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PubMed1992

Palliative care 2000--home care.

In summary, although I have reservations about the feasibility and cost-effectiveness of regional palliative care centres as described in the report, my recommendations strongly concur with those of the Expert Panel on Palliative Care. With reference to home care, I would like to reiterate the following major points: There must be a major shift of resources into home care and the establishment of "in-the-home projects" within palliative care units. The control of suffering--palliative care--must be a full and equal partner in cancer care. The specialized aspect of home care will benefit from the direct network of a regional medical advisory committee, a quick-response and consultant team, and the integrated coordination system that a regional model offers.

Canada↗
PubMed1988

The diagnosis and classification of Hodgkin's disease is still a problem.

The initial histopathologic diagnosis and Rye classification of 172 cases of Hodgkin's disease referred to a regional cancer centre during a period of 8 years was reviewed prospectively by a pathologist in the cancer center who referred 82 cases to a panel made up of pathologists practicing in the region. The proportion of cases with errors in the diagnosis of Hodgkin's disease or Rye classification fell from 47.6% in the first year to 23.1% in the third year and 17.4% in the final year. The performance of the panelists did not vary in any consistent way over the 8-year period. The mean level of agreement among the panelists was 86.7% for the diagnosis of Hodgkin's disease and 63.3% for the Rye classification. A regional program for the ongoing prospective review of all histological diagnoses of Hodgkin's disease can improve the accuracy of initial diagnosis and Rye classification but significant discrepancies persist.

Hodgkin Disease↗
PubMed1982

Monoclonal antibodies to Chlamydia trachomatis: antibody specificities and antigen characterization.

Nineteen independent hybrid cell lines that produce monoclonal antibodies to Chlamydia trachomatis surface antigens were prepared by the fusion of mouse myeloma cells with lymphocytes of mice that were immunized with C. trachomatis immunotypes B, C, and L2. Seven serologically distinct reaction patterns were detected by microimmunofluorescence (micro-IF) of elementary body (EB) preparations when culture fluids were tested against a panel of 18 chlamydial serotyping reference strains. These reaction patterns demonstrated genus-, species-, subspecies-, and type-specific distributions. Additionally, these antibodies were tested in parallel against reticulate body (RB) preparations of several chlamydial strains. Monoclonal antibodies that reacted with genus-specific antigens reacted preferentially with RB, whereas antibodies that reacted to species-, subspecies-, or type-specific antigens reacted equivalently to both RB and EB. Physiochemical characterization of antigens recognized by the different monoclonal antibodies was assessed by heat treatment, pronase digestion, periodate oxidation, and immuno-blot techniques. The genus-specific antigen was a heat-stable, pronase-resistant, and relatively periodate-sensitive component of less than 10,000 m.w. The species-, subspecies-, and type-specific antigens were heat stable, pronase sensitive, and periodate resistant. The antibodies that detected species- and subspecies-specific antigens predominantly reacted in immuno-blots with the 40,000 m.w. major outer membrane protein. These monoclonal antibodies now provide a new approach for the precise serologic classification and detection of different C. trachomatis strains.

Animals↗
PubMed1997

Prognostic significance of fluorescence intensity of surface marker expression in childhood B-precursor acute lymphoblastic leukemia. A Pediatric Oncology Group Study.

This report describes the prognostic significance of the intensity of surface membrane antigen expression in a series of 1,231 children older than 1 year with newly diagnosed B-precursor acute lymphoblastic leukemia (ALL) treated on Pediatric Oncology Group (POG) treatment protocols. All patients had dual-color flow cytometric immunophenotyping performed at a central reference laboratory with a standard panel of monoclonal antibodies. The flow cytometers used in the study were calibrated with a standard fluorescence microparticle that permitted conversion of relative fluorescence channels to standard units of mean equivalents of soluble fluorochrome (MESF). In univariate analysis, fluorescence intensity of CD45 and CD20 was significantly associated with event-free survival (EFS), whereas other markers showed no significant correlation with outcome. Patients whose blasts were greater than the 75th percentile of intensity for CD45 (corresponding to 18,000 MESF units with CD45-FITC, or about 8% of the intensity of normal lymphocytes) fared significantly worse than those with lower-density CD45, and those whose blasts were greater than the 25th percentile of intensity for CD20 (corresponding to 17,900 MESF units with CD20-PE) had a poorer EFS. The intensity of both CD45 and CD20 was independently correlated with outcome. There was no significant correlation between intensity of expression of either antigen and traditional clinical risk factors, ploidy, or t(9;22) or t(1;19). All patients with t(4;11) had CD45 intensity greater than the 75th percentile, but CD45 intensity retained its prognostic significance after adjusting for t(4;11). In multivariate analysis, both CD45 intensity greater than the 75th percentile and CD20 intensity greater than the 25th percentile were significantly correlated with poor outcome independently of previously reported poor prognostic factors including National Cancer Institute (NCI) risk group, ploidy, trisomies of 4 and 10, and adverse translocations including t(1;19), t(9;22), and t(4;11). We conclude that in childhood B-precursor ALL, the intensity of expression of CD20 and CD45 provides prognostic information not available from simple consideration of antigen expression as positive or negative, and adds to that obtained from traditional clinical and biologic risk factors.

Adolescent↗
PubMed1994

Olfactory bulbectomy leads to learning/memory impairments in 3-panel runway and 3-lever operant tasks.

The effects of olfactory bulbectomy on the learning and memory of rats were examined, using several memory tasks. In reference memory and working memory tasks using a 3-panel runway apparatus, acquisition was delayed markedly by bilateral ablation of the olfactory bulb (OB). OB lesion performed after acquisition markedly impaired both reference and working memories. Even when the tasks were repeated for several sessions, the impairment of memory in OB-lesioned rats did not recover to the control level of the sham operation group. The delayed matching-to-lever location (DMLL) performance, which was examined using a 3-lever operant apparatus, was markedly impaired by OB lesions. This impairment was mild immediately after surgery, but tended to increase with time. Rats with OB-olfactory tubercule lesions show more severe impairment of memory in the DMLL performance. Reversal learning, using a 2-lever operant apparatus, was markedly impaired by OB lesions. The impairment of working and reference memories in OB lesioned rats, which was assessed using a 3-panel-runway apparatus, was reduced by cholinesterase inhibitor physostigmine and NIK-247. These findings suggest that the OB plays a very important role in the learning and memory processes necessary for both a working memory task and a reference memory task and that, at least in part, the memory impairment in OB lesioned rats is mediated by lowering of cholinergic function.

Animals↗
PubMed1995

Concurrent blockade of beta-adrenergic and muscarinic receptors disrupts working memory but not reference memory in rats.

In order to clarify the interactions between monoaminergic and cholinergic systems in working and reference memory functions, the effects of administration of the alpha, beta-adrenergic, D1-, D2-dopaminergic or serotonergic receptor antagonist together with the muscarinic receptor antagonist scopolamine on this behavior were examined using a three-panel runway task. Both in working and reference memory tasks, the number of errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points) was significantly increased by 0.32 mg/kg scopolamine, but not by the doses up to 0.18 mg/kg. The beta-adrenergic antagonist propranolol at 10 mg/kg had no effect on the number of working memory errors. Combined administration of 10 mg/kg propranolol and scopolamine at 0.1 and 0.18 mg/kg significantly increased the number of working memory errors. However, in a reference memory task, propranolol at 10 mg/kg did not affect the number of errors, whether administered alone or together with 0.1 mg/kg scopolamine. Other monoaminergic receptor antagonists, including the alpha-adrenergic antagonist phentolamine (3.2 and 10 mg/kg), D1-antagonist SCH23390 (0.032 and 0.056 mg/kg). D2-antagonist sulpiride (100 mg/kg) and serotonin antagonist cinanserin (10 and 32 mg/kg) had no significant effect on working or reference memory errors, whether they were administered independently or in combination with scopolamine at 0.1 mg/kg. These results suggest that beta-adrenergic/muscarinic interactions play an important role in mediating processes involved in working memory performance of rats.

Adrenergic beta-Antagonists↗
PubMed1987

Susceptibility testing of fastidious organisms in the API microdilution panel.

It has become increasingly important to perform routine susceptibility tests on certain anaerobic bacteria, Haemophilus influenzae and Streptococcus pneumoniae, as a result of the decreasing predictability of their antimicrobial susceptibility patterns. The antimicrobial susceptibilities of 49 anaerobic isolates, 25 H. influenzae isolates, and 25 S. pneumoniae isolates were determined concurrently by API Uniscept MIC trays and a conventional broth microdilution method using Wilkins-Chalgren broth, 5% Fildes in Schaedler broth, or 5% lysed horse blood in Mueller-Hinton broth, respectively. Analysis of 490 anaerobic organism-antibiotic combinations, 144 H. influenzae-antibiotic combinations, and 125 S. pneumoniae-antibiotic combinations showed that 98.9%, 100%, and 99.2%, respectively, of the API results were within +/- 1 log2 dilution of the reference system. The API Uniscept MIC panel would be acceptable for use as a routine susceptibility system for anaerobic organisms in a clinical microbiology laboratory. To eliminate trailing endpoints, however, further studies need to be performed to evaluate additional broth media for the susceptibility testing of H. influenzae and S. pneumoniae in the API panels.

Anti-Bacterial Agents↗
PubMed1994

Chromosomal assignment of HepG2 3'-directed partial cDNA sequences by Southern blot hybridization using monochromosomal hybrid cell panels.

Large-scale sequencing of a 3'-directed cDNA library from the human liver cell line HepG2 has generated several hundred species of cDNA gene signatures, about 85% of which identify novel genes. They are useful molecular landmarks for human genome mapping. We used 160 of these novel signatures as probes for Southern hybridization to human DNA. We then identified the copy number of the corresponding genes and assigned them to chromosomes, with reference to monochromosomal hybrid cell mapping panels. The distribution profile of the expressing genes among chromosomes suggested that the expressing gene density is not uniform.

Animals↗
PubMed2006

Treating chronic noninfectious posterior segment uveitis: the impact of cumulative damage. Proceedings of an expert panel roundtable discussion.

Chronic noninfectious posterior segment uveitis refers to inflammation of the retina, choroid, vitreous, or optic nerve, and may result in permanent vision loss. The inflammation can be constant, or characterized by periodic exacerbations on an underlying baseline of inflammation. Recent studies indicate that this vision loss often results from cumulative damage over multiple recurrences of inflammation, rather than from a single initiating event. Most forms of local therapy provide only transient suppression of inflammation, and the use of systemic agents may be limited by serious side effects. The course of uveitis may, therefore, be marked by recurrent episodes of inflammation, each contributing to progressive and permanent loss of visual acuity. The goal of uveitis treatment should not only be to suppress inflammation when it recurs but also to attain complete remission of inflammation, and thus prevent complications such as cystoid macular edema (CME) and permanent cumulative damage. The RETISERT intravitreal implant offers sustained local control of inflammation without the systemic side effects that limit standard immunosuppressive and oral corticosteroid therapies. The recommendation of the expert panel was that RETISERT is a useful addition to the armamentarium for the treatment of chronic noninfectious posterior segment uveitis and may help to prevent cumulative damage from repeated occurrences of inflammation, especially when vision can be improved rather than only stabilized.

Anti-Inflammatory Agents↗
PubMed2005

Panel of prototypical infectious molecular HIV-1 clones containing multiple nucleoside reverse transcriptase inhibitor resistance mutations.

We have created a panel of recombinant HIV-1 infectious clones containing common patterns of reverse transcriptase (RT) mutations responsible for resistance to each of the currently available nucleoside reverse transcriptase inhibitors (NRTI), and we have submitted the panel to the National Institutes of Health AIDS Research and Reference Reagent Programme. Testing the activity of new antiretroviral compounds against this panel of drug-resistant clones will determine their relative activity against many clinically relevant NRTI-resistant viruses.

Clone Cells↗
PubMed1994

Comparison of sensititre broth microdilution and agar dilution susceptibility testing techniques for meropenem to determine accuracy, reproducibility, and predictive values.

The stability, accuracy, reproducibility, and predictive value of Sensititre MIC panels containing meropenem (Merrem) were evaluated by using National Committee for Clinical Laboratory Standards (NCCLS)-recommended American Type Culture Collection (ATCC) strains and 110 selected strains of rapidly growing and fastidious aerobes and anaerobes with various degrees of susceptibility to meropenem. The NCCLS-recommended agar dilution method was used as a standard reference method. Meropenem-containing Sensititre MIC panels were monitored for their stabilities at room temperature and reproducibilities over 24 months by using six ATCC strains. Ninety-nine percent of the MICs of both meropenem and imipenem obtained for NCCLS-recommended ATCC strains were within the established ranges after 2 years. The overall agreement (+/- 1 twofold dilution) between the Sensititre and the agar dilution meropenem MICs was greater than 93%. The predictive value of meropenem MICs for indicating suspeptibility or resistance obtained by the Sensititre method was greater than 90%. No major or very major interpretive errors were observed, and only 5% of meropenem MICs were associated with minor interpretive errors. Problematic organisms were not observed. The Sensititre MIC panels containing meropenem offer a convenient and valid alternative to the NCCLS reference method for the susceptibility testing of potential pathogens likely to be recovered from mixed infections.

Agar↗
PubMed2006

Chapter 23: International Standard reagents for harmonization of HPV serology and DNA assays--an update.

International reference materials such as International Standard reagents facilitate quality assurance of essential biopharmaceutical products and related in vitro diagnostic tests. Standardization of antibody and DNA measurements and harmonization of laboratory procedures are key to the success of cancer prevention strategies through screening methods as well as for development and implementation of vaccination against the human papillomavirus (HPV). The WHO supported the preparation and initial analysis of a panel of candidate serological and DNA reference reagents aimed at facilitating inter-laboratory comparisons and detection of HPV worldwide. Two international collaborative studies assessed the performance of various HPV antibody and HPV-DNA detection assays and examined the feasibility of generating HPV antibody and DNA standard reagents. These studies showed that improvement in performance and comparability of assays is urgently needed and that the use of the same International Standard reference reagent could significantly improve performance and comparability. It is hoped that the establishment of International Units and International Standards for HPV antibody and DNA analysis will be pursued with high priority.

Humans↗
PubMed2003

Determination of laboratory reference ranges for lymphocyte immunophenotype subsets in healthy adult Japanese using flow cytometry.

This study represents a comprehensive evaluation of normative values for lymphocyte immunophenotype subsets using flow cytometry techniques in a Japanese population. Lymphocyte reference ranges were determined for percentage and absolute count of T, B, and NK cells in healthy adult Japanese using an extensive two-color immunophenotyping panel and consistently applied quality control methodology. Reference values were also determined for activation markers on CD3+ lymphocytes CD3+/CD25+, CD3+/CD38+ and CD3+/HLA-DR+. Differences in age and gender were observed for specific lymphocyte subsets. Comparison of the Japanese study with a Thai multi-center study that used similar methodology also demonstrated ethnic differences in lymphocyte reference ranges. The results in this study strongly suggest that reference values derived from studies in one population may not be applied to another population even when similar protocols for reagents, instruments and procedures are used although such studies do appear useful for epidemiological comparisons.

ADP-ribosyl Cyclase↗
PubMed1992

An international collaborative study to assess a set of reference reagents for HIV-1 PCR.

An international collaborative study was performed to evaluate a set of PCR reference reagents for HIV diagnosis. Twenty-six laboratories from 9 countries analysed a proficiency panel of 10 coded DNA samples using the PCR reference reagents and protocols. For comparison, these coded samples were then assessed using a laboratory's own 'in-house' reagents and methodologies. The objectives of the study were: (i) to assess inter-laboratory variation of PCR sensitivity, (ii) to evaluate the DNA 'carryover' problem and frequency of false negative results and (iii) to examine the utility of the complete set of reagents and templates to act as reference preparations for HIV PCR. Using the reference reagents, 46% of laboratories reported no false positive results in any of their assays of the negative controls. The remaining laboratories all reported a false positive result(s) in at least one assay. The overall false positive result rate for the study was 9.3%. In contrast, an overall false negative result rate of 7.4% was observed, with some laboratories recording negative results even for samples containing 10,000 molecules of target DNA. The level of absolute sensitivity may be assessed accurately only from the 12 laboratories that obtained no false positive results. All 12 laboratories detected the sample containing 10 molecules of template DNA and 9 out of the 12 laboratories detected the sample containing 1 molecule. This is in close agreement with the theoretical detection rate based on a statistical probability model for the detection of a single molecule. These characterised reference reagents were at least as sensitive as any of the 'in-house' reagents and methodologies applied, including nested PCR. The complete set of characterised reference reagents is now available for quality control assessment of HIV-1 PCR from the MRC ADP.

Base Sequence↗
PubMed1997

Liver transplantation in Western Australia: improved services to an isolated population.

OBJECTIVE: To assess performance of the Western Australian Liver Transplantation Service in the light of debate about whether small transplant centres can produce optimal outcomes. DESIGN: Review of patient data collected prospectively and confirmed by retrospective casenote review. SUBJECTS: All patients referred to the Western Australian Liver Transplantation Assessment Panel. Those who underwent transplantation at the Western Australian Liver Transplantation Service (to June 1996) were compared with those referred to other transplant centres before the elective service was established in July 1994. OUTCOME MEASURES: Numbers of referrals and transplants; characteristics of the transplantation procedure; and patient outcomes. RESULTS: Annual referrals for liver transplant in Western Australia (WA) increased from 12 (1985-1993) to 41 (July 1994-June 1996), with five deaths on the "activated" list before July 1994, but none after. To June 1996, 30 patients had received 31 transplants by the Western Australian Liver Transplantation Service (two emergency transplants in 1992 and 1993, respectively, and 28 elective transplants and one retransplant after June 1994), with median operation time of 5.5 hours (range, 3-10.5), median red cell transfusion of 4 units (range, 0-55) and median hospital stay of 24 days (range, 12-128). There was no severe primary graft dysfunction. Major complications included hepatic artery thrombosis or stenosis (5 patients, one requiring retransplant), biliary stricture not associated with hepatic artery pathology, bile leak and perihepatic abscess (4 each), and cytomegalovirus infection (3). Patient survival was 83% and graft survival 81% at a mean follow-up of 13 months, compared with 86% and 83%, respectively, at one year for WA patients who received transplants elsewhere before July 1994. CONCLUSIONS: Performance of the Western Australian Liver Transplantation Service compares favourably with national and international standards, and WA patients receiving liver transplants have increased dramatically since the service was established. This supports the viability of committed liver transplantation centres with only 10-15 patients a year and argues the need for nationally decentralised services.

Adolescent↗
PubMed2003

Activities of 13 quinolones by three susceptibility testing methods against a collection of Haemophilus influenzae isolates with different levels of susceptibility to ciprofloxacin: evidence for cross-resistance.

The activities of nalidixic acid, ciprofloxacin, norfloxacin, ofloxacin, pefloxacin, flerofloxacin, sparfloxacin, grepafloxacin, gatifloxacin, moxifloxacin, trovafloxacin, levofloxacin and clinafloxacin against a panel of Haemophilus influenzae strains were assessed by three susceptibility testing methods: Etest, agar dilution and the reference broth microdilution method using Haemophilus test medium (HTM) in all cases. The panel included 62 clinical and two reference H. influenzae strains; 32 had decreased susceptibility to ciprofloxacin (MIC > or = 0.12 mg/L) and 30 were susceptible to this antibiotic (MIC < or = 0.06 mg/L). Both Etest and HTM agar dilution results (r = 0.96; 86.61% and 82.1% of MICs within + one log(2), respectively) correlated well with the reference microdilution method. The MIC(90) of ciprofloxacin was 4.0 mg/L (range 0.007-32.0 mg/L). Trovafloxacin activity was similar to that of ciprofloxacin but sparfloxacin, grepafloxacin, ofloxacin, pefloxacin and flerofloxacin activities were higher (with MIC values one log(2) dilution lower than ciprofloxacin). The least active were norfloxacin (MIC(90) 16 mg/L) and nalidixic acid (MIC(90) 128 mg/L). Levofloxacin and moxifloxacin were more active than ciprofloxacin (MIC(90) 2 mg/L); clinafloxacin and gatifloxacin were the most active with an MIC(90) of 0.25 mg/L. Cross-susceptibility among all quinolones was observed (r > 0.9). Resistance to ciprofloxacin was associated with a similar magnitude of activity loss to other new and old quinolones. Ciprofloxacin MIC determination should be sufficient to detect the decreased susceptibility to the whole group of quinolones.

Anti-Infective Agents↗
PubMed2003

An international external quality assessment of nucleic acid amplification of herpes simplex virus.

BACKGROUND: There is an increasing awareness of the need for external quality control of diagnostic virology. OBJECTIVES: To assess the quality of nucleic acid amplification tests (NAT) of herpes simplex within Europe. STUDY DESIGN: Herpes simplex virus (HSV) proficiency panels were produced at the Swedish Institute for Infectious Disease Control on behalf of the European Union Concerted Action for Quality Control of Nucleic Acid Amplification in 1999 and 2000. Nine reference laboratories evaluated the production process. Each panel consisted of 12 coded samples with various concentrations of inactivated, freeze-dried HSV type 1 (HSV-1), and HSV type 2 (HSV-2), or negative controls. Positive samples included HSV-1 and HSV-2 in a range of concentrations (2 x 10(2) to 2 x 10(7) genome copies per ml) similar to those found in cerebrospinal fluids from patients with HSV encephalitis. RESULTS: Sixty-six participants reported a total of 76 data sets for panel 1, and 71 reported 78 data sets for panel 2. The majority of the participants employed qualitative 'in-house' polymerase chain reaction (PCR) methods, either in a single, nested or semi-nested format. For panel 2, 9 laboratories reported use of 'real-time' PCR in contrast to 3 for panel 1. Three laboratories submitted quantitative results on both panels. Thirty percent of the data sets had correct results for the entire panel 1. In 6 data sets (8%) a total of 11 false positive results were reported. For panel 2, 28% of the data sets had correct result. Nineteen false positive results were reported in 14 data sets (18%), but most of the incorrect results reflected a lack of test sensitivity. CONCLUSIONS: The relatively high frequency of false positive results and the large number of false-negative results, albeit at low copy number, stress the need for improvement in the quality of HSV NAT and for external quality control programmes.

False Negative Reactions↗