Distorted perceptions of competence and incompetence are more than regression effects.

Students inaccurately assess their own skills, especially high- or low-performers on exams. This study assessed whether regression effects account for this observation. After completing the Infection and Immunity course final exam (IIF), second year medical students (N = 143) estimated their performance on the IIF in terms of percent correct and percentile rank. Second year grade point averages (M2GPAs) were combined with the IIF results to form five subgroups: 1 = true-low (lowest third on both IIF and M2GPA, 2 = false-low (lowest third on IIF only), 3 = middle (neither lowest nor highest third on IIF), 4 = false-high (highest third on IIF only), 5 = true-high (highest third on IIF and M2GPA). The false-low and false-high groups were considered more susceptible to regression effects due to likely group misclassification. Differences between self-assessment and actual performance within each group and between the five groups were used to estimate what portion of observed differences is due to general tendencies versus regression effects. Results found that students accurately assessed their percent correct, but inaccurately assessed their percentile rank. No statistically significant differences existed between the true and false-low subgroups nor the true- and false-high subgroups. Percentages of mean differences suggest that while regression effects resulted in 50-75% over/under-estimates of scores by students who were misclassified, when they were merged with the true-low/high groups, they do not account for more than 14% of low performer over-estimates of their performance and high performer under-estimates of their performance. Accurate percent correct assessments and distorted percentile rank assessments are challenges in using instructional methods dependent on student self-assessments of their learning needs. Identifying and helping students with distorted perceptions of their test performances may be a key issue in such instructional approaches.

Successful peer review of courses: a case study.

The authors describe their school's system of peer review for courses, established in 1988 to facilitate faculty evaluation and continual course and curriculum improvement. (The system has been temporarily suspended while the school's new curriculum becomes established.) They explain how the system was created and then report how faculty reviews of courses over the five-year operation of the system compared with students' reviews of the same courses. The faculty and students' ratings were in agreement 75% of the time. When not in agreement, the students' ratings tended to upgrade courses that were not very demanding, had easy grading, and emphasized clinical details, often at the expense of basic concepts and the big picture. The authors then document how the work of the peer review system favorably influenced the transformation of the school's curriculum. They also provide guidelines for the creation and operation of a course review process that uses faculty peers. The authors maintain that the peer review system worked because it was run by a committee of experienced and respected teachers who had been selected by their peers, the other faculty. Additional reasons for its success were that the school's faculty supported and respected the committee and its work, that course directors helped evaluate their courses, and that peer reviewers took their work seriously despite having no remuneration, and the clearly positive impact of the review system on faculty interaction, faculty-student interaction, and the reform of the curriculum.

Comparative analysis of human papillomavirus detection by PCR and non-isotopic in situ hybridisation.

AIMS--To assess the relative diagnostic performance of the polymerase chain reaction (PCR) and non-isotopic in situ hybridisation (NISH) and to correlate these data with cytopathological assessment. METHODS--Paired analysis of human papillomavirus (HPV) detection was performed by PCR and NISH on exfoliated cervical cells from 122 women attending a routine gynaecological examination. PCR amplification followed by generic and HPV type specific hybridisation was compared with NISH on a parallel cervical smear. RESULTS--Overall, 32 cases were positive by NISH and 61 positive by PCR. Of the 105 cases in which both PCR and NISH were interpretable, 76 (26%) were normal smears, 20 of which were HPV positive by NISH and 37 (49%) by PCR. Of 17 borderline smears, two were NISH positive and 12 PCR positive. Eight of nine smears containing koilocytes were positive by NISH and seven by PCR. Of three dyskaryotic smears, none were NISH and two were PCR positive. The concordance of NISH and PCR in these samples was 57%. To assess sampling error, NISH and PCR were performed on an additional 50 cases using aliquots from the same sample. This increased the concordance between assays to 74%. Filter hybridisation of PCR products with the cocktail of probes used in NISH (under low and high stringency conditions) demonstrated that several cases of NISH positivity could be accounted for by cross-hybridisation to HPV types identified by PCR but not present in the NISH probe cocktail. CONCLUSIONS--Sampling error and potential cross-hybridisation of probe and target should be considered in interpretation of these techniques. PCR is more sensitive because it provides for the amplification of target DNA sequences. In addition, the PCR assay utilised in this study detects a wider range of HPV types than are contained in the cocktails used for NISH. However, PCR assays detect viral DNA present both within cells and in cervical fluid whereas NISH permits morphological localisation.

Human papillomavirus detection and p53 expression in clear-cell adenocarcinoma of the vagina and cervix.

OBJECTIVE: To determine whether infection with oncogenic human papillomavirus (HPV) and/or altered expression of the tumor suppressor protein p53 is associated with clear-cell adenocarcinoma of the vagina or cervix. METHODS: Paraffin-embedded tissue specimens were studied from 14 women with clear-cell adenocarcinoma of the vagina or cervix. Nine women had a history of intrauterine diethylstilbestrol exposure. Human papillomavirus DNA was amplified via the polymerase chain reaction using consensus L1 primers and was detected by dot blot hybridization with a generic HPV probe and type-specific oligonucleotide probes. P53 protein was detected by immunohistochemical analysis with a mouse monoclonal antibody, DO-7. RESULTS: Three tumors contained HPV 31 DNA sequences. Eight tumors were HPV DNA-negative and three were indeterminate for HPV. P53 was detected in ten tumors; it was undetectable in the three tumors containing HPV 31 and in one tumor indeterminate for HPV. Three patients presented with or later developed metastatic disease. In each case, the tumor, including sites of metastasis, was HPV-negative and p53-positive. CONCLUSIONS: These findings suggest that infections with oncogenic HPVs may be a cofactor in the development of clear-cell adenocarcinoma of the vagina or cervix, though this association is less than that reported for squamous or non-clear-cell adenocarcinomas. Prior studies have shown that detection of the p53 protein by immunohistochemistry correlates with mutations in the p53 tumor suppressor gene. The detection of p53 in HPV-negative clear-cell adenocarcinoma suggests a second mechanism in the etiology of these rare tumors.

Distribution of human papillomavirus types in genital lesions from two temporally distinct populations determined by in situ hybridization.

We examined 341 paraffin-embedded cervical tissues for human papillomavirus (HPV) DNA by in situ hybridization. The genital lesions examined represented tissue biopsies from two temporally distinct populations (1964 to 1965 and 1988 to 1989). Biotinylated probes to 14 different HPV types were used in our analysis: HPV types 6, 11, 16, 18, 31, 33, 35, 42, 43, 44, 45, 51, 52, and 56. The number of HPV DNA-positive specimens and the distributions of HPV types were similar for these two populations. Human papillomavirus DNA sequences were detected in approximately 50% of the tissues from each time period. Of the low-grade lesions (condyloma/cervical intraepithelial neoplasia 1 [CIN 1]) 52% (1964 to 1965) and 35% (1988 to 1989) were positive for HPV DNA by in situ hybridization. Among the high-grade lesions (CIN 2/CIN 3), 41% (1964 to 1965) and 67% (1988 to 1989) had detectable HPV sequences. Approximately 15% of the tissues with minimal histopathologic changes also contained HPV DNA. Human papillomavirus types 16 and/or 18 were the most common viral types in lesions from both time periods, followed by types 31/33/35; 6/11, 51/52; and 42/43/44, 45/46. Types 16 and/or 18 were strongly associated with high-grade lesions. Five percent of the HPV-positive lesions demonstrated evidence of multiple infections. Our results indicate that HPV DNA sequences can be detected readily by in situ hybridization in archival materials, even those prepared more than 25 years ago. In addition, analysis of HPV type distributions demonstrates that recently isolated HPV types (42, 43, 44, 45, 51, 52, and 56) were equally represented in tissues from both time periods.

Evaluation of cerebral vasomotor reactivity by various vasodilating stimuli: comparison of CO2 to acetazolamide.

To evaluate the role of different vasomotor stimuli for the measurement of cerebrovascular vasomotor reactivity (VMR), 47 patients (i.e., 93 hemispheres) with various degrees of internal carotid artery (ICA) occlusive disease were studied. Patients were divided into clinical [asymptomatic, transient ischemic attack (TIA) or completed stroke] as well as angiological subgroups. Low-grade or high-grade unilateral ICA lesions were compared to bilateral ICA occlusive disease. Relative flow velocity changes within the middle cerebral artery were measured by means of transcranial Doppler during hyper- and hypocapnia (VMRTOT), during hypercapnia alone (VMRCO2), and after injection of 1 g acetazolamide (VMRACE). VMR was expressed as the percentage change in flow velocity after stimulus application as compared with flow velocity at rest. There was a close and statistically highly significant correlation of CO2-induced with acetazolamide-induced VMR (r = 0.69 in VMRTOT versus VMRACE and 0.79 in VMRCO2 versus VMRACE; P less than 0.0001; linear regression), indicating a strong similarity of the vasodilatative effects of CO2 and acetazolamide on cerebral arteries. Both stimulation techniques highly significantly differentiated between asymptomatic patients and those with TIA or completed stroke. Angiological subgroups were separated best by the acetazolamide test. Reclassification of patients into angiological subgroups by linear discriminant analysis was equally good with all three methods. We conclude that both acetazolamide- and CO2-induced stimulation of the cerebral vasomotors are valid techniques to measure reduction in perfusion reserve due to extracranial cerebrovascular occlusive disease.(ABSTRACT TRUNCATED AT 250 WORDS)

A tetramethylbenzidine/tungstate reaction for horseradish peroxidase histochemistry.

Tracing of neuroanatomical pathways commonly involves the histochemical demonstration of horseradish peroxidase, using the chromogen tetramethylbenzidine. A new modification of this reaction using ammonium paratungstate stabilizer retains high sensitivity while permitting the reaction to be performed at pH 6.0 in isotonic solutions. The reaction product resists solvents, allowing Nissl-stained sections to retain their peroxidase labeling. With subsequent stabilization by diaminobenzidine, the tissue is suitable for electron microscopic study and is compatible with post-embedding immunocytochemistry.

Antibodies to glutamate and aspartate recognize non-endogenous ligands for excitatory amino acid receptors.

Antisera raised against glutaraldehyde conjugates of glutamate (Glu) and aspartate (Asp) with hemocyanin proved highly specific for their respective unconjugated amino acid haptens when tested in immunocytochemical blocking experiments on sections of the rat spinal cord. In addition, immunocytochemical staining by the Glu antiserum was effectively blocked by quisqualate but not by kainate or N-methyl-D-aspartate (NMDA); staining with the Asp antiserum was effectively blocked by kainate, to a lesser extent by quisqualate, and was not affected by NMDA. These results may be explained by assuming that the specific binding regions of the antibodies tested share certain recognition characteristics with endogenous binding sites or receptors for excitatory amino acids and their agonists.

Demonstration of glutamate-positive axon terminals forming asymmetric synapses in cat neocortex.

Electron microscopic examination of sections immunocytochemically processed with an anti-glutamate serum reveals that many asymmetric synapses in the cat neocortex contain elevated levels of immunodetectable glutamate. These labelled axon terminals are likely to use glutamate as neurotransmitter. Axon terminals forming symmetric contacts were never labelled. Since glutamate is known to exert potent excitatory effects on neocortical neurons, the present finding gives immunocytochemical evidence that asymmetric synapses are excitatory.