Hydrophobic amino acid residues are critical for the immunodominant epitope of the Goodpasture autoantigen. A molecular basis for the cryptic nature of the epitope.

Goodpasture (GP) autoimmune disease is caused by autoantibodies to type IV collagen that bind to the glomerular basement membrane, causing rapidly progressing glomerulonephritis. The immunodominant GP(A) autoepitope is encompassed by residues 17-31 (the E(A) region) within the noncollagenous (NC1) domain of the alpha 3(IV) chain. The GP epitope is cryptic in the NC1 hexamer complex that occurs in the type IV collagen network found in tissues and inaccessible to autoantibodies unless the hexamer dissociates. In contrast, the epitope for the Mab3 monoclonal antibody is also located within the E(A) region, but is fully accessible in the hexamer complex. In this study, the identity of residues that compose the GP(A) autoepitope was determined, and the molecular basis of its cryptic nature was explored. This was achieved using site-directed mutagenesis to exchange the alpha3(IV) residues in the E(A) region with the corresponding residues of the homologous but non-immunoreactive alpha1(IV) NC1 domain and then comparing the reactivity of the mutated chimeras with GP(A) and Mab3 antibodies. It was shown that three hydrophobic residues (Ala(18), Ile(19), and Val(27)) and Pro(28) are critical for the GP(A) autoepitope, whereas two hydrophilic residues (Ser(21) and Ser(31)) along with Pro(28) are critical for the Mab3 epitope. These results suggest that the cryptic nature of the GP(A) autoepitope is the result of quaternary interactions of the alpha 3, alpha 4, and alpha 5 NC1 domains of the hexamer complex that bury the one or more hydrophobic residues. These findings provide critical information for understanding the etiology and pathogenesis of the disease as well as for designing drugs that would mimic the epitope and thus block the binding of GP autoantibodies to autoantigen.

Analysis of pressure achieved by various materials used for pressure dressings.

BACKGROUND: To minimize the risk of complications, pressure dressings are frequently applied to wounds. The actual pressures yielded by different dressing materials and application techniques have not been documented. OBJECTIVE: To measure and compare pressures produced using various types of dressing tapes with and without a gauze roll. METHODS: An infant blood pressure cuff was adapted for use in a pressure dressing model. Investigators independently applied four strips of each of five different types of tape to the cuff when it was located in three settings: a hard inanimate surface, a subject's distal volar forearm, and the subject's forehead. RESULTS: Foam and plastic tapes produced more pressure under a simple dressing than three other commonly used tapes. Higher, more consistent pressures were achieved on the forearm than the forehead. Adding a gauze roll to the dressing consistently increased the pressure. CONCLUSION: The experimental model demonstrated substantial differences in pressures yielded by various pressure dressing materials.

Correcting the bias of clerkship timing on academic performance.

OBJECTIVES: To document the time-of-year bias in National Board of Medical Examiners subject examination (NBME) scores in a third-year pediatrics clerkship and to develop a grading method that neutralizes the bias. DESIGN: Interventional modeling of final grades. SETTING: University-based medical school. SUBJECTS AND METHODS: During each of the past 3 academic years, we conducted six 2-month pediatric clerkships for third-year students. To counter the time-of-year bias, NBME scores, clinical evaluations, and departmental examination scores for the current rotation were pooled with those from the rotations from the same time of year during the previous 2 years. Final grades for the current rotation were determined by cutoff points derived from that entire 3-year pool. We analyzed this approach by testing the time-of-year effects on NBME scores, clinical evaluations, and final grades while maintaining step 1 of the US Medical Licensing Examination as a preclinical baseline control. RESULTS: The scores for step 1 of the US Medical Licensing Examination did not differ significantly by time of year. Clinical evaluations and NBME scores showed significant upward trends as the academic year progressed. By contrast, according to design, final grades showed no significant time-of-year trend. CONCLUSIONS: Our results support previous reports of significant improvements in NBME scores across the academic year. Our method of computing final grades corrects for this time-of-year bias by judging students only in relation to those who took the rotation at the same time of year. It is our belief that the prevalence and significance of the time-of-year trend warrants such an adjustment in grading to help minimize the academic disadvantage faced by students early in their clinical training.

Assessing the value of pediatrics journals.

The pediatric literature comprises more than 500 journals. This paper reviews the relative impact of 63 pediatric journals and 26 highly cited journals that also publish pediatric articles. Using the objective measures of citation analysis and an understanding of the type of literature appropriate for one's purpose of study, physicians, scientists and students can avoid the pitfalls of information overload created by the proliferation of journals and information technology, while effectively extracting the clinical and basic science knowledge that will aid their reading and research. As the medical and scientific knowledge database continues to grow, knowing where to look for significant articles may likely become as important as knowing how to apply the information contained within them. Realizing that a significant portion of influential and important articles can be found in a relatively small group of journals can guide one's initial literature search, but one must also remember that equally valuable information can be found in other publications. Armed with the tools to minimize the field of less appropriate sources, one can more readily achieve the real purpose of a search, which is to uncover the bloom of knowledge and to nurture, cultivate and share it.

Evaluation of remote stethoscopy for pediatric telecardiology.

OBJECTIVE: To investigate the interobserver reliability and diagnostic validity of a commercial electronic stethoscope for pediatric telecardiology. MATERIALS AND METHODS: Pairs of blinded pediatric cardiologists made independent diagnoses, recommendations concerning follow-up echocardiography, and specific judgments regarding heart sounds, murmurs, and congenital heart disease using an electronic (ES) or an acoustic (AS) stethoscope on 78 pediatric cardiology outpatients and at a distance of 450 km (280 miles) with 38 telemedicine cardiology outpatients. The kappa statistic (K) indexed the instruments' interexaminer reliabilities. The validity of ES was measured by K for ES versus AS and by the percentage of cases where the findings for ES and AS differed sufficiently to suggest an important ES screening error. RESULTS: For heart disease, AS, ES, and tele-ES reliabilities were satisfactory (K = 0.80, 0.67, and 0.80, respectively), as were AS agreement with hands-on ES (K = 0.65) and with tele-ES (K = 0.64). The AS and ES reliabilities and ES/AS agreement were also satisfactory for systolic regurgitant and diastolic pulmonic murmurs (K = 0.63-0.78) but were unsatisfactory for evaluable heart sounds and other murmurs (K = 0.16-0.60). The ES yielded clinically important disagreements with AS in 5.4% of the clinic cases and 10.5% of the telemedicine cases (P = 0.67). In determining the need for additional work-up (echocardiography) or follow-up appointments, hands-on ES and tele-ES had a combined accuracy of 92%, with a sensitivity of 88% and a specificity of 97%. CONCLUSIONS: Hands-on ES provided reliable and valid screening for congenital heart disease. Tele-ES was highly reliable but had reduced diagnostic validity. Examiner blinding, bandwidth limitations, and artificial restrictions on the remote assistant may have contributed to this reduced performance. As these factors are easily correctable, we regard the ES as a highly promising tool for pediatric telecardiology.

Balloon pulmonary valvuloplasty for isolated pulmonary valvular stenosis.

Fifteen balloon pulmonary valvuloplasties (BPVs) were performed on 13 infants and children with isolated pulmonary valvular stenosis (PVS). There were no complications. Two patients required repeat BPV, one for failure, the other for restenosis. At the time of the 13 latest BPVs, age ranged from three days to 13.1 years (mean 5.7 +/- SD 4.8 years). Average Doppler pulmonary valve pressure gradient preceding BVP was 75 +/- 22 mm Hg. At follow-up it was 25 +/- 9 mm Hg (p < .0001). Follow-up interval was 0.61 to 4.70 years (2.29 +/- 1.18). Restenosis occurred in 1/13 (8%) of the patients. The remaining 12/13 (92%) showed highly satisfactory sustained gradient reductions. Doppler gradients preceding BPV by as much as 4 months correlated highly with catheter gradients at time of BPV, confirming that Doppler echocardiography is a highly accurate indication of PVS severity. Catheterization for PVS should therefore not be used for diagnostic purposes alone. BPV can be performed safely, economically and effectively and is recommended as the treatment of choice for infants and children with moderate to severe isolated PVS. For very young patients, follow-up Doppler surveillance should be done semi-annually; for all others, annually.

Cognitive strategies and strategic learning. The socio-instructional approach.

Recent developmental studies have focused on children's learning strategies and on the socio-instructional dynamics that foster strategic learning. The introduction of Vygotsky's concept of the zone of proximal development has been central to this research effort. Zone theory is discussed in the context of traditional cognitive strategies research and in terms of its practical applications.

Memorizing: a test of untrained mildly mentally retarded children's problem-solving.

Forty untrained mildly mentally retarded and 32 untrained nonretarded junior high school students were given eight trails of practice on a self-paced memory problem with lists of letters or words. For each trail a new list was presented, requiring ordered recall of terminal list items followed by ordered recall of initial items. Subgroups of solvers and nonsolvers were identified at each IQ level by a criterion of strict recall accuracy. Direct measures of mnemonic activity showed that over trails, solvers at both IQ levels increasingly fit a theoretically ideal memorization method. At neither IQ level did nonsolvers show similar inventions. On early trials, for both IQ levels, fit to the ideal method was uncorrelated with recall accuracy. On late trials fit and recall were highly correlated at each IQ level and across levels. The results support a problem-solving theory of individual differences in retarded and nonretarded children's memory performances.

Instructed rehearsal strategies' influence on deaf memory processing.

Congenitally deaf subjects were compared with normal-hearing subjects on short-term retention accuracy and correct response latency. The subjects paced themselves through serial lists of consonant letters six- or seven-items long. Presentation of each list was followed by a position-probe test requiring the subjects to specify where in the list a particular letter had appeared. The subjects were first observed while generating their own input strategies (free strategy). In subsequent sessions they adopted instructed rehearsal strategies involving primary and secondary memory components. Overall, the normal-hearing subjects were more accurate and responded faster than the deaf subjects. Instructing rehearsal strategies resulted in immediate gains on these measures for both groups. For both measures the deaf subjects became at least as proficient as the normal-hearing subjects had been under free strategy. The patterns of correct response latencies for the groups revealed strikingly different comparisons for primary and secondary memory. Following strategy instruction, latencies for the terminal list items never differed for the two groups, indicating that primary memory in the deaf is fully intact. However, the deaf responded slower on the first items of the list, indicating secondary memory deficiencies.