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Development of a physiologically based pharmacokinetic model of isopropanol and its metabolite acetone.

A physiologically based pharmacokinetic (PBPK) model for isopropanol (IPA) and its major metabolite, acetone, is described. The structure of the parent chemical model, which can be used for either IPA or acetone by choosing the appropriate chemical-specific parameters, is similar to previously published models of volatile organic chemicals such as styrene. However, in order to properly simulate data on the exhalation of IPA and acetone during inhalation exposures, it was necessary to expand the description of the lung compartment to include a subcompartment for the upper respiratory tract mucus layer. This elaboration is consistent with published PBPK models of other water-soluble vapors in which the mucus layer serves to absorb the chemical during inhalation and then release it during exhalation. In the case of IPA exposure, a similar PBPK structure is used to describe the kinetics of the acetone produced from the metabolism of IPA. The resulting model is able to provide a coherent description of IPA and acetone kinetics in the rat and human for exposures to IPA by several routes: intravenous, intraperitoneal, oral, inhalation, and dermal. It is also able to consistently reproduce kinetic data for exposures of rats or humans to acetone. Thus, the model provides a validated framework for performing chemical-specific route-to-route extrapolation and cross-species dosimetry, which can be used in place of generic default calculations in support of risk assessments for IPA and acetone.

2-Propanol↗

Evolving connectionist system versus algebraic formulas for prediction of renal function from serum creatinine.

BACKGROUND: In clinical trials, equation 7 from the Modification of Diet in Renal Disease (MDRD) Study is the most accurate formula for the prediction of glomerular filtration rate (GFR) from serum creatinine. An alternative approach has been developed using evolving connectionist systems (ECOS), which are novel computing structures that can be trained to generate accurate output from a given set of input variables. This study aims to compare the prediction errors associated with each method, using data that reproduce routine clinical practice as opposed to the artificial setting of clinical trials. METHODS: The methods were compared using 441 radioisotope measurements of GFR in 178 chronic kidney disease patients from 12 centers in Australia and New Zealand. All clinical and laboratory measurements were obtained from the patients' center rather than central laboratories, as would be the case in routine clinical practice. Both the MDRD formula and ECOS used the same predictive variables, and both were optimized to the study cohort by stepwise regression and training, respectively. RESULTS: Mean measured GFR in the cohort was 22.6 mL/min/1.73 m(2). The bias and precision of the MDRD formula were -3.5 mL/min/1.73 m(2) and 34.5%, respectively, improving to -1.2 mL/min/1.73 m(2) and 31.1% after maximal optimization of the formula to study data. The bias and precision of the ECOS were 0.7 mL/min/1.73 m(2) and 32.6%, respectively, improving to -0.1 mL/min/1.73 m(2) and 16.6% after maximal optimization of the system to study data. The prediction of GFR using ECOS was improved by accounting for the center from where clinical and laboratory measurements originated within the connectionist model. CONCLUSION: Algebraic formulas will be associated with greater prediction error in routine clinical practice than in the original trials, and machine intelligence is more likely to predict GFR accurately in this setting.

Adult↗

[Modern typology of symptoms and obsessive-compulsive syndromes: results of a large French study of 615 patients].

OBJECTIVES: The most common strategy to search for homogenous subgroups of Obsessive-Compulsive Disorder (OCD) patients has been based on the OCD symptoms themselves as a classifying variables. The purpose of this study was to: expand recognition of major clinical OCD subtypes in a large cohort of patients recruited from the national french survey: "Screening-Understanding-Treating OCD"; reproduce preliminary data coming from a US collaborative study on OCD sub-types [Baer L, J Clin Psychiatry, 1994; 55 (3):18-23]. METHOD: From 731 OCD/OCS (OC disorder or syndromes) patients recruited in the phase 1 of the national french survey, complete collected data on the Y-BOCS Symptom Checklist (YBOCS-CL) were obtained in 615 patients and on the OCD spectrum inventory in 646 patients. Principal components analysis (PCA) was firstly applied on major symptom categories of the YBOCS-CL, and next on each individual symptom. Gender effect on clinical aspects of OCD was also explored by comparative descriptive analysis. RESULTS: The first PCA on major symptoms categories confirmed the grouping of all categories in three major factors, named as following: Facteur 1 = "Predominantly Compulsive" (loaded with items of symmetry, order, hoarding, repeting, counting, checking); Facteur 2 = "Predominantly Obsessive" (loaded with aggression, violent, religious, sexual obsessions) and Facteur 3 = "Mixed" (with contamination and somatic obsessions and washing compulsions). Our data seemed to be very close to US collaborative study that had found in a sample of 107 OCD patients, the presence of the same three major clinical factors. The second PCA applied on all YBOCS-CL individual items had provided interesting items groupings, suggesting a reorganization and re-labelling of YBOCS-CL symptoms categories. Therefore, a new presentation of the YBOCS-CL can be proposed with a more clinical relevance than the original version. Results from OC spectrum inventory showed high comorbidity rate with many of OCD related disorders. Finally, a gender influence on OC clinical manifestations was observed, especially more severity and higher rate of difficult OC-subtypes in male patients. The french national survey data on OC symptoms sub-typing and clustering showed a "natural" groupings of OC symptom categories which add more validity to the subtypes proposed by ICD-10 (based on syndromal predominance : obsessions, compulsions or mixed). These sub-categories are not part of the DSM III-R, neither of the new version of DSM IV!

Adult↗

Comparison of two instruments for quantifying intake of vitamin and mineral supplements: a brief questionnaire versus three 24-hour recalls.

Although methods of collecting food intake data have been studied intensively, there have been fewer investigations into the collection of supplement intake data. Use of eight types of vitamin and mineral supplements was reported between 1994 and 1997 by 2,377 subjects participating in a calibration substudy of the Hawaii-Los Angeles Multiethnic Cohort Study. Subjects gave information on supplement use as part of a dietary questionnaire (administered twice) and during three 24-hour dietary recalls. Multivitamins were the most commonly used supplements (55% of the subjects), followed by vitamin C (40%), vitamin E (33%), and calcium (29%). Vitamin A, beta-carotene, selenium, and iron supplements were each used by fewer than 10% of the subjects. Weighted kappa statistics for agreement between the recalls and the questionnaire across six categories of frequency of use ranged from 0.74 for vitamin E to 0.16 for vitamin A and were generally higher for frequently used supplements. The reproducibility of questionnaire responses at two time points varied from 0.64 to 0.39. In comparison with three recalls, a brief questionnaire can accurately and reproducibly capture data on supplement use for frequently consumed products, but it may perform less well for products used less often or more intermittently.

Aged↗

Adenosine-induced coronary vasodilation during transesophageal Doppler echocardiography. Rapid and safe measurement of coronary flow reserve ratio can predict significant left anterior descending coronary stenosis.

BACKGROUND: Less invasive methods are replacing traditional invasive means of measuring coronary flow reserve (CFR). Transesophageal echocardiography (TEE) is becoming a useful tool for evaluation of coronary artery disease and has recently been used to measure CFR. This has always been done using dipyridamole, but adenosine has a greater vasodilator potency and more favorable kinetics than dipyridamole. This study was done to evaluate the hypothesis that adenosine is safe, rapid, and accurate in measuring coronary blood flow reserve by TEE Doppler. METHODS AND RESULTS: Forty-nine patients who had recently undergone angiography had a transesophageal echocardiogram with visualization of the coronary arteries and measurement of blood flow velocity in the left anterior descending coronary artery (LAD) during adenosine infusion of 0.14 mg/kg per minute. Angiograms were analyzed by quantitative coronary angiography, and significant stenosis was defined as > 70% lumenal diameter narrowing. Thirty-nine of the 49 patients did not have a significant LAD stenosis (group 1); the remainder had significant disease (group 2). Good spectral Doppler recordings of blood flow velocity in the LAD were obtained in 41 of 46 patients (89%). There were no significant differences in baseline coronary blood flow velocities between the two groups. Hyperemic to baseline flow ratios were significantly higher in patients without significant LAD stenosis for peak (2.83 +/- 1.04 versus 1.78 +/- 0.36) and mean (2.68 +/- 0.96 versus 1.75 +/- 0.39) diastolic velocity. A CFR ratio > 2.1 had a sensitivity of 86%, a specificity of 79%, a positive predictive value of 46%, and a negative predictive value of 96% for the absence of critical LAD stenosis. The infusion was well tolerated. It had to be prematurely terminated in only 3 patients (6.5%), and they were asymptomatic. No patient experienced chest pain, palpitations, or flushing. Intraobserver and interobserver variabilities were low, and reproducibility of data was good (< 4%). CONCLUSIONS: Adenosine Doppler TEE is an effective, rapid, safe, and superior means of measuring CFR ratio. This method is convenient for serial measurements of CFR as well as in clinical settings such as evaluation of syndrome X, cardiomyopathy, and aortic regurgitation.

Adenosine↗

Host enzymes in gingival crevicular fluid as diagnostic indicators of periodontitis.

Host responses to periodontal infections include the production of several families of enzymes that are released by stromal, epithelial or inflammatory cells. Study of these enzymes in gingival crevicular fluid may lead to insights into pathogenesis and may provide a rational basis for the development of novel diagnostic tests. However, analogous to other diagnostic interventions in dentistry and medicine, validation of host enzymes as diagnostic indicators is dependent on clear-cut demonstrations of the identity of the enzyme, reproducibility, diagnostic accuracy and clinical utility. The enzyme of interest should be readily measured over a broad range of disease severity and in varied clinical settings. Ideally, the enzyme should also be an essential component of proposed pathogenic mechanisms. In this context, the connective tissue matrix degrading enzymes elastase, collagenase and gelatinase are promising because of their apparently central role in periodontal attachment loss and disease progression. Sensitive and specific assays are also available to quantify these enzymes. Other work on enzymes associated with cell death (aspartate aminotransferase, lactate dehydrogenase) and several neutrophil lysosomal enzymes (beta glucuronidase, arylsulphatase, cathepsins) has demonstrated positive associations between enzyme levels and attachment loss and inflammation. While numerous cross-sectional studies have indicated that the levels of hydrolytic enzymes in gingival crevicular fluid parallel the severity of periodontal lesions, there are much less data on reproducibility, diagnostic accuracy and clinical utility in longitudinal studies. As appropriate study design is an essential prerequisite for establishing the efficacy of host enzymes as diagnostic tests, future clinical investigations should include: (1) individuals who would most likely benefit by early diagnosis, i.e., rapidly progressive and recurrent periodontitis cases; (2) longitudinal, cohort study designs to show that attachment loss is temporally linked with large increases in enzyme activity; (3) the use of a battery of tests to overcome intrinsic problems of low predictive values when prevalence of active disease is low. In the final analysis, the utility of host enzymes as diagnostic indicators will need to be examined in randomized controlled trials in which the question is asked: are patients better off as a result of testing?

Esterases↗

[Clinical application of left ventricular volume and ejection fraction derived from gated SPECT data].

Left ventricular (LV) volume and ejection fraction (LVEF) derived from ECG-gated myocardial SPECT data are reproducible and objective. Those quantitative values, however, interacted according to varied factors such as a frame number per R-R interval, tracers, and processing-algorisms. A decrease of frame number per R-R interval yields underestimation of end-diastolic volume and overestimation of end-systolic volume, resulting in underestimation of LVEF. Thus, it is important to change a frame number per R-R interval by the examination purpose. A good correlation of LVEF is usually obtained, independent of a combination of tracer and processing-algorism. On the other hand, LV volume does not always show linearity between combinations of tracer and processing-algorism. An extraction of myocardial edge using QGS program is deteriorating in patients with small LV below 20 ml. It is crucial to assess LV functional values derived from ECG-gated SPECT data as clinical indices, taking the varied effects into consideration.

Algorithms↗

[Effects of digital rectal examination on serum prostate specific antigen].

OBJECTIVE: Prostate specific antigen (PSA) level is determined under precise conditions for the detection and follow-up of cancer of the prostate. The question is raised as to whether digital rectal examination has an effect on serum levels and whether an interval of time is required before PSA assay can give reliable results. METHODS: A prospective protocol was conducted for 6 months. PSA was assayed in 56 patients hospitalized in an internal medicine ward whose clinical status justified digital rectal examination. Blood samples were taken 2 to 3 hours before the digital rectal examination, performed by the same physician in all cases, then 21 to 22 hours after the examination. RESULTS: After digital rectal examination, there was a nearly significant increase in PSA level (p = 0.06), an increase which was clinically unimportant (0.25 ng/ml). The levels before and after rectal examination were perfectly correlated and reproducible. These data confirmed those reported in the literature showing marginally significant increases of little or no clinical importance, usually within 2 hours of the examination. CONCLUSION: The interval of time between the two assays in our study indicates that in everyday clinical practice, for both inpatients and outpatients, digital rectal examination has no effect on prostate specific antigen and that subsequently there is no need to delay assay.

Adult↗

[Sickle cell anemia: experience in a center].

BACKGROUND: Sickle cell anemia is a structural hemoglobinopathy in which morphological and physical changes in erythrocytes cause vaso-occlusive episodes in various organs and tissues. The disease is common among blacks and the African population. As a result of the growing migratory flow, this is an emerging disease in Spain. OBJECTIVE: To present the casuistics of a pediatric hospital: clinical onset, the most frequent features and complications, and treatment. MATERIAL AND METHODS: We performed a retrospective study of 22 patients aged less than 18 years old diagnosed with sickle cell anemia between January 1985 and December 2001. Epidemiologic data, symptoms, complications, blood test results, treatment, and response were recorded. RESULTS: The mean age of the patients was 39 months. In 54 %, diagnosis was established before the age of 2 years. No differences were found in sex. The countries of origin were Gambia in 32 %, Morocco in 23 %, and Senegal in 18 % as well as other African and Central America countries; 53 % of the children were born in Spain. The most common complaint was vaso-occlusive pain localized in the abdomen (45 %). The most frequent complications were infections and 13.7 % suffered stroke. Twenty-eight percent of the patients diagnosed before the age of 2 years presented complications. Eleven patients received hydroxyurea for recurrent vaso-occlusive crises with favorable results; one patient underwent splenectomy and another received an allogenic bone marrow transplant from an HLA-identical brother with excellent results. CONCLUSIONS: This study reproduces the data described in the literature from countries with a high prevalence of the disease. Morbidity could be minimized by early diagnosis and preventive treatment and good healthcare. Given the increasing incidence of the disease, screening of black and African neonates and genetic counseling are recommended together with guidelines for prompt and appropriate treatment in primary health centers and emergency departments.

Adolescent↗

Frequency-selective adaptation: evidence for channels in the vestibulo-ocular reflex?

The vestibulo-ocular reflex (VOR) is under long-term adaptive regulation to minimize retinal image slip during head movement; normally this process keeps VOR gain (eye velocity divided by head velocity) near 1.0. It has been common to think of the adaptive mechanism as a single pure gain element, although some properties of the system (e.g., frequency-selective changes in the gain of the VOR) argue that it must be more complex. We now report new observations on the frequency selectivity of the adaptive mechanism. Our data suggest a new model in which the VOR operates as a series of parallel, temporal frequency channels, each of which has an independently adjustable gain element. Adaptive changes were produced by oscillating monkeys sinusoidally at a single temporal frequency (0.2 or 2.0 Hz) in visual conditions that cause either increases (toward two) or decreases (toward zero) in VOR gain. When tested in darkness at the adapting frequency, the VOR showed large changes in gain and little or no change in phase. When tested at frequencies other than the adapting frequency, the VOR showed less pronounced changes in gain and unexpected changes in phase. The phase changes were orderly but depended in a complex way on adapting frequency, testing frequency, and VOR gain. We have tested the channels concept by calculating the response properties of a mathematical model that processed its inputs in parallel pathways. The model reproduced our data when we assumed that the vestibular primary afferents were distributed in an orderly way to parallel brain channels that had differing dynamics: vestibular inputs with more phase lead projected to higher frequency channels, which themselves had faster dynamics than their low frequency counterparts. Such an organization, when regulated by an adaptive controller that can selectively alter the gain of one channel, could play a key role in establishing and maintaining the frequency-independent performance seen in the adult VOR.

Adaptation, Physiological↗

Psychometric properties of the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25), Japanese version.

BACKGROUND: The importance of evaluating the outcomes of health care from the standpoint of the patient is now widely recognized. The purpose of this study is to develop and test a Japanese version of the National Eye Institute Visual Function Questionnaire (NEI VFQ-25). METHODS: A Japanese version was developed with a previously standardized method. The questionnaire and optional items were completed by 245 patients with cataracts, glaucoma, or age-related macular degeneration, by 110 others before and after cataract surgery, and by a reference group (n = 31). We computed rates of missing data, measured reproducibility and internal consistency reliability, and tested for convergent and discriminant validity, concurrent validity, known-groups validity, factor structure, and responsiveness to change. RESULTS: Based on information from the participants, some items were changed to 2-step items (asking if an activity was done, and if it was done, then asking how difficult it was). The near-vision and distance-vision subscales each had 1 item that was endorsed by very few participants, so these items were replaced with items that were optional in the English version. For example, more than 60% of participants did not drive, so the driving question was excluded. Reliability and validity were adequate for all subscales except driving, ocular pain, color vision, and peripheral vision. With cataract surgery, most scores improved by at least 20 points. CONCLUSION: With minor modifications from the English version, the Japanese NEI VFQ-25 can give reliable, valid, responsive data on vision-related quality of life, for group-level comparisons or for tracking therapeutic outcomes.

Adult↗

Steady states and oscillations in the p53/Mdm2 network.

p53 is activated in response to events compromising the genetic integrity of a cell. Recent data show that p53 activity does not increase steadily with genetic damage but rather fluctuates in an oscillatory fashion. Theoretical studies suggest that oscillations can arise from a combination of positive and negative feedbacks or from a long negative feedback loop alone. Both negative and positive feedbacks are present in the p53/Mdm2 network, but it is not known what roles they play in the oscillatory response to DNA damage. We developed a mathematical model of p53 oscillations based on positive and negative feedbacks in the p53/Mdm2 network. According to the model, the system reacts to DNA damage by moving from a stable steady state into a region of stable limit cycles. Oscillations in the model are born with large amplitude, which guarantees an all-or-none response to damage. As p53 oscillates, damage is repaired and the system moves back to a stable steady state with low p53 activity. The model reproduces experimental data in quantitative detail. We suggest new experiments for dissecting the contributions of negative and positive feedbacks to the generation of oscillations.

Animals↗

Association between a marker in the UCP-2/UCP-3 gene cluster and genetic susceptibility to anorexia nervosa.

Anorexia nervosa (AN) is an enigmatic syndrome affecting approximately 0.1% of the at risk population in the UK which equates to approximately 70000 sufferers. Data from a number of studies have demonstrated the heritability of this disorder, however it is only in the last few years that studies have begun to determine the involvement of particular candidate genes in this genetic predisposition. In the current study we have used classical case-control association analysis to determine whether two highly polymorphic microsatellite markers, located within a 3-cM region of the UCP-2/UCP-3 locus, show involvement of this region of the human genome in the predisposition to AN. Analysis of a cohort of 170 female Caucasian anorexia nervosa sufferers and 150 normal female controls shows evidence of association with the marker D11S911 but not D11S916. Allele 13 of the marker D11S911 is significantly over represented in the anorexia nervosa population suggesting that a mutation in linkage disequilibrium with this locus may form part of the genetic component of AN. Further work is now required to try to reproduce these data in a second independent cohort and to further characterise this region of the human genome.

Adolescent↗

Electrogastrographic norms in children: toward the development of standard methods, reproducible results, and reliable normative data.

BACKGROUND: Surface electrogastrography (EGG) is a noninvasive technique that detects gastric myoelectrical electric activity, principally the underlying pacemaker activity generated by the specialized interstitial cells of Cajal. Interest in the use of this methodology has grown because of its potential applications in describing functional gastrointestinal disorders, particularly as a tool in the evaluation of nausea, anorexia, and other dyspeptic symptoms. METHODS: Fifty-five healthy volunteers (27 female), ranging in age from 6 to 18 years (mean, 11.7 years), were studied for a 1-hour baseline preprandial period and a 1-hour postprandial period after consumption of a standard 448-kcal meal. Recordings were obtained with an EGG Digitrapper or modified Polygraph (Medtronic-Synectics, Shoreview, MN). Spectral analysis by an autoregressive moving average method was used to extract numerical data on the power and frequency of gastric electrical activity from the EGG signal. RESULTS: The authors present normative data for healthy children and adolescents studied under a standardized protocol. Mean dominant frequency was found to be 2.9 +/- 0.40 cycles per minute preprandially and 3.1 +/- 0.35 postprandially, with 80% +/- 13% of test time spent in the normogastric range (2-4 cycles per minute) before and 85% +/- 11% after the test meal. The response of several key parameters to meal consumption was considered, and the effects of age, gender, and body mass index (BMI) on the EGG were sought. CONCLUSIONS: There is a postprandial increase in the rhythmicity and amplitude of gastric slow waves, as other investigators have shown in adults. Key normative values are not dependent on age, gender, or BMI. The authors discuss limitations in the data set and its interpretability. The authors establish a normative data set after developing a standardized recording protocol and test meal and show that EGG recordings can be obtained reliably in the pediatric population. Development of similar norms by investigators using the EGG is crucial for future exploration of the validity and clinical application of the EGG. Differences in test conditions of signal detection and analytic methods influence EGG results substantially, and caution should be used when comparing results across centers.

Adolescent↗

Hepatic foci in rats after diethylnitrosamine initiation and 2,3,7,8-tetrachlorodibenzo-p-dioxin promotion: evaluation of a quantitative two-cell model and of CYP 1A1/1A2 as a dosimeter.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent hepatic tumor promoter in female rats. We used a quantitative, stochastic initiation-promotion model based on R. B. Conolly and J. S. Kimbell (Toxicol. Appl. Pharmacol. 124, 284-295, 1994) to analyze initiation-promotion results from a previously published study (H. C. Pitot et al., Carcinogenesis 8, 1491-1499, 1987) within the context of a negative selection model of tumor promotion. In this model, two types of initiated cells (called A and B cells) are produced by DEN initiation. Visually excellent correspondence between model predictions and data (i.e., foci/cm3 liver and percentage of liver occupied by foci) are obtained when TCDD is described as having dose-responsive effects on division and death (apoptotic) rates of these two cell types. For A cells, both the division and the death rates increase while the difference between division and apoptotic rates decreases. For B cells, the difference between division and apoptotic rates increases, primarily due to a decrease in the apoptotic rate. We also linked these alterations in cell kinetics to a pharmacokinetic model for TCDD incorporating a five subcompartment model of the liver acinus with induction of CYP1A1 and 1A2 genes in the subcompartments. Alterations in A cell kinetics correlate with effects of TCDD in the region most sensitive to induction (subcompartment 5-centrilobular region); B cell dynamics correlate with induction in subcompartments 3-5 (centrilobular and mid-zonal regions). In summary, these modeling exercises show that (1) the two-cell model, without presuming effects of TCDD on the mutation rate of normal hepatocytes, reproduces the data of Pitot et al. (1987) and (2) induction of CYP1A1/1A2 in different regions of the hepatic acinus can be used as a general correlate of these presumed changes in cell growth kinetics.

Animals↗

Use of computer-assisted analysis for myofiber size measurements of rat soleus muscles from photographed images.

Since myofiber cross-sectional area measurements are important in describing myofiber adaptations to physiological and pathological changes, we developed a reproducible method for measuring myofiber size using fluorescent stains. Several 35-mm slides of dystrophin-, laminin-, and concanavalin A (ConA)-stained muscle sections were used to calculate myofiber cross-sectional areas and to compare different techniques and settings of an image capture system. Although variation in equipment settings did result in variation in myofiber area, the overall effect was of little practical significance (< 6%). Using midrange values for the settings of illumination, black level, and gain, reproducible quantitative data were collected and analyzed from 35-mm slides of FITC-labeled conA taken from atrophic, normal, and hypertrophic muscle samples. As expected, the atrophic muscle fibers were smaller. However, in hypertrophic muscle from compensatory overload, the fibers were composed of both large and small fibers. We found it important that the myofiber cross-sectional area measurements be expressed both in terms of average fiber areas and as frequency distribution histograms. In addition, detailed methodology of fiber area measurement must be provided.

Animals↗

Hip simulator wear testing according to the newly introduced standard ISO 14242.

Ultra-high molecular weight polyethylene (UHMWPE) acetabular cups were tested against alumina-ceramic femoral heads using a new type of hip joint simulator according to ISO/FDIS 14242-1. Bovine serum as well as newborn calf serum were used as test fluids. Total polyethylene wear was determined by weight loss of the cups. In addition. wear depth and its distribution were recorded by means of a coordinate measurement system. Wear particle analysis and inspection of the worn polyethylene surfaces using light and scanning electron microscopy (SEM) were performed to analyse damage and identify the acting wear mechanisms. The total wear rate was determined to be 22.07 +/- 1.75 mg/10(6) cycles for the bovine serum group and 26.57 + 3.55 mg/10(6) cycles for the calf serum group. Unexpectedly, the formation of two wear vectors corresponding to recent clinical findings was detected. Retrieved polyethylene wear debris was comparable in size and shape with clinical findings. The test method described by ISO/FDIS 14242-1 produced reliable and reproducible wear data using UHMWPE acetabular cups articulating against alumina-ceramic heads. In the authors' opinion, the lubricant composition should be described in more detail, since the protein and additive content seem to have a high impact on the wear results. It needs to be emphasized that the findings of this study cannot be regarded as a general validation of hip wear tests according to ISO/FDIS 14242-1 but are limited to the material combinations investigated herein. Further testing of other clinically relevant materials and interlaboratory ring tests must follow.

Aluminum Oxide↗

Rapid DNA extraction for molecular epidemiological studies of malaria.

DNA isolation from blood samples collected in molecular epidemiological studies is crucial for the quality and reproducibility of data. Blood samples from two malaria endemic sites have been prepared by four different DNA isolation methods with subsequent PCR amplification of the msp2 locus of Plasmodium falciparum. We tested a rapid boiling method; the guanadine isothiocyanate DNA extraction; QIAmp blood kit; and the ISOCODE STIX PCR template preparation dipstick, and analysed the numbers of concurrent infections/sample. The rapid boiling method and the ISOCODE STIX provided overall the best sensitivity combined with ease of handling. The possibility to store and ship the ISOCODE STIX at ambient temperature adds further advantage to this method.

Animals↗