24-146), and 13.5 +/- 12 (range 0-65), respectively. On the fourth day the attained plasma concentrations were not significantly different from samples collected after the first dose.
Ther Drug Monit 1999 Dec
PMID:A reversed-phase high-performance liquid chromatography method for the determination of cotrimoxazole (trimethoprim/ sulphamethoxazole) in children treated for malaria. 1060 20

Water samples have been extracted from inside (from standpipes) and from outside (from boreholes) of the trenches at the low level radioactive waste disposal site at Drigg in Cumbria, UK. The samples were taken anaerobically from between 8.5 and 10.0 m below the surface using a submersible pump at low flow rates to ensure that the waters in the standpipes and boreholes were maintained at constant levels. To ensure representative samples, the Eh, pH. conductivity, temperature, iron and dissolved oxygen concentrations of the waters were taken during initial purging and during sampling. The gross tritium, gross non-tritium beta, gross alpha and gamma activities of each sample were determined using suitable sample preparation and counting techniques. Samples were then anaerobically, sequentially filtered through 12 microm, 1 microm, 30 kDa and 500 Da filter membranes. The filtrates were analysed for gross alpha, gross non-tritium beta and gamma activities. SEM and STEM analyses were used to determine the colloid population. An energy dispersive analyser on the SEM was used to determine the major elements present in the colloids. UV-visible spectrophotometry, fluorescence spectrophotometry and high performance size exclusion liquid chromatography were used to analyse the waters before and after treatment with ion exchange materials to determine whether natural organic matter was present in the waters. Results showed that two major types of colloids (iron containing colloids and silicon containing colloids) were present in the waters. There were also a small number of other colloids that contain, as major elements, aluminium, calcium and chromium. Organic colloids were also present. The majority of the radioactivity in the waters was due to tritium. Waters taken from outside the trenches contained low levels of non-tritium beta activities and alpha activities which were lower than the minimum detectable amount. Waters taken from the trenches contained non-tritium beta activities and low levels of alpha emitters. Filtration of the trench waters showed that some of the alpha activity was retained by the 30 kDa and 500 Da membranes suggesting that this activity was associated with small colloids. Radioactivity was not found to be associated with colloids present in the waters taken from outside the trenches. Possible reasons for this observation could be that radionuclide bearing colloids have not yet reached the far-field or that the radionuclide concentration is diluted to below the minimum detectable amount. After concentrating two of the samples by factors of x20 and x 16 respectively, 2.4+/-0.1 and 0.6+/-0.1 Bq dm(-3) of 137Cs were measured.
J Environ Monit 2002 Apr
PMID:Sampling and analyses of colloids at the Drigg low level radioactive waste disposal site. 1199 61

Airborne particulate matter has been collected from within, and proximal to, an opencast coal mine in south Wales. This work forms the first part of a three year project to collect and characterise, then determine the possible toxicology of airborne particles in the south Wales region. High-resolution Field Emission SEM has shown that the coal mine dusts consist largely of an assemblage of mineral grains and vehicle exhaust particles. SEM-EDX has shown that the mineralogical make-up of the PM10 is complex, heterogeneous, and constantly changing. These findings are supported by analytical TEM-EPXMA. However, patterns can be determined relating the mineralogical composition of the airborne particles to collection locations and mining activities within the opencast. At our study opencast, Park Slip West, quartz, which has known health effects, never exceeded 30% of the total collection mass, and average levels were much less. Vehicle exhaust emissions was the largest source in terms of particle numbers. The mass of airborne particulate matter within the pit averaged approximately twice that of outside the pit: importantly however, this higher mass was due to relatively large, and non-respirable, mineral grains. This study demonstrates that the physicochemical and mineralogical characterisation of airborne particles from mining and quarrying is essential to quantify the respirable fraction, and to identify potentially hazardous components within the PM10.
Environ Monit Assess 2002 May
PMID:Characterisation of airborne particles collected within and proximal to an opencast coalmine: South Wales, U.K. 1200 82

The spatial distribution and deposition of lead and zinc emitted from the Trail smelter, British Columbia, Canada, was studied by strategically locating moss bags in the area surrounding the smelter and monitoring the deposition of elements every three months. A combined diffusion/distribution model was applied to estimate the relative contribution of stack-emitted material and material emitted from the secondary sources (e.g., wind-blown dust from ore/slag storage piles, uncovered transportation/trucking of ore, and historical dust). The results indicate that secondary sources are the major contributor of lead and zinc deposited within a short distance from the smelter. Gradually, the stack emissions become the main source of Pb and Zn at greater distances from the smelter. Typical material originating from each source was characterized by SEM/EDX, which indicated a marked difference in their morphology and chemical composition.
J Environ Monit 2002 Jun
PMID:Sources of lead and zinc associated with metal smelting activities in the Trail area, British Columbia, Canada. 1209 35

The purpose of this work was to study the distribution of airborne particles in the surroundings of an iron and steel factory in southern Finland. Several sources of particulate emissions are lying side by side, causing heavy dust loading to the environment. This complicated multi-pollutant situation was studied mainly by SEM/EDX methodology. Particles accumulated on Scots pine bark were identified and quantitatively measured according to their element content, size and shape. As a result, distribution maps of particulate elements were drawn and the amount of different particle types along the study lines was plotted. Particulate emissions from the industrial or energy production processes were not the main dust source. Most emissions were produced from the clinker crusher. Numerous stockpiles of the industrial wastes and raw materials also gave rise to particulate emissions as a result of wind erosion. It was concluded that SEM/EDX methodology is a useful tool for studying the distribution of particulate pollutants.
Environ Monit Assess 2003 Jun
PMID:Distribution of airborne particles from multi-emission source. 1280 59


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