Sarcoid Myelopathy

A 45-year-old woman with history of iritis, uveitis, and sarcoidosis of the skin presented with a subacute cervical myelopathy. Magnetic resonance imaging (MRI) ;howed patchy, multifocal, gadoliniumenhancing intramedullary lesions of the spinal cord, and extramedullary lesions of the basal cisterns and fourth ventricle. Symptoms and MRI abnormalities were improved within 1 month of corticosteroid therapy.     

Biochemical analysis of acute and chronic wound environments

The process of wound healing involves a complex interaction between numerous cell types, extracellular matrix molecules, and soluble mediators including growth factors and cytokines. This complex milieu is under active investigation for the purposes of beginning to understand how this environment regulates tissue repair. Quantitation of growth factors, cytokines, and matrix metalloproteinases within surgical wound fluids may help to elucidate this regulatory network, not only in noncomplicated wound healing but also in pathologic lesions such as chronic ulcers.     

Evaluation of an Algorithm To Identify Women with Carcinoma of the Breast

Although claims data are increasingly being used to measure and manage the cost and quality of health care, few studies have evaluated algorithms developed for such analyses. Therefore, the present study was performed to evaluate prospectively a previously published algorithm used to identify women with the new diagnosis of carcinoma of the breast. This algorithm had been developed from the patterns of claims that suggested common clinical presentations of carcinoma of the breast. In the present study, this algorithm was used to identify 177 potential cases of women with newly diagnosed carcinoma of the breast from the claims database of a large health maintenance organization (HMO). The algorithm's positive predictive value for cases identified in the present study was 83% (147/177). To attempt to improve upon the positive predictive value, multiple modifications of the algorithm were performed. The previously defined best modification of the initial algorithm yielded a positive predictive value of 84% (147/174) in the present study with the loss of none of the true positive cases. These results demonstrate that logic-based algorithms can be used as a valid and efficient method of identifying large numbers of new breast cancer cases from claims data. This algorithm provides a powerful tool to perform health care analysis and research for women with newly diagnosed carcinoma of the breast.     

Synthetic and computer-assisted analyses of the pharmacophore for the benzodiazepine receptor inverse agonist site

The structural requirements for ligand binding to the benzodiazepine receptor (BzR) inverse agonist site were probed through the synthesis and in vitro evaluation of 3-substituted beta-carbolines 6, 7, 11, 12, gamma-carboline 13, and diindoles 18-21, 23-25, 27, 28, and 34. On the basis of the apparent binding affinities of these and other analogues, a hydrogen bond acceptor site (A2) on the receptor is proposed to interact with the N(9) hydrogen atom of the beta-carbolines or the N(7) hydrogen nuclei of the diindoles. Likewise, a proposed hydrogen bond donating site (H1) interacts with the N(2) nitrogen atom of the beta-carbolines or the N(5) nitrogen atom of the diindoles. It appears that interaction with both sites is a prerequisite for high affinity since analogues which have either one or both of these positions blocked exhibit substantial reduction in affinity. Moreover, H1 appears to be capable of engaging in a three-centered hydrogen bond with appropriately functionalized ligands, which explains the increase in potency observed in the following series of 3-substituted beta-carbolines: the n-butyl (12, IC50 = 245 nM), n-propoxy (9, IC50 = 11 nM), and propyl ketone (11, IC50 = 2.8 nM) congeners. In addition to H1 and A2, there appears to be a relatively narrow hydrophobic pocket in the binding cleft that can accommodate substituents at the 3-position of the beta-carbolines which have chain lengths less than or equal to C5. There is a 1 order of magnitude decrease in affinity between n-propoxy analogue 9 (IC50 = 11 nM, chain length = 4) and n-butoxy derivative 7 (IC50 = 98 nM, chain length = 5). Furthermore, alpha- and gamma-branching [e.g. ethoxycarbonyl (2), IC50 = 5 nM and tert-butoxycarbonyl (31) IC50 = 10 nM] but not beta- and delta-branching [e.g. isopropoxy (6), IC50 = 500 nM and (neopentyloxy) carbonyl (48), IC50 = 750 nM] at position 3 are tolerated. Occupation of this hydrophobic pocket is clearly important for high affinity as evidenced by the relatively low affinity of 30, a beta-carboline which possesses a hydrogen atom at the 3-position. This same hydrophobic pocket is partially filled by the D and E rings of the diindoles, which accounts for the high affinity of several members of this series. An excluded volume analysis using selected 3-substituted beta-carbolines and ring-E substituted pyridodiindoles is consistent with the presence of this hydrophobic pocket (see Figure 1).(ABSTRACT TRUNCATED AT 400 WORDS)     

Microscopic haematuria as a relative contraindication for tranexamic acid

Tranexamic acid has been advocated for patients with severe bleeding tendency due to thrombocytopenia not responding to platelet transfusions. Macroscopic haematuria is a well-known contraindication for its use in such patients. We present three clinical cases with microscopic haematuria, in whom tranexamic acid caused problems of clot formation in the urinary tract, indicating that microscopic haematuria should also be considered as a contraindication for tranexamic acid.     

Co-contraction of lumbar muscles during the development of time-varying triaxial moments

The recruitment and co-contraction of lumbar muscles were investigated during the voluntary development of slowly and rapidly varying trunk flexion and extension, lateral bending, and axial twisting moments. Myoelectric signals were recorded from 14 lumbar muscles in nine young men during maximum voluntary exertions and cyclic isometric exertions. System identification techniques were used to calibrate dynamic models of the relationship between myoelectric signals and force. To assess co-contraction, the predicted muscle forces were subdivided into a task-moment set of muscle forces that minimally satisfied moment equilibrium and a co-contraction set of muscle forces that produced zero net moment. The sum of co-contraction muscle forces was used to quantify the degree of co-contraction present. Co-contraction was largely dependent on the direction of exertion and relatively less dependent on the subject or the rate of exertion. Co-contractions were estimated to contribute approximately 16–19% to the sum of muscle forces at a lumbar cross section during attempted extension of the trunk. Estimated co-contractions during attempted lateral bending and axial twisting were two to three times greater, which demonstrates that co-contraction is a major determinant of spinal loading in these tasks. This analysis suggests that substantial contractions of lumbar muscles, especially during asymmetric exertions, are used for reasons other than equilibrating moments at the L3-L4 level.