In vitro expressed HPV 8 E 6 protein does not bind p 53

Summary The oncogene E 6 of human papillomavirus 8, which is associated with skin cancers inepidermodysplasia verruciformis, was transcribed and translated in vitro. The resulting 17 kDa protein did not bind to the cellular p 53 in contrast to E 6 of HPV 16.     

Complement-dependent lymphocytotoxic antibodies (CLA) in systemic lupus erythematosus preferentially inhibit the generation of alloreactive cytotoxic T cells in secondary CML.

Complement-dependent lymphocytotoxic autoantibodies (CLA) are invariably present in sera of patients with active systemic lupus erythematosus (SLE). This study aimed to test for the influence of such antibodies on the in vitro generation of human alloantigen reactive proliferative and cytotoxic T cell responses. Unsensitized or alloantigen primed memory cells were pre-treated with CLA in the presence or absence of complement. Following stimulation of the remaining cells with allogeneic peripheral blood mononuclears, the proliferative and cytotoxic capacity was evaluated. Results indicated that only pre-treatment with CLA and complement influenced these reactions whereas in the absence of complement antibodies were totally ineffective. Pre-treatment of unsensitized precursor cells reduced and delayed both proliferative and cytotoxic reactivity; in contrast, pre-treatment of memory cells exclusively reduced cellular cytotoxicity. It thus appears that such SLE associated autoantibodies in the presence of complement are capable of modifying the balance between different subsets of alloreactive T cells.     

Reliability of life event assessments: test-retest reliability and fall-off effects of the Munich Interview for the Assessment of Life Events and Conditions

This paper presents the findings of two independent studies which examined the test-retest reliability and the fall-off effects of the Munich Life Event List (MEL). The MEL is a three-step interview procedure for assessing life incidents which focuses on recognition processes rather than free recall. In a reliability study, test-retest coefficients of the MEL, based on a sample of 42 subjects, were quite stable over a 6-week interval. Stability for severe incidents appeared to be higher than for the less severe ones. In the fall-off study, a total rate of 30% fall-off was noted for all incidents reported retrospectively over an 8-year period. A more detailed analysis revealed average monthly fall-off effects of 0.36%. The size of fall-off effects was higher for non-severe and positive incidents than for severe incidents. This was particularly evident for the symptomatic groups. Non-symptomatic males reported a higher overall number of life incidents than females. This was partly due to more frequent reporting of severe incidents. The findings of the fall-off study do not support the common belief that the reliability of life incident report is much worse when the assessment period is extended over a period of several years as compared to the traditional 6-month period.     

Classifying clinical severity to help solve problems of stage migration in nonconcurrent comparisons of lung cancer therapy

To compare the effects of stage migration in the "traditional" 3-stage TNM (tumor, node, metastasis) system with those in a new "expanded" 5-stage system, which has two additional stages for the poor prognostic groups, we used both systems to classify a cohort of 178 patients with primary lung cancer. To check for migrations, the stages in both systems were first assigned using only "old" technological information and were then reassigned using all the available "new" as well as old technological data. Although the 5-stage system had more migrations than the 3-stage system, survival rates were relatively unaffected for patients in the two new stages with poor prognosis. In both TNM staging patterns, the effects of stage migration on survival statistics were most impressive in the prognostically better (TNM I and II) stages. A solution to the migration problem is offered by the "clinical severity" (CS) staging system. Like the expanded TNM system, the CS system has 5 stages and a sharp prognostic gradient among stages. The CS system, however, had fewer technology-induced stage migrations than either TNM system, and the migrations had no substantial impact on stage-specific survival results. The excellent prognostic discrimination and secular stability of the CS system make it superior to the TNM system for comparing treatment results from different eras, especially for patients with stage I and II disease.     

Pathogen and resistance spectrum in intraoral infections of the jaw-facial area with special reference to anaerobic bacteria]

The aim of the study was to obtain more knowledge about the aerobic and anaerobic species causing maxillofacial infections and their resistance patterns today. Samples of pus or infectious tissue obtained from 110 patients of maxillofacial surgery were investigated microbiologically by means of aerobic and anaerobic cultivation. After incubation, the cultivated species were isolated and identified. The resistance patterns of all bacteria to penicillin, doxycyclin, and clindamycin were determined. Additionally, the resistance of aerobic species to cefuroxim was documented, and the MICs of cefoxitin and metronidazole to the anaerobic species were assessed. The most frequent disease was periodontitis apicalis (70 patients). Aerobic species alone were found in 23% of the samples, 14% of the infections harbored only anaerobes, but 63% were mixed infections caused by aerobic and anaerobic bacteria. In case of detection of aerobic species, streptococci were always identified. Five patients were infected by Staphylococcus aureus and gram-negative aerobic rods were found in eight patients. Most of the anaerobic species were black pigmented prevotella species (62), nonpigmented prevotellae (56), and fusobacteria (37). Metronidazole and clindamycin were highly efficient to gram-negative anaerobic rods. Most of the oral species were resistant to penicillin and doxycyclin. The indication for applying antibiotics should always be noticed and these drugs should only be used after determination of the pathogenic microorganisms and their susceptibility to the antimicrobials.     

Inclusion of psychopathologic methods for diagnosis of early neurotoxic effects from lead and organic solvent mixtures

To verify occupational neurotoxic effects it will be necessary to enlist the help of clinical psychologists and psychiatrists. However, no unified professional test battery exists to date. 119 healthy workers (26 lead-exposed, 45 exposed to mixed organic solvents, and 48 controls) were tested using uniformly standardised psychological and psychiatric methods. Long-term lead-exposed employees showed an increased number of psychoneurovegetative symptoms and deficits in attention performance according to the results of the Seeber-PNF and the Brickenkamp-d2-tests. There was no difference between the control group and persons exposed to the organic solvents test. Many parameters correlated to the dose of the toxic agent in the lead-exposed group. SCL-90-R, AMDP, and HAMD merely hinted at differences between the exposed subjects and the controls. Psychological and pathopsychological methods are necessary but will not suffice to detect early effects after long-term exposure to lead or organic solvents.     

Hashimoto-Enzephalopathie Steroid-sensitive Enzephalopathie bei Hashimoto-Thyreoiditis

Hashimoto's encephalopathy is a steroid-responsive, relapsing or progressive encephalopathy associated with Hashimoto's thyroiditis. Characteristic clinical features are confusion, seizures, alteration in conscious level, stroke-like episodes, myoclonus, and tremulousness. High CSF protein levels without pleocytosis and a diffusely abnormal EEG are typical findings. Brain CT and MRI and cerebral angiogram are usually normal. We present two case reports of Hashimoto's encephalopathy in 55- and 77-year-old patients who both responded well to steroid therapy, and review the literature.     

Otoacoustic emissions as a screening test for hearing impairment in children recovering from acute bacterial meningitis

OBJECTIVES: To study the efficacy of otoacoustic emissions (OAEs) as a screening test for hearing impairment in children with acute bacterial meningitis. Hearing tests were performed before discharge from the hospital in an attempt to improve coverage and avoid delays in the diagnosis of postmeningitic hearing loss. METHODS: Children with bacterial meningitis were recruited from 21 centers. In the 48 hours before discharge from the hospital, all patients underwent a thorough audiologic assessment consisting of transient evoked OAEs, auditory brainstem responses (ABRs), otoscopy, and tympanometry. Hearing loss was defined as ABR threshold >/=30 dB. The results of OAE screening were compared with the gold standard of ABR threshold. RESULTS: Of 124 children recruited, we were able to perform both OAEs and ABRs on 110 children. Seven (6.3%) of the 110 children had ABR threshold >/=30 dB; 2 had sensorineural hearing loss and 5 had conductive hearing loss. At follow-up, hearing loss persisted in both cases of sensorineural hearing loss and no new cases were identified. All 7 children with hearing loss failed the OAE screening test. Ninety-four children with normal hearing thresholds passed the test, and 9 failed. Thus, the screening test had a sensitivity of 1.00 (95% confidence interval, 0.59 to 1.00), a specificity of 0.91 (0.85 to 0.97), a positive predictive value of 0. 44 (0.20 to 0.70), and a negative predictive value of 1.00 (0.96 to 1.00). CONCLUSIONS: OAE screening in children recovering from meningitis was found to be feasible and effective. The test was highly sensitive and reasonably specific. Inpatient OAE screening should allow early diagnosis of postmeningitic hearing loss and prompt auditory rehabilitation.     

Preparticipation cardiovascular screening for US collegiate student-athletes

Context  Sudden death in young competitive athletes due to unsuspected cardiovascular disease has heightened interest in preparticipation screening. Objective  To assess screening practices for detecting potentially lethal cardiovascular diseases in college-aged student-athletes. Design, Setting, and Participants  A total of 1110 National Collegiate Athletic Association member colleges and universities were surveyed between 1995 and 1997, with 879 (79%) responding to the questionnaire. Main Outcome Measures  Information on the administration and scope of the preparticipation screening process was obtained from the team physician or athletic director; preparticipation screening forms were evaluated for content and compared with 12 items recommended by the 1996 American Heart Association (AHA) consensus panel screening guidelines. Results  Preparticipation screening was a requirement at 855 (97%) of 879 schools, was performed on campus at 713 schools (81%), and was required annually by 446 schools (51%). Team physicians were responsible for examinations at 603 (85%) of 713 schools with on-campus screening, although 135 of these schools (19%) also approved nurse practitioners and 244 schools (34%) allowed athletic trainers to perform examinations. Of the history and physical examination screening forms analyzed from 625 institutions, only 163 schools (26%) had forms that contained at least 9 of the recommended 12 AHA screening guidelines and were judged to be adequate, whereas 150 (24%) contained 4 or fewer of these parameters and were considered to be inadequate. Smaller Division III schools were more likely than larger Division I schools to have inadequate screening forms (30% vs 14%; P<.001). Relevant items that were omitted from more than 40% of the screening forms included history of exertional chest pain, dyspnea, or fatigue; familial heart disease or premature sudden death; and physical stigmata or family history of Marfan syndrome. Conclusion  The preparticipation screening process used by many US colleges and universities may have limited potential to detect (or raise the suspicion of) cardiovascular abnormalities capable of causing sudden death in competitive student-athletes.      

Iron-induced oxidative DNA damage and its repair in primary rat hepatocyte culture

Iron-overload diseases frequently develop hepatocellular carcinoma. The genotoxic mechanism whereby iron is involved in hepatocarcinogenesis might involve an oxidative process via the intermediate production of reactive oxygen species. This was presently investigated by examining kinetics of formation and repair of DNA base lesions in primary rat hepatocyte cultures supplemented with the iron chelate, ferric nitrilotriacetate Fe-NTA (10 and 100 microM). Seven DNA base oxidation products have been identified in DNA extracts by gas chromatography- mass spectrometry, which showed a predominance of oxidized-purines (8- oxo-guanine, xanthine, fapy-adenine, 2-oxo-adenine) above oxidized pyrimidines (5-OHMe-uracil, 5-OH-uracil, 5-OH-cytosine) in control cultures. All these DNA oxidation products revealed a significant dose- dependent increase at 4 to 48 h after Fe-NTA supplementation, among which fapy-adenine showed the highest increase and 5-OH-cytosine was the least prominent. Involvement of iron in this oxidative process was established by a correlation between extent in DNA oxidation and intracellular level of toxic low molecular weight iron. DNA excision- repair activity was estimated by release of DNA oxidation products in culture medium. All the seven DNA oxidation products were detected in the medium of control cultures and showed basal repair activity. This DNA repair activity was increased in a time- and dose-dependent fashion with Fe-NTA. Oxidized-pyrimidines, among which was 5-OHMe-Uracil, were preferentially repaired, which explains the low levels detected in oxidized DNA. Since oxidized bases substantially differed from one another in terms of excision rates from cellular DNA, specific excision- repair enzymes might be involved. Our findings, however, demonstrate that even though DNA repair pathways were activated in iron-loaded hepatocyte cultures, these processes were not stimulated enough to prevent an accumulation of highly mutagenic DNA oxidative products in genomic DNA. The resulting genotoxic effect of Fe-NTA might be relevant in understanding the hepatocarcinogenic evolution of iron-overload diseases.