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Distribution of aryl hydrocarbon hydroxylase inducibility in cultured human lymphocytes.

We measured aryl hydrocarbon hydroxylase (AHH) in cultured human lymphocytes. A striking seasonal variation in AHH activity was observed with induced AHH activity levels from January through May measuring approximately 20% of the values during the remainder of the year. AHH inducibility was determined by comparing lymphocytes from the same person cultured with and without the inducer 3-methylcholanthrene. If measurements are limited to the summer and fall seasons when AHH activity is high, AHH inducibility is reproducible for most persons with repeat determinations on the same person averaging 11% from the mean. The values of AHH inducibility in 53 persons ranged from 0.9 to 5.0, but the distribution of values did not fall into three distinct, nonoverlapping classes as reported by others. We were not able to determine the distribution of AHH inducibility in lung cancer patients since lymphocytes from less than half of the patients tested could be successfully cultured.

Aryl Hydrocarbon Hydroxylases↗

[Anorectal manometry in hemorrhoidal disease].

Manometry is an important approach to anorectal function. In the haemorrhoids the evaluation of the anal resting tone, of the squeeze and of the sphincterial length is very useful to realize the best surgical treatment. Anorectal manometry is neither invasive nor expensive; it can be ready repeated and the results are reproducible. This examination must be considerated as essential part of the diagnostic routine of the anorectal diseases.

Anal Canal↗

Systemic contact dermatitis to hydroxyzine.

Systemic contact dermatitis is an underreported type of delayed hypersensitivity caused by a systemically administered substance. When interpreting patch test reactions, it is important to obtain a history of all current related oral medications. Many oral medications can cross-react with structurally similar topical antigens and induce systemic contact dermatitis. Identification and elimination of the inciting agent can lead to resolution of otherwise chronic, unresponsive eczema. We report a case of systemic contact dermatitis to hydroxyzine in a patient who was patch tested positive to ethylenediamine. Repeated oral provocation with hydroxyzine reproduced her eczema on several occasions. We conclude that systemic contact dermatitis to hydroxyzine, a common medication used to treat pruritus, must be considered as a potential cause for unresponsive eczema.

Antipruritics↗

Oral idarubicin pharmacokinetics--correlation of trough level with idarubicin area under curve.

Idarubicin is the first anthracycline that can be successfully administered via the oral route and thus may facilitate antineoplastic chemotherapy in an improved quality of life. These perspectives are somewhat hampered by the large variation in bioavailability between individual patients and the obvious requirement to monitor plasma concentration and area-under-the-curve values (AUC) for an appropriate adjustment of idarubicin dose. In this study we describe the pharmacokinetics of idarubicin and its main metabolite idarubicinol in 12 patients after oral application of 20 mg/m2 idarubicin on 3 consecutive days and demonstrate that the 24 h trough levels show a high correlation with AUC and may thus allow a rapid and easy determination of individual drug concentrations and an appropriate dose adjustment. The average terminal half-life was 30.5 h for idarubicin and 66.9 h for idarubicinol. The AUC for idarubicin and its main metabolite idarubicinol revealed a substantial interpatient variation with AUC values ranging from 25.7 to 114 ng x h/ml (average 58.1 ng x h/ml) for idarubicin and from 109.4-445.2 ng x h/ml (average 287.3 ng x h/ml) for idarubicinol. However, the ratio of idarubicin/idarubicinol differed only two folds from 1:3.7 to 1:7.7 with an average of 1:5.1. Both idarubicin and idarubicinol concentrations were highly reproducible, however, upon measurements after repeated applications within individual patients. Moreover, idarubicinol and idarubicin AUCs showed a good correlation with r = 0.78, indicating that the interindividual variation of idarubicin AUC reflects differences in absorption rather than in metabolism. In order to describe the interindividual bioavailability of idarubicin - represented by the respective AUC - measurement of a single data point with a high correlation with the AUC would be ideal. Our study demonstrates that the 24 h trough level shows such an excellent correlation (r = 0.96) with AUC, making it the perfect candidate for fast estimates of the individual bioavailability in a given patient. On this basis, the longitudinal measurement of the 24 h trough level may allow assessment of the impact of interindividual variations in AUC on clinical outcome and toxicity.

Administration, Oral↗

Cardiac effects of sumatriptan: findings of Holter monitoring and review of the literature.

The aim of this study was to elucidate possible electrocardiographic effects of sumatriptan in a selected group of patients with severe headache requiring in-patient treatment. The patients (n = 21) were treated with sumatriptan in addition to various other compounds and were asked to record any symptoms following the administration of sumatriptan. In addition, Holter monitoring was performed in all subjects. In agreement with other studies, the adverse events reported by the patients were not related to ECG changes and, vice versa, ECG changes were not accompanied by clinical symptoms. The Holter findings before and after administration of sumatriptan were significantly different in three patients, i.e. recurrent episodes of ST depression and increase in extrasystoles. These changes occurred within a period of 1.45 to 18 hours and were not reproducible when Holter monitoring was repeated without sumatriptan. Even though the findings might be explained by spontaneous variability of Holter monitoring or other factors, this study does not definitely discount the possibility that sumatriptan may cause ST segment changes and increase pre-existing extrasystoles. Controlled studies are required to clarify this issue.

Adult↗

1H-NMR studies of synthetic polypeptide models of Plasmodium falciparum circumsporozoite protein tandemly repeated sequence.

The major immunodominant region of the coating protein of Plasmodium falciparum sporozoites contains multiple tandem copies of the sequence Asn-Ala-Asn-Pro (NANP). Current efforts for the development of an antisporozoite vaccine are focused on the synthesis of polypeptides reproducing part of the circumsporozoite protein repeat sequence and, in an attempt to relate conformational properties and biological response, 1H-nmr one- and two-dimensional studies of the synthetic models (NANP)2NA and (NANP)6 were carried out in water and water/methanol mixtures, at 400 and 500 MHz. In water, (NANP)6 undergoes fast conformational averaging. At variance, in water/methanol, the molecule appears to adopt an extensive structure, but detailed analysis is impaired by high spectral degeneracy. Based on the results obtained with (NANP)2NA and from preliminary experiments in water/trifluoroethanol, an interpretation is suggested for the (NANP)6 data in water/methanol in terms of a mixed sequence of beta I-turns and half-turns (or/and gamma I-turns) around the positions Ni-1-Pi-Ni + 1.

Animals↗

Liquid chromatographic determination of monensin in premix and animal feeds: collaborative study.

An interlaboratory study of a liquid chromatographic (LC) method for determining monensin in premix (60-80 g/lb or 132-176 mg/g) and animal feeds (5-200 g/ton or 0.0055-0.22 mg/g) was conducted in laboratoriesin the United States, Canada, France, and Germany. The LC system used a reversed-phase column, postcolumn derivatization with vanillin, and UV detection. The method separates monensin from other ionophores such as narasin and salinomycin. Each laboratory analyzed a total of 20 samples of premix, liquid feed supplements, poultry, and cattle feeds. Concentrations of monensin in all samples ranged from 0 to 176 mg/g (80 g/lb). Reproducibility relative standard deviation (RSDR) for premix ranged from 2.8 to 3.4%. For feed samples containing monensin, repeatability standard deviation (sr) ranged from 0.9 to 7.0. Reproducibility standard deviation (sR) ranged from 1.2 to 11. Repeatability relative standard deviation (RSDr) ranged from 6.1 to 21% and RSDR values-ranged from 8.6 to 25%. Sample preparation for the LC method is less labor intensive than that for the microbiological assays. The LC assay is more efficient than the microbiological assays. This LC method for determination of monensin in premix and animal feeds has been adopted first action by AOAC INTERNATIONAL.

Animal Feed↗

Nasal nitric oxide measurements before and after repeated humming maneuvers.

BACKGROUND: It has been recently shown that humming greatly increases nasal nitric oxide (NO). This is most likely owing to a rapid washout of sinus NO caused by the oscillating sound waves. During repeated humming manoeuvres nasal NO gradually decreases, likely because NO accumulated in the sinuses is washed out. AIM: We studied whether humming before measurements would affect nasally exhaled NO. MATERIALS AND METHODS: NO output was measured by the chemiluminescence technique in orally and nasally exhaled air in 38 subjects: 18 healthy subjects (HS), 15 subjects with allergic rhinitis (AR) and five subjects with allergic nasal polyposis (AP). Each subject performed a NO measurement during quiet nasal exhalation either preceded by a period of silence/free speaking or immediately after five consecutive humming manoeuvres (posthumming). RESULTS: Mean nasal NO output (95% CI) after a period of silence/free speaking was 231 nL min-1 (178-284) in HS, 434 nL min-1 (347-522) in AR (P < 0.001) and 262 nL min-1 (163-361) in AP. Post-humming nasal NO output was 16% (5 to 50%) lower in HS and 14% (1 to 49%) lower in AR, while it remained unchanged in AP subjects. Intra-subject coefficient of variation of quiet nasal exhalation was 12% in HS, 13% in AR and 5% in AP. Post humming intraindividual coefficient of variation significantly decreased in both HS and AR, but it did not change in AP. CONCLUSIONS: Nasal NO levels measured immediately after repeated humming manoeuvres are consistently lower and more reproducible than nasal NO levels measured after a period of silence or free speaking. Repeated humming effectively empties the sinuses, thereby probably minimizing the normal contribution from the sinuses to nasal NO. This may be useful to better estimate NO output from the nasal cavity mucosa in health and disease.

Adolescent↗

Intra-laboratory reproducibility of human papillomavirus identification in cervical specimens by a polymerase chain reaction-based assay.

BACKGROUND: polymerase chain reaction (PCR)-based assays for human papillomavirus (HPV) sequences are in wide use in clinical and epidemiological studies. The reproducibility of these assays is not extensively studied. OBJECTIVES: to estimate the intra-laboratory reproducibility of generic and type-specific HPV diagnoses by the MY09/MY11/HMB01 consensus L1 primer-based PCR assay. STUDY DESIGN: systematically collected specimens (n=207) were masked and retested. RESULTS: when specimens negative in both initial and repeat assays were excluded from analysis, the diagnostic reproducibility was 98. 6% for beta-globin, 90.7% for generic HPV (any HPV type), and 76.9% for type-specific HPVs. The reproducibility of type-specific diagnosis increased with increase in signal strength in the hybridization reaction of the initial assay. When a specimen contained five or more HPV types in the initial assay, it was rare to identify all of the HPV types in the repeat assay. CONCLUSIONS: the degree of reproducibility of the PCR diagnosis should be taken into account in the interpretation of HPV data in clinical and epidemiological studies.

Cervix Uteri↗

Reproducibility of the women's module of the Behavioral Risk Factor Surveillance System questionnaire.

The Behavioral Risk Factor Surveillance System (BRFSS) is designed to provide statewide estimates of the prevalence of preventive health practices, including screening. We assessed the reproducibility of responses to the women's health module, which covers breast and cervical cancer screening, hysterectomy, and pregnancy. A random sample of women in Massachusetts (n = 91; response rate for the repeat interview, 70.0%) and a separate random sample of minority women in the state (n = 179; response rate for the repeat interview, 69.4%) were interviewed by telephone twice, 21 to 94 days apart. Differences across administrations in mean prevalence of screening were small. Concordance exceeded 85% for almost all the variables examined, but tended to be lower for nonwhite respondents. After correction for agreement occurring by chance, moderate to excellent values of kappa (range, 0.41 to 0.86) were observed. The women's health module of the BRFSS questionnaire yields highly consistent group mean estimates of prevalence when administered repeatedly to the same individuals. Individual reproducibility is excellent, but may be reduced among minority respondents.

Adolescent↗

Validation of the cerebellum as a reference region for SPECT quantification in patients suffering from dementia of the Alzheimer type.

In longitudinal brain studies of dementia of the Alzheimer type (DAT), the cerebellum is often used as a reference region for single photon emission computed tomography (SPECT) quantification, which assumes no significant regional influence of physiological fluctuations or pathology. With the use of absolute quantification in DAT patients, reproducibility of cerebellar uptake of technetium-99m-d,l-hexamethylpropyleneamine oxime (HMPAO) was tested and compared with the mean absolute cerebellar tracer uptake value in DAT patients and healthy control subjects. In 13 DAT patients SPECT studies were repeated within 2 weeks to assess reproducibility of cerebellar regional brain uptake (rBU). With calibrated point sources as scaling factors, cerebellar activity was expressed as rBU of HMPAO per cm3 brain tissue in percent of the injected lipophilic dose of 740 MBq (20 mCi). Also, mean cerebellar rBU in patients suffering from DAT was calculated and compared with a previously established database obtained in healthy volunteers. Repeated SPECT studies within a 2-week interval in clinically stable patients resulted in a mean rBU increase of 6.8 +/- 10.3% in the second SPECT study as compared with the first. A similar shift was previously reported in healthy volunteers. Mean cortical cerebellar rBU values in DAT patients and in the healthy reference population concurred, after cumulative corrections for body surface and for a mean brain volume of 1350 ml (obtained in healthy control subjects), showing respective mean values of 53.9 +/- 7.4 and of 52.0 +/- 7.3 x 10(-6) of the injected lipophilic dose 740 MBq (20 mCi) of HMPAO per cm3 of brain tissue. A unidirectional shift in mean absolute cerebellar uptake values occurs between repeat SPECT examinations in DAT patients similar to previous findings in a group of healthy volunteers. The origin of this phenomenon remains elusive but deserves further study with regard to SPECT (semi)quantification in DAT patients. Most interestingly, the presented findings suggest that with the use of HMPAO SPECT in DAT patients the cerebellum remains scintigraphically uninvolved.

Aged↗

Observer variability in microcomputer-assisted morphometric study of nuclear parameters.

To evaluate observer variability during microcomputer-assisted planimetry, nuclear features (area, perimeter, and form factor) were studied in a case of malignant lymphoma. Tissue fixed in glutaraldehyde, embedded in plastic and sectioned at 1 micron was studied using a Zeiss Kontron IBAS 2000 image analysis system. Manual tracing of nuclear outline was performed to obtain the parameters. Both interindividual and intraindividual reproducibilities were evaluated, the former among 8 observers and the latter by the observers repeating the measurements. With the present technique, intraindividual reproducibility was high and correlation was excellent for area, perimeter and form factor measurements. A high degree of interindividual inconsistency was demonstrated for all parameters. Interindividual correlation was poor for form factor. It is concluded that poor interindividual reproducibility even when the objective method of morphometry is used may be a significant problem in tissue investigations, especially when results from different laboratories are being compared.

Cell Nucleus↗

Genetic analysis of the Utah population: a comparison of STR and VNTR loci.

Genetic data are reported for nine short tandem repeat (STR) loci (D3S1358, vWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317, and D7S820) and six variable number of tandem repeat (VNTR) loci (D2S44, D10S28, D4S139, D1S7, D5S110, and D17S79) in samples of Utah African Americans, European Americans, and Hispanics. Little evidence of departures from Hardy-Weinberg equilibrium or gametic equilibrium was found in these populations. Because of their relatively higher mutation rates, the VNTR loci exhibited higher average heterozygosity and lower FST levels than did the STR loci. Genetic distance analysis showed congruence between the two types of systems, and a genetic distance analysis of the STR data showed that the three Utah populations are genetically similar to the same ethnic groups in other parts of the United States. In addition, this analysis showed that the African American population is the most genetically divergent, with greater similarity between the Hispanic and European American populations. This analysis demonstrates a high degree of consistency for population designations commonly used in forensic analysis.

Evolution, Molecular↗

Rapid and accurate characterisation of short tandem repeats by MALDI-TOF analysis of endonuclease cleaved RNA transcripts.

We describe the application of matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) for the characterisation of short tandem repeat (STR) sequences by the analysis of endonuclease cleaved RNA transcripts. Several simple bovine STR loci as well as interrupted and compound microsatellites were chosen as model loci to evaluate the capabilities of MALDI-TOF MS for STR analysis. In short, the described approach consists of a PCR amplification of the investigated STR sequence, which then is transcribed into RNA and cleaved by G-specific RNase T1. Base-specific cleavage of the transcript results in high informative fragment patterns from both the repetitive core sequence and the flanking region. Since sequence specificity from endonuclease cleavage is combined with the accuracy of MALDI-TOF measurements, this technique allows for fast and reliable determination of simple repeat lengths as well as for further characterisation of STR allele sequences, which is of high interest especially in more complex STR loci.

Dinucleotide Repeats↗

Comparison of the performance of the Nidek NT-2000 noncontact tonometer with the Keeler Pulsair 2000 and the Goldmann applanation tonometer.

We compared the performance of a new noncontact tonometer (NCT), Nidek NT-2000, with the Keeler Pulsair 2000 and the Goldmann applanation tonometer (AT). Twenty-two subjects with intraocular pressure (IOP) ranging from 10 to 21 mmHg were recruited and their IOP measured using each technique on 2 different days. The NT-2000 produces repeatable IOP readings and is comparable to the Goldmann AT. There is a significant between-visits difference in IOP when using the Pulsair 2000. The reproducibility of IOP measurements made with the Pulsair 2000 is relatively poor when compared to the Goldmann AT and the NT-2000. IOP measurements made with the Goldmann AT show good repeatability and reproducibility when the mean of three IOP readings are used. When a single Goldmann reading is used variability is increased. There is no significant difference in the IOP readings made on the first visit between techniques.

Adult↗

Repeated enflurane anaesthetics and model predictions: a study of the variability in the predictive performance measures.

We quantified the total variability (reproducibility) and the within-patient but between repeat anaesthetics variability (repeatability) in measures which are used to judge the predictive performance of our physiological model. We studied 14 patients who received enflurane closed-circuit anaesthesia on two occasions. The end-tidal concentrations measured and those predicted served to calculate the predictive performance measures of the model: root mean squared error (rmse = total error), bias (systematic error) and scatter (error around the bias). The overall results were: rmse 15 (7)%, bias 0 (14)% and scatter 9 (3)% (grand mean (total SD)). The within-patient SD values were smaller for the rmse (4%) and bias (10%), but not for scatter (3%). The repeat rmse values and biases were linked to the first results. This implies that these performance measures depended partly on the patient. As there was no association between the personal performance measures and age, sex, body weight, body surface area or body mass index, these characteristics cannot be used to further tune the model.

Adolescent↗

Incremental lines in root cementum of human teeth--a reliable age marker?

In root cementum of teeth, alternating dark and light lines become visible in cross-sections under the light microscope. These lines bear an apparent resemblance to the annual rings of trees. Numerous studies have been done to correlate the number of cementum lines with the dental age by examining a great number of teeth of known age. Our study used a different approach. If lines in root cementum develop in an annual rhythm and are thus comparable to annual rings of trees, the same or at least a very similar number of these structures should be found in all areas of the root cementum of the same tooth. We counted cementum lines in the buccal, lingual, distal and mesial region of different sections, all from the middle third of the same root. This was repeated in eight teeth. To our surprise, we had immense difficulty in counting reproducible line numbers in the same cementum area at repeated counts. Nevertheless, the same tooth was found to differ markedly in the number of lines in different sections as well as in different regions of the same sections. These differences cannot be ascribed to variations caused by difficulties with reproducible line counting. Therefore, we are more than skeptical about the reliability of counting lines in root cementum as a method for determining the age of human teeth.

Adult↗

A natural head position technique for radiographic cephalometry.

A three-part study was designed in order to test the applicability of the fluid-level method for registration of natural head position. In the first part the fluid-level method was utilized to make two repeated cephalometric radiographs of 33 young adults. The reproducibility of the craniovertical, craniocervical and cervicohorizontal relationships was comparable with previous results with the mirror method. In the second part, the fluid-level method was compared with the mirror method when used by two radiographers for repeated radiographs in 40 subjects. The reproducibility of the craniocervical and cervicohorizontal angles was less accurate with both methods and the only difference between them was a slightly better reproducibility of the craniovertical angle with the fluid-level method for one of the radiographers. In the third part, it was shown that using the fluid level, a patient can be transferred from a standing to a sitting position in the cephalostat without any systematic change in craniovertical, craniocervical or cervicohorizontal relationships.

Adult↗