Population Mean Values Research Articles

Bupivacaine Enantiomer Pharmacokinetics After Intercostal Neural Blockade in Liver Transplantation Patients

Bupivacaine, being a racemic local anesthetic, exists as an equal mixture of its component enantiomers R(+)-and S(-)-bupivacaine, which behave pharmacokinetically as independent drugs after injection into the body. Intercostal neural blockade using bupivacaine was performed for postoperative analgesia in 12 patients after orthotopic liver transplantation. Arterial blood, sampled serially, was assayed by enantioselective high-performance liquid chromatography for R(+)- and S(-)-bupivacaine. The average of the simultaneous R(+):S(-) ratios of blood bupivacaine concentrations in the 12 patients was 0.74 (SD 0.11); however, the use of a population mean value or a mean value for any patient denies the time-dependence of this entity. The blood enantiomer concentration difference was reflected in the maximum measured concentrations which, after the first dose, were, respectively, 0.38 (SD 0.19) and 0.52 (SD 0.28) mg centered dot L-1 centered dot 100 mg-1 RS-bupivacaine administered (P = 0.0003). The difference in blood concentrations between the enantiomers, reflected by the R(+):S(-) ratio being less than unity, could be explained by a greater mean total body clearance and a larger apparent volume distribution of R(+)-bupivacaine. Elimination of both enantiomers was prolonged in these patients after liver transplantation compared to data from the literature, but there was no tendency for either enantiomer to accumulate selectively, even upon repeated dosing. We conclude that this demonstration of differences in pharmacokinetics (and, in laboratory studies, also in pharmacodynamics) between the bupivacaine enantiomers points to the need for future studies to recognize the enantiomeric duality of this local anesthetic. (Anesth Analg 1995;80:328-35)

Biological Rhythmicity in Preterm Infants Prior to Discharge From Neonatal Intensive Care

The study of biological rhythms and the influence of environmental factors in the timing and synchronization of different rhythmic events have important implications for neonatal health. Preterm infants in the neonatal intensive care unit (NICU) are deprived of the patterned influences of maternal sleep, temperature, heart rate, and hormonal cycles. The impact of the NICU and nursing interventions on the development of the circadian system was studied in 17 stable preterm infants in the Intermediate Intensive Care Nursery at Stanford University for three consecutive days at about 35 weeks postconceptional age. Rectal temperature, abdominal skin temperature, heart rate, and activity were simultaneously recorded at 2-minute intervals during each 3-day study by a small microcomputer (Vitalog). Very low amplitude circadian rhythms were found for rectal and skin temperatures (maximum range 36.8 to 37.0 degrees C); population mean values for heart rate (158 bpm) and activity (3.5 counts per 2-min bin) did not differ significantly as a function of time of day. Rectal temperature, averaged in 6-hour bins over the 24-hour day as a function of both postconceptional age and postnatal age, was significantly higher during the first part of the circadian cycle. In all infants, rhythmicity in each variable was dominated by ultradian periodicities that were coincident with feedings and related interventions; moreover, several physiological variables charted during feeding differed significantly from values obtained during periods in which caregiving interventions did not occur. Quantitative data on the preterm infant circadian system may facilitate evaluation of factors that improve therapeutic responses, recovery, and outcome of neonatal intensive care patients.

Head posture and cephalometric analyses: An integrated photographic/radiographic technique

A photographic technique for natural head posture (NHP) recording that can be associated to standard radiographic exposures is presented. It allows the evaluation of radiographs, according to both the standard intracranial references and NHP. On the NHP photograph, the angle between the soft tissue nasion-pogonion line and the true vertical is calculated, and this value is used to rotate the standard radiograph around the Bolton point. The technique has been applied to 40 private orthodontic patients (24 females and 16 males, aged 7 to 20 years, mean 12.9 years). The hard tissue Frankfurt plane in NHP showed a wide variation: 80% of the patients had orbitale lower than porion (mean angle -6 degrees relative to the ground), 20% had orbitale higher than porion (mean angle 4 degrees). The position of this plane in NHP seemed to be different in the two sexes, with more males having the Frankfurt plane going upwards than females. The soft tissue Frankfurt plane (tragus-orbitale) in NHP was directed upwards (head extended) in 53% of patients. The two Frankfurt planes were never coincident in all subjects; the tragus was always lower and more anterior than porion. On average, the angle tragus-orbitale-porion was about 6 degrees. In young orthodontic patients NHP is therefore highly variable, gender dependent, and cannot be deduced from mean population values. Nevertheless, the evaluation of head position should be performed in each young patient before and during the treatment, to verify how the combined effects of therapy and growth act.

Effect of Glucocorticoid Replacement Therapy on Bone Mineral Density in Patients with Addison Disease

To study the influence of glucocorticoid replacement therapy on bone mineral density. Cross-sectional. University hospital in the Netherlands. 91 patients with Addison disease who had been receiving glucocorticoid replacement therapy for a mean of 10.6 years (range, 0.5 to 36.5 years). Bone mineral density of the lumbar spine and both femoral necks using a dual-energy x-ray absorptiometer and basal serum concentrations of adrenocorticotropin, gonadal hormones, and adrenal androgens. Decreased bone mineral density (less than 2 standard deviations [SD] of the mean value of an age-matched reference population) was found in 10 of 31 men (32%; 95% Cl, 17% to 51%) and in 4 of 60 women (7%; Cl, 2% to 16%). No statistically significant differences were found between men and women with regard to age, duration of glucocorticoid substitution, or glucocorticoid dose, either in absolute quantities or when expressed per kilogram of body weight. However, in men with decreased bone mineral density, the daily hydrocortisone dose per kilogram of body weight (0.43 +/- 0.08 mg/kg; mean +/- SD) was significantly (P = 0.032) higher than in men with normal bone mineral density (0.35 +/- 0.10 mg/kg). After correction for possible confounding variables, a significant linear correlation was found between hydrocortisone dose per kilogram of body weight and bone mineral density of the lumbar spine in the men (regression coefficient, -0.86; Cl, -1.60 to -0.13; P = 0.029) but not in the women. Long-term treatment with standard replacement doses of glucocorticoids may induce bone loss in men with Addison disease. Adjustment of glucocorticoid therapy to the lowest acceptable dose is mandatory in Addison disease, and regular measurement of bone mineral density may be helpful in identifying men at risk for the development of osteoporosis.

点滴静注用塩酸バンコマイシンの血中濃度予測におけるＢａｙｅｓｉａｎ法の検討

Five population parameter sets for intermittent intravenous drip infusion of vancomycin (VCM) were evaluated retrospectively to assess the effect of those on the predictive performance of the Bayesian method employing two measurements of one hour after the end of infusion and within 15 minutes of dose initiation (trough) in predicting plasma VCM concentration. Population mean values studied were taken from the literature of Moellering et al.(I), Matzke et al.(II), Uaamnuichai et al.(III), Grasela et al.(IV), and Burton et al.(V).Root mean squared errors (RMSEs) as a composite measure of bias and precision were 8.16, 8. 38, 8.42, 7.95 and 8. 00μg/ml in predicting the one-hour plasma concentration after the end of infusion, and were 5.04, 5. 53, 5. 32, 5. 18 and 5. 83 μg/ml in predicting the trough plasmaconcentration for the method using Is, Ills, IVs and Vs, respectively. The mean prediction error (ME) as a measure of bias demonstrated that the predictive performance of the Bayesian method in predicting trough plasma concentration underpredicted the measured concentration significantly.On reevaluation of Grasela's parameters in patients with different degrees of renal function, the predictive performances of the Bayesian method were more precise than those available by population parameter. The predictive performance of the Bayesian method employing two measurements using Grasela's parameters is concluded to be clinically acceptable.

Blood lead levels among populations differentially exposed to vehicular exhaust in Rohtak, India.

In the absence of local industrial sources of lead, leaded gasoline has been suggested as the major source of lead in the urban atmosphere of Rohtak town, situated near Delhi metropolitan city and with a high vehicular density. Blood lead levels were measured in 42 male volunteers from within the Rohtak area with varying degrees of exposure to vehicular exhaust. The occupationally exposed group with a daily exposure of 10-12 h in automobile workshops was found to have the highest levels of blood lead (mean value 21.26 microg dl(-1)) followed by roadside population (mean value 14.91 microg/dl(-1)). This group of people had a daily exposure of 8-10 h in their business establishments, situated at a distance of less than 5 to about 10 ft (< 1.5-c. 3.0 m) from the road with an average traffic density of 8000 vehicles day(-1). Urban residents were found to have higher blood lead levels (mean value 9.85 microg/dl(-1)) than the rural ones (mean value 3.34 microg/dl(-1)). The values were found to increase correspondingly with the increase in age and smoking habits within the particular categories of volunteers. The levels found in the present study are comparable to those reported from other major cities of India, but well within the tolerable limits as recommended by the European Economic Community.

Some Process Capability Indices are More Reliable than One Might Think

SUMMARY In this paper we obtain formulae for exact expected values and standard deviations of estimators of certain process capability indices discussed by Bissell. In particular, we show that for the index Cpk Bissell's formula gives values for the standard deviation which are too high especially when the actual population mean value is close to (or equal to) the average of the upper and lower specification limits.

A comparison of grab- and freeze-sampling techniques in the collection of gravel-bed river sediment

Freeze- and grab-sampling techniques for the collection of bulk sub-surface sediments in gravelly rivers are compared. Data obtained from sampling a substratum of known composition and at over 300 field locations, indicate that grab-sampling underestimates the proportion, by weight, of the fine sediment component but collects representative samples of the coarser gravel component. As a consequence of this sampling bias, the textural characteristics of the composite grab-sample means were significantly different ( p < 0.01) from the population means. Grab-samples were coarser, better sorted, had a stronger negative skew and were more leptokurtic by comparison. In contrast, freeze-sampling was shown to be a more accurate and precise technique for collecting bulk sub-surface sediments. One third the number of freeze-samples is required at-a-site in order to obtain representative estimates of all the true textural characteristics of the sediment. All sample estimates were within 10% of population mean values.

Location of branches within the apical hyphal region of Streptomyces granaticolor mycelia.

The location of branches (ramifications) within the apical hyphal region of Streptomyces granaticolor mycelia was studied in dependence on the specific growth rate by using batch and chemostat cultures. The site where a new branch emerged was correlated to the neighboured elongation sites (e-sites) as well as to the septae. In dependence on the growth rate the distance from a newly formed branch (i.e. e-site) to the apical e-site (tip of the main hypha) changed from 12 to 44 microns and to the e-site on the tip of the preceding neighboured branch from 12 to 27 microns. Thus, except for the slowest grown culture, the new branching site in the apical hyphal region did not represent the midst between the two preexisting e-sites. Comparing branching and septation sites, the data indicated a close correlation between them, if the respective mean values of whole populations were determined. But regarding individual hyphae, only 4-39%--depending on the growth rate--of the apical branches were directly neighboured to a septum. The remaining percentage was situated at one of several potential branching sites, the number of which per subapical cell corresponded to the number of nucleoids.

Variabilité des sols et stratégie d'échantillonnage dans les études pédologiques détaillées de la plaine de Montréal

In order to estimate variability of soil information presented in detailed soil surveys of the Montreal lowlands area, more than 2000 samples were collected along stratified random transects in 133 mapping units. The coefficient of variation (CV) was used as variability criteria. Variability of selected soil characteristics of the plow layer was studied according to phases of surface texture. The CV of clay, silt, pH, CEC and exchangeable cations decrease with an increase in clay content. The CV of sand content follows the opposite direction. Four modes of deposition (marine, fluvial, till and estuarine) were compared according to the variability within taxon (soil series or variant) of soil characteristics of the A, B and C horizons. More samples are needed to estimate the population mean value with the same relative error and the same confidence level for soils developed in fluvial deposits than in those formed in marine sediments. At the 90% confidence level, the allocation of 15 samples per map unit allows one to estimate the population mean with a relative error ranging from 5 to 30% for most soils and variables studied. Quality standards are proposed for soil sampling in future soil survey projects. Key words: Soil variability, accuracy, sampling, taxon, mapping unit

Prevalence and medical care of hypertension in four ethnic groups in the newly-industrialized nation of Mauritius.

Prevalence of hypertension was investigated in Mauritius in 2362 men and 2712 women among Hindu and Muslim Indian, Creole and Chinese ethnic groups aged 25-74 years. The age-standardized prevalence of hypertension varied from 9.4% to 17.3% in men and from 9.5% to 16.9% in women among the four ethnic groups and increased with age. The population mean values of systolic/diastolic blood pressure were 126/79 mmHg in men and 124/75 mmHg in women. The proportion of hypertensive persons aware of their condition was 50.5% in men and 66.6% in women. The proportion of treated and adequately controlled hypertensive patients was only 21.7% in men and 29.3% in women. Creoles had the highest mean value of systolic and diastolic blood pressure and the highest prevalence of hypertension whilst Muslim Asian Indians had the lowest values both in men and women. Further studies are needed to define the determinants of hypertension in the multi-ethnic Mauritian population. Diagnosis and treatment of hypertension need to be improved, especially in men and the Creole ethnic group.

Age-dependent alterations in the efficacy of phenylephrine-induced contractions in vascular smooth muscle isolated from the corpus cavernosum of impotent men

Steady-state contractile responses elicited by phenylephrine activation of the alpha 1-adrenergic receptor subtype were studied in vascular smooth muscle strips isolated from the corpus cavernosum of impotent men. The dissociation constant of phenylephrine was determined by the method of partial irreversible receptor inactivation over a wide range of alpha 1-adrenergic receptor alkylation levels. Statistical analysis of mean population values revealed a significantly greater mean efficacy for phenylephrine-induced contractions in older patients (60-73 years old) than in younger patients (40-59 years old), in the absence of similar alterations in the mean phenylephrine dissociation constant (affinity). In addition, there was no significant effect of the diabetic state on the mean phenylephrine affinity or efficacy estimates. However, despite the absence of age- or pathology-dependent variations in agonist affinity, as assessed by group mean calculations, a detailed examination of all isolated tissues on an individual basis revealed that the phenylephrine affinity estimates varied over a range of almost two orders of magnitude. Furthermore, a linear regression analysis revealed a highly significant positive correlation between agonist affinity and the location of the phenylephrine concentration-response curve, which was characterized by a slope significantly less than unity. In conclusion, an increased efficacy of phenylephrine-induced contractions in vitro is consistent with the hypothesis that augmented corporal vascular smooth muscle contractility in vivo may contribute to the pathophysiology of impotence in older patients.

Population variation in Spartina anglica C. E. Hubbard

summaryThe response of clonal replicates of nine populations of Spartina anglica C. E. Hubbard to environmental variation was examined in three pot environments, designed to test for differences between the populations in their response to environmental variation. ANOVA showed that the effect of environment was highly significant for all morphological and yield characters, and that the populations were also significantly different for several characters. For above and below ground vegetative biomass, there was a significant population x environment interaction, indicative of differences in plasticity between the populations. Linear regression of the population mean value in each environment on the mean value of all populations in each environment was performed for these two traits. This showed that the response to environmental change was not significantly due to a linear relationship in some populations, hence, the method could not be used to compare the response of each population. Nevertheless, norms of reaction plots for each population showed that the three populations collected from successionally mature sites showed less response to more favourable conditions. The three mature populations also had significantly lower tiller numbers per plant in all environments. These results substantiate previous results which suggest a decline in vigour and plasticity in successionally mature populations. Morphological characters, except third leaf width and culm diameter, all proved to be significantly correlated in pairwise comparisons. This is further evidence for the occurrence in S. anglica of ‘graceful’ and ‘stocky’ variants which contrast with the highly plastic ‘anglica’ growth form.

British perspective on the U.S. preventive services task force guidelines

The clinical approach to prevention, cogently documented in the Task Force guidelines, implies the medicalization of prevention. The concentration of resources on those most in need is efficient, the widening of physicians' responsibility is welcome, and the influence on the recipients diffuses into the community. The Task Force report, however, fails to stress the problems and the limitations of this approach. The adverse effects of "labeling" can be serious. They need to be measured and taken into account, and there should be no screening without counseling and long-term care; the latter cannot be guaranteed unless there is a comprehensive general practitioner system. Screening readily generates overmedication, particularly since many physicians lack the skills, the inclination, or the staff to provide expert and continuing health advice. Concern for high-risk individuals should be only one part of a much wider preventive strategy. This is illustrated by the close correlations between the prevalence of high-risk status and the population mean value (0.85 for hypertension vs. mean blood pressure, 0.97 for excess use of alcohol vs. population mean intake). The medical approach, important though it is, must not distract attention from the more fundamental population strategy of prevention.

Prognostic Implications of Serum α-Fetoprotein Levels in Neonatal Hepatitis

Serum alpha-fetoprotein (AFP) values in 61 patients with neonatal hepatitis were compared with the normal ranges of AFP in infants and were expressed as standard deviation (SD) scores. The size of SD score indicates how many standard deviations the measured AFP value is away from the mean value of the normal population. An extremely elevated AFP value is arbitrarily defined as a SD score higher than 4.0, i.e., above mean + 4 SD. The result showed that rapid recovery from jaundice before 6 months of age occurred in 16 of 17 (94%) with SD scores of AFP lower than 4.0. By contrast, in 26 with SD scores of AFP higher than 4.0, 17 (65%) has less favorable clinical courses, either slow in recovery or progressing to chronic liver disease and even death. This correlation between AFP level and prognosis was related to the fact that higher AFP values were associated with more severe inflammatory changes in the liver, as assessed from either biochemical parameters (peak total and direct bilirubin levels) or histological findings (portal inflammation and giant cell transformation.

Prognostic Implications of Serum α‐Fetoprotein Levels in Neonatal Hepatitis

SummarySerum β‐fetoprotein (AFP) values in 61 patients with neonatal hepatitis were compared with the normal ranges of AFP in infants and were expressed as standard deviation (SD) scores. The size of SD score indicates how many standard deviations the measured AFP value is away from the mean value of the normal population. An extremely elevated AFP value is arbitrarily defined as a SD score higher than 4.0, i.e., above mean + 4 SD. The result showed that rapid recovery from jaundice before 6 months of age occurred in 16 of 17 (94%) with SD scores of AFP lower than 4.0. By contrast, in 26 with SD scores of AFP higher than 4.0, 17 (65%) has less favorable clinical courses, either slow in recovery or progressing to chronic liver disease and even death. This correlation between AFP level and prognosis was related to the fact that higher AFP values were associated with more severe inflammatory changes in the liver, as assessed from either biochemical parameters (peak total and direct bilirubin levels) or histotogical findings (portal inflammation and giant cell transformation).

Population pharmacokinetics of mitoxantrone performed by a NONMEM method.

To date, the pharmacokinetics of mitoxantrone (1,4-dihydroxy-5,8-bis[[2-[(2- hydroxyethyl)amino]ethyl]amino]anthraquinone) has been described either by an open two- or three-compartment model, showing high interindividual variability. In order to evaluate this variability, residual intraindividual variability, and measurement error, we carried out a population study. A sensitive HPLC method allowed analysis of blood samples drawn from 21 patients with breast cancer or acute nonlymphocytic leukemia. Individual data treatment (22 kinetics) using weighted nonlinear least squares regression confirmed the huge interindividual variability whatever the administration protocol of mitoxantrone: bi- or tri-exponential models fitted the data. The NONMEM population method used herein describes all concentration-time curves by a single three-compartment model, considering biphasic kinetics as fragmentary data. Residual intraindividual variability was 21.4%. Population mean values (+/- interindividual SD) of clearance, terminal half-life, and total volume of distribution were, respectively, 23.40 (+/- 10.76) L/h, 46.87 (+/- 12.18) h, and 385.49 (+/- 196.60) L. These results are of particular interest in clinical routines to calculate dosage regimens by Bayesian estimation methods.

What do mimics do when they imitate a voice?

Imitations by both professional and amateur mimics were studied to determine what similarities are achieved between the imitated voice and the imitation thereof. A wide variety of characteristics was approximated, including the following: mean F0, F1, and F2; frequency contours of F0, F1, and F2; degree of nasalization (but not frequency of nasal formants); speech rate and dynamics, including timing, attack, and release characteristics. Contours of F0, F1, and F2 were often matched accurately, even when their absolute frequencies differed considerably from those of the original. Specific images of words and phrases were used, as well as general phonetic characteristics. Imitators tended to concentrate on imitating unusual characteristics of a voice, rather than attempting to imitate all characteristics equally. This observation may be formalized as a model according to which the importance of a parameter is nonlinearly related to the extent to which it diverges from its mean population value. Professional mimics exaggerated the distinctive characteristics of voices and thus may be considered caricaturists rather than mimics, per se.

Use of alternative rules (other than the 1(2)s) for evaluating interlaboratory performance data.

Previous studies have documented the ineffectiveness of using either the group mean +/- 2 group standard deviations (SD) or the 1(2)s rule as the standard of acceptable performance in evaluating interlaboratory proficiency testing (PT) data. Using computer simulation of PT data, we evaluated the efficiency of 244 alternatives to the 1(2)s rule, all based on the PT population's mean and SD. Using the traditional interlaboratory PT format, we determined the ability of each rule to correctly identify both good and deficient intralaboratory performance. The rules are based on results from one to five PT samples "analyzed" at the same time. Because the effectiveness of the criteria set for acceptable performance in a PT program is influenced by the population SD, each rule's capabilities were examined for PT populations with interlaboratory SDs ranging from 1% through 10% of the population mean value. All rules achieve their maximum efficiency over a narrow range of interlaboratory SDs. For PT evaluations of intralaboratory performance to be optimally effective, selection of the rule must be based on the SD of the PT population.

Length estimate for KNM-ER 736, a hominid femur from the lower pleistocene of East Africa

Our knowledge concerning stature in earlyHomo is scanty. In this paper, based on comparison with the fossil femur KNM-ER 999, an estimate of 482 mm femur length is derived for KNM-ER 736, the latter dating from the Lower Pleistocene. From comparison with other fossil and modern femora, KNM-ER 736 appears to be the longest hominid femur so far recovered from a site of Early Pleistocene age. Moreover, the estimated femur length is higher than the published mean values of most modern populations. Provided that trunk and head proportions were not radically different from modernH. sapiens, the finding would suggest that a stature similar to that of modern man was already reached by East AfricanHomo as early as about 1.6 Myr before present.