The cholera toxin B subunit is a mucosal adjuvant for oral tolerance induction in type 1 diabetes

When conjugated to various proteins, the nontoxic B-chain of cholera toxin (CTB) significantly increases the ability of these proteins to induce immunological tolerance after oral administration. Here, we investigated if a nonconjugated form of CTB enhances the induction of immune tolerance after oral insulin administration. Induction of immunological tolerance was studied after oral administration of insulin preparations in three mouse models; an insulin/ovalbumin coimmunization model, a model of virus-induced diabetes in transgenic RIP-LCMV-NP mice and in nonobese diabetic (NOD) mice serving as a model of spontaneous diabetes. In the immunization model, we demonstrate that mixing with CTB increases the tolerogenic potential of insulin, approximately 10 fold. Titration of the CTB concentration in this system revealed that an insulin : CTB ratio of 100 : 1 was optimal for the induction of bystander suppression. Further studies revealed that this insulin : CTB ratio also was optimal for the prevention of diabetes in a virus-induced, transgenic diabetes model. In addition, the administration of this optimal insulin-CTB preparation significantly prevented the onset of diabetes in old NOD mice with established islet infiltration. The data presented here demonstrate that CTB, even in its unconjugated form, functions as a mucosal adjuvant, increasing the specific tolerogenic effect of oral insulin.     

Intracranial peripheral primitive neuroectodermal tumors of the cavernous sinus: a diagnostic peculiarity

Peripheral primitive neuroectodermal tumors (pPNETs) are aggressive, poorly differentiated neoplasms that occur in children and young adults. These tumors are associated with a peak incidence in the second decade and a slight male preponderance. Recently, Ewing sarcoma and pPNET tumors have been proven to carry identical translocations, the most common being t(11;22)(q24;q12). Intracranial Ewing sarcoma/pPNETs have rarely been described in the literature. We studied a case of intracranial pPNET arising in the right cavernous sinus of a 46-year-old man. On imaging, the tumor had both sellar and suprasellar components and was centered within the right parasellar region. Histologically, the tumor was composed of intermediate to large cells with round to oval hyperchromatic nuclei with distinct nucleoli. The cells contained a moderate amount of slightly basophilic cytoplasm. The tumor was markedly fibrotic and had collagen bands surrounding both individual and groups of cells. A large immunohistochemical panel was positive only for CD99 and vimentin. Fluorescence in situ hybridization did not show translocations associated with Ewing sarcoma/pPNET. However, a small percentage of these tumors can be negative for this translocation. In these cases, histology and immunohistochemical techniques in the absence of an alternative diagnosis are the only tools available to establish the diagnosis.     

Post-traumatic stress disorder: evidence for diagnostic validity and methods of psychological assessment

Post-traumatic stress disorder (PTSD) is a diagnosis that has been the subject of considerable criticism in the clinical literature. Of primary concern has been the question of whether PTSD is a disorder that can be discriminated reliably from already existing diagnoses, such as depression, dysthymia, or generalized anxiety disorder. This paper reviews the evidence that surrounds this controversy and employs the guidelines for validating a diagnosis established by Robins and Guze (1970) as the framework for the review. A second purpose of this paper is to present a multiaxial approach for the assessment of PTSD. This approach includes the use of structured interviews, psychometrics, and a psychophysiological assessment procedure. Studies that support the reliability and validity of the components of the multiaxial method are reviewed.     

Laser induced thermal injury of rabbit cornea and treatment with anti-inflammatory agents

A moderately severe thermal injury of the central cornea of 48 Dutch-belted rabbit eyes was produced with a carbon (CO₂) laser. The lesions were photographed with a slit lamp (SL) camera immediately following the injury and at 1, 2, 4, 7, 14, 21, 30 and 60 days after the exposure. Lesion size, opaqueness, and depth were graded clinically by SL biomicroscopy at the same intervals. No significant differences were found (p 0.05) between groups of eyes treated with flurbiprofen (0.03%), prednisolone acetate (1%), and vehicle control four-times-a-day for three weeks following injury. Additionally, eyes were studied histopathologically at 3 and 60 days following injury by light and transmission electron microscopy, and clinically at 30 and 60 days by endothelial specular microscopy. Important clinical and histopathological findings included coagulative necrosis of the corneal epithelium, epithelial sloughing, fusion of stromal collagen, stromal edema and inflammatory cell infiltration, stromal scar formation, corneal thinning, endothelial hyperplasia and metaplasia, fibrinous anterior chamber reaction with hypopyon, and retrocorneal fibrous membrane formation.     

Fibrositis: symptom frequency and criteria for diagnosis. An evaluation of 291 rheumatic disease patients and 58 normal individuals

We administered a 17-item symptom questionnaire modified from Campbell to 155 patients with fibrositis diagnosed at 3 centers, each using different criteria sets. A high degree of agreement in symptom proportions was found among centers. "Fibrositic" symptoms were also common in 136 patients with a variety of rheumatic diseases but not in the 58 normal individuals studied. Symptoms distinguished fibrositis patients from normals easily, but had insufficient specificity to distinguish them from other rheumatic disease patients. The tender point count better separated fibrositic and nonfibrositic patients than historical criteria. No combination of questions and tender point count performed better than the tender point count alone.     

Effectiveness of interactive videodisc instruction for the continuing education of paramedics

OBJECTIVES. To evaluate the effectiveness of interactive videodisc (IVD) instruction of paramedics through the use of computer analysis of trip sheets. DESIGN/SETTING. Prospective, controlled, in an urban 9-1-1, paramedic, emergency medical services (EMS) system with total call volume of 62,000/year; 15,000 advanced life support (ALS). INTERVENTIONS. All 150 paramedics in the system received eight hours of IVD instruction covering five subject areas: 1) airway; 2) head/cervical trauma; 3) chest; 4) shock; and 5) cardiac arrest. Trip sheets from 9,943 runs in the pre-IVD period were subjected to computer analysis, and a compliance score was generated using previously developed algorithms that assigned a weight to each omission and commission. After a nine-month IVD training period, 4,303 cases were collected and analyzed in the post-IVD period. Statistical analyses were made using "Student's" t-test and Chi-square with alpha set at 0.05. EXCLUSIONS. Only those records of adult patients who fit one of the five protocols were eligible for computer analysis. Of the 9,943 cases in the pre-IVD group, 480 (4.8%) were excluded, all due to inadequate data recording by the paramedics. A statistically similar portion, 233 (5.4%) of the 4,303 post-IVD instruction cases were excluded (p = .15). RESULTS. Overall the mean compliance score of the pre-IVD group was 0.65 +/-0.19 (+/-SD). The post-IVD group score was 0.65 +/-0.19 (p = 0.99). Analysis of scores for each algorithm also showed no significant differences. This study had an observed power of .94 to detect a difference in compliance as small as 0.030. CONCLUSION.(ABSTRACT TRUNCATED AT 250 WORDS)     

Improving readiness and fitness of the active military force through occupational medicine tenets

The United States Military deploys its forces with minimal lead time. These forces must be medically qualified and physically fit for any locale and mission scenario. Historically, up to half of the force identified for deployment at any given time were not medically qualified. Matching individuals to specific occupations using validated medical and physical performance standards is an occupational medicine tenet that increases the effectiveness and efficiency of the workforce. To establish a cost-effective, valid medical program ensuring a fit and ready force, the military must: (1) develop validated physical fitness/occupational standards; (2) consolidate one fitness standard for males/females on the basis of workload requirements; (3) eliminate differing age standards; (4) provide statistically relevant medical screening, testing for health maintenance, and fitness for duty; and (5) mandate one joint medical standard for all military services.