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The influence of depressive symptomatology on alcoholics' locus of control: a methodological note and a correction.

In a previously published experiment from our laboratory, we reported two findings. First, controls showed the expected negative correlation between internal and external LOC dimensions, while alcoholics did not. Second, a difference score between LOC-internal and LOC-external was correlated significantly and positively with alcoholics' abstracting impairment. Data from two new independent samples of alcoholics and controls confirmed the first finding, but not the second; further, a calculation error was discovered in the previously published data that invalidated the second result. However, in all three studies, depressive symptomatology was found to be correlated negatively with the internal-external LOC difference score in both alcoholics and controls. It is suggested that depressive symptomatology be assessed in any study that investigates LOC.

Adult

Mutagenic activity of disinfection by-products.

Data on raw water quality, disinfection treatment practices, and the resulting mutagenic properties of the treated water were compiled from pilot- and full-scale treatment experiments to evaluate that parameter which might produce variability in the results of a mutagenic study. Analysis of the data and comparison of treatment practices indicated that the measured mutagenic activity is strongly related to the characteristics of the organic matter in the raw water, the methodology used to sample and detect mutagens, the scale of the study both in terms of treatment flow and period of study, and the point at which and the conditions under which oxidants are added during treatment. Conclusions regarding disinfection systems in full-scale water treatment plants include the following: When raw water is pretreated and high concentrations of organics are present in the raw water, both ozonation and chlorination increased mutagenic activity. However, no significant difference in mutagenicity was found between the two oxidants. Both in the case of a nitrified groundwater and a clarified surface water, the mutagenic activity of the water after ozonation was related to its mutagenic activity before ozonation. With ozonation, mutagenic activity decreased after granular activated carbon (GAC) filtration. Thus, when GAC filtration follows ozone disinfection, early addition of oxidants may not be deleterious to the finished water quality. When chlorine or chlorine dioxide is added after GAC filtration, chlorine dioxide was found to produce a less mutagenic water than chlorine. Although these conclusions suggest means of controlling mutagenic activity during treatment, it must be stressed that the measurement of mutagenicity is a presumptive index of contamination level.

Carbon

[Event-related desynchronization and the selection of an alpha-frequency band for quantifying cortical pre- and poststimulus activation].

The amount of event-related decrease of increase in alpha-band power is termed "Event-Related Desynchronization" or ERD. In this study, ERD is used as an index of cortical activation, which not only can be applied to monitor poststimulus but prestimulus processes as well. Usually, ERD is analyzed within a fixed range of alpha-frequency, typically within a range of 8-12 Hz. alpha-frequency, however, shows a considerable between subject variation, even in a sample of subjects with comparable age. The purpose of this study, thus is to show as to how the range of alpha-frequency affects the calculation of ERD. Two different methodological approaches were compared. First, ERD was calculated within a fixed range of 8-12 Hz. Second, ERD was calculated within an individual range, which was adjusted to the individually determined alpha-frequency of each subject. A sample of ten right handed subjects participated in an episodic memory experiment, in which target words, shown in a earlier session of the experiment, were to be identified. A time span of 375 ms preceding and following the presentation of a word was defined as the "pre-" and "poststimulus" interval. EEG-signals were recorded unipolarly from 29 leads. The results show a rather localized increase of ERD in the poststimulus interval. In the prestimulus interval on the other hand, the average magnitude of ERD is much lower and the topographical distribution less localized. Most importantly, however, when comparing the two methods of analyzing ERD, those ERD-values calculated within an individually determined alpha-band, are superior in order to differentiate between the pre- and poststimulus interval.

Adult

Case-control studies of the effect of environmental sanitation on diarrhoea morbidity: methodological implications of field studies in Africa and Asia.

The problems and prospects in the use of case-control studies to assess the effects of improvements in environmental sanitation on diarrhoea morbidity are discussed on the basis of two field studies. It is concluded that an adequate design is available for assessing the effects of a single improvement on diarrhoeal disease. The estimates of effect appear to be valid and sufficiently precise. For addressing more complex questions of interactions, sample sizes would have to be increased substantially. The experience with two field studies suggests that there is hope that a simpler protocol may be feasible, in which only limited information is collected, in which few home visits are made, and in which analytical techniques are simple. Until more field studies have been conducted definitive conclusions cannot be reached on the applicability of such a simple, rapid and inexpensive approach.

Child, Preschool

The use of network sampling for locating the seriously ill.

Network sampling, based on the experience of conducting the large-scale 1986 Robert Wood Johnson Foundation National Access to Health Care Survey, was shown to be a viable alternative to more conventional procedures for oversampling persons with a low incidence and prevalence of health conditions. The network sampling approach was a more economical and methodologically less obtrusive means of increasing sample size of persons with desired characteristics than conventional procedures. The approach requires estimating the incidence, prevalence, or both of the required characteristics in the population. As the proportion of persons in the population with the characteristic increases, network sampling may lose its attractiveness. However, this has to be judged both in economic terms and in terms of the methodologic consequences of using other procedures to increase the size of subgroups of interest. As discussed, additional methodologic work is required on the consequences of network sampling for study group representativeness and sampling bias. However, network sampling, in the authors' opinion, is sufficiently promising to warrant methodologic explorations to answer these and other relevant questions about its use.

Adult

Childhood Experience of Care and Abuse (CECA): a retrospective interview measure.

The development of a retrospective, investigator-based interview measure of Childhood Experience of Care and Abuse (CECA) used with two community samples of adults in London is described. The component ratings are shown to have satisfactory inter-rater reliability and also validity as determined by agreement between sisters' independent accounts. The association between the different childhood scales is explored as well as the relationship of childhood experiences to adult depression. Methodological issues concerning investigator-based versus respondent-based measures of childhood are discussed and a case made for use of the former. Advantages of using the CECA, a retrospective, time-based measure of childhood, are outlined.

Adult

Measuring intrasubject variability: use of the jacknife in doubly labeled water experiments.

The doubly labeled water technique measures energy expenditure; however, very little has appeared in the literature regarding estimation of the intrasubject variation. By use of a statistical resampling procedure called the jackknife, the standard deviation of the determination of energy expenditure in each subject is evaluated. Jackknife methods exploit the regression techniques that are already used with the doubly labeled water technique and are very easy to implement. Estimates of sample sizes for future experiments can easily be done with the jackknife. These formulas give the number of determinations of isotopic enrichment of hydrogen and oxygen over time that are needed to achieve a given degree of accuracy in estimating energy expenditure. An example with two human subjects illustrates the methodology of the jackknife.

Body Water

[Coping with disease from the psychosomatic-psychotherapeutic viewpoint exemplified by pancreatectomized patients].

In the past few years psychosomatic medicine, apart from investigating the psychosocial sources of bodily disorders, has begun to focus also on the opposite side of the problem, the question of how people experience illness and cope with it. This "somatopsychic" view can be regarded as a supplement to the so far prevailing psychosomatic perspective and its approach. The present study describes and analyzes various strategies of coping with illness as observed in a group of pancreatectomized patients, a group of patients which has not been investigated before in this field of research. Based upon the experience of long-term psychotherapeutic care, the study differentiates between the more problematic and the more beneficial forms of coping, and empirically verifies their prevalence and adaptivity in a sample of pancreatectomized patients, not selected with regard to the extent of care needed. The findings are discussed from the methodological and the psychosomatic-psychotherapeutic point of view.

Adaptation, Psychological

Menu planning competencies in administrative dietetic practice. II. Practitioners' ratings of competence.

A nationwide sample of administrative and generalist dietitians rated five competencies with sub-competencies and ninety-two descriptors related to menu planning. Each item was rated numerically for importance and frequency of time consideration. Data were grouped according to three levels of practitioner experience. It was concluded that an effective methodology was developed for analyzing competencies for dietetic practice.

Administrative Personnel

A generalized modified-chi2 analysis of categorical bacteria survival data from a complex dilution experiment.

A well-known method of estimation for the density of bacteria in a sample solution is the most probable number (MPN) procedure. This paper considers the change in density through time of bacteria populations which are undergoing extinction. The MPN with its estimated variance for a fixed time point is a basic module of these investigations and is treated as a general implicit function of the cell proportions in linear categorical data analysis. These quantities are then used to fit exponential decay models over time by weighted least squares. When such models are supported by the data, comparisons of decay rates between populations under possibly different experimental conditions can be undertaken. This methodology is illustrated with an example pertaining to the survival experience of Leptospira autumnalis.

Bacteriological Techniques

Thiocyanate levels in human saliva: quantitation by Fourier transform infrared spectroscopy.

A new quantitative method, based on Fourier transform infrared spectroscopy, was developed to evaluate the thiocyanate concentration in human saliva. Saliva samples were collected following a typical protocol and infrared spectra obtained from very small volumes (5 microl) deposited on a barium fluoride substrate. Exogenous potassium thiocyanate was used for calibration of the endogenous thiocyanate. This methodology does not require separation or extraction procedures. Human saliva spectra contain a characteristic marker band, due to thiocyanate, at 2058 cm-1. The integrated area of this band can be used for linear regression analysis and provides a good correlation between band area and thiocyanate concentration. Recovery of thiocyanate added to saliva was 100%. Centrifugation and dialysis experiments demonstrated that thiocyanate in saliva exists as a free or loosely bound ion. Saliva collected in the afternoon from 25 different subjects had a thiocyanate concentration of 0.83 +/- 0.42 (mean +/- SD) mmol/liter. In 4 subjects whose circadian pattern was investigated there was evidence of a higher thiocyanate concentration in saliva samples collected in the morning hours.

Cyanates

Simple and reliable enumeration of micronucleated reticulocytes with a single-laser flow cytometer.

A flow cytometric procedure for scoring micronuclei in mouse peripheral blood erythrocytes, especially reticulocytes, is described. The methods reported herein were developed in an effort to simplify the techniques and to reduce the equipment requirements associated with automated micronucleus analyses. With this procedure, fluorescein-conjugated monoclonal antibodies which bind to the CD71-defined antigen (the transferrin receptor) are used to label reticulocytes. The nucleic acid dye propidium iodide is used to identify cells with micronuclei. Given 488 nm excitation, four populations of erythrocytes are clearly resolved: normochromatic erythrocytes with and without micronuclei, and reticulocytes with and without micronuclei. Since the method is capable of simultaneously providing the incidence of micronuclei in both mature and immature erythrocyte populations, it is compatible with either chronic or acute treatment regimens. To demonstrate cell handling and flow cytometric procedures for quantitatively analyzing peripheral blood micronuclei, an experiment with the model clastogen methyl methanesulfonate is described. Additionally, a reconstruction experiment was performed whereby three mouse blood samples were spiked with successively greater volumes of blood from a clastogen-treated animal so each preparation differed slightly, but definitely, in micronucleus content. Each sample was scored six times by conventional microscopy and by flow cytometry so that the two methods could be directly compared. Collectively, the results from the methyl methanesulfonate experiment and the reconstruction study demonstrate the accuracy and reliability of the flow cytometric method. Furthermore, advantages associated with objective, high throughout scoring methodology are clearly indicated.

Animals

Sample collection, processing and storage.

We review issues related to the inclusion of biospecimens in epidemiological studies. Technical advances and the revolution in molecular biology have rendered the use of biomarkers increasingly feasible in epidemiological investigations, however the cost and complexity require interdisciplinary expertise and careful attention to methodological detail in order to ensure validity. The widespread banking of biospecimens for long-term (cohort) studies requires special attention to be paid to these issues. Blood, urine and tumour tissue are in common use in medicine and at least some aspects of sample handling derives directly from this clinical experience, although special considerations apply in the epidemiological setting. An increasingly broad array of biospecimen types have been studied, including exhaled air, nail clippings, buccal cells, saliva, semen, faeces and breast milk. Relevant issues in the processing, storage, shipping, timing of collection and safety procedures are examined in terms of their potential to distort results. The role of carefully developed quality control protocols is emphasized. In order to take full advantage of the opportunities afforded by the use of biomarkers in epidemiological studies, careful attention to biospecimen processing, the stability of the biomarker and the precautions to be taken during transportation and storage of samples is necessary.

Biomarkers, Tumor

Novel strategies for clinical drug analysis with new column technology in liquid chromatography.

Clinical drug analysis has been the focus of much attention and controversy because of the increase in substance abuse testing of addicts, patients, employees and others, in addition to the rapidly growing fields of therapeutic drug monitoring and clinical toxicology. This review focuses on the latest methodological and technological advances in liquid chromatography (LC) as it is applied to clinical drug analysis. Based on the author's experience, key chromatographic parameters such as carbon load, functionalities and temperature are proposed for the separation of structurally similar metabolites and for resolving chromatographic interferences by other drugs and metabolites. Novel sample preparation for cyclosporine and gradient elution of its metabolites are reviewed, followed by an update on monitoring of 3'-azido-3'-deoxythymidine with emphasis on automated sample preparation. Various approaches of direct sample analysis are advocated for increased efficiency as a result of minimal sample preparation and potential advantages such as decreased exposure of personnel to infectious samples. An update of microbore LC indicates that 2-mm columns may be readily used for clinical paediatric and neonatal analysis without dedicated chromatographs. Potential applications of multidimensional-multimodal chromatography include analyses of a cocaine impurity, anticonvulsants, antidepressants, and five ingredients of a common cold medication.

Body Fluids

Salivary excretion of drugs in children: theoretical and practical issues in therapeutic drug monitoring.

Studies suggest that saliva could be used instead of blood in the therapeutic monitoring of many drugs. This has distinct advantages in pediatrics and neonatology as saliva sampling is painless and spares blood. Stimulation of saliva secretion with a chemical stimulus (i.e. citric acid applied over the tongue) facilitates the study of younger patients. Secretory and reabsorptive processes which take place in the ductal system of the salivary glands, and the rate of flow of the secretion play major roles in the determination of the concentration of solutes in saliva. Drug passage into saliva follows the general principles of movement of drugs across biologic membranes. Only the unbound fraction of the drug in plasma is available for diffusion into saliva and a relationship exists between saliva pH and the saliva/plasma concentration ratio of many polar drugs (tolbutamide, propranolol, procainamide, etc.). However, deviations from the pH theory exist and the inter -and intra-individual variations in saliva/plasma concentration ratios of salicylate and procainamide cannot be explained solely on the basis of fluctuations of salivary pH; on the other hand, a useful relationship exists between plasma and saliva phenobarbital concentrations with no need to correct for saliva pH. The use of stimulated saliva has several advantages over resting saliva: a larger volume of the sample is obtained, the pH gradient between plasma and saliva is smaller, the variability in saliva/plasma concentration ratios of some drugs is narrowed, and less specimens are too viscous or discolored to allow drug analysis. Thorough rinsing of the mouth is required prior to saliva sampling as remnants of orally administered medicines may contaminate saliva specimens and give spuriously high values. Deviation from a simple but strict methodology accounts for some of the discrepancies found in the literature. Studies in children uniformly recommend saliva for therapeutic monitoring of phenytoin, carbamazepine and phenobarbital. Saliva sampling for therapeutic monitoring of ethosuximide, primidone and digoxin in infants and children, and of theophylline and caffeine in the neonate is promising, but little pediatric experience is available as yet. The value of saliva in therapeutic monitoring of theophylline in children is still controversial. Little of highly polar compounds such as aminoglycosides, and of polar highly protein bound drugs such as valproic acid is present in saliva. More data are still needed on the excretion of drugs in saliva in infants and in acutely ill children, and few data exist in the premature and full-term neonate.

Child

A review of laboratory methods for the analysis of opiates and diluents in illicit drug traffic.

The paper summarizes the utility of currently available analytical techniques for the detection of heroin and other opiates in nonbiological samples. It focuses on the following techniques: thin-layer chromatography/high-performance thin-layer chromatography, gas-liquid chromatography, high-performance liquid chromatography, gas chromatography/mass spectrometry. Recent innovations for the identification of compounds using high-performance liquid chromatographic techniques are also discussed. The applications of each methodology based on the experience of the authors are outlined.

Chromatography