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Prospective comparison of small bowel meal with pneumocolon versus ileo-colonoscopy for the diagnosis of ileal Crohn's disease.

BACKGROUND AND AIMS: Both endoscopy and barium radiography are used routinely to diagnose terminal ileal (TI) Crohn's disease (CD). A prospective study was undertaken to compare ileoscopy with biopsy to small bowel meal with pneumocolon (SBMP) in patients with suspected TI CD. METHODS: A cohort of outpatients investigated for diarrhea with features of TI disease underwent SBMP followed by colonoscopy with ileal intubation and biopsy within 21 days. All results were reported in a standardized, sequential format to assign SBMP TI diagnoses by the duty radiologist and by dual reading with consensus, ileoscopy by the attending endoscopist, and ileoscopy with biopsy by a blinded panel of endoscopists and pathologists. Reference standard TI diagnoses were determined by a consensus panel with full access to medical records. RESULTS: Among 120 subjects, the reference standard TI diagnosis was normal in 47 (39.1%), lymphoid nodular hyperplasia (LNH) in 24 (20.0%), CD in 48 (40.0%), and NSAID enteropathy in 1 (0.9%). Colonoscopy provided TI images and/or biopsies in 97 cases (80.8%), while SBMP provided TI images in 119 (99.1%). When ileoscopy with biopsy succeeded, its accuracy was similar to SBMP with dual reading (89.7%vs 89.9%, p = NS) but superior to SBMP if interpreted only by the duty radiologist (80.0%, p < 0.05). Biopsy improved the accuracy of ileoscopy, while dual reading improved that of SBMP. Both ileoscopy with biopsy and SBMP with dual reading are highly accurate for diagnosing TI CD. Choice of initial test should reflect local expertise and availability, and the likelihood of associated disease in the proximal small bowel or colon.

Adolescent↗

Validation of commercial dry-form broth microdilution panels for susceptibility testing of AZD2563, a new long-acting oxazolidinone.

The MIC results using a dry-form broth microdilution panel (TREK Diagnostic/Sensititre, Westlake, OH, USA) were validated for AZD2563, a novel oxazolidinone compound. In comparision studies against reference frozen-form panels, the commercial MIC results were the same as the reference calue for 82.7% of organisms and all results were within +/- one log2 dilution. Using 462 organisms, most from three genus groups (enterococci, staphylococci, streptococci), test results indicate that Sensititre MIC values were comparable to the reference test and can be utilized in clinical trials of for routine laboratory use when testing AZD2563 and linezolid, the drug class comparator.

Anti-Bacterial Agents↗

Comparison of the Sensititre YeastOne colorimetric microdilution panel and the NCCLS broth microdilution method for antifungal susceptibility testing against Candida species.

We evaluated the commercially prepared Sensititre YeastOne colorimetric antifungal panel to determine the susceptibility of 170 Candida spp isolates to amphotericin B, fluconazole, itraconazole, and flucytosine. The NCCLS reference microdilution method (M27-A document) was used as reference method. The YeastOne panel was performed according to the manufacturer's instructions. For the colorimetric method, MICs were determined at 24 h of incubation. MICs for the NCCLS reference method were read at 48 h of incubation. The overall agreement within +/-2 dilutions by both methods was calculated against the four antifungal agents. This agreement was 92.9, 68.2, 77.6 and 80% for amphotericin B, fluconazole, itraconazole, and flucytosine, respectively. Thirteen isolates (7.6%) showed very major discrepancies for fluconazole and 12 (7%) for itraconazole. We found that the reading of MIC with the YeastOne panel was somewhat easier than the reading of reference MIC, although the determination of endpoint was sometimes difficult, especially for azoles, because the trailing effect appeared in a high percentage of isolates.

Amphotericin B↗

Origin and framework of the development of dietary reference intakes.

This report is the first in a series of publications resulting from the comprehensive effort being undertaken by the Food and Nutrition Board's Committee on the Scientific Evaluation of Dietary Reference Intakes and its panels and subcommittees. The history and rationale behind the development of the Dietary Reference Intakes are discussed.

Calcium↗

Multisite reproducibility of MIC results by the Sensititre YeastOne colorimetric antifungal susceptibility panel.

Reproducibility of MIC results between laboratories, a major performance criterion used for evaluation of any susceptibility test method, was determined at three test sites using the Sensititre YeastOne Antifungal Panel, which incorporates Alamar Blue as a colorimetric indicator. MICs of five antifungals were determined using a set of 10 isolates of Candida species. Each isolate was tested a total of nine times against each antifungal agent in each of the three laboratories. A total of 1350 MICs were evaluated. MICs were read visually after incubation at 35 degrees C for 24 and 48 h. Overall, 99 to 100% of MIC values were encompassed by a range defined by the modal MIC +/- 1 dilution for each antifungal agent tested at both 24 h and 48 h. Replicate testing of the quality control isolates recommended by the National Committee for Clinical Laboratory Standards demonstrated excellent agreement between results obtained with the Sensititre YeastOne panel and the MIC reference range for each antifungal agent. These studies demonstrated that the Sensititre YeastOne Antifungal Panel may be used to generate MIC values for at least five different antifungal agents with a high degree of intra- and interlaboratory reproducibility.

Antifungal Agents↗

A review of the interactions between milk proteins and dairy flavor compounds.

The effect of sodium caseinate and whey protein concentrate on vanillin, benzaldehyde, citral, and d-limonene was determined by quantitative descriptive analysis deviation from reference. A trained taste panel evaluated samples containing a single flavor compound in 2.5% sucrose solution against a reference sample. Vanillin, benzaldehyde, and d-limonene flavor intensity decreased as the concentration of whey protein concentrate increased. In a separate study, the ability of delipidated methyl ketones to bind straight and branched chain methyl ketones was determined. The concentration of straight chain methyl ketones bound by the milk protein powder was inversely proportional to the size of the ligand. Branched chain methyl ketones did not exhibit a trend in binding based on ligand size.

Animals↗

Evaluation of the new automated enzymun-test anti-HBc plus for the detection of hepatitis B virus core antibody.

The new automated Enzymun-Test anti-HBc Plus for the detection of antibodies to hepatitis B virus (HBV) core antigen (anti-HBc) after pretreatment with reducing agents dithiothreitol (25 degrees C; + DTT) or potassium bisulfite (37 degrees C; + MBS) was evaluated by testing 571 serum and plasma samples. The panel included dilution series of reference standards and samples from chronic carriers, one seroconversion panel, samples from patients in acute or chronic stage of the disease or resolved hepatitis B, preselected sera from blood donors that were initially reactive in an anti-HBc assay without pretreatment, potentially cross-reactive serum samples obtained from patients suffering from other diseases or with passed infections other than HBV, pregnant women and individuals with HBV vaccination. The IMx CORE(TM) (Abbott Diagnostics) served as reference assay. Discrepant samples were further investigated with two different commercial anti-HBc enzyme immunoassays, other HBV-specific serological markers and HBV DNA hybridization. The sensitivity of the Enzymun-Test Anti-HBc Plus (25 degrees + DTT, and 37 degrees C; + MBS) in comparison to the reference assay was 100%. The IMx CORE showed a twofold higher sensitivity than Enzymun-Test Anti-HBc Plus for anti-HBc detection in dilution series of serum samples from HBV carriers. The agreement in terms of specificity of the Enzymun-Test Anti-HBc Plus (25 degrees C; + DTT, and 37 degrees C; + MBS) and in comparison to IMx CORE was 97.4 and 96.4%, respectively. After resolution of discrepant results (3 samples were tested false negative with IMx CORE), the agreement in terms of specificity of the Enzymun-Test Anti-HBc Plus (25 degrees C; + DTT, and 37 degrees C; + MBS) in comparison to the combination of the comparative assays was 98.3 and 97.4%, respectively. In conclusion, the new automated Enzymun-Test Anti-HBc Plus with sample pretreatment with DTT (25 degrees C; + DTT) or MBS (37 degrees C; + MBS) permits a highly sensitive and specific detection of anti-HBc in diagnostic virology and blood donation testing.

Hepatitis B Antibodies↗

New HLA-D alleles associated with DR1 and DR2.

The present study describes two new HLA-D specificities : LD 13, associated with DR1, and LD14 associated with DR2. LD13 is defined by an HTC who is the bc offspring of an a: A25, B18, DR7, Dw7/b: A33, B14, DR1, Dx father, and of a c: A24, B14, Dr1, Dx/d: A26, B41, DR5, Dw5 mother. This HTC was included both as a responder and as a stimulator in our cross-reference studies of 8W HTCs. While failing to cluster with any other 8W HTC, it typed 2 of 64 panel members carrying a "blank" HLA-D, linked to DR1. To exclude the possibility that HTC-LD13 might be a split of Dwl, the entire family was tested with the Family Set of 8W HTCs. No typing responses to any 8W Dw1 HTCs were observed. Furthermore, checkerboard experiments between HTC-LD13 and 8WDw1 HTCs showed strong reciprocal stimulation. The LD13 specificity was only found in Ashkenazi Jews and may be in linkage disequilibrium with HLA-B14. LD14 is defined by three, SD different, HTCs deriving from the same family of Sicilian descent. The family was included in the 8th Workshop and each HTC was shown to have inherited DR2, MT1 from both parents. When tested as stimulators, on our HLA-D reference panel, these cells were clustered in a distinct group, LD14, associated with DR2. None of the 8W HTCs appeared to belong to this cluster. The antigen frequency of LD14 is 0.03.

Alleles↗

The role of the primary care physician in recognizing obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is a common disorder among middle-aged adults. However, OSA is a recently described disorder for which most primary care physicians do not have formal training. The primary objectives of this article are to evaluate what percentage of patients referred by primary care physicians for sleep studies had OSA; to characterize the clinical features of these patients and compare them with our known OSA population; and to determine whether primary care physicians asked key questions contained in a work sheet to make the diagnosis of OSA. METHODS: A retrospective chart review at a hospital-based sleep center that is accredited to evaluate all sleep disorders, not just OSA. The health maintenance organization is a staff model one. PATIENTS: Sixty-nine patients who were referred for a sleep study by a health maintenance organization internist or family practitioner between June 1, 1994, and May 30, 1995. RESULTS: Ninety-six percent of the 68 patients referred for polysomnography had OSA. Most were very symptomatic and obese. These 68 patients represent 0.13% of the primary care patient panel. In addition, most of the patients were referred by a few physicians; 6 (11%) of the 55 physicians ordered 33% of the 68 studies. CONCLUSIONS: Primary care physicians did recognize obese patients with prominent symptoms of sleep apnea. However, only a small percentage of their patient panel was referred, suggesting that this condition is still underdiagnosed. This seems particularly true as most of the sleep studies were ordered by a small group of physicians. Future work incorporating educational interventions is necessary to improve detection and treatment of OSA.

Adult↗

Pattern of antitumor activity of a novel camptothecin, ST1481, in a large panel of human tumor xenografts.

PURPOSE: ST1481 is the lead compound of a novel series of 7-modified camptothecins, the 7-oxyimino methyl derivatives, characterized by potent topoisomerase I inhibition and cytotoxic activity. Based on its therapeutic efficacy in a human non-small cell lung carcinoma model and its favorable pharmacological profile, the novel analogue was selected for further preclinical development. EXPERIMENTAL DESIGN: We investigated the growth-inhibitory effects of ST1481 and topotecan, used as a reference compound, in a panel of human tumor cell lines of various tumor types (ovarian carcinoma, glioblastoma, osteosarcoma, and melanoma), including sublines with acquired resistance to cisplatin. We explored the antitumor efficacy in a large panel of human tumor xenografts, with particular reference to intrinsically resistant tumor types, using oral administration and an intermittent treatment schedule. RESULTS: ST1481 showed a potent antiproliferative activity with comparable effects in all tested cell lines. Only U-87-MG glioma cells were less sensitive, presumably as a consequence of the efficiency of the S-phase checkpoint. ST1481 produced a remarkable antitumor effect (tumor volume inhibition > 85%) in 16 of 18 examined models, with an appreciable rate of complete tumor regressions in 11 of 18 models (despite the nonoptimal intermittent treatment schedule). The most impressive antitumor effects were observed against lung carcinoma, melanoma, and osteosarcoma models, as documented by the high rate of complete responses (up to 100%). The efficacy of ST1481 was significantly superior to that of topotecan in 9 of 17 tumors. The novel drug was also markedly effective against slowly growing tumors (A549 lung carcinoma and HT29 colon carcinoma) when a daily protracted treatment was used to fully exploit the therapeutic potential of camptothecins. CONCLUSIONS: The unusual potency of ST1481 in a variety of tumor cell lines suggests the ability of the drug to overcome several resistance factors. The profile of antitumor efficacy further supports the therapeutic interest in the novel analogue and provides a rational basis for clinical evaluation in selected tumor types.

Administration, Oral↗

European multi-centre validation study of NucliSens Extractor in combination with HCV Amplicor 2.0 assay for HCV-NAT screening of plasma pools.

The NucliSens Extractor in combination with the 2.0 version of the Roche Cobas HCV Amplicor test has been validated by five European blood screening laboratories in a multi-centre study. For testing the performance characteristics of this HCV-NAT method, the European Pharmacopoeia validation guidelines were followed. The CLB VQC reference reagents were used for testing robustness and sensitivity. After a technical improvement in the extraction stations, the NucliSens Extractor appeared to be contamination-free as was proved by testing negative controls alternating with samples containing a high HCV-RNA concentration. The Pelicheck HCV-RNA genotype 1 dilution panel was tested 74 times in the five laboratories and an overall 95% detection limit of 80 genome equivalents (geq)/ml was found. In one laboratory the Pelicheck panel was tested in 25 runs and here a 95% detection limit of 32 geq/ml was achieved. In this laboratory the Pelispy HCV-RNA run control samples of 140 geq/ml were consistently picked up in all extractor stations. In addition the laboratories have tested a WHO HCV-RNA genotype 1 standard dilution series 39 times and a Pelicheck HCV-RNA genotype 3 reference panel in 32 test runs. The limiting dilution analysis enabled us to compare the detection efficiency of the NucliSens-Amplicor method for the genoype 1 and genotype 3 isolates and to calibrate the reference reagents against each other. The combined Nuclisens-Amplicor method was found to detect the genotype 3 isolate in the Pelicheck HCV-RNA panels with 2-3 fold lower efficiency than the genotype 1 standard (assuming that the historical calibration of the genotype 3 against the genotype 1 standard is correct). In this study of a single method 1 IU of the WHO HCV-RNA standard was found to be equivalent to 5.1 geq of the VQC HCV-RNA standard (95% confidence intervals 3.1-9.1 geq). To avoid confusion with the use of the CLB VQC reagents we accept the NIBSC collaborative study in which calibration by a variety of methods showed that the Pelispy 380 geq/ml run control is equivalent to 100 IU/ml of the WHO standard. This multi-centre validation study demonstrates that the 95% detection limit of the NucliSens HCV Amplicor method lies far below the detection limits required by the international regulatory bodies.

Europe↗