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PubMed2006

Captive breeding of the white rhinoceros, Ceratotherium simum, and the Cape buffalo, Syncerus caffer.

Breeding records of 40 white rhinoceros and 155 Cape buffalo were analysed. Three rhinoceros cows bred in captivity, themselves conceived for the first time at 84, 87 and 95 months of age, respectively. Rhinoceros cows breed throughout the year. There is no evidence of a relationship between calving interval and month of birth. Calving intervals were normally distributed about the mean of 34 months and there were no significant differences between bulls, cows or sex of calf. There was no difference in the sex ratio of calves born to young cows nor older cows. The male:female ratio of the calves was 1:1. Younger cows did not have shorter birth intervals. Although captive Cape buffaloes breed throughout the year, there is a preponderance of births in midsummer. There was some evidence that larger cows produce heavier calves and that season of birth may influence birth weight. Male calves weighed 41.20 +/- 0.68 kg vs 39.00 +/- 0.73 kg (range 24-60 kg) for female calves but this difference was not significant. Calving intervals were normally distributed about the mean of 395 days and the male:female ratio of the calves was 1:1.2.

Age Factors↗

PubMed2006

Ketoconazole renders poor CYP3A phenotype status with midazolam as probe drug.

Drugs metabolized by cytochrome CYP3A isoenzymes have wide interindividual variability and normally distributed plasma clearance distributions. This makes precise dosing difficult to achieve clinically, which may compromise safe therapy. We hypothesized that with potent inhibition of CYP3A, we could clinically render patients "poor metabolizer" phenotype status, and thus reduce interindividual pharmacokinetic variability of midazolam, a well-known CYP3A substrate. Intravenous bolus midazolam at doses of 2.5 mg and 1 mg were administered to 28 and 29 patients with cancer with and without co-administration of 200 mg of oral ketoconazole twice per day respectively for 3 days, starting 1 day before midazolam. Pharmacokinetic analyses of midazolam on both groups were derived using noncompartmental methods and compared. The mean clearance (CL) of midazolam was reduced 6 times by ketoconazole. Midazolam CL were normally distributed in both groups, and ranged from 1.7 to 51.9 and 1.4 to 8.2 L/hour in the control and ketoconazole groups, respectively, corresponding to a 7-fold reduction in dispersion between the 2 groups. Area-under-the-curve variability was reduced by >100%. A limited sampling model consisting of time points at 15 and 300 minutes was validated as a phenotype for CYP3A activity to facilitate the use of midazolam as a probe drug for CYP3A activity. Potent inhibition of CYP3A by ketoconazole reduced midazolam CL and area-under-the-curve variability, allowing for more precise achievement of therapeutic target drug exposure. Prospective evaluation of this approach, together with dose adjustment based on limited sampling, seems warranted.

Administration, Oral↗

PubMed1989

GENCOV: a Fortran program that generates randomly censored survival data with covariates.

We present a Fortran program for simulating censored survival data with covariates under the assumption of random censoring. The program generates times distributed according to the uniform distribution, the generalized Gamma distribution, the log-normal distribution and Pettitt's generalized logistic distribution with Box-Cox transformation of the time variable. Covariates can be introduced in the definition of the survival time, resulting in the generalized log-gamma, log-normal and Pettitt's regression models. Thereby the program provides the means for generating censored survival data according to parametric versions of three common regression models for censored survival data: the Accelerated Failure Time, the Proportional Hazards and the Proportional Odds models.

Computer Simulation↗

PubMed2000

Statistical method for predicting when patients should be ready on the day of surgery.

BACKGROUND: Previously, mathematical theory was developed for determining when a patient should be ready for surgery on the day of surgery. To apply this theory, a method is needed to predict the earliest start time of the case. METHODS: The authors calculated a time estimate such that the probability is 0.05 that the preceding case in the patient's operating room (OR) will be finished before the patient is ready for surgery. This implies there will be a 5% risk of OR personnel being idle and waiting for the patient. This 0. 05 value was chosen by considering the relative cost valuation of an average patient's time to that of an average surgical team based on national salary data. Case duration data from a surgical services information system were used to test different statistical methods to estimate earliest start times. RESULTS: Simulations found that 0.05 prediction bounds, calculated assuming case durations followed log-normal distributions, achieved actual risks for the OR staff to wait for patients of 0.050 to 0.053 (SEM = 0.001). Nonparametric prediction bounds performed no better than the parametric method. Having patients ready a fixed number of hours before the scheduled starts of their operations is not reliable. If the preceding case in an OR had been underway for 0.5 to 1.5 h, the parametric 0.05 prediction bounds for the time remaining achieved actual risks for OR staff waiting of 0.055 to 0.058 (SEM = 0.001). CONCLUSION: The earliest start time of a case can be estimated using the 0.05 prediction bound for the duration of the preceding case. The authors show 0.05 prediction bounds can be estimated accurately assuming that case durations follow log-normal distributions.

Appointments and Schedules↗

PubMed1979

The role of beta-adrenoceptors in coronary blood flow distribution in normal and ischemic canine myocardium.

beta-Adrenoceptor agonists increase myocardial ischemic injury, mainly by elevating myocardial oxygen consumption. Moreover, it has been shown that isoprenaline may "steal" regional myocardial blood flow (RMBF) from ischemic to non ischemic areas and from epicardium to endocardium. The mechanisms of these two isoprenaline-induced redistributions of RMBF have been investigated by the use of radioactive microspheres in an experimental model of canine myocardial ischemia with simultaneous measurement of ST-segment elevation. Isoprenaline increased RMBF in both epi- and endocardial non ischemic areas and in epicardial ischemic areas, leading to a significant decrease in the endo/epi ratio. After atenolol, isoprenaline still increased RMBF but to a lesser extent and the endo/epi ratio was still decreased. Salbutamol, in doses inducing no significant changes in cardiac parameters or myocardial oxygen consumption, produced effects similar to those of isoprenaline. These results indicate a non-homogeneous beta2-stimulation-induced vasodilation in endo- and epicardium, which might be due either to the higher epicardial coronary vasocilatory reserve or to a heterogeneous distribution of transmural beta2-adrenoceptors. Isoprenaline also decreased the ischemic/non ischemic total blood flow ratio (I/NI) and caused further increases in ST-segment elevation. These effects were abolished by atenolol pretreatment, indicating the deleterious effects of isoprenaline-induced tachycardia in this I/NI decrease and in the ischemic injury.

Albuterol↗

PubMed2005

Clinical multiple sclerosis occurs at one end of a spectrum of CNS pathology: a modified threshold liability model leads to new ways of thinking about the cause of clinical multiple sclerosis.

Multiple sclerosis (MS) is a complex trait, the causes of which are elusive. A threshold liability model influences thinking about the causes of this disorder. According to this model, a population has a normal distribution of genetic liability to MS. In addition, a threshold exists, so that MS begins when an individual's liability exceeds the MS threshold; environmental and other causative factors may increase or decrease an individual's MS liability. It is argued here, however, that this model is misleading, as it is based on the incorrect assumption that MS is a disorder that one either has or does not have. This paper hypothesizes, instead, that patients with a diagnosis of MS share identical CNS pathology, termed MS pathology, with some individuals who have a diagnosis of possible MS and with some apparently healthy individuals, who may never have a diagnosis of MS. In order to accommodate this hypothesis, the current threshold liability model is modified as follows. (1) In addition to a normal distribution of MS liability within a population, a spectrum of MS pathology occurs in some who have a high MS liability. (2) A clinical MS threshold exists at a point on this liability distribution, where the burden and distribution of MS pathology permits a diagnosis of clinical MS. (3) Additional thresholds exist that correspond to a lower MS liability and a lesser burden of MS pathology than occur at the clinical MS threshold. This modified threshold model leads to the postulate that causes act at various time points to increase MS liability and induce MS pathology. The accumulation of MS pathology sometimes leads to a diagnosis of clinical MS. One implication of this model is that the MS pathology in clinical MS and in some with possible MS differs only in the extent but not in the type of CNS injury. Thus, it may be possible to obtain insight into the causative environmental factors that increase MS liability and induce MS pathology by focusing on patients who have clinical MS; some environmental factors that induce new lesions in patients with clinical MS may be identical to those that induce MS pathology in genetically susceptible individuals who do not have clinical MS. Identification of these causative factors has importance, as specific treatment may prevent the accumulation of MS pathology that leads to the significant CNS damage associated with clinical MS.

Central Nervous System Diseases↗

PubMed2000

Detecting failed WBC-reduction processes: computer simulations of intermittent and continuous process failure.

BACKGROUND: By regulation, ongoing process control of WBC-reduced processes is performed on 1 percent of WBC-reduced components, typically four to five samples per month. However, prospective study of the power of this small sample has been difficult. Using computer-generated "residual WBC" distributions, sample size sensitivity to continuous or intermittent WBC-reduction failure was examined. STUDY DESIGN AND METHODS: Populations of log-normally distributed values (mean +/- SD, 4.5+/-0.5; n = 10(5)) were generated. Continuous failure (log-normality maintained) was simulated by incrementally increasing the population mean or its SD. Intermittent failure (bimodal distributions with discrete subpopulations of WBCs > the FDA cutoff) was simulated by admixing increasing percentages of secondary outlier populations. Sample sizes of 4 to 60 were examined (500 repetitions each) for their power to detect drift or failure by standard control criteria. RESULTS: Normally distributed low variance failure was easily detected by comparison of the mean of four samples to an upper control limit (95% confidence of detecting 2% failure). However, 40 samples were required to detect > 5 percent intermittent (bimodal) failure or high variance failure with 90-percent confidence, and only if individual WBC values were compared to cutoff. CONCLUSION: Sampling error limits the detection of high variance or bimodal distributions. While the mean of a small sample is highly sensitive to shifts in a low-variance normal distribution, the detection of a high-variance bimodal population requires a large number of individual values compared to cutoff. Therefore, the number of samples required for confident failure detection depends on both the nature of the underlying distribution and the interpretive criteria. Further research is necessary to determine the true distributions of WBC-reduction process failure, as well as clinically relevant quality limits.

Blood Component Removal↗

PubMed2004

Case-finding for depressive and exhausted mood in the general population: reliability and validity of a symptom-driven diagnostic scale. Results from the prospective MONICA/KORA Augsburg Study.

PURPOSE: Depressed and exhausted mood warrants epidemiological scrutiny as a cardiovascular risk factor. We evaluated the reliability and validity of a symptom-driven diagnostic scale. METHODS: To assess a depressed mood, items were derived from an extended battery of psychosocial questionnaires in a population-based study including 11,949 subjects aged 25 to 74 years. RESULTS: Eight items from the 24-item von Zerssen checklist were extracted by factor analysis resulting in an approximately normally distributed scale (range 0-24; mean=8.23, SD 4.76). Median for men was 8.00 and 10.00 for women. Its internal consistency was high (Cronbach's alpha 0.88). Test-retest reliability of a sub-sample was 0.83. Determining concurrent validity, correlation coefficients against a single depression questionnaire in 8237 subjects (p < 0.001) and SF-36 subscales (vitality and mental health) (both p < 0.0001) in 4226 subjects proved to be significant. Construct validity was confirmed by significant associations (all p < 0.001) with sleeping complaints, social isolation, and unhappiness. Test values for men above the 80th percentile exhibited significant hazard ratios for subsequent total mortality (80th percentile: HR 2.17, 95% CI: 1.31-13.55). CONCLUSION: The scale comprises eight items describing motivational depletion, decreased vitality, irritability, and an anxious mood with sufficient internal and external reliability, concurrent and construct validity. Its normal distribution allows a graduated analysis of different thresholds. The instrument may be particularly useful to identify exhausted and depressed mood of otherwise apparently healthy subjects in the general population.

Adult↗

PubMed1997

Temperament and the structure of personality disorder symptoms.

This paper attempts to construct a simplified system for the classification of personality disorders, and relates this system to normally distributed human personality characteristics. One hundred and forty-eight subjects with a variety of psychiatric diagnoses were evaluated using the SCID-II structured clinical interview for personality disorders. A four-factor solution of personality disorder symptoms was obtained and we labelled these factors 'the four As': antisocial, asocial, asthenic and anankastic. The factors related to the four temperament dimensions of the Tridimensional Personality Questionnaire (TPQ), but less closely to Eysenck Personality Questionnaire (EPQ) dimensions. The four factors were similar to those identified in a number of studies using a variety of assessment methods and this lends some credibility to our findings. It suggests that a more parsimonious set of trait descriptors could be used to provide simpler, less overlapping categories that retain links with current clinical practice. In addition, these factors can be seen as extremes of normally distributed behaviours obtained using the TPQ questionnaire.

Adolescent↗

PubMed1988

Adoption of fluoride-based caries preventive innovations in a public dental service.

In dentistry comparative studies of diffusion of disease preventive innovations are rare and usually atheoretical. For these reasons the present study was designed 1) to determine whether or not normal distribution assumptions applied to decisions to adopt caries preventive fluoride programs in a public dental service; 2) to compare rates of adoption of two school-based and one clinic-based fluoride program, and 3) to look for evidence indicating which type of decision-making may have been involved. The programs studied were school-based fluoride brushing 4-5 times per year, fluoride mouthrinsing at least once a month, and professional topical fluoride applications at least once a year. Data were collected by postal questionnaires from public dental officers in Norway in 1972, 1977 and 1982. To determine the length of time which had elapsed from the time of innovation of the technologies to adoption, the dental literature was reviewed. The adoption curves for school-based fluoride brushing and rinsing, as well as for clinic-based topical fluoride application did not comply with the normal distribution assumption. The time lapse from innovation to adoption was in excess of 10 yr and the rates of adoption differed between programs. Decision-making would appear to have been primarily individual or collective. It was concluded that generalization beyond the innovations studied and the social and organizational setting of this particular investigation is inadmissible. Consequently, there is a need for more and larger scale comparative analytical studies to increase our understanding of diffusion and adoption of innovations in dentistry.

Adolescent↗

PubMed2002

A comparison of methods to handle skew distributed cost variables in the analysis of the resource consumption in schizophrenia treatment.

BACKGROUND: Transformation of the dependent cost variable is often used to solve the problems of heteroscedasticity and skewness in linear ordinary least square regression of health service cost data. However, transformation may cause difficulties in the interpretation of regression coefficients and the retransformation of predicted values. AIMS OF THE STUDY: The study compares the advantages and disadvantages of different methods to estimate regression based cost functions using data on the annual costs of schizophrenia treatment. METHODS: Annual costs of psychiatric service use and clinical and socio-demographic characteristics of the patients were assessed for a sample of 254 patients with a diagnosis of schizophrenia (ICD-10 F 20.0) living in Leipzig. The clinical characteristics of the participants were assessed by means of the BPRS 4.0, the GAF, and the CAN for service needs. Quality of life was measured by WHOQOL-BREF. A linear OLS regression model with non-parametric standard errors, a log-transformed OLS model and a generalized linear model with a log-link and a gamma distribution were used to estimate service costs. For the estimation of robust non-parametric standard errors, the variance estimator by White and a bootstrap estimator based on 2000 replications were employed. Models were evaluated by the comparison of the R2 and the root mean squared error (RMSE). RMSE of the log-transformed OLS model was computed with three different methods of bias-correction. The 95% confidence intervals for the differences between the RMSE were computed by means of bootstrapping. A split-sample-cross-validation procedure was used to forecast the costs for the one half of the sample on the basis of a regression equation computed for the other half of the sample. RESULTS: All three methods showed significant positive influences of psychiatric symptoms and met psychiatric service needs on service costs. Only the log- transformed OLS model showed a significant negative impact of age, and only the GLM shows a significant negative influences of employment status and partnership on costs. All three models provided a R2 of about.31. The Residuals of the linear OLS model revealed significant deviances from normality and homoscedasticity. The residuals of the log-transformed model are normally distributed but still heteroscedastic. The linear OLS model provided the lowest prediction error and the best forecast of the dependent cost variable. The log-transformed model provided the lowest RMSE if the heteroscedastic bias correction was used. The RMSE of the GLM with a log link and a gamma distribution was higher than those of the linear OLS model and the log-transformed OLS model. The difference between the RMSE of the linear OLS model and that of the log-transformed OLS model without bias correction was significant at the 95% level. As result of the cross-validation procedure, the linear OLS model provided the lowest RMSE followed by the log-transformed OLS model with a heteroscedastic bias correction. The GLM showed the weakest model fit again. None of the differences between the RMSE resulting form the cross- validation procedure were found to be significant. DISCUSSION: The comparison of the fit indices of the different regression models revealed that the linear OLS model provided a better fit than the log-transformed model and the GLM, but the differences between the models RMSE were not significant. Due to the small number of cases in the study the lack of significance does not sufficiently proof that the differences between the RSME for the different models are zero and the superiority of the linear OLS model can not be generalized. The lack of significant differences among the alternative estimators may reflect a lack of sample size adequate to detect important differences among the estimators employed. Further studies with larger case number are necessary to confirm the results. IMPLICATIONS: Specification of an adequate regression models requires a careful examination of the characteristics of the data. Estimation of standard errors and confidence intervals by nonparametric methods which are robust against deviations from the normal distribution and the homoscedasticity of residuals are suitable alternatives to the transformation of the skew distributed dependent variable. Further studies with more adequate case numbers are needed to confirm the results.

Adolescent↗

PubMed2003

The evolution of trade-offs: geographic variation in call duration and flight ability in the sand cricket, Gryllus firmus.

Quantitative genetic theory assumes that trade-offs are best represented by bivariate normal distributions. This theory predicts that selection will shift the trade-off function itself and not just move the mean trait values along a fixed trade-off line, as is generally assumed in optimality models. As a consequence, quantitative genetic theory predicts that the trade-off function will vary among populations in which at least one of the component traits itself varies. This prediction is tested using the trade-off between call duration and flight capability, as indexed by the mass of the dorsolateral flight muscles, in the macropterous morph of the sand cricket. We use four different populations of crickets that vary in the proportion of macropterous males (Lab = 33%, Florida = 29%, Bermuda = 72%, South Carolina = 80%). We find, as predicted, that there is significant variation in the intercept of the trade-off function but not the slope, supporting the hypothesis that trade-off functions are better represented as bivariate normal distributions rather than single lines. We also test the prediction from a quantitative genetical model of the evolution of wing dimorphism that the mean call duration of macropterous males will increase with the percentage of macropterous males in the population. This prediction is also supported. Finally, we estimate the probability of a macropterous male attracting a female, P, as a function of the relative time spent calling (P = time spent calling by macropterous male/(total time spent calling by both micropterous and macropterous male). We find that in the Lab and Florida populations the probability of a female selecting the macropterous male is equal to P, indicating that preference is due simply to relative call duration. But in the Bermuda and South Carolina populations the probability of a female selecting a macropterous male is less than P, indicating a preference for the micropterous male even after differences in call duration are accounted for.

Animals↗

PubMedDate not supplied

Box-Cox transformation for QTL mapping.

The maximum likelihood method of QTL mapping assumes that the phenotypic values of a quantitative trait follow a normal distribution. If the assumption is violated, some forms of transformation should be taken to make the assumption approximately true. The Box-Cox transformation is a general transformation method which can be applied to many different types of data. The flexibility of the Box-Cox transformation is due to a variable, called transformation factor, appearing in the Box-Cox formula. We developed a maximum likelihood method that treats the transformation factor as an unknown parameter, which is estimated from the data simultaneously along with the QTL parameters. The method makes an objective choice of data transformation and thus can be applied to QTL analysis for many different types of data. Simulation studies show that (1) Box-Cox transformation can substantially increase the power of QTL detection; (2) Box-Cox transformation can replace some specialized transformation methods that are commonly used in QTL mapping; and (3) applying the Box-Cox transformation to data already normally distributed does not harm the result.

Chromosome Mapping↗

PubMed1985

Maximum Shannon information content of diagnostic medical testing. Including application to multiple non-independent tests.

The increase in Shannon information available from a diagnostic test associated with grading of the test results into many outcomes, rather than simply positive or negative, was examined to determine its upper limit as the number of test outcomes is increased indefinitely. Numerical methods were employed to find the optimal locations of outcome boundaries when a single normally distributed test variable is classified into 2, 3, 4, 5, 6, 8, 14, or 20 outcome categories. In each case Shannon information was computed for values of prior probability between 0.01 and 0.99 and for distances between the means in diseased and nondiseased populations ranging from 0.5 to 5.0 standard deviations. There is an important improvement in Shannon information as the number of outcomes defined is increased, but the increment in information diminishes rapidly with each additional category. A 20%-30% increment in information may be achieved with three outcomes instead of two. A further important increase in information occurs with four to seven outcomes, but beyond this the increment in inforation is negligible. The findings were similar over a wide range of prior probabilities and distances between the means. The analysis was extended to the case of multiple nonindependent tests by demonstrating their application to a Fisher discriminant function incorporating such tests. It was concluded that for normally distributed test variables: grading of test results significantly improves the information content of both single and multiple tests; the value of information content for 8-20 outcomes represents very nearly the maximum information content of a test; there is little value in using more than five to seven test outcomes; multiple grading should not be neglected for discriminant functions.

Bayes Theorem↗

PubMed2002

Changes in intraocular pressure following diagnostic mydriasis with cyclopentolate 1%.

PURPOSE: To assess the effect of diagnostic mydriasis with 1% cyclopentolate on the intraocular pressure (IOP) of patients attending glaucoma, medical retina and cataract clinics. METHODS: Levels of agreement for IOP assessment were determined and 95% of repeated readings found to be within +/-2 mmHg. The IOP of 83 cataract, 87 medical retinal and 100 glaucoma patients was measured with Goldmann applanation tonometry before and 45 min after dilatation with 1% cyclopentolate. Those showing a substantial (>10 mmHg) increase in IOP underwent gonioscopy to determine if their angles remained open and were medically treated to lower their IOP. RESULTS: An approximately normal distribution of change in IOP following dilatation was seen in all three groups (mean change 0.4 mmHg (95% CI 0.1-0.8)). The proportion of patients with a rise of 5 mmHg or more in the right eye was 7% (95% CI 4-10%). Logistic regression using all right eyes, looking at age, sex, diagnosis, ethnicity, ocular medication, iris colour and lens status (phakic/pseudophakic/aphakic) as risk factors for a rise of IOP of 5 mmHg or more did not reveal any significant contribution. Correlation between results obtained for right and left eyes in the glaucoma group was lower (0.43) than for the other groups (0.66 and 0.72), but the extent to which the direction of change in one eye predicted that in the other was shown to be high. Two glaucoma patients with open angles developed a clinically important (>10 mmHg) sustained rise in IOP requiring treatment. CONCLUSIONS: Individual variability in the effects of cyclopentolate on aqueous dynamics may account for the approximately normal distribution of IOP seen following dilatation in all three groups. This variation was in excess of that due to observation error alone. It is recommended that the IOP be rechecked after dilation in glaucoma patients with significantly damaged optic nerve heads. In medical retina and cataract patients, sustained clinically important rises in intraocular pressure following dilation seem rarer.

Adult↗

PubMed1998

Resampling methods in sparse sampling situations in preclinical pharmacokinetic studies.

Toxicokinetic studies often require destructive sampling and the determination of drug concentrations in the various organs. Classically, the corresponding information is summarized in one mean concentration-time profile, which is regarded as representative for the animal population. On the basis of a mean profile, only estimates of the secondary pharmacokinetic parameters (for example AUC, t1/2) but no variability measures may be obtained. In this paper two resampling techniques are contrasted to Bailer's approach. The results obtained show that the resampling techniques can be considered a reliable alternative to Bailer's approach for the estimation of the standard error of the AUC t(k)0 in the case of normally distributed concentration data. They can be extended to the estimation of a variety of other secondary pharmacokinetic parameters and their respective standard deviations. One disadvantage with Bailer's method is its restriction to linear functions of the concentrations. On the other hand, using the population approach, prior knowledge of the underlying pharmacokinetic model is necessary. The resampling techniques discussed here, the "pseudoprofile-based bootstrap" (PpbB) and the "pooled data bootstrap" (PDB), are noncompartmental approaches. They are applicable under nonnormal data constellations and permit the estimation of the usual secondary pharmacokinetic parameters along with their standard deviations, standard errors, and other statistical measures. To assess the accuracy, precision, and robustness of the resampling estimators, theoretical data from three different pharmacokinetic models with different add-on errors (up to 100% variability) were analyzed. Even for the data sets with high variability, the parameters calculated with resampling techniques differ not more than 10% from the true values. Thus, in the case of data that are not normally distributed or when additional secondary pharmacokinetic parameters and their variability are to be estimated, the resampling methods are powerful tools in the safety assessment in preclinical pharmacokinetics and in toxicokinetics where generally sparse data situations are given.

Area Under Curve↗

PubMed1999

Distribution of serum creatine kinase activity in young healthy persons.

The normal distribution of serum creatine kinase (CK) was determined in 428 men (mean age = 21.5) and 540 women (mean age = 20.2). The bootstrap method was employed to obtain statistical parameters of CK reference range and correlations with physical activity habits, BMI, cigarette smoking and alcohol consumption. CK distribution was non-Gaussian and skewed toward the higher values; 18.9% of the men and 4.6% of the women had values above the upper reference limits defined for the commercial assay kit. The median 97.5 percentile value was 532 u/l for men and 248 u/l for women (95% confidence interval of 384-738 u/l and 184-340 u/l, respectively). A significant correlation was found only between CK and alcohol consumption in men. Myoglobin level in a representative group of subjects correlated well with CK activity for both genders. Our findings define the range of CK values in a healthy, young, heterogeneous population. We suggest that only CK levels above the determined 97.5 percentile should warrant further clinical investigation.

Adult↗

PubMed1975

The loss of bone mineral with aging and its relationship to risk of fracture.

Longitudinal studies have shown that individuals lose bone mineral at unequal rates with aging. It has been postulated that individuals with the more rapid rates of loss constitute a separate population having an increased risk for developing fractures, i.e., osteoporosis. To examine this postulate, we made a search for a separate population of elderly women using a precise and objective measurement technique of bone mineral, photon absorptiometry. Bone mineral content (BMC) was measured in the radius of 571 Caucasian females who were age 50 or older. It was found that BMC values adjusted for width had a normal distribution in all decades and the variation in BMC values did not increase with age. Subjects with vertebral fractures (n = 108) were estimated to be losing bone mineral at the same rate as those without vertebral fractures (n= 161). Thus evidence for a separate population of rapid losers of bone mineral was not found. Reconciliation of longitudinal studies which show unequal rates of loss with the present population survey, in which evidence for unequal rates was not found, would require that (a) the rate of loss of bone mineral for an individual is not constant and/or (b) the rate of mineral loss is proportional to the amount of mineral present at maturity. The incidence of vertebral fractures was inversely proportional to BMC values. In a group of 278 women followed for 470 subject-yr, the incidence of all fractures during the study (n = 31) was also inversely proportional to BMC. These data suggest that the BMC values of osteoporotics would be at the lower end of normally distributed values for the population.

Adult↗