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PubMed2003

Genotypic analysis of pulmonary Langerhans cell histiocytosis.

Reported studies show that the systemic form of Langerhans cell histiocytosis (LCH) is a clonal expansion of Langerhans cells (LC) associated with aberrant expression of several oncogenes or tumor-suppressor genes. LCH of the lung is a heterogenous group of lesions thought to be a reactive rather than neoplastic process. The histogenesis of the LCH of the lung is uncertain, and to date there are no studies investigating its underlying molecular abnormalities. We performed comparative genotypic analysis by using allelic loss (LOH) of polymorphic microsatellite markers associated with tumor suppressor genes. Fourteen cases of formalin-fixed, paraffin-embedded LCH of the lung were studied. Microdissection of a total of 26 nodules from 14 patients and paired reference lung tissue was performed under stereomicroscopic visualization. To evaluate allelic loss, we used a panel of 11 polymorphic microsatellite markers that were situated at or near tumor suppressor genes on chromosomes 1p, 1q, 3p, 5p, 9p, 17p, and 22q. The PCR products were analyzed by using capillary electrophoresis to identify germline heterozygous alleles and LOH. Allelic loss at 1 or more tumor suppressor gene loci was identified in 19 of 24 nodules. The total fractional allelic loss (FAL) ranged from 6% (1q) to 41% (22q), with a mean of 22%. The FAL in individual cases ranged from 0 (7 nodules) to 57% (1 nodule). Fifteen discordant allelic losses at 1 to 3 chromosomal loci were identified in 8 patients with multiple synchronous nodules. Our results show that LOH of tumor suppressor genes is present in the LCH of the lung, and they indicate that the putative tumor suppressor genes situated on chromosomes 9p and 22q may play a role in the development of a subset of the LCH of the lung.

Adult↗

PubMed2004

Prognostic role of CD8+ tumor-infiltrating lymphocytes in stage III colorectal cancer with and without microsatellite instability.

Previous studies have identified high numbers of intraepithelial T lymphocytes to be associated with good prognosis in various types of cancer. Few studies addressing this issue have been published for colorectal cancer. In a simulated prospective approach ("phase II prognostic factor study"), all nonmetachronous International Union Against Cancer (UICC) stage III colorectal cancers that were accessioned in the years 1994 to 1999 were included in the study (152 cases). Follow-up information as to vital status and occurrence of metachronous metastases could be obtained for all patients in the years 2001 and 2002. CD8+ intratumoral lymphocytes were quantified after immunostaining and referred to tumor cell area (CD8+ densities). Microsatellite status was determined by using the Bethesda panel of microsatellite markers. CD8+ densities ranged from 0 per square millimeter to 1436 per square millimeter of tumor area in a nonnormal distribution that was skewed toward low values. Univariate survival analyses revealed the 66th percentile as a stringent cutoff (CD8+high versus CD8+low), with CD8+high cases taking a significantly better clinical course. This prognostic impact appeared even more pronounced in the subset of patients with colon carcinomas who were receiving 5-fluouracil/leucovorin as adjuvant treatment (79 patients). Seventeen patients had carcinomas with high microsatellite instability (MSI-H). MSI-H-CD8+high cases (n = 11) showed an excellent prognosis, with tumor-free survival for 9 of the 11 patients. The prognostic effect of CD8+high was retained in Cox regression analyses when including UICC substages (IIIA to IIIC). Our results identify CD8+ tumor-infiltrating lymphocytes as a promising candidate for further evaluation in the ongoing search for prognostic and predictive factors of colorectal cancer, particularly if combined with microsatellite status.

Adenocarcinoma, Mucinous↗

PubMed2006

Price of beer and violence-related injury in England and Wales.

OBJECTIVES: Relationships between violence-related injury and potential risk factors in England and Wales were investigated over a five-year period, 1st May 1995 to 30th April 2000. METHODS: Records from all 10 economic regions of England and Wales relating to price of alcohol, youth real income, wealth, ethnic density, dates of major sporting events and seasonality were studied with reference to violent injury data derived from 58 Emergency Departments (EDs) over the same period. Panel estimation and multi-level modelling was used to evaluate associations between variables. RESULTS: Overall, 353,443 violence-related A&E attendances were identified over the five-year period. High regional violence-related injury rates correlated with low real price of alcohol as measured by price of beer. Rates of violence were higher during summer months and on days of major sporting events. CONCLUSIONS: Risk of injury in violence was closely linked to alcohol price. Beer price rises should therefore reduce violent injury. Injury reduction efforts should be intensified during the summer and on days of major sports events.

Alcohol Drinking↗

PubMed2005

Prevalence of diarrheagenic Escherichia coli in acute childhood enteritis: a prospective controlled study.

OBJECTIVE: Since diarrheagenic E. coli are not identified by common clinical laboratory techniques, we hypothesized that these organisms might be an unrecognized cause of enteritis in children in the U.S. STUDY DESIGN: 1327 children with acute gastroenteritis were identified prospectively by active surveillance in the Emergency Department (ED) and the inpatient units at Cincinnati Children's Hospital Medical Center. Stool samples were evaluated for diarrheagenic E. coli using a panel of DNA probes and adherence pattern to HEp-2 cells. Stool samples from a reference group of 555 well children were studied for comparison. RESULTS: Gene probe studies, but not HEp-2 cell adherence, demonstrated that enteroaggregative, diffusely adherent and enteropathogenic E. coli were associated with clinical illness. Each was isolated significantly more often from study subjects in the ED than controls. In children <1 year of age, enteroaggregative E. coli were isolated significantly more often from both inpatients (4.7%, Odds Ratio = 3.4, 95% confidence intervals 1.3-9.1, p <0.03) and ED patients (10.0%, Odds Ratio = 7.2, 95% confidence intervals 2.9-18.2, p <0.001) than from well children (1.4%). CONCLUSIONS: Diarrheagenic E. coli , especially enteroaggregative E. coli , may be an important, unrecognized cause of childhood diarrhea in the U.S.

Adolescent↗

PubMed1985

Clinical importance of analysing malignant tumours of uncertain origin with immunohistological techniques.

The value of immunohistology in the histopathological diagnosis of malignant tumours was evaluated in a series of 120 consecutive routinely processed biopsy specimens, all of which had been referred by histopathologists because of diagnostic difficulties. The specimens were analysed by means of a panel of monoclonal and polyclonal antibodies reactive with antigens which resist routine tissue processing. The tumours had previously been considered unclassifiable (24 cases) or categorised as probable carcinomas (43 cases) or lymphomas (53 cases). All but 8 of the 120 cases could be classified with the immunohistological technique. Lymphoma was the commonest diagnosis (66%) and accounted for 29 of the 43 cases initially thought most likely to be anaplastic carcinomas. Immunohistological methods can now resolve the majority of difficulties arising over the histological diagnosis of malignant tumours, and these methods should therefore be used on a wide scale by diagnostic histopathology laboratories.

Antibodies, Monoclonal↗

PubMed2003

Standardisation and establishment of a rabies ELISA test in European laboratories for assessing the efficacy of oral fox vaccination campaigns.

A simple and rapid enzyme linked immunosorbent assay (ELISA) to detect rabies antibodies in field fox sera has been standardised and established in several European laboratories. The same panels of 100 coded sera were investigated by four laboratories using this ELISA assay and reference serum neutralisation techniques (fluorescent antibody virus neutralisation (FAVN) test and rapid fluorescent focus inhibition test (RFFIT)). This indirect ELISA technique is highly correlated with conventional seroneutralisation test on cell culture. Results obtained with this ELISA test provide an almost perfect agreement between laboratories while the agreement of FAVN test and RFFIT results is substantial and very satisfactory. In view of this study, this simple and rapid ELISA test is a suitable tool for evaluating the sero-conversion rate in fox populations following oral rabies vaccination campaigns in European countries.

Administration, Oral↗

PubMed1998

Applicability of SSCP analysis for MHC genotyping: fingerprinting of Ovar-DRB1 exon 2 alleles from Finnish and Russian breeds.

The applicability of single strand conformation polymorphism (SSCP) analysis for major histocompatibility complex (MHC) genotyping in sheep was studied. A panel of Ovar-DRB1 exon 2 'allele fingerprints' was defined. The panel could accelerate DRB1 genotyping of new breeds when already existing sequences are used as references in SSCP analysis. In this study, seven new exon 2 sequences and 19 different alleles in total were detected from 31 animals of Finnish and Russian sheep breeds. Ovar-DRB1*0201 was detected in all the six grey Finnsheep animals included in this study, suggesting reduced MHC diversity within these animals.

Alleles↗

PubMedDate not supplied

Dose-related color vision impairment in toluene-exposed workers.

Occupational exposure to various neurotoxic chemicals can impair color vision. We evaluated this possibility in toluene-exposed workers. Thirty-three rubber workers and 16 referents were studied. We estimated toluene exposure by measuring urinary excretion of the unmodified form of the solvent (i.e., TolU). Color vision was tested with the Lanthony D-15 desaturated panel, and the outcomes were expressed quantitatively with the Color Confusion Index and the Total Confusion Index. Toluene-exposed workers had a subclinical reduction in color vision, compared with referents. We related this effect to solvent cumulative exposure--estimated as the product of urinary excretion of unmodified toluene by previous toluene exposure duration. This approach supports the hypothesis that impairment progresses as exposure continues. In the examined group of workers, toluene exposure was within the occupational limit proposed by the American Conference of Governmental Industrial Hygienists. The observed loss in color vision raises doubts on the real protection afforded by this limit--at least for effects of the solvent on the eyes. Finally, the Total Confusion Index was a more sensitive index than the Color Confusion Index in the evaluation of toluene-related color-vision impairment, suggesting that this index should be adopted in future studies of the effects of chemicals on color perception.

Adult↗

PubMed2002

Rare blood donors: the past and the future.

For many years, there has been a clinical requirement for the provision of units of rare blood for patients with either single or multiple blood group antibodies present. To co-ordinate this need, the Rare Blood Donor Working Party of the International Society of Blood Transfusion was established in 1985. Since then, the Working Party has been active in promoting information on the procedures and methods for testing, packaging, transport and delivery of rare blood internationally. The Working Party has a close relationship with the Blood Group Reference Laboratory in the United Kingdom. The availability of the World Health Organization International Donor Panel permits the rapid and accurate locating of rare blood units. The Rare Blood Donor Working Party conducts surveys, attends to technical queries and is active in education. This can assist countries that are upgrading their blood services and give them a greater understanding of the international help available when confronted with a difficult-to-transfuse patient. In the future, it is anticipated that a wider range of countries will contribute to the International Donor Panel. It is likely that with the many major population movements throughout the world and the potential consequent development of rare antibodies or mixtures of antibodies, the need for the availability of rare blood donations will remain for the foreseeable future.

Blood Banks↗

PubMed2005

Preclinical and clinical performance of the Efoora test, a rapid test for detection of human immunodeficiency virus-specific antibodies.

Barriers to effective diagnostic testing for human immunodeficiency virus type 1 (HIV-1) infection can be reduced with simple, reliable, and rapid detection methods. Our objective was to determine the accuracy, sensitivity, and specificity of a new rapid, lateral-flow immunochromatographic HIV-1 antibody detection device. Preclinical studies were performed using seroconversion, cross-reaction, and interference panels, archived clinical specimens, and fresh whole blood. In a multicenter, prospective clinical trial, a four-sample matrix of capillary (fingerstick) whole-blood specimens and venous whole blood, plasma, and serum was tested for HIV-1 antibodies with the Efoora HIV rapid test (Efoora Inc., Buffalo Grove, IL) and compared with an enzyme immunoassay (EIA) (Abbott Laboratories) licensed by the Food and Drug Administration. Western blot and nucleic acid test supplemental assays were employed to adjudicate discordant samples. Preclinical testing of seroconversion panels showed that antibodies were often detected earlier by the rapid test than by a reference EIA. No significant interference or cross-reactions were observed. Testing of 4,984 archived specimens yielded a sensitivity of 99.2% and a specificity of 99.7%. A prospective multicenter clinical study with 2,954 adult volunteers demonstrated sensitivity and specificity for the Efoora HIV rapid test of 99.8% (95% confidence interval [CI], 99.3 and 99.98%) and 99.0% (95% CI, 98.5 and 99.4%), respectively. Reactive rapid HIV-1 antibody detection was confirmed in 99.6% of those with a known HIV infection (n = 939), 5.2% of those in the high-risk group (n = 1,003), and 0.1% of those in the low-risk group (n = 1,012). For 21 (0.71%) patients, there was discordance between the results of the rapid test and the confirmatory EIA/Western blot tests. We conclude that the Efoora HIV rapid test is a simple, rapid assay for detection of HIV-1 antibodies, with high sensitivity and specificity compared to a standardized HIV-1 EIA.

HIV Antibodies↗

PubMed2006

A multi-centre evaluation of nine rapid, point-of-care syphilis tests using archived sera.

OBJECTIVES: To evaluate nine rapid syphilis tests at eight geographically diverse laboratory sites for their performance and operational characteristics. METHODS: Tests were compared "head to head" using locally assembled panels of 100 archived (50 positive and 50 negative) sera at each site using as reference standards the Treponema pallidum haemagglutination or the T pallidum particle agglutination test. In addition inter-site variation, result stability, test reproducibility and test operational characteristics were assessed. RESULTS: All nine tests gave good performance relative to the reference standard with sensitivities ranging from 84.5-97.7% and specificities from 84.5-98%. Result stability was variable if result reading was delayed past the recommended period. All the tests were found to be easy to use, especially the lateral flow tests. CONCLUSIONS: All the tests evaluated have acceptable performance characteristics and could make an impact on the control of syphilis. Tests that can use whole blood and do not require refrigeration were selected for further evaluation in field settings.

Humans↗

PubMed1998

Assignment of the mouse and cow CXC chemokine genes.

Gene specific PCR primers were constructed for five mouse and three bovine CXC chemokine genes. The mouse genes were assigned using SSCP analyses of the Jackson BSS backcross panel to two groups on chromosome 5. One group containing Gro1 and Mip2 cosegregated with reference markers Alb1 and Btc, and was positioned 2.2 cM proximal to a group comprising Ifi10, Mig, and Scyb5. The bovine genes IL8, GRO1, and GRO3, mapped using bovine x hamster somatic cell hybrids, were all found to be located on chromosome 6. The locations of these genes in these two animal species are consistent with the positions in humans (4q13-->q21), and previous syntenic relationships among these three mammals.

Animals↗

PubMed2004

Evidence of possible evasion of protective immunity by NAD-independent isolates of Haemophilus paragallinarum in poultry.

An indication of the ability of NAD-independent variants of Haemophilus paragallinarum to evade the immune system has been obtained from data obtained from several experiments. Firstly, it was noted that there was a difference in the serovar distribution between the NAD-dependent isolates in the 1990s and the NAD-independent isolates, as there was a significant decrease in the incidence of serogroup A NAD-dependent isolates. This can possibly be attributed to the extensive use of vaccines. On the other hand, most of the earlier NAD-independent isolates were serovar A. This is a possible indication of evasion of the protective immunity by the NAD-independent isolates. Further evidence of possible evasion of the protective immunity was obtained from results obtained when different isolates, both NAD dependent and NAD independent, were tested with a panel of monocional antibodies (Mabs). The V1 Mab reaction pattern was only seen in the reference strain 0083 among all of the NAD-dependent isolates tested in South Africa. This Mab was, however, found to react with some of the NAD-independent isolates. Furthermore, the isolation of NAD-dependent isolates in Australia which react with the V1 Mab also suggest possible evasion of the protective immunity by the NAD-independent isolates as no vaccines containing strain 0083 are used in Australia. In order to investigate the hypothesis of immune-evasion by NAD-independent H. paragallinarum, vaccinated and unvaccinated chickens were challenged with a NAD-independent serogroup C isolate. As a control, chickens were also challenged with NAD-dependent H. paragallinarum of the same serogroup. The results obtained indicate that there is no significnat difference in the disease profiles obtained in vaccinated and unvaccinated chickens challenged with the NAD-independent isolate, thus providing further evidence of evasion of the productivity immunity by the NAD-independent isolates. The ability of the NAD-independent isolates to evade the immune system suggests that a different vaccination strategy, or alternative control methods may be needed for the control of IC caused by these isolates.

Animals↗

PubMed1975

Is the insanity defense "unconscionable"?

The debate over the meaningfulness and utility of the insanity defense has continued unabated ober the years. President Nixon has referred to the "unconscionably abuse" of the defense. This paper, presented as part of a panel on the subject, has propounded the view that the defense is unconscionable, using that aspect of the definition dealing with unreasonableness. The historical antecedents and the religious and social philosophy of the concept of responsibility and nonresponsibility have been reviewed. In addition to the inapplicability of the concept to current social problems, and the difficulties of applying current psychiatric knowledge to effect a rational delineation between the two legal entities encompassed under the rubric of responsibility and nonresponsibility, the potential problems and the potential opportunities which may result from the abolition of the plea are presented. With these factors in mind, as well as the obvious failure of the legal-social-penal system in handling the problems of the behaviorally deviant, I believe that the use of the current system has hampered the development of possibly more reasonable alternative systems and that, therefore, the maintenance of the insanity defense is unreasonable and harmful to our society. The insanity defense, as currently constituted and institutionalized, has evolved into a rigid and archaic vestige of the legal system of an earlier era and therefore its use has, in the sense defined, indeed become "unconscionable" and lacking in social meaningfulness.

Ethics↗

PubMed2004

[Contribution of bone quality to fracture risk].

Recently Bone quality has been recognized as an important contributing factor of bone strength, as clearly stated in NIH (National Institute of Health) consensus development panel of 2000 that bone strength reflects both bone density and bone quality. Bone quality refers to architecture, turnover, damage accumulation, mineralization and matrix. In the treatment of osteoporosis anti-resorptive agents increase bone strength with decreasing bone turnover. It is important to control bone turnover within favorable range to increase bone strength without deterioration of bone quality.

Bone Density↗

PubMed1991

Preclinical antitumor activity of a new Vinca alkaloid derivative, S 12363.

S 12363 is a new Vinca alkaloid derivative obtained by appending an optically active alpha-aminophosphonate at the C23 position of O4-deacetyl vinblastine. S 12363 was evaluated for cytotoxic and antitumor activity against a spectrum of murine and human tumors. This compound was, respectively, on average, 72- and 36-fold more cytotoxic than were vincristine and vinblastine, when tested on a panel of 2 murine and 37 human tumor cell lines using the microculture tetrazolium assay. S 12363 exhibited significant antitumor activity against murine transplantable tumors (i.p. and s.c. P388 leukemia, i.p. L1210 leukemia, i.p. and i.v. B16 melanoma, i.p. M5076 sarcoma, and s.c. colon adenocarcinoma 38), while no activity was observed on s.c. Lewis lung carcinoma. S 12363, when administered i.p., showed moderate activity on human NCI-H460 lung and PANC-1 pancreas tumor xenografts in nude mice. However, when it was administered i.v., it exerted a significant activity against human HT-29 colon, NCI-H460 lung, NCI-H125 lung, PANC-1 pancreas, and A-431 vulvar tumor xenografts. S 12363 was also active in vivo against a P388 leukemia subline resistant to vincristine. On the in vivo panel of tumors used in this study, S 12363 was at least as active as reference compounds, while its optimal dosage was 10- to 40-fold lower than that of vinblastine, depending on the models studied. The effects of schedule and route of administration on the antitumor activity of S 12363 were studied in both i.p. inoculated P388 leukemia and B16 melanoma, in which the activity was improved by single and intermittent treatment (Days 1, 8, and 15) and i.p. route. S 12363, which differs only by the configuration of the asymmetric carbon atom of the side chain, was 300-fold less cytotoxic and 1000-fold less potent in vivo than was S 12363. These results suggest that S 12363 could present a therapeutic advantage over its congeners and deserves further pharmacological evaluations.

Animals↗

PubMed1994

A prospective study of factors determining the outcome of unrelated marrow donor searches: report from the International Marrow Unrelated Search and Transplant Study Working Group on behalf of collaborating centres.

Outcomes of searches for unrelated bone marrow donors were analysed to identify factors influencing the probability of identifying an HLA-matched donor and proceeding to an unrelated donor bone marrow transplant (UD-BMT). Between March 1989 and January 1991, 649 unrelated marrow donor searches were entered into the study. Searches were referred from transplant centres in Europe and North America to the Anthony Nolan Research Centre panel and/or the British Bone Marrow and Platelet Donor Panel, two predominantly Caucasian donor registries. Patient immunogenetic and clinical characteristics were documented on study search request forms and search outcomes were monitored at the donor registry. Data were analysed using proportional hazards regression. Major factors predicting favourable search outcomes were patient common Caucasian HLA phenotype and Caucasian ethnic group. Probability of search failure was increased by advanced disease, rare Caucasian HLA phenotype and referral to the smaller registry. Search failure frequently occurred at the mixed lymphocyte reaction stage. This study illustrates the relative roles of clinical, immunogenetic and registry factors in determining the outcome of searches. The information may be used to devise strategies to locate HLA-matched donors for a higher proportion of patients for whom UD-BMT is the preferred treatment.

Adult↗

PubMed1993

Evaluation of the automated VIDAS system for the detection of anti-HIV-1 and anti-HIV-2 antibodies.

A new, modular 'walk away' system for HIV 1 and HIV 2 antibody detection (VIDAS HIV 1 + 2 enzyme linked fluorescent assay) was compared with EIAs (Wellcozyme HIV recombinant, Wellcome; and Enzygnost HIV 1 + 2, Behringwerke) and Western blot (New LAV I Blot; Pasteur). 434 serum samples from HIV seropositive patients at different stages of disease, individuals at high risk, patients with conditions unrelated to AIDS and healthy blood donors were used for this evaluation together with 4 seroconversion panels, 4 serum dilution series and 'difficult' sera (repeatedly positive results in EIA, but negative or indeterminate by Western blot; n = 87). With the Western blot as the reference assay, the overall sensitivity of VIDAS HIV 1 + 2 and the alternative EIAs was 100%. Significant differences in sensitivity between the 3 EIAs were not observed for the antibody detection in the seroconversion panels and the dilution series. The specificity of VIDAS HIV 1 + 2, Enzygnost and Wellcozyme were 93.5%, 89.6% and 92.4% respectively if Western blot strips were interpreted according to CDC-criteria. A high rate of false positive results was obtained with the 3 EIAs since serum samples were not selected randomly and a large collective of 'difficult sera' was investigated. So-called 'walk away' systems like VIDAS HIV 1 + 2 offer a rapid screening for HIV antibody detection for routine laboratory diagnosis.

Acquired Immunodeficiency Syndrome↗