Pulmonary manifestations of intentionally released chemical and biological agents

Recent events have underscored the importance of knowledge and understanding of biological and chemical agents that are intentionally released on civilian populations. Preparedness of the medical community to recognize and manage the resulting clinical syndromes will be a major determinant in the outcome of such attack, or a community's 'prognosis' for survival. The biological and chemical agents that have been weaponized produce diseases and toxidromes that are not commonly seen by clinicians in most parts of the United States. Patients or clusters of patients who present with febrile syndromes that are unusual for the geographic or seasonal setting should trigger notification of public health authorities and the use of state or national reference lab systems for augmented diagnostic support. In many cases, early, empiric therapy, administered before definitive diagnosis, is required for survival. The basic principles in the management of exposure to chemical agents include containment, prevention of secondary exposure, rapid decontamination, implementation of supportive and symptomatic care, and specific antidotes as indicated and available.     

Automated generation of curved planar reformations from volume data: method and evaluation

The authors developed and evaluated a method to automatically create interactive vascular curved planar reformations with computed tomographic (CT) angiographic data. The method decreased user interaction time by 86%, from 15 to 2 minutes. Expert reviewers were asked to indicate their confidence in differentiating automatically created images from clinical-quality manually produced images. The area under the receiver operating characteristic curve was 0.45 (95% CI: 0.39, 0.51), and a test of equivalency indicated that reviewers could not distinguish between images. They also graded image quality as equivalent to that with manual methods and found fewer artifacts on automatically created images. Automatic methods rapidly produce curved planar reformations of equivalent quality with reduced time and effort.     

Comparison of two methods used to assess first-ray mobility

Mobility of the first-ray is associated with several common lower extremity disorders. However, the reliability and validity of clinical measurement remains unclear. In this study we examined first-ray mobility by using one hand to stabilize the lesser metatarsals while the clinician's other hand applied a displacement force to the head of the first metatarsal. The amount of mobility was graded as stiff, normal or hypermobile. We then used a well-validated mechanical device to perform similar tests and assessed validity, intrarater reliability and interrater reliability. Three clinicians having varied levels of experience graded first-ray mobility on 15 subjects. A separate investigator measured dorsal mobility with a mechanical device. Both methods of testing were repeated to assess measurement reliability. Reliability was estimated by kappa (K) statistics. Spearman correlation assessed the relationship between mobility graded manually and dorsal mobility measured by device. Manual examination intrarater K values ranged from 0.50 to 0.85, and interrater agreement from 0.09 to 0.16. Manual grading was not related (r = -0.21) to the absolute measure of total dorsal mobility made by device. This brings into question the validity and reliability of manual estimates of first-ray mobility.     

Randomized, placebo-controlled trial of clodronate in patients with primary operable breast cancer.

PURPOSE: The development of bone metastases depends on tumor-induced osteoclastic resorption of bone, which may be inhibited by the antiosteolytic bisphosphonate clodronate. Given to patients with primary breast cancer, clodronate might reduce the subsequent incidence of bone metastases. PATIENTS AND METHODS: This double-blind, multicenter trial accrued 1,069 assessable patients with operable breast cancer between 1989 and 1995. All patients received surgery, radiotherapy, chemotherapy, and tamoxifen as required. Patients were randomized to receive oral clodronate 1,600 mg/d or a placebo for 2 years starting within 6 months of primary treatment. The primary end point was relapse in bone, analyzed on an intent-to-treat basis, during the medication period and during the total follow-up period (median follow-up, 2,007 days). Secondary end points were relapse in other sites, mortality, and toxicity. RESULTS: During the total follow-up period, there was a nonsignificant reduction in occurrence of bone metastases (clodronate, n = 63; placebo, n = 80; hazards ratio [HR], 0.77; 95% confidence interval [CI], 0.56 to 1.08; P =.127). During the medication period there was a significant reduction in the occurrence of bone metastases (clodronate, n = 12; placebo, n = 28; HR, 0.44; 95% CI, 0.22 to 0.86; P =.016). The occurrence of nonosseous metastases was similar (clodronate, n = 112; placebo, n = 128; P =.257), but there was a significant reduction in mortality (clodronate, n = 98; placebo, n = 129; P =.047) during the total follow-up period. CONCLUSION: Clodronate, given to patients with primary operable breast cancer, may reduce the occurrence of bone metastases, although this reduction was only significant during this medication period. There was a significant reduction in mortality.     

Temporal changes in collagen composition and metabolism during rodent palatogenesis

Cleft lip and palate is a common craniofacial malformation in man. The aetiology is multifactorial and not known. Since collagen is a major structural component of the developing palate, we studied its composition and metabolism during palate shelf formation and elevation in the rat. Palatal shelves were harvested at embryonic days (E) 15, 16 and 17 as well as post-partum. Palatal collagen increased threefold from E15 to E17 and tenfold from E17 to 5-day-old pups. Palatal calcification was seen in the main, post-partum. Collagen cross-linking, which may be important in shelf elevation and union, varied. The concentration of hydroxylysyl-pyridinolone cross-links was greatest prior to shelf elevation, declining thereafter. Similarly, the highest concentration of dihydroxylysinononorleucine was seen at E16 and this supports the concept of a compliant mesenchymal shelf responding to an intrinsic elevating force. We then determined if enzymes responsible for matrix degradation, matrix metalloproteinases (MMP) and the tissue inhibitors of metalloproteinases (TIMPs) altered over the same time periods. MMP-2, and TIMP-1 and TIMP-2 were identified by gelatin zymography and reverse zymography, respectively. MMP-3 activity was determined with a fluorogenic substrate assay. TIMP-1, TIMP-2 and MMP-3 levels remained constant from E15 to E17. The MMP-2 levels showed a significant elevation from E15 to E16 and E16 to E17. This suggests the regulation of extracellular matrix is likely to be of importance in palate morphogenesis.     

Demonstration of increased proteoglycan turnover in cartilage explants from dogs with experimental osteoarthritis

The turnover of proteoglycans (assessed by the release into the medium of newly synthesised [35S]-proteoglycan) in explant cultures of articular cartilage from various anatomical sites of the knee joints (stifle) of mature beagles with experimental osteoarthritis has been studied with the following findings: (a) The proportion of newly synthesised proteoglycans released from cartilage explants maintained in vitro was generally increased for cartilage from operated compared with nonoperated control joints. (b) At 3 weeks after surgery there was a significant increase in the release of [35S]-proteoglycans from explants of the lateral and medial tibial plateaux of operated joints compared with sham-operated joints but not from other sites. On the other hand, when this comparison was made at 3 to 6 months after surgery, significant increases in the release of [35S]-proteoglycans were observed from cartilage of all anatomical areas except the patellar groove. (c) The release of [35S]-proteoglycan from cartilage explant cultures was dependent on live chondrocytes, since freeze-thawing the tissue immediately after labelling markedly reduced the release from both normal and osteoarthritic cartilage.