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PubMed2005

Course and prognosis of knee complaints in general practice.

OBJECTIVE: Patients frequently present with knee complaints in general practice. Information about the course and prognosis of knee complaints is needed to inform patients and facilitate decisions on referral and treatment. The objective of the study was to assess the course of knee complaints and to identify predictors of outcome in patients visiting their general practitioner with a new episode of knee complaints. METHODS: Data were collected by means of self-administered questionnaires. After 3 and 12 months of followup, the following outcomes were assessed: perceived recovery, change in pain, and change in physical functioning. As potential predictors of outcome, several sociodemographic variables, characteristics of the symptom, baseline scores of the outcome measures, and intra- and extra-individual variables were analyzed using multiple regression analyses. RESULTS: We included 251 patients with a new episode of knee complaints presented in general practice. Only 25% reported recovery after 3 months, increasing to 44% after 12 months. A history of knee complaints, a longer duration of the current episode of knee complaints, other coexisting musculoskeletal complaints, and a higher level of distress were associated with a worse prognosis. In the linear regression models, 41-53% of the variance in pain reduction and improvement in functioning could be explained by the predictors. The area under the receiver operating characteristic curves, estimating the predictive accuracy of the Cox regression models concerning perceived recovery, was 0.77 after 3 months and 0.72 after 12 months. CONCLUSION: Many patients did not recover after 12 months. Distress was found to be strongly associated with less pain reduction and less improvement in functioning.

Cohort Studies↗
PubMed1986

Increase of circulating beta-endorphin-like immunoreactivity correlates with the change in feeling of pleasantness after running.

Twenty-one male regular long distance runners participated in two 10 km runs one week apart. Their beta-endorphin-like immunoreactivity (beta-EIR) was assayed in plasma before and immediately after running. Mood was monitored by an adjective check list (Eigenschaftswörterliste, EWL) pre- and post-run. beta-EIR was significantly elevated post-run. Self-reliance and good mood scored higher after running. Both mood elevation and plasma beta-EIR increase showed a considerable individual variability but there was a significant correlation in the mean values of the two runs between individual beta-EIR increases (delta beta-EIR) and the changes of ratings in feeling of pleasantness (delta FP). High delta beta-EIR corresponded to positive mood change post-run.

Adult↗
PubMed2006

Pneumocystis pneumonia revisited: delayed diagnosis in an HIV infected individual with high blood and low lung CD4 T cell counts.

The peripheral blood CD4 count is a useful marker of immunological status in HIV infection. However, it makes up only 1% of total body CD4 cells [Parslow T. Lymphocytes and lymphoid tissue. In: Stites D, Terr A, Parslow D, editors. Basic and clinical immunology. Appleton and Lange; 1994. p. 22-40.] has a wide intra- and inter-individual variability [Turner BJ, Hecht FM, Ismail RB. CD4+ T-lymphocyte measures in the treatment of individuals infected with human immunodeficiency virus type 1. A review for clinical practitioners. Arch Intern Med 1994;154:1561-73.] and CD4 cell pathology is just one of the immune defects caused by HIV [Fauci S. Multifactorial nature of human immunodeficiency virus disease. Science 1993;262:1011-8.]. Thus a given value should always be interpreted within a specific clinical context. We describe an individual with Pneumocystis pneumonia (PCP) who was reviewed by HIV medical services several times before the correct diagnosis was made. On each occasion the possibility of PCP was discounted as he had a well-preserved blood CD4 count. Subsequent examination of his pulmonary T-lymphocyte subsets revealed marked CD4 lymphopenia.

AIDS-Related Opportunistic Infections↗
PubMed2004

Self-injurious behaviour: a comparison of caffeine and pemoline models in rats.

Self-injurious behaviour (SIB) is a debilitating behaviour disorder that can have life-threatening consequences. It is often exhibited in intellectually handicapped and autistic populations, and it has been modeled with pharmacological manipulations in animals. We have characterized the induction of SIB using high doses of caffeine and pemoline in rats. Caffeine only produced very mild SIB in a small proportion of the rats, when administered repeatedly at very high doses (140-185 mg/kg/day). All the caffeine-treated rats showed profound signs of caffeine-toxicity at these doses, and lower doses did not induce any self-injury. On the other hand, pemoline was effective across a range of doses (100-300 mg/kg/day), including doses that did not produce overt signs of toxicity (100-200 mg/kg/day). The topography of the tissue injury sites (tail vs. paws and ventrum) differed between caffeine and pemoline treatments, and across doses of pemoline. The speed of onset, the incidence, and the severity of SIB occurred in a dose-orderly manner across the pemoline doses, and there was substantial individual variability in the induction of SIB when a moderately high dose (200 mg/kg/day) was used. These individual differences in vulnerability to self-injure are reminiscent of the fact that some humans with specific neurobiological disorders express SIB and some individuals with those same disorders do not. Accordingly, the pemoline model of SIB may be useful to investigate the neurobiological basis of factors that contribute to etiology of SIB.

Adrenocorticotropic Hormone↗
PubMed2001

Simultaneous validation of ten physical activity questionnaires in older men: a doubly labeled water study.

OBJECTIVE: The purpose of this study was to simultaneously validate 10 physical activity (PA) questionnaires in a homogenous population of healthy elderly men against the reference method: doubly labeled water (DLW). DESIGN: Cross-sectional study. SETTING: Community-based sample from Lyon, France. PARTICIPANTS: Nineteen healthy old men (age 73.4 +/- 4.1 years), recruited from various associations for elderly people in Lyon, agreed to participate in the study. MEASUREMENTS: The questionnaire-derived measures (scores) were compared with two validation measures: DLW and maximal oxygen uptake (VO2max). With the DLW method three parameters were calculated: (1) total energy expenditure (TEE), (2) physical activity level (PAL), i.e., the ratio of TEE to resting metabolic rate, (3) energy expenditure of PA. RESULTS: Relative validity. Correlation between the questionnaires and TEE ranged from 0.11 for the Yale Physical Activity Survey (YPAS) total index to 0.63 for the Stanford usual activity questionnaire. This questionnaire also gave the best correlation coefficients with PAL (0.75), and with VO2max (0.62). Significant results with TEE measured by the DLW method were also obtained for college alumni sports score, Seven Day Recall moderate activity, and Questionnaire d'Activité Physique Saint-Etienne sports activity (r = 0.54, r = 0.52, and r = 0.54, respectively). Absolute validity. No difference was found between PA measured by the Seven Day Recall or by the YPAS and DLW, on a group basis. The limits of agreement were wide for all the questionnaires. CONCLUSIONS: Only a few questionnaires demonstrated a reasonable degree of reliability and could be used to rank healthy older men according to PA. Correlation coefficients were best when the Stanford Usual Activity Questionnaire was compared with all the validation measures. The two questionnaires reporting recent PA, the Seven Day Recall, and YPAS accurately assessed energy expenditure for the group. The individual variability was high for all the questionnaires, suggesting that their use as a proxy measure of individual energy expenditure may be limited.

Activities of Daily Living↗
PubMed2005

Association of Vitamin K epoxide reductase complex 1 (VKORC1) variants with warfarin dose in a Hong Kong Chinese patient population.

OBJECTIVE: To evaluate the association of VKORC1 genetic variants with warfarin dose requirements in a Hong Kong Chinese patient population. METHODS: A retrospective study of Hong Kong Chinese patients chronically maintained on warfarin was conducted. Single nucleotide polymorphisms (SNPs) in VKORC1 and CYP2C9 were genotyped. Stable warfarin dose data were retrieved from patient medical records. RESULTS: Sixty-nine patients were included in the analysis. VKORC1 haplotypes H1 (group A) and H7 (group B) were most common, accounting for 86% and 13% of all haplotypic variation in this cohort. Patients carrying at least one copy of a VKORC1 group B haplotype (n = 16) required a significantly higher stable warfarin dose (5.17+/-1.53 mg/day) than patients that were homozygous for group A haplotypes (n = 53; 2.93+/-1.22 mg; P < 0.001). In the VKORC1 A/A group, four patients (5.8%) were heterozygous for CYP2C9*3 and had a lower dose requirement (1.94+/-0.43 mg) than patients that exhibited the CYP2C9 *1/*1 genotype (3.01+/-1.23 mg), P = 0.004. In multivariate analysis, VKORC1 and CYP2C9 explained 31% and 7.9% of the variability in warfarin dose, respectively. CONCLUSIONS: VKORC1 genotype is the dominant genetic influence on inter-individual variability in warfarin dose in Hong Kong Chinese. The lower mean dose of warfarin in Chinese, relative to Europeans, appears to be a reflection of their preponderance of the 'low-dose' VKORC1 H1/H1 (homozygous group A) genotype.

Anticoagulants↗
PubMed1977

Absorption and endogenous faecal excretion of calcium by low birthweight infants on feeds with varying contents of calcium and phosphate.

Low birthweight infants aged 4-41 days were given from birth one of three experimental milk formulae varying widely in content of calcium and phosphate. Ca and P in feed, urine, and faeces were measured between carmine markers corresponding to a metabolic period of 48 hours. Calcium enriched in 46Ca to provide a marker for the dietary Ca was added to one feed and 46Ca measured in urine and faeces. True absorption of Ca and endogenous excretion into the bowel could then be inferred. True absorption of Ca was proportional to Ca intake and independent of P intake. Endogenous faecal excretion seemed to be independent of both Ca P intakes, and varied widely between different infants in the range 4-150 mg/day. Urine Ca was low and retention was essentially the difference between true absorption and endogenous faecal excretion. Retention of Ca tended to be much greater on a high Ca intake, but the variability in retention between infants on a given intake was large, paralleling the variability in endogenous faecal excretion. The variability in plasma Ca concentrations in newborn infants may in part be a consequence of wide individual variability in endogenous faecal excretion. The 46Ca marker technique provides a means of investigating the factors determining this variability.

Calcium↗
PubMed1985

Effect of small doses of aspirin and acetaminophen on total menstrual loss and pain of cramps and headache.

90 women participated in a 4-month study. During the first 2 periods, they took no pain relievers whatsoever; during their last 2 periods they took 2 X 325 mg aspirin, acetaminophen or an identically packaged placebo every 4 h to total 8 tablets during the first 24 h of their periods beginning with spotting. For statistical analysis, periods 1 and 2 were combined and averaged, then compared with periods 3 and 4 combined and averaged. Total menstrual loss in grams, number of days of flow, and pain of cramps and headaches were analyzed by MANOVA for each of the three treatment groups. An ANOVA for each of these variables as well as for daily menstrual loss for the first 3 menstrual days was also performed. The MANOVA for all variables by the three treatment groups failed to show any significant differences. Similarly, ANOVAs for the individual variables failed to indicate significant differences except for the variable pain of cramps (p = 0.0072). The Duncan's Multiple Range Test for pain of cramps showed that the average pain for the placebo group was higher than for either the aspirin or the acetaminophen group, although the means for these two groups were not significantly different. These results indicate that neither aspirin nor acetaminophen in the doses given alter either total menstrual loss or the pattern of loss during the first 3 menstrual days. However, both preparations were found to be more effective than placebo in reducing pain of cramps.

Acetaminophen↗
PubMed1981

An ergo-ophthalmological battery of tests to classify truck drivers.

16 healthy and ophthalmologically normal truck drivers are tested with a battery of tests according to the routine described in the following paper. This includes isopter perimetry, colour discrimination, recovery of sensitivity during dark adaptation and refraction at both far and near points, in order to record night myopia as well as night presbyopia. The ranges of individual variability are reported. As far as refraction is concerned, it seems of interest to stress the individual differences in a sort of "transient anisometropia" under incoming twilight.

Accidents, Traffic↗
PubMed2006

Weight-adjusted genome scan analysis for mapping quantitative trait Loci for menarchal age.

CONTEXT: Twin and family studies indicate that genetic factors contribute to the variability of age at menarche (AAM), a multifactorial trait of major importance to human reproductive success. Individual variability of premenarcheal fatness is known to be an important determinant of AAM. OBJECTIVE: The objective of the study was mapping quantitative trait loci (QTLs) for AAM. DESIGN AND METHODS: AAM was assessed in 98 sister pairs of recent European ancestry whose growth charts were available. There was a negative correlation between menarcheal body weight sd score (SDS) and AAM (r = 0.47, P < 0.0001). We designed a genome scan approach and used the variance components model implemented in Merlin for quantitative traits to evaluate linkage of AAM and AAM adjusted for menarcheal weight SDS to 418 genome-wide microsatellites. RESULTS: Multipoint linkage analysis for AAM revealed nominal QTLs defined by LOD scores between 1.06 and 1.69 on chromosomes 1p, 1q, 7p, 8q, 16p, 19q, and 20q. The genome scan for AAM adjusted for menarcheal weight SDS revealed several QTLs with strongly suggestive LOD scores in 16q21 (LOD = 3.33), 16q12 (LOD = 3.12), and 8p12 (LOD = 2.18) and a number of other nominally significant QTLs yet viewed as hypothetical. CONCLUSIONS: We found several regions that may contain determinants of AAM, but there is still a long series of steps to confirm these QTLs and identify the genomic polymorphisms implicated in AAM variability.

Age Factors↗
PubMed1995

Trough-to-peak versus surface ratio in the assessment of antihypertensive agents. APTH Investigators. Ambulatory Blood Pressure and Treatment of Hypertension.

This study investigated whether the 'surface ratio', a novel index to characterize long-acting antihypertensive agents, would provide a more reproducible estimate of the duration of the antihypertensive effect than the more commonly used trough-to-peak ratio. In 66 hypertensive patients (diastolic pressure on conventional measurement > 95 mmHg), the ambulatory blood pressure was measured on a placebo at baseline and 2 months later, while the patients took 10 mg lisinopril once a day between 7 p.m. and 11 p.m. Diurnal treatment effect curves were obtained by subtracting the blood pressure at baseline from the corresponding value at 2 months for all time intervals considered in the analysis. In order to calculate the surface ratio, the area under the treatment effect curve was divided by the product of the maximal blood pressure lowering effect and the dosing interval (24 h). Reproducibility of the trough-to-peak and surface ratios was investigated by the Bland and Altman techniques. At 2 months, lisinopril reduced (+/- standard deviation) the 24 h pressure by 13 +/- 16 mmHg systolic and by 8 +/- 8 mmHg diastolic (p < 0.001). According to the usual approach, disregarding inter-individual variability, the trough-to-peak ratio was 0.7 for systolic and diastolic pressure. When in individual patients diurnal treatment effects curves with a 1 h resolution were investigated, the median trough-to-peak ratio was 0.30 for systolic pressure (5th-95th percentile interval [PI]: -0.51, 0.82) and 0.28 for diastolic pressure (PI: -0.37, 0.78); the corresponding values for the surface ratio were 0.33 (PI: 0.03, 0.58) and 0.30 (PI: -0.01, 0.55). In the same manner, the trough-to-peak ratios and surface ratios became larger when the individual blood pressure profiles were progressively smoothed by substituting 1 h averages by 2 h moving averages, 2 h averages, 3 h moving averages or by 3 h averages. The distributions of the trough-to-peak ratios and surface ratios were non-normal in 37 of 40 instances (p < 0.001, Shapiro-Wilk's test). Consistency was higher (p < 0.001) for the surface than for the trough-to-peak ratios. The within-subject reproducibility of the surface ratios tended to be superior to that of the corresponding trough-to-peak ratios. In conclusion, the surface ratio provides an index of the duration of action of antihypertensive agents. Moreover, in the present patients, the surface ratio tended to be characterized by a higher within-subject reproducibility than the trough-to-peak ratio.

Adult↗
PubMed1992

Once-a-day dosing with theophylline: a comparison of four sustained-release products.

This study compared once-a-day dosing of Slo-bid, Theo-Dur, Theo-24 and Uniphyl, sustained release theophylline preparations, in the treatment of 12 mild to moderate asthmatic patients (FEV1 greater than 60%). Eight hundred milligrams was given once-a-day in the morning for 2 weeks for each drug in this 4-way, crossover, open-label study. At the end of each 2-week period, pharmacokinetics were assessed by measuring theophylline levels every two hours for 24 hours. Efficacy was evaluated by spirometry, physical examination, daily peak flow measurements, and daily symptom diaries. In an additional 2-week period, Slo-bid 800 mg, was taken once-a-day after the evening meal and the same measures of pharmacokinetics and efficacy were performed. Slo-bid (range 8.8, coefficient variation 19.5) exhibited significantly less intrapatient variability than Theo-Dur (range 12.2, coefficient of variation 36.5) and Theo-24 (range 8.2, coefficient of variation 25.8). Patients taking Slo-bid also had significantly better evening peak flow values than patients taking Theo-Dur (424.5 L/min versus 395.4 L/min). Analysis of other measures of theophylline pharmacokinetics (area under the curve, minimum serum level, occupancy times) as well as diary variables, physical examination findings, and spirometry values showed no differences among the four formulations, although expected individual variability in pharmacokinetics was observed. When Slo-bid was dosed in the evening, higher blood levels were achieved compared with morning administration, suggesting a therapeutic advantage of evening dosing with this product.

Adolescent↗
PubMed2003

Hypervariability of the membrane-associated mucin and cancer marker MUC1.

The highly heterogeneous epithelial mucins show considerable inter-individual variability attributable to allelic variations in their tandem repeat (TR) peptide domains. Most mucins are known to show variations in repeat number but variation in the sequence of the individual TRs is not as well characterised. Here, we have studied variation in the immunodominant PDTR motif in the TR domain of the membrane-associated "cancer" mucin MUC1 by using the Minisatellite Variant Repeat-Polymerase chain reaction (MVR-PCR) technique. We have fully or partially mapped two nucleotide changes that encode two amino-acid changes, PDTR to PESR, across the arrays of 149 alleles. A total of 103 different maps was obtained when these changes alone were considered and additional variations were also observed. Most maps showed blocks of PDTR repeats interspersed with PESR repeats, although these were possibly more irregular in the longer alleles that also tended to have more PESR repeats. This variability has potential functional consequences and possible implications for some individuals with respect to the efficacy of immune targetting and immune therapy.

Amino Acid Sequence↗
PubMed1991

Application of automatic image analysis (IBAS system) to age calculation. Efficiency in the analysis of several teeth from a single subject.

In a previous paper (M. López-Nicolás et al., Forensic Sci. Int., 45 (1990) 143-150) we obtained a model of multiple regression to estimate age using computerized image analysis (IBAS) to study teeth. This method should provide more precise measurements of the parameters involved and to test this hypothesis we have carried out a blind study using more than one tooth from the same individual in order to check the diagnostic accuracy of the method. Our results show that individual variability introduced serious errors in tooth age estimation using computerized image analysis. However the study of more than one tooth per individual improves the accuracy of age estimation. Specific cases should therefore be interpreted cautiously, as a degree of variability can be expected using the parameters defined in this method.

Adult↗
PubMed1999

Variability of stereotypic body-rocking in adults with mental retardation.

The variability of stereotypic body-rocking motions of adults with severe and profound mental retardation not on medication was examined through a kinematic analysis. A matched nonretarded group of adults was also examined in the production of preferred rates of body-rocking. The inter- and intra-individual variability of the body-rocking motions was, on average, higher for the individuals with mental retardation, although a few participants showed as low a variability as the least variable participants in the nonretarded group. These findings provide further evidence that the kinematic variability of stereotypies is not lower than that displayed by others engaged in similar movement activities and support the proposition that low variability of discrete kinematic variables may not be a defining feature of stereotypy.

Adult↗
PubMed1996

Dose-rate sparing for micronucleus induction in lymphocytes of controls and ataxia-telangiectasia heterozygotes exposed to 60Co gamma-irradiation in vitro.

We investigated the reproducibility of the cytochalasin B micronucleus (MN) assay in irradiated human lymphocytes to assess its suitability in predicting cancer predisposition and response to radiotherapy by virtue of defects in the processing of clastogenic lesions. G0 lymphocytes were exposed to 3.0 Gy 60Co gamma-rays at high (HDR) or low dose-rate (LDR). Six healthy donors were assayed three times each in nine experiments and compared with six ataxia-telangiectasia (A-T) heterozygotes. In controls, significant interexperiment variability in MN yields was observed at HDR and LDR, also in dose-rate sparing (i.e. reduction in MN yield at LDR compared with HDR). Significant inter-individual variability was seen at HDR, but not at LDR or for sparing. Average sparing was 66.4 +/- 4.8%. In spite of the experimental variability, a significant difference between controls and A-T heterozygotes was detected at LDR, and 5/6 heterozygotes had sparing values below the control range. This gives encouragement for the use of this assay in predictive testing if sources of experimental variability can be identified so as to improve discrimination between individuals. HDR and to a lesser extent LDR irradiation induced significant mitotic inhibition, seen as a reduction in binucleate cells after cytocholasin treatment. A positive correlation between mitotic inhibition and MN frequency suggests that similar lesions may be involved in these effects.

Adult↗
PubMed2000

Major strain differences in response to chronic systemic administration of the mitochondrial toxin 3-nitropropionic acid in rats: implications for neuroprotection studies.

Chronic systemic treatment with 3-nitropropionic acid in rats produces persistent dystonia and bradykinesia, and striatal lesions reminiscent of Huntington's disease. However, the interpretation of results obtained with this model are complicated by a heterogeneous distribution of the response to a given toxic dose of 3-nitropropionic acid: approximately half of the animals develop selective striatal lesions, which in certain cases are associated with extrastriatal lesions, and the other half are apparently spared. Thus, the chronic 3-nitropropionic acid lesion model can be difficult for neuroprotection studies in which a consistent response to neurotoxic treatment is prerequisite. We hypothesized that some of the variability in the model was related to the use of Sprague-Dawley rats, since inter-individual variability in response to various stressful conditions has been described previously in this rat strain. We therefore compared 3-nitropropionic acid toxicity in rat strains known to be highly (Fisher 344) or poorly (Lewis) responsive to stress and compared the distribution of responses to that of Sprague-Dawley rats. In a protocol of intraperitoneal injection, toxicity of 3-nitropropionic acid was highest in Fisher rats, intermediate in Sprague-Dawley rats and lowest in Lewis rats. In addition, survival curves showed a more heterogeneous response to 3-nitropropionic acid toxicity in Sprague-Dawley rats than that observed in Lewis and Fisher rats. These differences between Sprague-Dawley and Lewis rats were confirmed in a protocol of subcutaneous 3-nitropropionic acid intoxication using osmotic minipumps, where doses up to 36-45mg/kg per day for five days were necessary to induce striatal lesions in Lewis rats as compared to 12-14mg/kg per day for five days in Sprague-Dawley rats. The selectivity of the striatum to lesions, and homogeneous progression of symptoms and neurodegeneration, were more consistently observed in Lewis as compared to Sprague-Dawley rats. These results suggest that vulnerability to 3-nitropropionic acid may depend on genetic factors, which could also influence the physiological response to stress. The present findings also establish an improved model of progressive striatal degeneration in the rat adapted for the testing of new neuroprotective strategies.

Animals↗
PubMed1998

Risk assessment in cervical dysplasia patients by single cell gel electrophoresis assay: a study of DNA damage and repair.

Precancerous lesions of cervix, commonly known as dysplasia, present a complex problem because of their biological behavior. Increased genetic instability, either inherent or induced by some external mutagen, is considered as a primary event or a predisposing factor to neoplastic transformation. The relationship between genetic instability and susceptibility towards cervical cancer was evaluated with the comet or single cell gel electrophoresis (SCGE) assay. Among precancerous individuals, genomic instability was observed in cervical epithelial cells and peripheral blood leukocytes. The mean basal DNA damage and mean susceptibility to DNA damage by the mutagen (MNNG) treatment increased whereas repair capacity decreased with progression of the disease in a stepwise manner. Inter and intra individual variability was maximum in cancerous group. Risk was estimated by giving a predictive value for each precancerous individual. In combination with morphological, biochemical, and cytogenetic parameters, the SCGE assay may serve as a novel tool to predict the fate of cervical dysplasia.

Adolescent↗