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[Delayed-action neuroleptics and maintenance treatments].

Neuroleptic therapeutic trial is a short time experience, usually lasting three months, or even less. A reference treatment (sometimes a placebo) or the studied neuroleptic are given respectively to two randomized samples from the same population. One variable is fixed, chemotherapy, and the other therapeutic variables--psychologic and socio-familial--are supposed to be constant during that short interval of time, though they are linked to the evaluation criteria. In a long term perspective, this robust methodology is questionnable. Psychosocial variables cannot be abstracted from the experience, and the treatment itself, volens nolens, is a composite variable in which biologic and psychologic variables interact. The singularity of the neuroleptic efficacy cannot be measured. Short term neuroleptic treatment answers a first question: how to cure a schizophrenia? Long term treatment, and incidentally long acting neuroleptics, respond to a second question: how to cure and prevent schizophrenia in one particular schizophrenic patient? Some empirical guidelines are given.

Antipsychotic Agents

Time-interval analysis of interjudge and intrajudge agreement for stuttering event judgments.

In response to the recognized need for a valid and reliable way to measure stuttering, this study investigates a measurement methodology based on time-interval analyses of stuttering event judgments. Three groups of judges, differing in stuttering judgment experience, identified stuttering events in 12 repeated presentations of five 1-min speech samples. Fixed time intervals ranging from 0.2 sec to 7.0 sec were then superimposed on the event judgments by a data analysis program. Inter- and intrajudge interval-by-interval agreement, and agreement for total numbers of intervals containing stuttering event judgments, were calculated for each judge group. Results showed that agreement was superior among more experienced judges and in longer interval lengths. Agreement varied across speech samples but not across the repeated judgment opportunities. Agreement was maximized at greater than chance levels for an interval of approximately 3.0 sec, but even this best agreement did not exceed a mean of approximately 60% for experienced judges.

Adolescent

Feasible model for locoregional and systemic longterm administration of drugs and concomitant blood sampling in Sprague-Dawley rats.

This methodological study describes three surgical procedures for locoregional and systemic drug administration, which are based on a similar experimental design. Cannulation of the arterial and portal access to the liver in comparison to the general venous system, and arterial access to the large intestine through a permanently implantable system, suitable for serial bolus injections and infusions in unrestrained rats, is presented (experiment I). Furthermore, an infusion system for longterm administration (experiment II) and a method for blood sampling during locoregional or systemic infusion procedures (experiment III) have been developed. The positioning and free flow of the catheters were checked by means of scintigraphy, administration of fluorescein under UV light and angiography in animals of experimental series I. After 7 days, no obstruction was detected. On day 15 and 30 following implantation 73.3% and 58.3% of the animals, respectively, showed unimpeded flow through the catheter system. The methods described here were well tolerated by the animals without alteration of their general condition and are currently in use in a series of chemotherapeutic and pharmacokinetic investigations.

Animals

Single cuff comparison of two methods for indirect measurement of arterial blood pressure: standard auscultatory method versus automatic oscillometric method.

With the introduction of automatic oscillometric systems for indirect measurement of arterial blood pressure (e.g. DINAMAP), the problem of correspondence between that method and the standard auscultatory method arose. For an exact and valid comparison of two methods, for physiological and methodological reasons, both measurements have to be performed simultaneously and using only one single cuff. Applying a methodological approach fulfilling these preconditions and offering in addition the advantage of a graphic documentation of the individual measurement cycles, we were able to investigate both methods in a sample of 216 comparative experiments. We found a mean difference (auscultatory method minus oscillometric method) between the methods (bias) of -0.82 mm Hg (-0.109 kPa) for systolic pressure, 1.25 mm Hg (0.166 kPa) for diastolic pressure and 1.00 mm Hg (0.133 kPa) for mean pressure. Except for systolic pressure, the differences were statistically significant (paired t-test and analysis of variance). We also obtained a significant negative correlation between the differences and the average of both pressure values (decreasing error with increasing pressure) and a significant negative correlation between differences and heart rate (decreasing differences with increasing heart rate). The conclusions drawn from the comparative study are that, although the oscillometric method exhibited a tendency to higher systolic and lower diastolic measurement values compared to the auscultatory method, both methods are well comparable and the differences are below the level of physiological and clinical significance.

Blood Pressure Determination

Epidemiological methods in prevention of blindness.

A major objective of the Prevention of Blindness programme of the World Health Organisation (WHO PBL Programme) is that by the year 1989 National Prevention of Blindness Programmes should be established in 60 developing countries which have a huge excess of avoidable blindness. To date, this has been achieved in 57 developing countries. Centres in a number of academic institutions have been designated "WHO Collaborating Centres for Prevention of Blindness". These are actively supported by the WHO PBL Programme to undertake collaborative survey and research work in developing countries. A principal aim of such work is to generate epidemiologically sound information that could form the bases for rational planning, implementation and proper evaluation of programmes for prevention of blindness. This paper outlines the main epidemiological methods that have been employed recently, by a WHO collaborating centre based at the Institute of Ophthalmology in London, in population based eye surveys and in epidemiological research in a number of developing countries. The key aspects of the methodology are discussed in detail in the context of practical experience. The outcome of the studies are also mentioned briefly. The three distinct types of epidemiological studies discussed are: (1) Population-based sample surveys, (2) Longitudinal cohort (follow-up) studies and (3) Hospital-based case-control studies.

Adult

A field worker's guide to a nutritional status survey.

This guide has been prepared specifically for the medical worker in a developing country who has little experience for survey methodology and few outside sources on which to draw. All, or only portions of the guide, may be used as local needs dictate. It provides an outline of necessary preparations, sampling, field organization, measuring techniques and recording form. To aid the statistical treatment and presentation of the data, a sample recording form is given together with coding instructions and output table layout.

Adolescent

A mathematical model of a blood-gas service.

A mathematical model depicting operation of a blood-gas workstation was developed by two systems analysts working closely with two clinical pathologists. This model was used to provide estimates of average as well as maximum turnaround times under various conditions of workload, specimen types (capillary vs. syringe), methodology (use of IL 513 vs. IL 313 for capillary samples), and reporting procedures (report each sample as analyzed vs. report after analysis of all samples in batch). These estimates have been validated against actual experience in our laboratory. Such an objective mathematical model can be used to plan optimal service.

Blood Gas Analysis

Estimation of repeatability of blood constituents in gestating beef cattle on protein- and energy-restricted diets.

Repeatabilities of blood constituents were calculated for 104 Angus heifers on two separate experiments fed adequate, protein-deficient, energy-deficient, or both protein- and energy-deficient diets. Four statistical methodologies were compared including analysis of variance, principal component (structural) analysis based on the sample covariance and sample correlation matrix, and maximum likelihood. Of 12 blood constituents tested only seven were considered sufficiently important to be included in the analysis. These blood constituents included blood urea nitrogen (BUN), creatinine (Creat), alkaline phosphatase (Alk Phos), total protein (T Prot), total bilirubin (T Bil), cholesterol (Chol) and Iron (Fe). If the standard linear model assumptions were met for heifers on the adequate diet, the estimators appeared to be quite similar for both years except when the correlation coefficient was relatively small. If the assumption of homogeneity of the variance-covariance matrix (compound symmetry) was relaxed, the structural analysis method based on the sample correlation matrix appeared preferable. However, when combining all diets, the maximum likelihood methodology was preferred. Among the specific blood constituents, Alk Phos had the highest repeatability, not only for the heifers on the adequate diet, but also for heifers on other treatments in both years. Repeatabilities for T Prot appeared to be the most consistent over all rations in both years. Repeatability estimates for Fe were high and relative rankings were consistent for both years, while repeatabilities for the other variables were either low and(or) inconsistent.

Animals

[Evaluation studies of experimental carcinogenesis].

In many cases, epidemiological studies demonstrate carcinogenic risk of occupational exposures and industrial processes, but do not allow to assess carcinogenic potential of the various substances involved in exposures (speciation). Expert judgment combining human and animal data is needed for classifying and labelling of the pure substances. For decision aiding purpose, a method was established for reviewing critically experimental carcinogenesis: 1. Standardized toxicological profiles are established according to pure substances, species, strains and administration routes. 2. Methodological evaluation is made using a scheme based on 3 critical parameters: study duration which should extend to the life expectancy of the species under study; sample size, the statistical significance of negative experiments being ascertained depending on size of samples; survival rates of groups, since sufficient numbers of animals should be at risk during most of their life span. 3. Classification of the results for risk assessment, taking into account the relevance of the administration routes.

Animals

Health survey methods with minority populations: some lessons from recent experience.

Until recently, minority populations have been inadequately or inaccurately represented in health research. Researchers are now recognizing the need to improve the validity and reliability of data on the health status and health-related behaviors of minorities. This paper discusses important methodological issues in conducting health survey research in minority communities: construction of an appropriate sampling frame, response rates, attrition from panel studies, and response patterns. These themes are illustrated with data from three field studies at the New England Research Institute. Two of these studies focus on inner-city Puerto Rican youth, a group rapidly increasing in size. The extent and multiplicity of problems experienced by this group affect the complexity of survey protocols. The third study is a random-digit-dial telephone survey on health care utilization for coronary heart disease by black and white adults from three inner-city neighborhoods in Boston. The conclusions drawn from the Institute's experience are corroborated by other scientific studies. First, the sociocultural characteristics of the community or group selected for study must be considered in planning and implementing any survey research on minority populations. Second, ensuring the quality of field work with minority groups may be expensive because of high residential mobility and lack of preexisting sampling frames. Third, there is no reason to expect any diminution of data quality with minority groups, provided the resources for data collection are adequate. The quality of data is undoubtedly proportional to the field efforts expended, but the costs of high-quality survey work are often not appreciated. The paper questions the utility of the term "minority research," for it disregards the considerable variation between and within minority groups and subcultures.

Black or African American

Toward large-scale mass spectrometry-based omics for clinical applications.

INTRODUCTION: As healthcare advances toward personalized medicine, mass spectrometry-based research is advancing our understanding of cellular biology and disease states, and translating these findings into clinical applications. This review highlights recent advances in methodology and technology that demonstrate the capabilities of mass spectrometry-based proteomics, lipidomics, and metabolomics in clinical practice. AREAS COVERED: The ability to directly analyze functional molecules with mass spectrometry uncovers crucial clinical information. Each data modality (proteins, lipids, and metabolites) provides essential insight into healthy and disease states. As technology advances, integrating data from different modalities unlocks new possibilities for clinical research. To gain the most from this multi-omic data, unsupervised integration methods can provide detailed insights into complex biological processes. As the field applies this knowledge, healthcare could experience significant leaps in the near future. This review examines recent advancements in mass spectrometry-based proteomics, lipidomics, and metabolomics, focusing on how improvements in sample preparation, automation, and multi-omics data integration are making large-scale clinical studies more accessible. EXPERT OPINION: Recent technical and methodological advancements in mass spectrometry analysis have propelled healthcare toward a tipping point, shifting from traditional RNA- and DNA-based research to downstream analysis of protein, lipid, and metabolite effectors.

Humans

Methodological errors in radioisotope flux measurements.

We examined several sources of error in isotopic flux measurements in a commonly used experimental model: the study of 22Na and 36Cl fluxes across rat ileal tissue mounted in the Ussing flux chamber. The experiment revealed three important sources of error: the absolute counts per minute, the difference in counts per minute between serial samples, and averaging of serial samples. By computer manipulation, we then applied hypothetical changes in the experimental protocol to generalize these findings and assess the effect and interaction of the absolute counts per minute, the sampling interval, and the counting time on the magnitude of the error. We found that the error of a flux measurement will vary inversely with the counting time and the difference between the consecutive sample counts per minute used in the flux calculations and will vary directly with the absolute counts per minute of each sample. Alteration of the "hot" side specific activity, the surface area of the tissue across which flux is measured and the sample volume have a smaller impact on measurement error. Experimental protocols should be designed with these methodological considerations in mind to minimize the error inherent in measuring isotope flux.

Animals

Are social-psychological smoking prevention programs effective? The Waterloo study.

Recent evaluations of smoking prevention programs have suggested considerable promise for curricula emphasizing resistance of social influences. The present study extends these evaluations by addressing key methodological limitations in previous work. Twenty-two matched schools were randomized to experimental and control conditions. Grade 6 students received a 6-week core curriculum, plus additional sessions through Grades 7 and 8. Questionnaires, and saliva samples to validate self-reported smoking behavior, were collected at five times over the 2-year study period. Cross-sectional and longitudinal analyses examined program impact for five levels of initial smoking experience, ranging from "never smoker" through regular, weekly smoker. Significant program effects were documented, most clearly for those having some experience with smoking before the program began and for those with smoking peer and family models. This study provides the methodologically most rigorous test to date of social influence programs for smoking prevention and documents for the first time significant effects for those at high risk for smoking.

Adolescent

AIDS survey methodology with black Americans.

Unique substantive and methodological issues are involved in conducting survey research on sexual and HIV risk related behaviors among Americans of African descent. Problem conceptualization, sampling, design of instruments, mode of data collection, interviewer/respondent characteristics, community resistance, and data analysis and interpretation are discussed. The lack of survey research on sensitive health issues is noted. Possible methods for addressing these issues are drawn from the experiences of the authors in conducting national research on the general and at risk Black community populations. It is concluded that attention to these issues can substantially improve the quality of research on AIDS related behaviors on Black communities. Finally, it is suggested that behavioral theories and sophisticated methodological and analytic approaches, sensitive to the special cultural dimensions of racial/ethnic life in the United States, would contribute substantially to the scientific armamentarium needed to successfully meet the challenge of the AIDS epidemic.

Acquired Immunodeficiency Syndrome

Left ventricular ejection time. multiple relation to physiological and biometrical data; prediction of reference standards.

The relationship between left ventricular ejection time, and physiological or biometrical data, is submitted to multivariate statistical analysis. Methodology is intended to attain three objectives: 1) to simulate a controlled-condition experiment in clinical research, by using the statistical method of multiple regression; 2) to get a wide inference of conclusions, by selecting a sample of two hundred subjects whose biological data cover a wide field; 3) to check the really prospective value of results, by applying the formula worked out in a group of a hundred subjects to another independent group of a hundred subjects. The prediction formula of ejection time takes into account: stroke volume, cardiac cycle duration, body height, sex, age, pulse pressure, blood capacity in oxygen, presence or absence of digitalis treatment or atrial fibrillation. The first aim of the formula is to better evaluate the normal relationship between considered variables. Secondarily it leads to a proposal for estimating mechanical performance of the left ventricle.

Adolescent

[Nucleic acid molecular hybridization as a method for the laboratory diagnosis of influenza: its potentials and prospects].

Experiments carried out by the present moment in a number of laboratories indicate that the method of molecular hybridization (MH) has great diagnostic potential. Sufficient methodological mastery of the reaction of radioactively labeled DNA probes with RNA samples applied into a polymer membrane and good supply of commercially available materials make it possible to recommend this method for use in reference laboratories at specialized diagnostic centers. Hybridization should be used in combination with traditional virological and serological tests; the combined use of MH and the enzyme immunoassay for the determination of viral antigens permits the documentation of 90-98% of all cases of influenza A with sufficient rapidity. In the near future DNA probes for the diagnosis of influenza B and C are likely to appear. MH has rather good prospects for the analysis of experimental infection in laboratory animals, as well as for the study of the replication of influenza virus in all cultures. The prospects of the study of the processes of expression of individual genes seem to be particularly attractive. MH may play an important role as a tool for documenting vaccinal reaction, as well as for the study of the action of different chemical preparations in volunteers. And finally, the greatest expectations are linked with the use of MH for the search of inapparent (persistent, latent, etc.) forms of influenza virus infection both in experimental systems and in humans. Optimistic prospects of the studies in this field are based on high sensitivity of this method combined with its equally high specificity. An additional reserve for enhancing sensitivity is also present here due to the amplification of target molecules.

DNA Probes

Tentacle regeneration in Hydra: a quantitative methodological approach.

A quantitative method is proposed for the evaluation of distal regeneration in Hydra attenuata; it is based on estimates of tentacle elongation during 10 days of regeneration, determination of a Tentacle Regeneration Index, and a statistical analysis of profiles obtained from various samples in different experiments. The results show that: polyps under normal conditions have similar regeneration patterns, regardless of individual variability; and ATxII, a neurotoxin of cnidarian origin, produces a statistically significant increase in the Tentacle Regeneration Index. The results are discussed in relation to pattern formation and growth in Hydra.

Animals

An epidemiological study of rotavirus diarrhoea in a cohort of Nigerian infants: I. Methodology and experiences in the recruitment and follow-up of patients.

A community-based prospective study was carried out in the city of Ibadan, Nigeria, to determine the epidemiology of rotavirus infection and diarrhoea among children in the first two years of life. Implementation of the proposed study methods was hindered by a number of factors common to large urban areas in developing Africa. These factors included difficulties in recruiting the study sample because of maternal fears, cultural beliefs, and lack of paternal consent. Following recruitment, longitudinal surveillance was made difficult by inefficient telecommunications, a haphazard house numbering system, transportation difficulties, mobility of the population, and lack of incentive for continued participation. Despite these difficulties, 73% of the recruited newborns remained in the study until they reached the age of 12 months. The drop-out rate in the second year of study was higher, largely because fewer incentives could be provided during the second year. This paper reviews the operational considerations of implementing a longitudinal study protocol under these conditions, and discusses the potential impact of these problems and the measures taken to overcome them on the results of this study.

Cohort Studies