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A suppressor mechanism controlling lymphocyte recruitment.

The duration of the inductive effect of an antigen (alum-precipitated trinitrophenyl-keyhole limpet haemocyanin) was measured, in the presence and absence of responding spleen cells, by transfering a test population of spleen cells to irradiated mice at various times relative to antigen injection. Using allotype-congenic mice, the response of a test (Iga) population was estimated in the presence of responding (Igb) cells. In the absence of responding cells the inductive effect fell to 10% of the peak value in 9-10 days, but in their presence it reached this level in less than 5 days. Removal of T cells from the responding (Igb) population reduced their suppressive efficacy. It was concluded that B lymphocyte recruitment is curtailed not by the elimination of antigen but by an active suppressor mechanism involving suppressor T cells.

Animals↗

Evaluation of an indirect serum ELISA and a bacteriological faecal culture test for diagnosis of Salmonella serotype Dublin in cattle using latent class models.

AIMS: To evaluate a conventional bacteriological test based on faecal culture and an indirect serum ELISA for detection of S. Dublin infected cattle. To compare the predictive values of the two tests in relation to the prevalence. METHODS AND RESULTS: A total of 4531 paired samples from cattle in 29 dairy herds were analysed for presence of S. Dublin bacteria in faeces and immunoglobulins directed against S. Dublin lipopolysaccharide in an indirect serum ELISA. Sensitivity and specificity were estimated at two ELISA cut-off values using a validation method based on latent class models, which presumably provides less biased results than traditional validation methods. Stratification of data into three age groups gave significantly better estimates of test performance of the ELISA. Receiver operating characteristic (ROC) curves were constructed for comparison of overall performance of the ELISA between the three age groups. The sensitivity of the faecal culture test was low (6-14%). ELISA appeared to have a higher validity for animals aged 100-299 days of age than older or younger animals. Overall, the negative predictive value of the ELISA was 2-10 times higher than for the faecal culture test at realistic prevalence of infection in the test population. CONCLUSIONS: The diagnostic sensitivity of the faecal culture test for detection of S. Dublin is poor, the specificity is 1. The superior sensitivity and negative predictive value of the serum ELISA makes this test preferable to faecal culture as an initial screening test and for certification of herds not infected with S. Dublin. SIGNIFICANCE AND IMPACT OF THE STUDY: A quantitative estimate of the sensitivity of a faecal culture test for S. Dublin in a general population was provided. ELISA was shown to be an appropriate alternative diagnostic test. Preferably, samples from animals aged 100-299 days of age should be used as these give the best overall performance of the ELISA. Plots of ROC curves and predictive values in relation to prevalence facilitates optimisation of the ELISA cut-off value.

Animals↗

Incidence of Fusarium spp. and levels of fumonisin B1 in maize in western Kenya.

Maize kernel samples were collected in 1996 from smallholder farm storages in the districts of Bomet, Bungoma, Kakamega, Kericho, Kisii, Nandi, Siaya, Trans Nzoia, and Vihiga in the tropical highlands of western Kenya. Two-thirds of the samples were good-quality maize, and one-third were poor-quality maize with a high incidence of visibly diseased kernels. One hundred fifty-three maize samples were assessed for Fusarium infection by culturing kernels on a selective medium. The isolates obtained were identified to the species level based on morphology and on formation of the sexual stage in Gibberella fujikuroi mating population tests. Fusarium moniliforme (G. fujikuroi mating population A) was isolated most frequently, but F. subglutinans (G. fujikuroi mating population E), F. graminearum, F. oxysporum, F. solani, and other Fusarium species were also isolated. The high incidence of kernel infection with the fumonisin-producing species F. moniliforme indicated a potential for fumonisin contamination of Kenyan maize. However, analysis of 197 maize kernel samples by high-performance liquid chromatography found little fumonisin B1 in most of the samples. Forty-seven percent of the samples contained fumonisin B1 at levels above the detection limit (100 ng/g), but only 5% were above 1,000 ng/g, a proposed level of concern for human consumption. The four most-contaminated samples, with fumonisin B1 levels ranging from 3, 600 to 11,600 ng/g, were from poor-quality maize collected in the Kisii district. Many samples with a high incidence of visibly diseased kernels contained little or no fumonisin B1, despite the presence of F. moniliforme. This result may be attributable to the inability of F. moniliforme isolates present in Kenyan maize to produce fumonisins, to the presence of other ear rot fungi, and/or to environmental conditions unfavorable for fumonisin production.

Animals↗

Immunogenic complexes obtained from Salmonella typhi-murium and Salmonella typhi Ty2 by the bacterial acetone powder method.

An immunogenic complex was isolated from Salmonella typhi-murium and another one from Salmonella typhi Ty2. Both were prepared by the bacterial acetone powder method which eliminated the cell wall, the DNA almost completely and the membrane phospholipids. The complexes were denominated "New Vaccines". The S. typhi-murium new vaccine induced, even at doses of 0.5 microgram dry weight per mouse, a high degree of protection against the challenge of the virulent microorganism. By immunoelectrophoresis, 21 antigen-antibody systems could be detected, two of them corresponding to O antigens. The S. typhi Ty2 new vaccine induced better protection than the standard vaccine (heat-phenol inactivated typhoid vaccine) when both vaccines were compared in the relative potency test. Moreover, the new vaccine had very low toxicity when inoculated in humans at doses of 1 microgram dry weight, able to elicite a high antibody titre (1/1,790 mean of 10 sera) in 75% of the tested population, estimated by the complement fixation test. In contrast, the standard vaccine induced a low antibody titre (1/222, mean of 5 sera) in 50% of the humans inoculated with 1 X 10(8) bacterial cells. The new vaccine did not induce undesirable effects whereas the standard vaccine induced an important inflammatory process in 100% of the cases, with intense local pain in 67% after 24 h post-first inoculation as well as other less severe symptoms.

Acetone↗

The University of Manchester Age and Cognitive Performance Research Centre and North East Age Research Longitudinal Programmes, 1982 to 1997.

The United Kingdom Medical Research Council and Economic and Social Research Council have funded, since 1982, a longitudinal study of cognitive change in old age carried out on over 6000 volunteers aged between 50 and 96 years and resident in Newcastle-upon-Tyne and Greater Manchester. The Medical Research Council has guaranteed further funding until 1977. This paper describes the history of the study, the test batteries employed, the demographics of populations tested and the amount, and selectivity, of attrition by death and withdrawal from the study. Further aims of the study, and parallel work carried out on a number of related projects concerned with the epidemiology, time-course and everyday impacts of cognitive changes in normal old age are also discussed.

Aged↗

Nickel sensitivity in the general population.

The incidence of nickel sensitivity in a population above the age of 10 was examined through epicutaneous tests with 5% nickel sulphate performed on certain school and occupational test subjects and on subjects at a home for elderly people. Nickel sensitivity was observed in 4.5% (in 44 cases of 980 tested subjects), in 8% of the females and in 0.8% of the males. In 42 of the 44 nickel-sensitive subjects there was a history of dermatitis from metal contact. At the time of testing, 16 (34%) of the nickel-sensitive subjects revealed eczema. A manifest nickel sensitivity was thus found in 1.6% of all tested subjects, in 2.8% of females and in 0.4% of males. Nickel sensitivity and a simultaneous hand eczema was noted in 0.9% of the tested population, in 1.6% of females and in 0.2% of males. Hand eczemas were rarer (20.5%) in the nickel-sensitive subjects in the population study than in the nickel-sensitive patients tested at the same time in the clinic (56.6%). No case of nickel sensitivity was occupationally related.

Adolescent↗

Ganglion cells influence the fate of dividing retinal cells in culture.

The different retinal cell types arise during vertebrate development from a common pool of progenitor cells. The mechanisms responsible for determining the fate of individual retinal cells are, as yet, poorly understood. Ganglion cells are one of the first cell types to be produced in the developing vertebrate retina and few ganglion cells are produced late in development. It is possible that, as the retina matures, the cellular environment changes such that it is not conducive to ganglion cell determination. The present study showed that older retinal cells secrete a factor that inhibits the production of ganglion cells. This was shown by culturing younger retinal cells, the test population, adjacent to various ages of older retinal cells. Increasingly older retinal cells, up to embryonic day 9, were more effective at inhibiting production of ganglion cells in the test cell population. Ganglion cell production was restored when ganglion cells were depleted from the older cell population. This suggests that ganglion cells secrete a factor that actively prevents cells from choosing the ganglion cell fate. This factor appeared to be active in medium conditioned by older retinal cells. Analysis of the conditioned medium established that the factor was heat stable and was present in the <3 kDa and >10 kDa fractions. Previous work showed that the neurogenic protein, Notch, might also be active in blocking production of ganglion cells. The present study showed that decreasing Notch expression with an antisense oligonucleotide increased the number of ganglion cells produced in a population of young retinal cells. Ganglion cell production, however, was still inhibited in cultures using antisense oligonucleotide to Notch in medium conditioned by older retinal cells. This suggests that the factor secreted by older retinal cells inhibits ganglion cell production through a different pathway than that mediated by Notch.

Animals↗

A comparison of the genetic infrastructure of the Ye'cuana and the Yanomama: a likelihood analysis of genotypic variation among populations.

A general procedure is described for measuring and testing population differences in gametic frequencies. The total dispersion among populations is subdivided in hierachical fashion. The multiple-locus treatment is simply the sum of the single-locus analyses, provided gametic equilibrium obtains among the loci. In the event that gametic equilibrium does not obtain, correlations among loci need to be dealt with.--The analysis is then used to examine the genetic infrastructure of two Indian tribes from South America, the Ye'cuana (Makiritare) and the Yanomama. From historical evidence, we may identify several "clusters" of villages within each tribe. The demographic and cultural practices affecting village formation and the maintenance of peer integrity are rather different in these tribes, however, and lead us to postulate rather different patterns of genetic variation among villages. Analyses of five codominant two-allele loci, four dominant two-allele loci and two complex loci (with four codominant haplotypes each) demonstrate that Yanomama clusters are more disparate than Ye'cuana clusters, as would have been predicted on sociocultural grounds.

Blood Group Antigens↗

Brazilian Society of Surgical Oncology Analysis in Cost-Effectiveness of Population-Based BRCA Testing for Ovarian Cancer in the Public Health System.

Although ovarian cancer is the most lethal among gynecological cancers, access to massive BRCA testing is still limited. Its cost-effectiveness is still a topic of discussion in several countries. In Brazil, olaparib was recently incorporated into the public health system, access to BRCA testing is still limited. In this article, we aim to review the cost-effectiveness of offering BRCA testing to the at-risk population. A working group composed of 14 specialists in surgical oncology and cancer genetics was established to discuss the cost-effectiveness of population-based BRCA testing for ovarian cancer. The project was divided into five main areas, each with subtopics assigned among the 14 participants. They were: the existing clinical testing guidelines, the current healthcare infrastructure in the Brazilian public health system, cost-effectiveness analysis, challenges in implementing prophylactic surgeries, and family counseling and risk communication. A comprehensive literature review was conducted, followed by a series of meetings among the article's contributors to reach consensus on unresolved issues. These discussions aimed to build recommendations based on the best available scientific evidence. Using as a basis the current structure already existing within the Brazilian public health service (SUS [Sistema &#xda;nico de Saude]), and based on the testing of the at-risk population chosen by our experts, we estimated savings. The net savings for a population of 100&#x2009;000 women would range from BRL 7030.30 (US$1255.41) to BRL 1853.92 (US$331.05). And these costs could have an even greater impact when public service PARP inhibitors are incorporated. The working group of the Brazilian Society of Surgical Oncology understands that large-scale BRCA testing is cost-effective, especially when risk-reducing surgery is implemented. Other measures are important, such as training teams of non-specialists to recognize the population at risk, in addition to creating an entire line of care for patients with ovarian cancer in the SUS.

Humans↗

Epidemiological significance of bufexamac as a frequent and relevant contact sensitizer.

Bufexamac-containing ointments and creams are widely used by many patients with eczematous disorders as an alternative to topical corticosteroids. Recent studies provide evidence of a notable prevalence of contact sensitization in patch test populations. The aim of this study was to assess the frequency of use of this topically-applied drug by eczema patients in general, and to evaluate its potential to cause allergic contact reactions. 500 routinely patch tested patients (f:m = 377:123) were tested with bufexamac 5% and Parfenac ointment (the only commercial product available in Austria) in addition to the standard and other series of the German Contact Dermatitis Group. The packaging of the commercial product was shown to the entire study population, to decide whether or not they had ever used this product. In addition, their general practitioner was contacted to verify the anamnestic data. A total of 30 patients agreed that they had definitely used bufexamac, 5 others having probably applied it. The indication for and the duration of treatment were noted. Positive and relevant patch test reactions to bufexamac, as well as the bufexamac-containing ointment, were seen in 20 out of these 35 patients (57%), and sensitization occurred even after short-term application. Our study demonstrates that bufexamac has to be assumed to be a topical drug with a very high sensitization rate in an unselected patch test population (4% of 500 patients), and should therefore be added to the standard series.

Administration, Topical↗

Geographic variation in exercise testing by family physicians.

BACKGROUND: The purposes of this study were to determine the extent to which exercise stress testing is performed by family physicians; whether rural physicians are more likely to utilize exercise stress testing than their urban counterparts; and what factors influence their decisions. METHODS: A random sample of 211 practicing members of the Nebraska Academy of Family Physicians was surveyed. Responses were received from 163 (77%). To ensure independence, if two or more subjects were members of the same group practice, one was randomly assigned to the study, for a total of 125 respondents available for analysis. Questionnaire items included performance of exercise stress tests, population base, and distance to the nearest specialist who performed the test. Respondents were classified as urban, rural, or frontier, based on population per square mile in their county. RESULTS: Seventy-three of the 125 respondents (58%) reported that they perform exercise stress testing. Physicians in rural or frontier counties were twice as likely to perform the test as urban physicians (P < .001). Similar results were found for distance to the closest specialist who performs exercise stress tests (P < .001) and reported population base (P < .01). Of those performing the procedure, 42 (58%) indicated they had learned it during residency, whereas 15 (21%) were self-taught or had learned from a colleague. CONCLUSIONS: Family physicians in rural Nebraska are significantly more likely to perform exercise stress testing than those in urban areas and much more likely to do stress testing than previous national studies indicate. National guidelines should acknowledge the need for family physicians to perform exercise tests and promote training in this procedure.

Adult↗

Evaluation of AMPLICOR Neisseria gonorrhoeae PCR using cppB nested PCR and 16S rRNA PCR.

Certain strains of Neisseria subflava and Neisseria cinerea are known to produce false-positive results with the AMPLICOR Neisseria gonorrhoeae PCR (Roche Diagnostic Systems, Branchburg, N.J.). The analytical sensitivity and analytical specificity of three PCR tests were assessed with 3 geographically diverse N. gonorrhoeae strains and 30 non-N. gonorrhoeae Neisseria spp. The sensitivities of the in-house nested cppB gene and the 16S rRNA PCR methods were greater than that of the AMPLICOR N. gonorrhoeae PCR with purified DNA from all 3 N. gonorrhoeae strains. Six of 14 clinical strains of N. subflava (1 from a vaginal swab, 5 from respiratory sites) produced false-positive AMPLICOR N. gonorrhoeae PCR results and were negative by the two other PCR methods. When applied to 207 clinical specimens selected from a population with a high prevalence ( approximately 9%) of infection, the results for 15 of 96 (15.6%) AMPLICOR-positive specimens and 14 of 17 (82.3%) AMPLICOR-equivocal specimens were not confirmed by the more sensitive nested cppB PCR method. Only 2 of 94 (2.1%) of AMPLICOR N. gonorrhoeae PCR-negative specimens from the same population tested positive by the nested cppB method. These results suggest that for this population the AMPLICOR N. gonorrhoeae PCR test is suitable as a screening test only and all positive results should be confirmed by a PCR method that is more specific and at least as sensitive. This study also illustrates that caution should be used when introducing commercially available nucleic acid amplification-based diagnostic tests into the regimens of tests used for populations not previously tested with these products.

Bacterial Outer Membrane Proteins↗

The prevalence and direct costs of pre-immunization testing for hepatitis A in general practice.

Two hundred and twenty patients in one general practice travelling to destinations where immunization against hepatitis A virus (HAV) is recommended were tested for their HAV immune status before immunization. Age-specific prevalence of prior immunity to HAV was estimated. The relative costs of pre-immunization testing and immediate immunization were compared. The most cost-effective testing method for this practice was found to be total population testing prior to immunization with HAV vaccine. Individual general practices can estimate the optimal age at which to commence testing for HAV in their own practice population.

Adolescent↗

A comparison of different bedside tests for essential tremor.

OBJECTIVE: To compare the performance of different bedside tests for essential tremor (ET). BACKGROUND: Numerous tests (for example, writing, arm extension) may be used to elicit tremor in patients with ET. In large epidemiological surveys in which many patients must be evaluated efficiently, knowledge about the relative performance of these tests would be useful. METHODS: 154 subjects (42 with ET and 112 control subjects) were part of a community-based family study of ET in northern Manhattan, New York. Subjects underwent a tremor interview and a videotaped tremor examination which included six different tests for ET. Each of the six tests was performed with both the dominant and the nondominant arms. Two neurologists reviewed the videotaped examination and rated the severity of tremor during each test. Tremor ratings were 0 (none), +1 (mild), +2 (moderate), and +3 (severe). RESULTS: Among ET cases, there was considerable variation in the performance of each bedside test. With some tests (nondominant arm extension), as few as 48.8% of the ratings were >+2 and 29.8% of the ratings were 0 (no tremor). With other tests (finger-to-nose maneuver using nondominant arm), as many as 88.1% of the ratings were >+2 and only 2.4% were 0. Among the control subjects, there was also considerable variation in the performance of each test. Using some tests (finger-to-nose maneuver using nondominant arm), as many as 26.3% of the ratings were >+2, 72.8% were >+1 tremor, and only 27.2% of the ratings were 0. CONCLUSIONS: The performance of the tests varied considerably. In settings in which only one or two tests must be selected to screen a population, tests that are most likely to be abnormal in an ET case (finger-to-nose maneuver) could be used. In settings in which it is also desirable to exclude normal subjects, tests such as sustained arm extension, pouring water, or drawing a spiral could be used. Data regarding the performance of bedside tests for diagnosing ET are central to the design of research strategies for the clinical evaluation of patients with ET.

Aged↗

The beta 3-adrenergic receptor gene Trp64Arg mutation is overrepresented in obese women. Effects on weight, BMI, abdominal fat, blood pressure, and reproductive history in an elderly Australian population.

A tryptophan to arginine (Trp64Arg) mutation in the beta 3-adrenergic receptor (beta 3-AR) gene has been implicated in diabetes and obesity. We investigated the relationship of the beta 3-AR gene mutation with total body weight, BMI, central abdominal fat, blood pressure (BP), and reproductive history in 686 elderly subjects (429 women, 257 men; mean age 69.8 +/- 6.9 [+/-SD] years) from a cross section of a normal population in Australia. About 14% of the test population were heterozygote carriers of the Trp64Arg mutation; however, significant effects on clinical parameters were only observed in women. The frequency of the mutation was significantly increased in obese women compared with lean women (BMI > or = 27: 20% compared with BMI < 27: 11%, P = 0.02). Significantly higher total body weight (67.5 +/- 12.9 vs. 64.1 +/- 12.2 kg, P = 0.03) and BMI (26.3 +/- 4.7 vs. 25.1 +/- 4.5 kg/m2, P = 0.03) was observed in heterozygote women compared with normal subjects (homozygous for tryptophan). Central abdominal fat was not significantly different, except in women under 70 years, where heterozygotes had 16% higher abdominal fat compared with normal subjects. Female heterozygotes had significantly higher diastolic BP, even after adjustment for age and BMI (88.9 +/- 11.1 vs. 84.2 +/- 10.8 mmHg, P = 0.003) and a longer reproductive life, with an earlier menarche (12.8 +/- 1.3 vs. 13.4 +/- 1.5 years, P = 0.006), a higher gravidity (4.4 +/- 2.4 vs. 3.5 +/- 2.1, P = 0.01), and higher parity (3.8 +/- 2.0 vs. 3.0 +/- 1.9, P = 0.005). Clearly, the beta 3-AR mutation has pleiotrophic effects on a number of physiological systems, including BMI, BP, and reproductive history, perhaps suggesting evolutionary reasons for its maintenance in the population.

Aged↗

HLA antigens in the Arab population of the Gaza Strip.

The HLA antigen system was studied in the Arab population of the Gaza Strip. The lymphocytes of 113 individuals were typed for 13 and 16 antigens at loci A and B, respectively. The distribution of the HLA antigens was found to be similar to that of an average Caucasoid Middle Eastern population. This was more marked when the tested population was compared with Arab populations living in northern Israel or originating from Lebanon, suggesting that they probably all share a common gene pool. The only noteworthy variation in the Gaza population was the high frequency of BW21, previously found only in Eritreans and Turks.

Gene Frequency↗

Comparative evaluation of adsorption with E. coli on ELISA tests for Lyme borreliosis.

OBJECTIVE: To evaluate prospectively in a clinical setting the use of a soluble fraction of E. coli to adsorb nonspecific antibodies which can cause false positive ELISA tests for Lyme borreliosis. METHODS: The patient population tested was obtained from individuals referred to or initially presenting at a pediatric Lyme disease clinic in Wilmington, DE. Patients were followed for a minimum of 6 months subsequent to primary presentation at the clinic. RESULTS: A total of 209 met criteria for study inclusion, 93 of whom were diagnosed as having Lyme borreliosis and 116 of whom had other diagnoses. Results of ELISA tests were compared with different diagnoses and, when available, ELISA results from commercial laboratories. Findings indicate that some commercial laboratories have excessively high rates of false positive results (> 90% of positives were found to be false positives). CONCLUSION: Adsorption with E. coli antigens effectively removed antibodies causing false positive results including those occurring at commercial laboratories and did not cause any significant reduction in assay sensitivity.

Adsorption↗

Comparison of the clientele of an anonymous HIV test centre and persons tested in the general population.

This study compares the clientele of a Swiss anonymous test centre with the general population tested. Information was obtained through similar questionnaires submitted to two samples of HIV-tested people aged from 17 to 45 years: the first administered in the context of a general population telephone survey (n = 245) and the second completed during face-to-face interviews of the clientele of an anonymous test centre (n = 250). The test centre sample has higher proportions of younger and single people. Attenders for anonymous testing were more likely to have acquired a new regular partner during the year preceding the interview (48.0% versus 14.4%). These differences remain when controlling for age and gender. Decision to test comes mostly from the respondent's own initiative, but suggestion from a doctor is more frequent in the general population (23.8% versus 0.8%), whereas suggestion from partner or friends is more frequent in the anonymous centre (44.4% versus 3.0%). The anonymous test centre clientele is not different from the general population tested except for the relational situation and origin of decision for testing. The test centre has become a place where the general population finds a response to a situation-specific need for HIV testing.

Adolescent↗