A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns.

Idiopathic generalized epilepsies account for about 40% of epilepsy up to age 40 and commonly have a genetic basis. One type is benign familial neonatal convulsions (BFNC), a dominantly inherited disorder of newborns. We have identified a sub-microscopic deletion of chromosome 20q13.3 that co-segregates with seizures in a BFNC family. Characterization of cDNAs spanning the deleted region identified one encoding a novel voltage-gated potassium channel, KCNQ2, which belongs to a new KQT-like class of potassium channels. Five other BFNC probands were shown to have KCNQ2 mutations, including two transmembrane missense mutations, two frameshifts and one splice-site mutation. This finding in BFNC provides additional evidence that defects in potassium channels are involved in the mammalian epilepsy phenotype.

Searching for human epilepsy genes: a progress report.

Application of new genetic techniques has brought remarkable discoveries in the study of genetic diseases. The potential benefits from applying such technology to idiopathic epilepsies include improved understanding of cellular mechanisms and potential new methods of prevention and treatment. The complex problems involved in studying the hereditary epilepsies include: defining of specific phenotypes; detecting genetic and non-genetic heterogeneity; and specifying the appropriate mode of inheritance and penetrance. The gene loci for three primary epilepsies have been localized to specific chromosomal regions, and serve to demonstrate the process used in generalized linkage studies of hereditary epilepsy syndromes. Benign familial neonatal convulsions (BFNC) and Unverricht-Lundborg progressive myoclonus epilepsy are rare single-gene disorders that are sufficiently localized to chromosomal regions that positional cloning studies are likely to succeed. Juvenile myoclonic epilepsy (JME), a common hereditary syndrome with an uncertain mode of inheritance, has been reported to be linked to chromosome 6p. JME presents a challenge for generalized linkage methodology that may be overcome by attending to potential problems reviewed here. The candidate-gene method, combined with studies using animal models, holds promise for understanding these as well as other hereditary epilepsies.

Techniques for evaluating residents and residency programs.

A comprehensive, functioning evaluation system is an important component of a residency program. It should focus on the residency program as well as on the residents and should provide feedback to the residents, their teachers, and the program director. Such a system allows residents and their faculty advisors to receive timely, ongoing, formative feedback concerning resident progress. Likewise, it can help the faculty recognize the strengths and weaknesses of the training program by providing data that can lead to the curriculum changes needed to improve resident experiences. Additionally, it can alert the residency program director to residents whose performance is significantly below that of their peers, allowing intensive faculty and advisor help for these individuals. The practical aspects of providing feedback and implementing an evaluation system apply no less to community-based educational experiences than they do to inpatient and outpatient training areas.

Effectiveness of computer-generated appointment reminders.

Previous studies of appointment reminders among general pediatric patients have been done exclusively among low socioeconomic populations in clinics with low continuity of care and using block scheduling methods. This study of mailed computer-generated appointment reminders took place in a setting with patient demographics and practice techniques similar to those of many private pediatric practices. During a 6-month period, 901 appointments that were made more than 7 days prior to the scheduled date were randomly assigned to receive reminder postcards or to serve as controls. The overall broken appointment (no-show) rate was reduced from 19% in the control group to 10% in the reminder group, representing a 48% reduction (P = .0002). The magnitude of reduction of no-shows was similar for appointments scheduled more than 14 days prior to the appointment time (39%) as well as those scheduled more recently (58%). Equivalent results were seen with well-child appointments (47%) as with other visits (50%). Both lower and higher socioeconomic groups demonstrated similar results. The mailed postcards cost $0.20 each and were highly cost effective, generating an estimated $7.50 for each $1 spent during the study. With reductions similar to those found in this study, computer-generated appointment reminders are likely to be cost effective in other practices if current no-show rates are greater than 2% to 4%.

In-training examinations as predictors of resident clinical performance.

Previous attempts to predict resident clinical performance based solely on measures of cognitive skills have been uniformly unsuccessful. For the past 8 years, a formative residency evaluation system has been used that includes yearly comprehensive oral in-training examinations (OITEs) assessing each resident's performance in the three areas of professional competence: cognitive, psychomotor, and affective. The results of these examinations and scores received on the written in-training examination (WITE) given by the American Board of Pediatrics were compared with faculty ratings received during the subsequent year of residency. No significant correlation was found at any level of training between WITE scores and clinical performance. Analysis based on clinical setting did not improve these results. Oral in-training examination scores, however, were highly correlated with clinical performance ratings. In addition, with oral in-training examination scores, the "problem" interns--those whose clinical performance rating placed them in the lower 10% of interns--were predicted with a high degree of significance, sensitivity, and specificity. Predictions based on WITEs were not significant. Simultaneous evaluation of all three areas of professional competence should be done when predictions of resident performance are attempted. The OITE is a powerful formative evaluation tool, providing valuable learning experiences as residents are objectively assessed while they perform patient-centered tasks that represent critical skills in the practice of medicine. It allows early detection and possible amelioration of future problems in the clinical performance of a resident.

Sustained proliferation accompanies distraction osteogenesis in the rat.

These studies were conducted to compare the local cellular proliferation patterns in the rat tibia during distraction osteogenesis with those during nondistracted fracture healing. Bone specimens from distraction osteogenesis and nondistracted fracture groups were analyzed 2, 10, and 20 days after surgery. Proliferation was determined by metabolic labeling with [3H]thymidine and by immunocytochemistry with an antibody to proliferating cell nuclear antigen. Videomicroscopy was used to count the cells staining positively within specified regions. The number of cells incorporating [3H]thymidine was positively correlated (r2 = 0.78) with the number of proliferating cell nuclear antigen positive cells on alternating serial slides. At day 2, the latter cells were largely confined to the bone marrow and periosteum in both groups, and the cell numbers per mm2 were also equivalent. At days 10 and 20, the proliferating cell nuclear antigen positive cells predominated in both the proximal and distal primary matrix front zones in the distraction osteogenesis group. In contrast, the proliferating cell nuclear antigen positive cells in the nondistracted fracture group were scattered throughout the healing area. Significantly more of these cells were in the primary matrix front zones than in any location within the nondistracted fracture-healing area. The number of these cells in the bone marrow adjacent to the surgical area declined from day 2 to day 10 in both groups. The results suggest that (a) proliferating cell nuclear antigen immunostaining is a reliable indicator of cycling cells; (b) by day 10, distraction osteogenesis is characterized by a zone-specific pattern of proliferating cells; and (c) distraction osteogenesis prolongs the stimulation of proliferation within the gap after fracture.

A multiuser MUMPS language patient/physician scheduling system for microcomputers.

A microcomputer based patient and physician scheduling system is described that accommodates the special needs unique to residency training programs. Appointments are scheduled automatically according to the type of problems the patient brings to the office as well as the differing time requirements of attending physicians and residents at various levels of training.

Implementation of multiuser MUMPS language database systems on microcomputers.

This paper outlines the problems involved in implementing multiuser MUMPS language database systems on microcomputers and discusses practical solutions. Examples of the techniques presented are derived from experience with a large database system, PTIN/PTQ/MEDAR, running on an IBM AT with up to 10 separate users.

An interactive data base system for assessing and managing outpatient experiences in residency training.

A computerized system is described for assessing and managing a residency program's outpatient experience for its residents. The utilization of MUMPS hierarchical files allows rapid interactive searches, making this system an effective tool for its intended uses. The rationale behind the design of the data files and searches and the usefulness of the data in residency training are discussed.

Computerized patient scheduling in outpatient residency practices.

A computerized appointment system is described that accommodates the special needs unique to residency training programs. Appointments are scheduled automatically according to the type of problem with which the patient presents to the office as well as the differing time requirements of faculty physicians and residents at various levels of training. The system provides for the easy and flexible scheduling of residents and the automation of appointment reminders.

Estimates of need for transfusions during hypertransfusion therapy in sickle cell disease.

The relationship between Hemoglobin S (Hb S) level and simultaneous values of reticulocyte count, hemoglobin (Hb), and hematocrit (Hct) were studied in six patients with sickle cell disease who were receiving a transfusion protocol because of cerebrovascular accidents. There was good correlation between Hb S and reticulocyte count (r = 0.601), Hb (r = -0.530), and Hct (r = 0.479). Although three of the six patients had similar patterns of relationship of Hb S to reticulocyte count and four of six had similar patterns of relationship of Hb S to Hb and Hct, the other patients had distinctly different patterns. "Decision levels" of reticulocyte count, Hb and Hct, indicating the probable need for transfusion, were determined by the point at which the regression line plus 1 standard error would yield the maximum Hb S considered safe. Although all individual decision levels could separate patients with regard to the need for transfusion, decision levels for the group as a whole could not do so for Hb or Hct and could do so for reticulocyte count only with reduced specificity and predictive value. After an individual patient's pattern of relationship has been established, estimates of Hb S based on reticulocyte count, Hb, or Hct can be used as an inexpensive screen for the need for transfusion.

Predicting resident clinical performance with in-training examinations.

Yearly oral in-training examinations that assess resident performance in the three domains of professional competence (cognitive, psychomotor, and affective) given over a seven year period correlated highly with subsequent resident clinical performance and also predicted with a high degree of significance, sensitivity, and specificity those "problem" interns whose clinical performance placed them in the lower 10% of interns. Scores received on written in-training examinations were not significantly correlated with clinical performance and did not identify "problem" residents.

Significant attitude changes among residents associated with a pediatric nurse practitioner.

In the study reported here, significant changes in attitudes occurred over a three-year period among pediatric residents who had close association with a pediatric nurse practitioner (PNP) in their residency program. Residents entering the training program had an overall uncertain attitude toward PNPs but did respond favorably to the PNP's participation in the care of well children, patient education, and follow-up care. The greatest number of attitude changes toward the PNP took place after the first year of interaction between the residents and the PNP. After the first year, the residents favored the PNP's participation in the care of minor illnesses and stable chronic illnesses and in management of telephone calls from parents with concerns. Second-year residents also felt that the PNP was accepted by patients and physicians, that the PNP contributed to the reduction of health care costs, and that the PNP should have an expanded role. Upper-level residents continued to express favorable attitudes. The findings support the authors' hypothesis that favorable attitudes on the part of physicians toward PNPs can be cultivated during residency training by exposing residents to a PNP role model. In addition, the findings suggest that subsequent years of exposure will reinforce these favorable opinions if favorable opinions are established early in residency training.

Sudden death among postoperative patients with tetralogy of Fallot: a follow-up study of 243 patients for an average of twelve years.

Two hundred and forty-three patients were evaluated following total correction of tetralogy of Fallot with special emphasis on postoperative conduction disturbances and on the occurrence of sudden death. The average follow-up period was 12 years with a range of 6 1/2 to 16 1/2 years. Sudden death occurred in seven patients. Four deaths were among those with right bundle branch block pattern (RBBB) and three of the four had premature ventricular contractions (PVC) for more than one month postoperatively. PVCs were documented in ten of the 158 patients with RBBB; sudden death occurred in three (30%). Three of the ten (30%) patients with trifascicular block pattern (TB) died suddenly, while no deaths occurred in 24 patients with bifascicular block pattern (BB). Progression of RBBB to BB and TB occurred in 18 patients from one month to seven years postoperatively (58% of BB and 40% of TB). The risk of sudden death in patients with RBBB and PVCs following tetralogy repair is high and warrants consideration of suppressive therapy. TB also carries a high risk. The finding that RBBB may progress to BB or TB mandates long-term careful follow-up of all tetralogy patients with postoperative conduction disturbances.

Comparison of continuity in a resident versus private practice.

BACKGROUND: There is widespread agreement among pediatric educators that continuity (following a panel of patients on a first contact basis for all their health care) is an important part of the education of pediatricians. OBJECTIVE: To measure continuity in a pediatric residency practice and to compare this continuity with 2 nearby private general pediatric group practices. We also examined measures of continuity suggested in the literature. DESIGN: Visit data were obtained from the practice billing system for a resident continuity practice and 2 nearby private practices for the 3-year period from July 1, 1992, to June 30, 1995. Visit data used were restricted to patients seen in the office of the practices during regular office hours. Continuity was measured using 5 different indices: 1) the usual provider of care index, visits by the usual clinician/total visits, 2) continuity for patient, the average proportion of visits that an individual patient was seen by his or her own physician, 3) continuity for physician (PHY), the average proportion of visits that an individual physician saw his or her own patients, 4) Continuity of Care Index (COC), and 5) the Modified, Modified Continuity Index. During the period examined, pediatric residents were present in the continuity practice for 1 half-day each week. The resident continuity practice (RCP) had 57 residents and saw 3386 patients for 18 955 visits. Private practice 1 (PP1) had 4 pediatricians who saw 4968 patients for 33 537 visits. Private practice 2 (PP2) had 5 pediatricians who saw 11 953 patients for 75 778 visits. RESULTS: For all visit types, continuity in the RCP was not as high as in the private practices, PHY-RCP versus PP1, PP2; 53% versus 70%, 77%. However, continuity in RCP was greater than 50% for all measures except the COC index, which precipitously decreases as the number of clinicians seen increases. Examining continuity for health maintenance visits (PHY-RCP, PP2 vs PP1; 96%, 96% vs 82%) RCP was equal to the best of the private practices. The percentage of patients not seen for a health maintenance visit during the study period was lowest in the resident practice (RCP/PP1/PP2, 15/22/30). CONCLUSIONS: Although continuity for all visits in this RCP was less than in private practice, it was surprisingly high, considering the limited time residents spend in clinic. In a particularly important area for continuity, health maintenance visits, continuity was identical to one and superior to the other private practice.

Benign familial neonatal convulsions linked to genetic markers on chromosome 20.

Recurrent seizures, commonly known as epilepsies, occur in 1.7% of the general population by age 40. The factors that initiate or underlie seizures are not well understood, but trauma, infectious disease and genetics have been implicated. An understanding of the molecular basis of seizures would shed light on the basic mechanisms of neuronal homeostasis and allow new therapeutic strategies to be explored. Here, we report the mapping of an epilepsy gene to a specific chromosomal region, on the basis of cosegregation of two closely-linked DNA markers with a form of epilepsy known as benign familial neonatal convulsions (BFNC2, 12120 in ref. 3). The linked markers confirm the genetic basis and autosomal dominant inheritance of this trait, and localize the gene causing BFNC in this family to the long arm of chromosome 20. This regional placement is the first step towards the isolation of a gene involved in neuronal activity in the human brain.