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Hydroxyurea as a reference standard in teratological screening. Comparison of the embryotoxic and teratogenic effects following single intraperitoneal or repeated oral administrations to pregnant rats.

The antimitotic drug hydroxyurea (HU) has been evaluated as a positive standard for teratological screening in rats. Single intraperitoneal administration of HU to pregnant Sprague Dawley rats at the dose level of 750 mg/kg induced embryolethality or specific anomalies depending on the day of treatment: HU administration on days 7, 8, 9, 10 or 11 produced lethal effects in a high percentage of embryos; cardiovascular malformations were specifically induced by a single dose on day 10, ocular anomalies on day 10 or 11, palatoschisis or diaphragmatic hernia on day 12, limb or paw deformities on day 10, 11, 12 or 13. This experiment demonstrated the high susceptibility of the genotype of our colony of rats to the embryotoxic potential of HU. Repeated oral administration of HU during the organogenetic period (from day 6 to day 15 of gestation), at dose levels ranging from 50 to 450 mg/kg, led to a dose dependent embryolethal and teratogenic effect. Live foetuses at term generally showed severe ocular and craniofacial anomalies; hydrocephalus, cardiovascular anomalies, vertebral and costal defects were also registered. Limb malformations were not frequent and paw abnormalities were totally absent. In our experimental conditions, the dose level of 300 mg/kg is regarded as a suitable positive control dosage in teratological testing of new molecules by oral route.

Abnormalities, Drug-Induced↗

Open cholecystectomy: its morbidity and mortality as a reference standard.

In a retrospective study of 10,471 cholecystectomies, performed between 1971 and 1990, the incidence and causes of death and morbidity of cholecystectomy were analysed. There were 47 postoperative deaths (0.4%); 6 deaths occurred in 5841 patients less than 50 years old, 23 in 3898 patients between 50 and 70 years old and 18 in 732 patients more than 70 years old. Death rates in each group were, respectively, 0.1%, 0.6% and 2.5% (p < 0.001). The death rate in 9339 patients who had cholecystectomy alone was 0.3% and the death rate in 1132 patients who had a concomitant common bile duct exploration (CBDE) was 1.6% (p < 0.001). Cardiovascular complications were the main cause of death, and biliary, pulmonary and wound complications were the most common. There were 614 complications in 529 patients; 176 of these patients were less than 50 years old, 252 were between 50 and 70 years old and 101 were more than 70 years old. Complication rates were, respectively, 3.0%, 6.5% and 13.8% (p < 0.001). For patients with cholecystectomy alone the morbidity was 3.6% and for patients who had a concomitant CBDE the morbidity was 17% (p < 0.001). The mortality and morbidity of cholecystectomy increase significantly with age and a concomitant CBDE. However, patients who underwent cholecystectomy electively or for acute cholecystitis had comparable mortality and morbidity.

Acute Disease↗

Evaluation of the diagnostic value of pneumatic otoscopy in primary care using the results of tympanometry as a reference standard.

The aim of this study was to determine the value of pneumatic otoscopy in diagnosing otitis media with effusion in primary care. Pneumatic otoscopy was carried out for 111 children aged one to 16 years and the results obtained compared with those obtained from tympanometry. The children were those who had attended for a regular ear, nose and throat check up in the health centre of a school for the deaf during the period November 1989 to January 1990. Pneumatic otoscopy and tympanometry with the GSI 28 instrument (Grason-Stadler) were carried out by a trained ear, nose and throat nurse. All relevant features determined using otoscopy--the colour, position and mobility of the tympanum--and an overall assessment were recorded. The results of tympanometry were evaluated independently of the otoscopic findings. In the population examined the predictive values of positive and negative results of pneumatic otoscopy for diagnosing effusion were high; the sensitivity was low. Serious retraction of the eardrum and absence of mobility under positive pressure were the most predictive features but the colour of the tympanum did not show any relation to effusion. In the youngest age group (one to five years) 56% of the children had abnormal otoscopic findings in either one or both ears (odds ratio for this group versus remaining children 3.75; 95% confidence interval (CI) 1.75 to 15.2). The odds ratios of past and present history of upper respiratory tract infection with respect to abnormal results from otoscopy were 2.41 (95% CI 1.05 to 5.53) and 2.95 (95% CI 1.17 to 7.45), respectively. Pneumatic otoscopy carried out by an experienced health care worker is of high diagnostic value when compared with the results of tympanometry. Pneumatic otoscopy can improve the diagnostic capabilities of general practitioners and other primary care workers with regard to otitis media with effusion.

Acoustic Impedance Tests↗

Long-term stability of a cyanmethemoglobin reference standard.

A comparative analysis performed in late 1974 revealed that a cyanmethemoglobin secondary standard prepared by the laboratory at the Michigan Department of Public Health in 1966 was still suitable for use in hemoglobin assays. These results would suggest that the current one-year expiration time used for commercial standards could be extended considerably.

Animals↗

Assessment of nutritional status by anthropometry: a comparison of different standards of reference.

Anthropometric measurements of mid-arm circumference, mid-arm muscle circumference, and triceps skinfold thickness were made on 318 subjects and expressed as percentages of Jelliffe's reference standards, and in relation to centile categories published by Frisancho in 1981. There was no consistent agreement between the two standards of reference, both in and between sexes, and these results show that in any nutritional assessment it must be clearly stated which standard of reference is used.

Adolescent↗

Relative bioavailability of two brands of ornidazole in twelve healthy volunteers.

AIM OF THE STUDY: To determine the bioequivalence of two marketed ornidazole formulations in healthy volunteers. METHODOLOGY: A single dose relative bioavailability of Ornidazole 1.5 g (3 x 500 mg tablets) of test product (Giro, Panacea Biotec Ltd.) and that of standard reference (Dazolic, Sun Pharmaceutical Industries), was investigated in healthy adult males. A total of 12 subjects wee enrolled in the study and investigations consisted of two treatment phases separated by a washout period of seven days. Both treatment phases were of 12 hours durations each. Blood samples were collected at 0, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10 and 12 hours post-administration of assigned drug product. Appropriate fasting restrictions were employed during both the treatment phases. Drug assay was done using HPTLC method. The statistical significance of difference in pharmacokinetic parameters between preparations was tested using ANOVA. RESULTS: The mean peak plasma concentration (Cmax) of 32.67 +/- 4.45 microg/ml was achieved at 1.54 +/- 0.81 hours following administration of test product as against mean Cmax of 31.55 +/- 5.04 microg/ml at 1.79 +/- 0.89 hours for reference standard. The area under time concentration curve (AUC(0-12)) hours was 261.67 +/- 77 microg/ml hours with reference standard and 265.41 +/- 30.82 microg/ml hours for test product. CONCLUSION: There was no statistically significant difference between the two formulations and the two products

Adult↗

Validating methods for measuring delta18O and delta13C in otoliths from freshwater fish.

The ability of the phosphoric acid digestion technique to extract carbon dioxide from biogenic carbonates and reliably reproduce delta(18)O and delta(13)C signatures from standard reference materials (NBS-18, NBS-19) was tested and shown to produce accurate, unbiased measurements of non-biologic materials. The effects of roasting preparation methods commonly reported when analyzing biogenic carbonates were also tested in a series of experiments using reference standards and otoliths obtained from aquacultured Arctic charr and rainbow trout. Roasting had no effect on the isotope measurement of reference standards. No significant differences between mean oxygen isotope signatures from paired experiments with roasted and non-roasted fish otoliths were found. However, otolith oxygen isotope measurements were significantly enriched in comparison to rearing water-based measurements for both species. Agreement between expected isotopic equilibrium and measured otolith delta(18)O values varied as a function of roasting temperature and between species. Criteria for the selection of appropriate roasting temperatures are suggested and favour 350 degrees C in freshwater fish where unbiased estimates of average rearing water temperatures and known differences in rearing temperatures were obtained. Carbon isotopic disequilibria were observed for both species. A mixing model analysis established differences in the percentage of metabolically derived carbon in studied otoliths, with Arctic charr deriving a greater proportion of otolith delta(13)C from metabolism as a result of higher metabolic rates.

Animals↗

Petrolatum prevents irritation in a human cumulative exposure model in vivo.

BACKGROUND: Protective creams (PCs) have been studied in different models indicating a protective effect of some products. In order to compare PCs in different studies, a generic reference standard should be available. OBJECTIVE: The purpose of this study was to investigate if petrolatum prevents epidermal barrier disruption induced by various irritants in a repetitive irritation test (RIT) and to assess its potential as a standard reference product. METHODS: White petrolatum was evaluated against a set of 4 irritants [10% sodium lauryl sulphate (SLS), 1% sodium hydroxide (NaOH), 30% lactic acid (LA) and undiluted toluene (TOL)] in the RIT. Twenty subjects were tested on the paravertebral skin of the midback. Irritation was assessed by visual scoring, transepidermal water loss and colorimetry. RESULTS: Petrolatum was very effective against SLS, NaOH and LA irritation, and it provided a moderate protection against TOL. CONCLUSION: Petrolatum can be recommended as a standard reference substance against which PCs may be compared as it is effective against water-soluble and water-insoluble irritants in a standardized test procedure.

Adolescent↗

Standards for reference services in health sciences libraries: the reference product.

Standards for reference services were prepared by a committee of the Oregon Health Sciences Libraries Association (OHSLA). The standards are qualitative and address the following: quality control, appropriateness, accuracy, documentation, timeliness, accessibility, confidentiality, and evaluation. The standards are components of minimally competent reference service as reflected in the reference product. A discussion of concerns and prescriptive measures accompanies the statement of each standard. While prepared specifically for health sciences libraries, the standards are applicable to all types of libraries and may be used as guidelines in evaluating the reference product, in upgrading library service, and in writing policies and procedures.

Information Services↗

The identification and quantitation of alkylated nucleobases by high-performance liquid chromatography with UV photodiode array detection.

The application of UV diode array detection in high-performance liquid chromatographic (HPLC) identification and quantitation of several classes of synthetic and commercially available alkylated nucleobases is investigated. Quantitative spectral overlays of these compounds to methyl standard references from a spectral library and absorbance ratios at two maximal wavelengths (lambda max) are found to be useful in categorizing the solutes. They can be grouped into classes of compounds originating from a specific nucleobase and classes of analogs having different alkyl substituents (e.g., methyl, ethyl, propyl, allyl, and benzyl) at the same position of the heterocycle. At a selected wavelength for alkylated nucleobases in the same class, the detector response factors are independent of the alkyl group (+/- 10%). This technique provides a practical means for both qualitative and quantitative analysis of product distribution of DNA base alkylation by using only readily obtainable methylated derivatives as the reference standards.

Adenine↗

[Difficulties and problems in external quality control of immunoassay].

Present status and problems in external quality control of immunoassays were described. Despite the increasing popularity of these methods, there are many difficulties in achieving good analytical performance. Consequently, immunoassay results demonstrate poor interlaboratory comparability. To exclude these difficulties, several changes should be made, for example, preparation of common reference standards, consent methods to give values to laboratory working standards, reference methods, matrix of test samples similar to actual clinical samples etc, before constructing suitable external quality control systems.

Humans↗

Determination of As, Cd, Cr, and Hg in SRM 2584 (trace elements in indoor dust) by high-resolution inductively coupled plasma mass spectrometry.

Standard reference material (SRM) 2584 (Trace Elements in Indoor Dust) was developed as a reference standard for evaluating field methods and for validating laboratory and reference methods for the assessment of lead contamination and exposure. In addition to lead, the toxic trace elements As, Cd, Cr, and Hg, at approximately 17, 10, 140, and 5 microg g(-1), respectively, have been certified in the SRM. These four analytes were successfully determined by use of high-resolution inductively coupled plasma mass spectrometry (HR-ICP-MS). Isobaric interferences at masses of As and Cr were resolved by using the high resolution mode (nominal 8000) and the medium resolution mode (nominal 3000), respectively, of the instrument. The effects of a significant drift in analyte sensitivity in the course of measurement were rectified by use of internal standardization, single spike standard addition, and an optimized analysis sequence. The results were compared with those obtained by instrumental neutron activation analysis (INAA) and isotope dilution inductively coupled plasma mass spectrometry (ID-ICP-MS). The results for the quality control, SRM 2704 (Buffalo River Sediment), were in good agreement with the certified values, indicated by the uncertainty intervals of the measured values overlapping the certified intervals at 95% confidence level.

Arsenic↗