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A study of keratin expression in benign familial chronic pemphigus.

We studied keratin expression in the involved and uninvolved skin of six benign familial chronic pemphigus (BFCP) patients, using monoclonal antibodies specific for various keratin polypeptides and immunohistopathologic techniques. Normal and psoriatic (i.e., hyperproliferative) skin specimens served as controls. The uninvolved BFCP epidermis showed keratin profiles identical to that of normal epidermis. In the acantholytic epidermal segments of the involved BFCP skin, some of the lower suprabasal acantholytic cells failed to express keratin polypeptides 10 and 11 (Moll's catalog). This delay in expression of suprabasal keratins was not accompanied by an expression of hyperproliferative keratin polypeptide 16. Also, some of the lower suprabasal acantholytic cells of the involved BFCP epidermis retained staining by the antikeratin KS-1A3 antibody, which in the normal, psoriatic, and uninvolved epidermis was limited to the basal cell layer. Staining for keratin polypeptide 18 was negative in the epidermis of all four types of specimens. We believe that the delay in suprabasal keratin expression in the involved BFCP epidermis was more likely secondary to the acantholysis (i.e., "arrest of differentiation" due to acantholysis) rather than due to a primary defect in keratin expression.

Adult↗

Detection of a novel pigment network feature in reticulated black solar lentigo by high-resolution epiluminescence microscopy.

Epiluminescence light microscopy (ELM) of pigmented skin lesions has led to a catalog of pigment network (PN) features. The objective of this study was to determine whether high-resolution ELM detects additional pigment structures not seen with conventional ELM. Epiluminescence light microscopy was performed by placing the lens of a standard light microscope directly on the skin surface, with resulting enhanced optical resolution compared with ELM systems currently in general use. Eight reticulated black solar lentigines were studied. All lesions were viewed and analyzed using dermatoscopic criteria for the PN. In addition, they were all photographed, excised, and examined histologically. Two subtypes of black solar lentigines could be distinguished using generally accepted dermatoscopic criteria for the PN. Furthermore, a new pigment structure was detected, namely, pigment spots of equal color, shape, and size, which were regularly superimposed on and juxtaposed to the PN. Clinicopathologic correlation showed these spots to represent individual hyperpigmented corneocytes. Because such cells result from physiologic excessive pigment translocation via the epidermal melanocytic unit, we called them pigmented corneocytes. Pigmented corneocytes were seen in seven of eight black solar lentigines. The ELM technique presented here allows for more detailed analysis and classification of the PN components. Pigmented corneocytes are proposed as an additional dermatoscopic criterion.

Adult↗

A review of major factors contributing to errors in human hair association by microscopy.

Forensic hair examiners using traditional microscopic comparison techniques cannot state with certainty, except in extremely rare cases, that a found hair originated from a particular individual. They also cannot provide a statistical likelihood that a hair came from a certain individual and not another. There is no data available regarding the frequency of a specific microscopic hair characteristic (i.e., microtype) or trait in a particular population. Microtype is a term we use to describe certain internal characteristics and features expressed when observing hairs with unpolarized transmitted light. Courts seem to be sympathetic to lawyer's concerns that there are no accepted probability standards for human hair identification. Under Daubert, microscopic hair analysis testimony (or other scientific testimony) is allowed if the technique can be shown to have testability, peer review, general acceptance, and a known error rate. As with other forensic disciplines, laboratory error rate determination for a specific hair comparison case is not possible. Polymerase chain reaction (PCR)-based typing of hair roots offer hair examiners an opportunity to begin cataloging data with regard to microscopic hair association error rates. This is certainly a realistic manner in which to ascertain which hair microtypes and case circumstances repeatedly cause difficulty in association. Two cases are presented in which PCR typing revealed an incorrect inclusion in one and an incorrect exclusion in another. This paper does not suggest that such limited observations define a rate of occurrence. These cases illustrate evidentiary conditions or case circumstances which may potentially contribute to microscopic hair association errors. Issues discussed in this review paper address the potential questions an expert witness may expect in a Daubert hair analysis admissibility hearing.

Adult↗

The diagnostic utility of the keratin profiles of hepatocellular carcinoma and cholangiocarcinoma.

A total of 32 hepatocellular carcinomas (HCC), 10 cholangiocarcinomas (CC), one combined HCC-CC, and 10 adenocarcinomas metastatic to the liver were studied immunohistochemically using AE1 and Cam 5.2, monoclonal antikeratin antibodies with different specificities. AE1 recognizes keratins with molecular weights of 56.5, 50/50', 48, and 40 kd (keratin nos. 10, 14, 15, 16, and 19, according to Moll's catalog), and labels many epithelia, including bile duct epithelium, but not hepatocytes. Both biliary epithelium and hepatocytes are stained by Cam 5.2, which reacts with keratins of molecular weights 50, 43, and 39 kd (corresponding to keratin nos. 8, 18, and 19). Tissues were formalin fixed, paraffin embedded, and a three-stage immunoperoxidase technique was employed. Of 32 pure HCCs, 29 were unreactive with AE1 yet were positive with Cam 5.2. The intensity and extent of immunostaining with Cam 5.2 did not correlate with tumor grade. In contrast to the HCCs, all 10 CCs and the 10 hepatic metastases were strongly positive with both AE1 and Cam 5.2. The combined HCC-CC was also labeled by both antibodies. We conclude that most HCCs express an immunohistochemical keratin profile identical to that of nonneoplastic hepatocytes, which differs from the keratin patterns of bile ducts, CCs, and metastatic adenocarcinomas from a variety of primary sites. These differences in immunoreactivity with antikeratin antibodies may prove useful in diagnostic surgical pathology.

Adenoma, Bile Duct↗

Extrinsic tension results in FGF-2 release, membrane permeability change, and intracellular Ca++ increase in immature cranial sutures.

There are numerous studies cataloging the temporal profiles of the various growth factors during the morphogenesis of cranial sutures. There are also many clearly documented mutations of the receptors of some of these growth factors such as fibroblast growth factor (FGF)R-2 and FGFR-3 in clinical craniosynostosis. It is obvious, and often concluded, that growth factors play a role or are involved in craniofacial development. However, precisely what that role is, what causes the changes in the growth factor levels, and why these changes occur in the particular temporal and spatial patterns observed remains elusive. Using simple physics, we applied a plasma membrane disruption model and the principles of complex adaptive systems to arrive at a conjecture of calvarial morphogenesis. The purpose of this article is to introduce the concept of complex adaptive systems, to propose our conjecture, and to provide experimental proof of some key steps in this conjecture: tension induces rapid and demonstrable physiological responses in some cells within the immature cranial sutures. These responses include increases of intracellular Ca++, plasma membrane permeability, and the release of growth factors, e.g., FGF-2. Paired coronal sutures from 1-week-old Sprague-Dawley rat pups were subjected to either 0.59 N of tensile force or no force for 5 minutes in a protein-free medium. FGF-2 levels in the media were measured by slot blot analysis. Western blot analysis was used to determine FGF-2 levels in the sutures. To determine cell membrane permeability changes, fluorescein-conjugated dextran, with a molecular weight of 10 kd, was added to the media during the 5 minutes with or without tensile force. Laser confocal microscopy was used to compare the amount of entry of this impermeant tracer and the pattern of permeability change at the tissue level. To determine the intracellular pCa++, the sutures were first loaded with a calcium indictor, FURA-2 AM, and then subjected isotonically to 0.059 N of tension. The intracellular pCa++ was expressed as ratio of Ca++-bound FURA-2 to Ca++-free FURA-2. The experimental findings were as follows: 1) Sutures, in response to tension, release FGF-2. 2) Sutures contain higher levels of FGF-2 when strained. 3) There is an increase in the sutural cell membrane permeability as a result of tensile strain. 4) The cells along the leading edges of the ossification fronts (at the insertion sites of Sharpey's fibers) demonstrated the maximum permeability increase. 5) There was an immediate (within seconds) increase in intracellular Ca++. and 6) This increase in intracellular Ca++ caused by tension was reversible and independent of the extracellular Ca++ ion availability. In summary, these data support, in part, the conjecture that growth of the brain places strain on the cells within the immature sutures, which causes the iteration of a set of cellular subroutines. These subroutines integrate to generate the emergent property of directed cranial expansion with dissipation of the initiating strains.

Adaptation, Physiological↗

Educational materials reviewed for AVLINE.

The need for a central source of information regarding the availability, suitability, and quality of educational materials has led to the development of AVLINE. AVLINE is a computer information service available through the MEDLARS system of the National Library of Medicine. The Association of American Medical Colleges is gathering information from faculty members concerning useful materials and is bringing together content specialists, instructional designers, and technical specialists to review these materials. Information on materials that are recommended is provided to the National Library of Medicine to be cataloged, indexed, and abstracted for ultimate listing in AVLINE. Twenty-eight percent of the material has not been recommended; the many reasons for low ratings are categorized under content quality, instructional design, and technical quality.

Audiovisual Aids↗

Language as a tool in medicine: methodology and theoretical framework.

Since language is the predominant instrument by which information is transmitted between doctor and patient, an understanding of the uses and functions of language in medicine is crucial to effective medical care. This paper describes a framework for the study of language as a tool in medicine. The work is based on a large volume of doctor-patient conversations tape-recorded in natural settings. A method of cataloging recorded material has been developed which allows rapid access to segments of interest on the tape itself. The writers' framework of analysis suggests that, in addition to the knowledge of social speech conventions, seven levels of linguistic information are necessary for successful communication. Based on this research, a curriculum is being designed to teach medical students the use of language as a tool in medicine in order to refine their skills as effective listeners and speakers.

Curriculum↗

U.S. medical students' rotations in epidemiology and public health at state and local health departments.

Elective rotations in health departments expose medical students to public health practice and career opportunities in applied epidemiology and preventive medicine. State and county epidemiologists and health officers can serve as excellent role models for medical students. In 2000-2001, the authors identified such electives by consulting medical schools' Web sites and by contacting state epidemiologists, teachers of preventive medicine, and medical school associate deans. The authors found that electives were offered in nine state and five local health departments; these are described in detail. Those electives usually focused on infectious diseases, involved students in outbreak investigations when possible, lasted four or more weeks, were open to other students and medical residents, and were overseen by a health department preceptor with a medical school faculty appointment and a commitment to train students. Some electives included more didactic components, encouraged the student to publish a manuscript, or were coordinated by a preventive medicine residency director. The authors observe that health departments can benefit from training enthusiastic medical students via such electives; these students bring fresh ideas to the departments. Medical school catalogs, Web sites, and word of mouth are important means for promoting these electives. Ideally, in the future every medical school will offer a state or local health department elective so that all medical students will become aware of epidemiology and public health career options. The electives reported in this article can help guide additional medical schools and health departments as they initiate such rotations.

Clinical Clerkship↗

Sharing digital teaching resources: breaking down barriers by addressing the concerns of faculty members.

PURPOSE: Regional and institutional databases have been created to improve access to educational resources and to avert unnecessary duplication. The growth and success of these databases depend upon the willingness of faculty members to contribute their materials. This qualitative study seeks to identify the barriers that block the free exchange of educational multimedia and the incentives that could be created to overcome educators' concerns. METHOD: In 2001, 34 faculty members from 13 U.S. medical schools each participated in one of five focus groups. They responded to three hypothetical scenarios depicting opportunities for sharing educational resources. Participants' responses were categorized hierarchically and sent back to them for feedback. RESULTS: Participants strongly supported multimedia databases, particularly those that serve a national audience. Obstacles for contributing materials included the lack of institutional recognition for educational innovation, confusing intellectual property policies, the hassle involved in sharing materials, and the perceived commercial potential of the materials. Peer review of educational materials was seen as an important incentive. CONCLUSIONS: Medical schools could benefit from the free exchange of high-quality educational multimedia but need to address the concerns of faculty by clarifying institutional copyright rules, streamlining the donation process, and providing assistance with cataloging assets. Removing departmental pressures to commercialize materials and recognizing peer-reviewed donations as academic achievement could foster a culture of sharing.

Attitude of Health Personnel↗

Reading habits of practicing physiatrists.

OBJECTIVE: Over the past 30 yr, the number of ACGME accredited specialties has quadrupled, and the number of journals cataloged on MEDLINE has doubled. Given this increase of information, this study sought to determine the amount and extent that pertinent journals are read by specialists in the field of physical medicine and rehabilitation. DESIGN: From a randomly selected list of board-eligible physiatrists and diplomates of the American Board of Physical Medicine and Rehabilitation, 1204 resident physicians, fellows, and attending physicians were sent questionnaires concerning their reading habits. The questionnaire contained a list of 36 journals adapted from a list of journals previously published as being pertinent to physical medicine and rehabilitation. Physicians were asked to specify which journals they read over the past year and how extensively these were read. Respondents were also asked to note whether they participated in an academic or private practice and if they read as much as they would like. RESULTS: The results revealed that very few journals were always read thoroughly, with the modal response among the more popular journals being that of "always scanned the table of contents and read the most important articles." Academic physiatrists were noted to read more than their private practice counterparts. Of the subspecialists who replied, 67% read a journal pertinent to their subspecialty. Eighty-three percent of all respondents reported that they did not read as much as they would like. CONCLUSION: Physiatrists are rarely able to completely read the most relevant journals in their field. When reading journals, most physiatrists only scan the table of contents and read the most important abstracts.

Attitude of Health Personnel↗

The vocational integration of the mentally retarded: a program to develop vocational maturity.

In many countries there are minimum standards for entry into vocational training programs, but until now there has been no instrument for determining whether retarded applicants possess the motor skills required to enter and complete such programs. To construct such an instrument, experts representing most of the skilled vocations in West Germany were consulted about typical skills required during the vocational education in their fields. Based on their responses, a catalog of essential skills was compiled and testing procedures (Handwerklich-Motorischer Eignungstest HAMET) were developed to determine vocationally-oriented motor skills for use in diagnostic and remedial programs for the retarded. A test administered to more than 100 mentally retarded youth showed significant and typical deficiencies in motor skills compared with those of non-retarded individuals. By using a factor analysis of the HAMET-items, it was possible to isolate elementary motor functions which are common to all the skilled vocations. Knowledge of these factors made it possible to start one-year training courses to develop vocational maturity. With selected exercises based on the HAMET-items the courses were very successful. In contrast to traditional programs for the mentally retarded it could also be shown that frequent changes of workshops and of vocational education staff are not necessary and that the entire training program can be carried out in one equipped workshop.

Adolescent↗

Quantitative analysis of solitary lesions of bone.

RATIONALE AND OBJECTIVES: To quantitate the radiographic features of common solitary lesions of bone using vector analysis to optimize their radiographic description. METHODS: Plain radiographs of 709 solitary bone lesions were reviewed. Relevant demographic, anatomic, and structural data were cataloged. These data were used to approximate the vector space defined by all possible solitary lesions of bone. Vector space analysis on the entire set of lesions was performed to determine similarities among and between lesion types. RESULTS: The 709 lesions generated 614 separate vectors within the appearance vector space. Only 10 vectors were represented more than 3 times, indicating great variability among and between most lesion types. Osteochondromas (with two vectors repeated 10 and 15 times, respectively) and peripheral chondrosarcomas (with one vector repeated 5 times) were relatively uniform in appearance. Gender bias was present for multiple types of lesions. Larger lesions that involved more than one anatomic center were more likely to be malignant. Lesions occurring in the femoral diaphysis and pelvic flat bones were statistically more likely to be malignant. CONCLUSIONS: Analysis shows that most lesions have highly varied vectors in the appearances within the vector space. More in-depth analysis of each lesion type using this quantitative technique is required to better define individual lesion subspaces and hence their radiographic appearances with respect to other bone lesions.

Bias↗

Psychological effects of Hurricane Andrew on an elementary school population.

OBJECTIVE: To explore the prevalence and progression of posttraumatic symptomatology (PTS), using emotional and behavioral indices of psychopathology in school-age children in the pathway of Hurricane Andrew (HI-IMPACT) and in a comparison group north of Miami (LO-IMPACT). METHOD: Pynoos' Posttraumatic Stress Disorder Reaction Index and Achenbach's Teacher's Report Form (TRF) were administered 8 weeks and 32 weeks after the hurricane. In addition, 21 measures of disruptive behavior cataloged by Dade County Public Schools were aggregated and compared by grading period between pre- and posthurricane school years. RESULTS: There were no statistically significant differences between the two schools in PTS at 8 weeks after the hurricane, although the children in the HI-IMPACT school were more likely to have severe PTS. TRF findings at 8 weeks revealed that children in the HI-IMPACT school evidenced lower means on the eight TRF scales and on the broader Internalizing and Externalizing measures. Analysis of the disruptive behavior revealed a drop in the marking period immediately after the hurricane in the HI-IMPACT area, but an opposite effect was observed in the LO-IMPACT area. CONCLUSIONS: After the hurricane there was an initial increase in PTS and a concomitant decrease in other measures of behavior and psychopathology. PTS remained relatively high throughout the school year, but there was a rebound and subsequent normalization of the measures of disruptive behavior.

Child↗

The micropsychopathology of hebephrenic/catatonic schizophrenia.

All hospital records, interviews, and notes are reviewed on a group of 52 chronic hebephrenic/catatonic schizophrenics who were institutionalized before the era of antipsychotic medications. The authors catalog the presence or absence of individual symptoms of schizophrenia on a year by year basis over a span of 25 years and present this data in a series of bar graphs. Symptoms such as avolition, impaired social interaction, and flat affect become more frequent over the 25 years of follow-up. Hallucinations and delusions become less frequent. Eighteen of the patients are noted to have had a DSM-III personality disorder premorbidly and eight of these are characterized as schizoid personality disorder. Level of insight is found to be poor at the onset of schizophrenia and deteriorates further over the next 5 years. Although the study design contains a sampling bias in favor of chronically institutionalized cases, several lines of evidence suggest that the trends reported here are not artifacts of institutionalization but are due to schizophrenia.

Adult↗

A computerized approach to injury description.

The study of trauma has been handicapped from its inception by the absence of a single coherent method of cataloging injuries. The AIS and ICD-9 systems have failed to fill this void because they lack the precision necessary to describe surgically treated injuries. We conceived a simple system of injury description in which injuries are rapidly encoded using a microcomputer in sufficient detail to distinguish among millions of different injuries. This system is easily searched by a microcomputer and allows for the automatic assignment of AIS, ISS, and CPT codes. In this system a patient is described by a 'paragraph' consisting of any number of identically patterned 'sentences,' each describing one of the patient's injuries. Each 'sentence' is composed of a string of six 'words' from controlled vocabularies and has the following structure: "Body region, Organ, Anatomic region, Injury, Physiology, Treatment." Defining the vocabulary allowed for each 'word' in a 'sentence' is complex because the allowed vocabulary is dependent upon the preceding 'words' in a 'sentence,' but in practice a microcomputer simply provides short lists of acceptable choices at each step of injury description, and records the user's selections. Additionally, the microcomputer assigns AIS, ISS, and CPT codes appropriate to the injury description sentence. The ease of data entry, the fineness of detail captured, the automation of code assignment, and the accuracy of database searching for specific injuries, classes of injuries, or combinations of injuries, we believe will give this approach widespread application in academic trauma centers where an accurate and accessible trauma database is important.

Humans↗

Trauma registry injury coding is superfluous: a comparison of outcome prediction based on trauma registry International Classification of Diseases-Ninth Revision (ICD-9) and hospital information system ICD-9 codes.

BACKGROUND: Trauma registries are an essential but expensive tool for monitoring trauma system performance. The time required to catalog patients' injuries is the source of much of this expense. Typically, 15 minutes of chart review per patient are required, which in a busy trauma center may represent 25% of a full-time employee. We hypothesized that International Classification of Disease-Ninth Revision (ICD-9) codes generated by the hospital information system (HI) would be similar to those coded by a dedicated trauma registrar (TR) and would be as accurate as TR ICD-9 codes in predicting outcome. METHODS: One thousand eight hundred twelve patients admitted to a Level I trauma center during 2 years had International Classification of Disease Injury Severity Scores (ICISS) calculated based on HI and TR ICD-9 codes. The relative predictive powers of these two ICISSs were then compared for every patient using Receiver Operator Characteristic Curve Area (ROC) and Hosmer Lemeshow Statistics. RESULTS: Eighty-nine percent of patients (1,608 of 1,812) had identical HI and TR ICISSs. Eleven patients' ICISSs differed by >0.1, and only two patients' scores differed by >0.2. ICISS proved to be a powerful predictor of outcome whether derived from HI (ROC = 0.884; 95% confidence interval (CI) = 0.850-0.917) or TR (ROC = 0.872; 95% CI = 0.837-0.908). Although these predictive powers were not significantly different (p = 0.076), the trend was for HI to perform better than TR. ISS calculated for the same data set using the MacKenzie dictionary proved significantly less predictive of outcome than either ICISS (ROC(MacKenzie) = 0.843; 95% CI = 0.792-0.884; p = 0.034). CONCLUSION: We conclude that in our hospital TR data on individual injuries can be replaced by HI data without loss of predictive power. ISS based on the MacKenzie dictionary should be abandoned because it is much less predictive of outcome than ICISS.

Adolescent↗

Arctic and Antarctic exploration including the contributions of physicians and effects of disease in the polar regions.

A history of Arctic and Antarctic exploration, whether to find a Northwest Passage, North Pole, or South Pole, is a story of triumph and tribulation. The hardship experienced by polar explorers in the last 1000 years permeates the tales of achievement. Physicians and surgeons have played prominent roles in all major polar explorations. No significant Arctic voyage, particularly in the last 300 years, was made without a member of the party trained in the management of medical emergencies and in basic surgery. During times of health, surgeons functioned as the voyage naturalists with expertise in biology, botany, zoology, and the writing of scientific catalogs. Spurred by our interest and fascination with the history of polar exploration, we reviewed the roles of physicians and natural scientists in Arctic and Antarctic adventures.

Antarctic Regions↗

The reality of virtual learning for nurses in the largest integrated health care system in the nation.

The health care network and hospital system within the Department of Veterans Affairs (VA), the Veterans Health Administration (VHA), provides employment to more than 56,000 nursing personnel and serves as clinical education site to countless other nursing and health professional students. Nurse administrators and educators are posed with the challenge of providing an environment in which each nurse is able to gain needed knowledge, learn new skills, and share and communicate this knowledge with other colleagues. The education of nurses improves the health status of veterans while also realizing individual professional enhancement. Regional and cultural diversity of the system present challenges to education, in both delivery and content. VHA's learning organizations, the Employee Education System and the Office of Special Projects, have maximized new technologies and information systems to provide innovative, virtual education opportunities, capitalizing on the benefits of informal and formal learning, thus moving VHA to the forefront in knowledge sharing and dissemination. The Virtual Learning Center, VA Knowledge Network, Learning Catalog, and VA Learning Online provide VHA's nurses with interactive, desktop virtual learning opportunities.

Computer-Assisted Instruction↗