PADGEM (GMP140) is a component of Weibel-Palade bodies of human endothelial cells

PADGEM protein (PADGEM), also known as GMP140, is a platelet alpha- granule membrane protein that is translocated to the external membrane after platelet activation. Although the biosynthesis of this protein was originally thought to be confined to megakaryocytes, the synthesis of PADGEM in endothelial cells was recently demonstrated (McEver et al: Blood 70:1974a, 1987). We now describe the subcellular localization of this protein in endothelial cells. Immunofluorescence staining of permeabilized human umbilical vein endothelial cells with KC4, a well characterized monoclonal antibody to PADGEM, showed positively stained elongated structures similar in distribution and shape to Weibel-Palade bodies. Their identity as Weibel-Palade bodies was confirmed by double label immunofluorescence using KC4 and a polyclonal antiserum to von Willebrand factor (vWf), a protein known to be specifically stored in these organelles. All Weibel-Palade bodies were found to contain PADGEM. In contrast to strong perinuclear staining produced with anti- vWf antibodies, no significant perinuclear staining was obtained with KC4, indicating that relatively little PADGEM is present in the endoplasmic reticulum and in the Golgi apparatus. In endothelial cells treated with secretagogues that stimulate vWf release the elongated structures positive for PADGEM disappeared, further identifying these structures as Weibel-Palade bodies. This observation extends the parallels between Weibel-Palade bodies and alpha-granules and suggests a possible functional association between vWf and PADGEM.     

Significant efficiency findings while controlling for the frequent confounders of CAI research in the PlanAlyzer project's computer-based,self-paced,case-based programs in anemia and chest pain diagnosis

Richard E. Clark in his widely published comprehensive studies and meta-analyses of the literature on computer assisted instruction (CAI) has decried the lack of carefully controlled research, challenging almost every study which shows the computer-based intervention to result in significant post-test proficiency gains over a non-computer-based intervention. We report on a randomized study in a medical school setting where the usual confounders found by Clark to plague most research, were carefully controlled. PlanAlyzer is a microcomputer-based, self-paced, case-based, event-driven system for medical education which was developed and used in carefully controlled trials in a second year medical school curriculum to test the hypothesis that students with access to the interactive programs could integrate their didactic knowledge more effectively and/or efficiently than with access only to traditional textual “nonintelligent” materials. PlanAlyzer presents cases, elicits and critiques a student's approach to the diagnosis of two common medical disorders: anemias and chest pain. PlanAlyzer uses text, hypertext, images and critiquing theory. Students were randomized, one half becoming the experimental group who received the interactive PlanAlyzer cases in anemia, the other half becoming the controls who received the exact same content material in a text format. Later in each year there was a crossover, the controls becoming the experimentals for a similar intervention with the cardiology PlanAlyzer cases. Preliminary results at the end of the first two full trials shows that the programs have achieved most of the proposed instructional objectives, plus some significant efficiency and economy gains. 96 faculty hours of classroom time were saved by using PlanAlyzer in their place, while maintaining high student achievement. In terms of student proficiency and efficiency, the 328 students in the trials over two years were able to accomplish the project's instructional objectives, and the experimentals accomplished this in 43% less time than the controls, achieving the same level of mastery. However, in spite of these significant efficiency findings, there have been no significant proficiency differences (as measured by current factual and higher order multiple choice post-tests) between the experimental and control groups. Very careful controls were used to avoid what Clark has found to be the most common confounders of CAI research. Accordingly, this research proved Clark's rival hypothesis, that the computer, in itself, does not appear to contribute to proficiency gains, at least as measured by our limited post-testing. Clark's position is that the computer is primarily a vehicle—as is either a pill or a hypodermic needle for delivering a drug. The hypodermic needle can deliver the drug more efficiently than can the pill, (as can the computer deliver the subject matter content more efficiently, as our research indicates), but the same content is delivered. At the same time, we proved our own hypothesis, as far as efficiency gains resulting from the computer are concerned. However, going beyond Clark's research, we may be teaching processes both more effectively and efficiently with the computer (experience in problem-solving or clinical reasoning and pattern recognition) which our current post-tests do not adequately measure. Our on-going research suggests additional inquiry in several areas: better evaluation instruments to measure the clinical reasoning skills PlanAlyzer was designed to teach; the addition of more advanced cases to determine if this might transform efficiency gains of the computer group into proficiency gains; the addition of enhanced graphic decision support tools and other pedagogical enhancements including cognitive feedback to strengthen PlanAlyzer's power to teach complex concepts of medical decision-making.     

Occurrence of the t(2;5)(p23;q35) in non-Hodgkin's lymphoma

Primary CD30(Ki-1)-positive anaplastic large-cell lymphoma (ALCL) is considered by some to be a distinct clinicopathologic entity associated with the t(2;5) (p23;q35). However, the specificity of t(2;5) for ALCL has not been carefully studied. Therefore, we performed a detailed analysis of all cases of ALCL with abnormal cytogenetics results in the Nebraska Lymphoma Study Group registry, as well as all other cases of non-Hodgkin's lymphoma with t(2;5) in the registry. We found the t(2;5) in only five of 10 cases of ALCL, four of whom were young patients. However, we also found the t(2;5) in 11 other cases of nonanaplastic lymphoma, including eight children with typical peripheral T-cell lymphomas of various types. The t(2;5) was also found in three older adults with B-cell lymphomas of various types. Thus, the t(2;5) was not specific for CD30+ ALCL. However, t(2;5) may define a clinicopathologic entity in children and young adults characterized by variable morphologies with a T-cell or indeterminate phenotype, CD30-positivity, nodal disease with frequent extranodal involvement, advanced stage, and an excellent response to therapy, including bone marrow transplantation for relapsed disease. The clinical relevance of the t(2;5) in older patients requires further study.     

Admission rates for peptic ulcer in the Trent Region, UK, 1972–2000: Changing pattern, a changing disease?

BACKGROUND AND AIM: Peptic ulcer disease is believed to be less common and less severe as a result of modern medical treatment. We therefore examined changes in the admission rates for patients with duodenal ulcer and gastric ulcer, both emergency (for haemorrhage, perforation or severe pain) and for elective surgery, before and since the introduction of the new advances in therapy. These admission indices reflect disease prevalence and severity. PATIENTS AND METHODS: We identified admission rates during 1972--2000 within the Trent Regional Health Authority, UK (population 4.7 million), from computerised patient information using diagnostic search codes ICD8-10 and expressed as rates per million resident population. Drug expenditure details were obtained from the Department of Health. RESULTS: Emergency admission rates as a whole changed little, a decline in the young being offset by an increase in the elderly. Haemorrhage was the most common reason (approximately 115 per million for duodenal ulcer and 87 for gastric ulcer) throughout [compared with perforation (80 and 21) and pain (90 and 68)]. In contrast, elective surgery has almost disappeared; this reduction began before the introduction of modern treatment. CONCLUSION: Emergency admission rates for duodenal and gastric ulcer for complications or severe pain have fluctuated over the last three decades but with little overall change. In contrast, elective surgery has declined dramatically, as a result of advances in treatment but also from changes in the natural history.     

General case simulation instruction and the establishment and maintenance of work performance

This study was conducted to determine whether general case simulation instruction on selected job task sequences and teaching examples, which sampled the range of stimulus/response variation encountered in two community jobs, resulted in the generalized performance of specific community job requirements by four young adults with severe handicaps. A multiple baseline across subjects and behaviors design was used to assess subject performance in simulation instruction, on concurrent and subsequent actual job probes, and in actual job instruction. Data indicated that simulation instruction on two representative teaching examples for each of two job task sequences resulted in concurrent generalized performance on six response examples for each task sequence, and in subsequent improvements in job entry skills which were maintained and extended during actual job instruction and instructor withdrawal phases. Results are discussed in terms of potential uses and misuses of general case simulations of community job skills.     

Conjunctival granuloma caused by surgical talc.

Talc from surgical gloves has been known to be a cause of granulomas within the surgical cavity. We report a case in which recurrent conjuntival inflammation was found to be caused by talc.