Technetium-99m dimercaptosuccinic acid and ifosfamide tubular dysfunction in children with cancer

Quantitative ^99mTc-dimercaptosuccinic acid (^99mTc-DMSA) renal scintigraphy was used to asses ifosfamide-induced changes in renal function in 11 children who received chemotherapy for various malignancies. Serial measurements of absolute ^99mTc-DMSA renal uptake, calculated on conjugated views, were performed during and after chemotherapy. Data of 37 studies obtained before and at different cumulative dose levels of ifosfamide were analysed in relation to clinical and biochemical parameters. A highly significant relationship between ^99mTc-DMSA uptake and cumulative ifosfamide dose was found (P<0.001). The most frequently observed abnormal pattern on scintigraphic images was decreased kidney uptake together with increased accumulation in bladder. ^99mTc-DMSA uptake was more consistent than ₂-microglobulin values in urine and more sensitive than quantitative hyperaminoaciduria and tubular resorption of phosphate for the detection of ifosfamide-induced tubular dysfunction. ^99mTc-DMSA uptake was decreased in both patients with and patients without clinical toxicity. Persistently reduced ^99mTc-DMSA uptake was observed in four patients during follow-up; in one of them, who was asymptomatic after ifosfamide therapy, sudden onset of Fanconi syndrome was observed when he was retreated with carboplatin 1 year later. It is concluded that ^99mTc-DMSA renal scintigraphy is a suitable method to assess progressive ifosfamide-induced tubular injury whereas scintigraphic imaging is helpful for interpreting renal uptake changes. The test is able to detect subclinical injury and may potentially predict high risk at retreatment.     

Obesity and subcutaneous fat patterning in relation to survival of postmenopausal breast cancer patients participating in the DOM-project

Summary The effect of obesity and fat distribution on survival of breast cancer patients was studied prospectively in 241 women with a natural menopause who participated in a breast cancer screening project, the DOM-project in Utrecht, The Netherlands. Mean follow-up time was 9.1 years and endpoint of interest was death from breast cancer. Fat distribution was assessed by contrasting groups of subscapular and triceps skinfold thickness.No significant differences in survival time between more obese (Quetelet's index 26 kg/m²) and leaner (Quetelet's index < 26 kg/m²) patients or between patients with central fat distribution and patients with peripheral fat distribution were observed. Analyses were stratified by axillary node status, estrogen receptor status, and way of detection (by first screening or afterwards). Results of the stratified analyses were suggestive of a modifying effect of these factors.The absence of an association between obesity and survival time might be explained by two counteracting mechanisms. On the one hand obesity might be related to impaired survival, due to a tumor growth promoting effect of extra-ovarian estrogens. On the other hand obesity might be related to improved survival in a screened population, because obese patients profit more from screening by earlier detection of tumors than leaner counterparts.     

The Burden of Obesity and Its Sequelae

Obesity [body mass index (BMI) ≥30 kg/m²] is common in many parts of the world, especially in the established market economies, formerly socialist economies of Europe and Latin America and the Caribbean, as well as the Middle Eastern Crescent. Worldwide, as many as 250 million people may be obese (7% of the adult population) and 2 to 3 times as many may be considered overweight (BMI 25 to 30 kg/m²). The prevalence of obesity seems to be increasing in most parts of the world, even in areas where obesity used to be rare.A waist circumference greater than 102cm in men and 88cm in women may be a more sensible classification than BMI to identify individuals who are at increased health risk because of obesity, but information on this point is still scarce.Increased fatness measured by a high BMI, large waist circumference or high waist/hip circumference ratio is associated with many chronic diseases as well as poor physical functioning. These all contribute to the costs associated with excess bodyweight. The economic costs of obesity can be broken down into 3 levels Direct costs: costs to the community related to the diversion of resources to the diagnosis and treatment of diseases directly related to obesity as well as the treatment of obesity itself. These costs have been estimated to account for 2 to 8% of total healthcare costs of various countries. Indirect (or societal) costs: these costs are related to the loss of productivity caused by absenteeism and premature death and disability pensions. There is a lack of good economic analysis in this area, although research from Sweden, Finland and The Netherlands has clearly shown that obesity is associated with increased sick leave and the need for disability pensions. Personal costs: obese individuals may earn less than their lean counterparts because of job discrimination (related to the stigma associated with obesity or because of diseases and disabilities caused by obesity). Many insurance companies (particularly life insurance) charge higher premiums with increasing degrees of overweight.In conclusion, there is much indirect information that obesity and overweight are important and growing public health concerns that contribute substantially to healthcare-related costs. Effective strategies for the prevention and management of obesity are needed.     

Model validation for external doses due to environmental contaminations by the Chernobyl accident

The objective of the present paper is to validate the deterministic JSP5 model for external exposures to population groups living in the areas contaminated with radionuclides after the Chernobyl accident. For this purpose inhabitants of contaminated areas wore TL-dosimeters for about 1 mo in the spring/summer periods of the years 1989 to 1994. External doses due to the Chernobyl accident were determined from the dosimeter readings by subtracting the natural background. 2,342 results for rural inhabitants and 420 results for inhabitants of the town Novozybkov passed reliability checks. These data show that the average dose in inhabitants of a rural settlement predicted by the model is in the range 0.69-1.55 of the measured values with a confidence level of 95%. Differences are attributed to settlement specific location factors, which are supported by the very good agreement of model and measurements in Novozybkov. In this case location factors of the model were obtained from Novozybkov directly.     

Detection of polycyclic aromatic hydrocarbon metabolites by high-pressure liquid chromatography after purification on immunoaffinity columns in urine from occupationally exposed workers

Objective: The objective in our study was to quantitate benzo[a]pyrene (B[a]P) metabolites by a combination of immunoaffinity chromatography and high-pressure liquid chromatography (HPLC) with fluorescence detection in urine from workers exposed to high levels of polycyclic aromatic hydrocarbons (PAH). Furthermore, by the simultaneous quantitation of 1-hydroxypyrene, the correlation between the B[a]P-tetrol and 1-hydroxypyrene would provide a means of evaluating the validity of 1-hydroxypyrene as a surrogate biomarker for occupational exposure to the potent carcinogen B[a]P in an electrode paste plant. Methods: The study was carried out at an electrode paste plant that produces electrode paste for Söderberg electrodes. A total of 34 pre- and post-shift urine samples and 17 personal air samples were collected from 17 workers during a normal work week. The concentration of 1-hydroxypyrene was measured in all urine samples. A recent method of quantitating B[a]P-r-7, t-8, t-9, c-10-tetrol in urine of humans exposed to low levels of PAH has been described. A modified version of this method involving purification of urine samples on immunoaffinity columns and HPLC analysis with fluorescence detection was used on urine samples from workers exposed to high levels of PAH. A monoclonal antibody (8E11) with binding affinity to B[a]P-tetrols was used. This antibody also binds several PAH-DNA adducts and metabolites, including 1-hydroxypyrene. Gas chromatography/mass spectroscopy (GC/MS) was also used for identification of metabolites isolated by HPLC fractionation. Results: From personal air sampling the mean exposure to particulate PAHs was 38?μg/m³. The mean concentration of urinary 1-hydroxypyrene was 3.9?μmol/mol creatinine in preshift samples and 10.2?μmol/mol creatinine in postshift samples. We could not identify detectable amounts of urinary B[a]P-tetrol by HPLC or fluorescence spectroscopy after purification on immunoaffinity columns. However, in the HPLC analysis we identified several hydroxyphenantrene metabolites that were detected at relatively high concentrations in all of the workers' urine samples. We could not separate 2- and 3-hydroxyphenanthrene (2?+?3-OH-Phe) in peak 1, and peak 2 contained both 1- and 9-hydroxyphenanthrene (1?+?9-OH-Phe). The phenanthrene metabolites were mainly conjugated to glucuronic acid and sulfate. There was a significant correlation between the 1-hydroxypyrene concentration and 2?+?3-OH-Phe (r?=?0.73) and 1?+?9-OH-Phe (r?=?0.64) in the urine samples. 1-Hydroxypyrene was measured in all post-shift urine samples but was not significantly correlated with workplace pyrene exposure, indicating that skin exposure is an important route of pyrene exposure in this factory. As with 1-hydroxypyrene, dermal PAH uptake may also account for the poor correlation between 2?+?3- and 1?+?9-OH-Phe and ambient phenanthrene. Discussion: Since dermal uptake is likely to be important in occupational PAH exposure in addition to inhalation, estimation of total PAH exposure is best achieved by quantitation of PAHs excreted into body fluids. However, it remains unclear whether there might be a difference in uptake and urinary excretion of 3-ring, 4-ring, or 5-ring PAHs and in the correlation between these metabolites and ambient-air PAH measurements. In summary, using immunaffinity chromatography, we did not find detectable amounts of B[a]P-tetrol in urine from workers occupationally exposed to PAH. However, by an HPLC/immunoaffinity method, relatively high amounts of 1-hydroxypyrene as well as 2?+?3- and 1?+?9-OH-Phe were quantitated in the urine samples, both of which are relevant as biomarkers of PAH exposure.     

Sulfonium salts as derivatizing agents. 3. Quantitation of the cocaine metabolite benzoylecgonine in urine using gas chromatography with ion-pair extraction/on-column alkylation

Recent studies have demonstrated the utility of quantitative assays for benzoylecgonine in assessing the efficacy of cocaine-dependence-treatment programs to determine if the amount of cocaine consumed has been reduced. We describe a simple gas chromatographic method for determining benzoylecgonine concentrations in urine. BZE is extracted from urine as an ion pair with tri-n-propylsulfonium ion. Injection into the heated injection port of the gas chromatograph results in thermal conversion of the ion pair to the n-propyl ester of BZE. Using the structural analogue of BZE, m-toluylecgonine, as the internal standard, the analysis is carried out on a (5% phenyl)methylpolysiloxane capillary column with nitrogen-phosphorus detection. There was a good correlation between BZE concentrations determined by gas chromatography-mass spectrometry and concentrations determined by the method described in this paper. Application to cocaine-dependence-treatment programs is discussed.     

Cocaine metabolite kinetics in the newborn

The study goal was to determine the half-life elimination of cocaine and benzoylecgonine (BZE) in the newborn. Three 0.3-mL blood samples were collected during the first day of life. Urine was collected once daily. Cocaine and BZE concentrations were determined by gas chromatography-mass spectrometry. An extraction method was developed for measuring low concentrations of cocaine and BZE in small (0.1 mL) blood samples. Cocaine had a half-life of 11.6 h in one subject. The half-life of BZE during the first day of life, based on blood data in 13 subjects, was 16 h (95% confidence interval [CI], 12.8 to 21.4 h). The half-life of BZE during the first week of life, based on urine data in 16 subjects, was 11.2 h (95% CI, 10.1 to 11.8 h). The novel extraction method for small blood sample volumes should be applicable to other basic drugs.     

Tumour necrosis factor alpha and interleukin 2 in normal and infected human seminal fluid

The presence of cytokines such as the tumour necrosis factoralpha (TNF) and interleukin 2 (IL2) in human spermatozoa isstill to be defined. The aim of this study was to measure theconcentration of both soluble factors in seminal fluid. Datafrom normal semen samples (n = 24) confirmed the presence ofIL2 (258 ± 84 fmol/ml corresponding to 953 ± 369fmol/total volume of ejaculate) and TNFa (62.2 ± 16.4fmol/ml corresponding to 231.3 ± 86 fmol/total volumeof ejaculate). A significant positive correlation (r = 0.59;P < 0.01) was observed between the TNFa and the IL2 concentrations.The concentrations of these cytokines were not related to spermparameters. In contrast, IL2 concentrations (196.9 ±60.4 fmol/ml; 686.2 ± 236.7 fmol/total volume of ejaculate)evaluated in 16 seminal fluids with identified bacterial agentswere lower than in the control group, whereas TNF concentrations(68.6 ± 12.3 fmol/ml; 241.3 ± 78.9 fmol/totalvolume of ejaculate) were not significantly different from thecontrols. Further studies are needed to determine the potentialrole of these cytokines in the physiology of semen and theirusefulness as indicators of reproductive pathology.     

Summation and discrimination of gratings moving in opposite directions

We have measured the amount of summation occurring at threshold between gratings which move in opposite directions. The small amount of summation observed at low spatial and high temporal frequencies is approximately consistent with the action of direction-selective mechanisms, as proposed by Levinson and Sekuler (1975), provided that probability summation between such mechanisms is taken into account. However, at high spatial and low temporal frequencies much more summation is found, an amount approximately consistent with detection by directionally non-selective mechanisms.We have also measured thresholds for identifying the direction of a moving grating. For those gratings which show little summation, direction of motion is judged correctly at the detection threshold, while for those gratings which show the most summation, the identification threshold is considerably above the detection threshold.