The association of circulating endotoxin with the development of the adult respiratory distress syndrome

Despite extensive investigation, the pathogenesis of the adult respiratory distress syndrome (ARDS) remains uncertain. As yet, there is no clear explanation of why some patients at risk for ARDS develop the syndrome, whereas others do not. Neutrophils and complement fragments have been implicated in the acute lung injury, but it is clear from published data that evidence of complement activation alone predicts neither the development nor the severity of ARDS. We investigated whether the combination of endotoxin, a leukocyte-priming agent, and complement fragments, leukocyte-stimulating agents, was associated with the development of ARDS. Ninety-eight patients were identified as being either at risk for the development of ARDS or having ARDS, and serial blood samples were obtained. There was no correlation between C5 fragments and the development of ARDS. C3 fragment levels were increased in 89% of the patients with ARDS, but they were also increased in 62% of patients at risk. Endotoxin was detected in 74% of the plasma samples obtained from patients at risk who subsequent developed ARDS and in 64% of the plasma samples obtained from the patients with ARDS. In contrast, only 22% of the plasma samples obtained from the patients at risk who did not develop ARDS had measurable endotoxin. We suggest that the combination of endotoxin and complement fragments may be one mechanism involved in the development of ARDS.     

Cleveland Clinic Lerner College of Medicine: an innovative approach to medical education and the training of physician investigators.

Cleveland Clinic Lerner College of Medicine (CCLCM) is an innovative, five-year medical education track within Case Western Reserve University School of Medicine (Case) with a focused mission to attract and educate a limited number of highly qualified persons who seek to become physician investigators. CCLCM curriculum governance, faculty appointments and promotions, and admissions committees are integrated with respective Case committees. The CCLCM curriculum is based on faculty-defined professional attributes that graduates are expected to develop. These attributes were used to create curricular and assessment principles that guided the development of an integrated basic science, clinical science, and research curriculum, conducted in an active learning environment. An organ-system approach is used to solidify an understanding of basic science discipline threads in the context of relevant clinical problems presented in PBL and case-based discussion formats. Clinical skills are introduced in the first year as part of the two-year longitudinal experience with a family practice or internal medicine physician. The research program provides all students with opportunities to learn and experience basic and translational research and clinical research before selecting a research topic for their 12- to 15-month master-level thesis project. All Case students participate in required and elective clinical curriculum after the second year, but CCLCM students return to the Cleveland Clinic on selected Friday afternoons for program-specific research and professionalism-learning activities. A unique portfolio-based assessment system is used to assess student achievements in nine competency areas, seven of which reflect the Accreditation Council for Graduate Medical Education competencies.     

Extraneural metastases in ependymoma

Summary Ependymomas, glial neoplasms usually arising in the posterior fossa or spinal cord, rarely metastasize outside the central nervous system. We have reviewed all 81 ependymomas evaluated at MSKCC between 1956–1989. Five (6.2%) had extraneural metastases (ENM). The primary tumor was in spinal cord in 3 patients and the cerebral hemisphere in 2. Two tumors were histologically anaplastic; 3 were histologically benign. The 5 patients were 3, 3, 3.5, 16 and 37 years old. Time from initial diagnosis to development of ENM was 0, 15, 35, 40, and 288 months. At the time of ENM the primary tumor was progressing in 4/5 patients. Prior therapy had included resection plus radiation therapy (RT) (1), RT plus chemotherapy (1), resection plus RT plus chemotherapy (2). One patient had not received prior therapy because ENM were present at diagnosis. The sites of ENM included lung and thoracic lymph nodes (2), pleura and peritoneum (2), and liver (1). Both patients with peritoneal ENM had had ventriculoperitoneal shunts. ENM did not correlate with histologic grade, age, or degree of surgical resection. When patients with ependymoma develop signs or symptoms of systemic disease such as abdominal pain, cough, or adenopathy, ENM should be considered.     

Patient characteristics, methods of diagnosis and treatment of melanoma in the United States.

The American College of Surgeons performed a patient care and evaluation study of melanoma for 1981 and 1987 to determine the presenting symptoms, methods of evaluation, clinical management and resulting outcome. Melanomas of the skin, eye, mucous membrane, metastases with unknown primary site and miscellaneous sites were included. Details concerning 5,004 patients from 681 hospitals in the study in 1981 and 6,900 patients from 844 hospitals in the study in 1987 were obtained--most melanomas were located in the skin; a decline in symptoms occurred at initial diagnosis; an increase in age at first diagnosis was reported; most melanomas were in Caucasian patients; slightly more melanomas occurred in men than women; more melanomas occurred in men on the head and neck and trunk, and more in the lower extremity in women; most tumors were not large in diameter; a significant shift was reported to lower levels of Clark's invasion, and a significant amount of unknowns existed in the Breslow's thickness of invasion. The large number of unknowns makes analysis difficult, but there seems to be some shift toward thinner levels of Breslow's in tumors in which it was known, from 1981 to 1987. Only a small proportion of patients in the current series was known to have node involvement or known distant metastases. An overall decline in diagnostic studies occurred between 1981 and 1987.     

Does ageing have an effect on midbrain premotor nuclei for vertical eye movements?

Currently, there is debate in the clinical literature as to whether defects in vertical gaze are a consequence of normal ageing or a component of an underlying neurodegenerative disorder. Although pathological changes have been demonstrated in diseased subjects, no study to date has addressed the question of normal ageing effects. In this retrospective study, we examined 23 neurologically and pathologically normal subjects (age 18-91). Using an unbiased, frame-based sampling method, we quantified neuronal and glial cell densities in 10 young (<50) and 13 aged (>65) subjects in the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF), the key premotor substrate in the vertical gaze pathway. We found no statistically significant difference in neuronal density, glial cell density, or neuron-to-glial cell ratios between the young and the aged. We conclude, therefore, that neuronal loss, neuronal atrophy, or gliosis in the riMLF are not consequences of normal ageing.     

Spatial classification of glaucomatous visual field loss.

AIMS--To develop and describe an objective classification system for the spatial patterns of visual field loss found in glaucoma. METHODS--The 560 Humphrey visual field analyser (program 24-2) records were used to train an artificial neural network (ANN). The type of network used, a Kohonen self organising feature map (SOM), was configured to organise the visual field defects into 25 classes of superior visual field loss and 25 classes of inferior visual field loss. Each group of 25 classes was arranged in a 5 by 5 map. RESULTS--The SOM successfully classified the defects on the basis of the patterns of loss. The maps show a continuum of change as one moves across them with early loss at one corner and advanced loss at the opposite corner. CONCLUSIONS--ANNs can classify visual field data on the basis of the pattern of loss. Once trained the ANN can be used to classify longitudinal visual field data which may prove valuable in monitoring visual field loss.