Performance of children on symptom validity tests: TOMM, MSVT, and FIT

Symptom validity testing is a major topic in the field of neuropsychological research, but until now, few studies focus on effort testing in children. Three symptom validity tests (SVTs), the Medical Symptom Validity Test, the Test of Memory Malingering, and the Fifteen Item Test plus several standard neuropsychological tests were administered to 73 German-language school children from 6 to 11 years.Participants were either instructed to give full effort or to follow a malingering scenario. It could be demonstrated that, except for one child, all participants with a basic reading level of grade 2 were able to pass all administered SVTs according to established cutoffs for poor effort (i.e., earned a score higher than the cutoff). For the experimental malingerers, however, it was fairly difficult to act according to the scenario throughout the session. While they scored worse in the neuropsychological tests, all but one of them failed at least one SVT. The results support the use of SVTs in childhood age. More elaborate experimental designs and studies with bona-fide patients and suspected malingerers are needed in order to evaluate both the appropriateness of available effort tests and the capabilities of children to fake poor performance.     

Single-Step Multiplex PCR Assay for Characterization of New World Leishmania Complexes

We have developed a PCR assay for one-step differentiation of the three complexes of New World Leishmania (Leishmania braziliensis, Leishmania mexicana, and Leishmania donovani). This multiplex assay is targeted to the spliced leader RNA (mini-exon) gene repeats of these organisms and can detect all three complexes simultaneously, generating differently sized products for each complex. The assay is specific to the Leishmania genus and does not recognize related kinetoplastid protozoa, such as Trypanosoma cruzi, Trypanosoma brucei, and Crithidia fasciculata. It correctly identified Leishmania species with a broad geographic distribution in Central and South America. The sensitivity of the PCR amplification ranged from 1 fg to 10 pg of DNA (0.01 to 100 parasites), depending on the complex detected. Crude extracts of cultured parasites, prepared simply by boiling diluted cultures, served as excellent templates for amplification. Crude preparations of clinical material were also tested. The assay detected L. braziliensis in dermal scrapings from cutaneous leishmanial lesions, Leishmania chagasi in dermal scrapings of atypical cutaneous leishmaniasis, and L. mexicana from lesion aspirates from infected hamsters. We have minimized the material requirements and maximized the simplicity, rapidity, and informative content of this assay to render it suitable for use in laboratories in countries where leishmaniasis is endemic. This assay should be useful for rapid in-country identification of Leishmania parasites, particularly where different Leishmania complexes are found in the same geographical area.     

Trends in HIV prevalence among public sexually transmitted disease clinic attendees in the Western region of the United States (1989-1999)

OBJECTIVES: Using data from anonymous unlinked testing of routinely collected sera, trends in HIV are compared among sexually transmitted disease patients in 4 Western urban centers. METHODS: Between 1989 and 1999, remnant sera obtained for routine syphilis testing from 256,819 patient visits to Denver, Los Angeles, San Francisco, and Seattle clinics were tested for HIV antibodies in an unlinked survey. HIV antibody test results were linked to anonymous demographic and risk information abstracted from the medical record. RESULTS: Overall cumulative HIV seroprevalences among women and among men who had sex exclusively with women were < or = 2%, declined over time, and did not exceed 8% among those who injected drugs. In contrast, cumulative HIV seroprevalences among men who have sex with men ranged from 13% in Seattle to 30% in San Francisco and declined a mean of 2.1% (95% CI, 1.6, 2.6) to 2.8% (CI 2.6, 3.1) per year, after adjustment. CONCLUSIONS: HIV infection declined over time across counties. Relative levels of HIV differed little by demographic and behavioral risk group despite differences in the severity of each county's epidemic. Because of the unique contribution of unlinked serosurveillance studies in monitoring these trends, their reinstitution in high-risk settings should be considered.     

Analog validation of German-language symptom validity tests and the influence of coaching.

Although symptom validity testing is an integral part of the repertory of neuropsychologists in a number of countries, this is not yet true for Germany. The German adaptations of two effort tests, the Medical Symptom Validity Test (MSVT) by Green and the Amsterdam Short-Term Memory Test (ASTM) by Schmand et al., were investigated with a German-language sample. An analog study was performed with 18 healthy experimental malingerers and 18 controls with a mean age of 25.4 years. The scenario contained detailed information about mild post-traumatic cognitive impairment, as well as an explicit warning against symptom exaggeration. In addition to MSVT and ASTM, the Trail Making Test (TMT), the Complex Figure Test (CFT), and Digit Span were performed. Half of the sample were also given Rey's 15-Item-Test (FIT). Both groups were significantly different in all effort and performance measures, with the exception of the ratio TMT-B:TMT-A. With MSVT and ASTM, correct classification of group membership was between 97 and 100%. For the ratio TMT-B:TMT-A, there was a considerable overlap in the test scores for the two groups and the sensitivity of the FIT was too low. Although the ASTM and the MSVT were identified by a number of subjects as possible effort measures, both tests obtained very good results within this analog design.     

B cell chronic lymphocytic leukaemia cells have reduced capacity to upregulate expression of MHC class I in response to interferon-gamma

AIMS: An important consideration in the design of a tumour vaccine is the ability of tumour-specific cytotoxic T lymphocytes (CTL) to recognise unmanipulated tumour cells in vivo. To determine whether B-CLL might use an escape strategy, the current studies compared B-CLL and normal B cell MHC class I expression. METHODS: Flow cytometry, TAP allele PCR and MHC class I PCR were used. RESULTS: While baseline expression of MHC class I did not differ, upregulation of MHC class I expression by B-CLL cells in response to IFN-gamma was reduced. No deletions or mutations of TAP 1 or 2 genes were detected. B-CLL cells upregulated TAP protein expression in response to IFN-gamma. Responsiveness of B-CLL MHC class I mRNA to IFN-gamma was not impaired. CONCLUSIONS: The data suggest that MHC class I molecules might be less stable at the cell surface in B-CLL than normal B cells, as a result of the described release of beta(2)m and beta(2)m-free class I heavy chains from the membrane. This relative MHC class I expression defect of B-CLL cells may reduce their susceptibility to CTL lysis in response to immunotherapeutic approaches.     

Presynaptic inhibition leading to disinhibition of acetylcholine release from interneurons of the caudate nucleus: Effects of dopamine, β-endorphin and d-Ala2-Pro5-enkephalinamide

The release of acetylcholine from slices of the rat striatum has been studied in two groups of animals: untreated rats and rats pretreated by intracerebroventricular injections of 6-hydroxydopamine in doses sufficient partially or completely to destroy the nigrostriatal dopaminergic tract. The amount of acetylcholine released was much greater, both under resting conditions and in the presence of ouabain. from striatal slices from the latter group. Dopamine, β-endorphin, d-Ala²-Pro⁵-enkephalinamide and morphine enhanced the ouabain-induced release of acetylcholine from normal striatal slices, but inhibited the release of acetylcholine from striatal slices of 6-hydroxydopamine pretreated rats Naloxone prevented the effects of the opioid peptides.Thus there appear to be receptors, both on the cholinergie interneurons of the striatum and on the terminals of dopaminergic fibres, which are sensitive to dopamine, β-endorphin, enkephalin and morphine. Dopamine, released from nigrostriatal neurons, inhibits acetylcholine release from striatal interneurons. It is suggested that β-endorphin, or some other enkephalin-like peptide present in the striatum, might moderate the dopaminergic inhibition of acetylcholine release by presynaptically inhibiting the release of dopamine. A disinhibition phenomenon of this type might play an important role in the modulation of neurochemical transmission.     

Cytomegalovirus infection in solid organ transplant recipients: new challenges and their implications for preventive strategies.

BACKGROUND: Late-onset CMV disease is being increasingly recognized as a significant post-transplantation complication. OBJECTIVES: To discern the impact of antiviral prophylactic strategies on the emerging syndrome of late-onset CMV disease in organ transplant recipients. STUDY DESIGN: Review of existing reports and published data relevant to antiviral prophylaxis in organ transplant recipients. RESULTS: Prevention of CMV using prophylaxis has proven effective and is widely employed in organ transplant recipients. However, late-onset CMV disease is increasingly being recognized as a significant complication in these patients. The more potent the activity of the antiviral drug and the longer duration of prophylaxis, the greater likelihood of late-onset CMV disease. CMV seronegative recipients of seropositive donor allografts appear to be at a uniquely high risk. A higher proportion of patients with late-onset CMV have tissue invasive disease. Late-onset CMV disease in liver transplant recipients conferred an independently higher risk of mortality in the first post-transplant year. Prolonged antiviral therapy may impair the recovery of CMV-specific T-cell responses. Preemptive therapy appears to be less likely to be associated with CMV disease. CONCLUSIONS: Discernment of the pathophysiologic basis of late-onset CMV warrants investigation. Preemptive therapy may be the preferable approach to CMV prophylaxis.     

Telomerase reactivation is an early event in laryngeal carcinogenesis.

The exact role and timing of reactivation of telomerase, a key enzyme implicated in cellular immortalization and transformation in the multistep process of laryngeal carcinogenesis, is still unknown. We attempted to (1) determine that quantitative differences exist in the levels of telomerase catalytic subunit (hTERT) mRNA expression among different grades of laryngeal epithelial abnormalities classified according to the Ljubljana classification; (2) determine that telomerase reactivation is an important, most probably early event in laryngeal carcinogenesis; and (3) analyze whether the relative quantity of hTERT mRNA can be used as a molecular biomarker in the early detection of precancerous lesions. The relative quantity of hTERT mRNA, expressed as an hTERT index, was analyzed in 140 frozen laryngeal tissue specimens representing different morphological stages of laryngeal carcinogenesis by using a commercially available LightCycler Telo TAGGG hTERT Quantification kit. The presence and relative quantity of hTERT mRNA in laryngeal epithelium increases progressively with the degree of epithelial abnormalities. hTERT mRNA was detectable in 1/15 normal laryngeal epithelia (7%, mean hTERT index 0.02), 3/15 simple hyperplasias (20%, mean hTERT index 0.09), 10/27 abnormal hyperplasias (37%, mean hTERT index 0.18), 9/12 atypical hyperplasias (75%, mean hTERT index 0.74), 8/9 intraepithelial carcinomas (89%, mean hTERT index 1.82), and 53/62 invasive laryngeal squamous cell carcinomas (85%, mean hTERT index 2.51). Statistical analysis revealed two groups of laryngeal epithelial changes with significant differences in the levels of hTERT mRNA expression (P <.0033): (1) normal and reactive hyperplastic laryngeal epithelium (simple and abnormal hyperplasia) and (2) atypical hyperplasia (precancerous lesion), intraepithelial and invasive laryngeal squamous cell carcinoma. The results of the present study suggest that telomerase reactivation is an early event in laryngeal carcinogenesis, detectable already at the stage of precancerous laryngeal epithelial changes. Nevertheless, other genetic abnormalities appear to be necessary for progression of these epithelial abnormalities toward invasive laryngeal squamous cell carcinoma.     

The genome of bacteriophage phiKMV,a T7-like virus infecting Pseudomonas aeruginosa

The complete DNA sequence of a new lytic T7-like bacteriophage phiKMV is presented. It is the first genome sequence of a member of the Podoviridae that infects Pseudomonas aeruginosa. The linear G + C-rich (62.3%) double-stranded DNA genome of 42,519 bp has direct terminal repeats of 414 bp and contains 48 open reading frames that are all transcribed from the same strand. Despite absence of homology at the DNA level, 11 of the 48 phiKMV-encoded putative proteins show sequence similarity to known T7-type phage proteins. Eighteen open reading frame products have been assigned, including an RNA polymerase, proteins involved in DNA replication, as well as structural, phage maturation, and lysis proteins. Surprisingly, the major capsid protein completely lacks sequence homology to any known protein. Also, the strong virulence toward many clinical P. aeruginosa isolates and a short replication time make phiKMV attractive for phage therapy or a potential source for antimicrobial proteins.