Relationship between cefpirome clearance, serum creatinine, weight and age in patients treated for infection.

Cefpirome serum concentrations were measured by microbiological assay in 30 patients after five to nine days of treatment with 1 or 2 g bd for moderate to severe infection of presumed bacterial origin. Patients with serum creatinine (SCr) greater than 220 mumol/L were excluded. The age of patients ranged from 34-86 years. Creatinine clearance (Clcr) was calculated from age, sex, weight and SCr. The range of SCr was 63-220 mumol/L and the range of Clcr was 18-169 mL/min. The correlation coefficient with cefpirome clearance was 0.464 for SCr and 0.747 for Clcr. More than half of the patients with Clcr less than 50 mL/min had SCr within the normal range of 70-150 mumol/L. Mean cefpirome clearance in patients with Clcr 18-50 mL/min was 42.7 mL/min, which is very similar to the figure of 43.5 mL/min reported in a single dose volunteer study in patients with renal failure. Mean cefpirome clearance in patients with Clcr greater than 80 mL/min was 107.6 mL/min. In conclusion, these data on cefpirome clearance obtained after multiple dose treatment of patients with presumed bacterial infection are consistent with data previously obtained from single dose volunteer studies and support the currently recommended dose regimens. Clinicians should take account of age, weight and sex when estimating renal function from SCr.     

Apparent dissociation between myosin light chain phosphorylation and maximal velocity of shortening in KCl depolarized swine carotid artery: effect of temperature and KCl concentration

Stimulation of swine carotid artery medial fibers with 110 mM KCl at 37°C results in increases in myosin light chain (MLC) phosphorylation levels and maximal shortening velocity (V _o) during the period of stress development. During the period of stress maintenance, MLC phosphorylation levels andV _o are not maintained, but fall to suprabasal levels, resulting in a correlation between MLC phosphorylation andV _o and suggesting that MLC phosphorylation regulatesV _o. This study identifies other conditions of KCl depolarization of swine carotid medial fibers in which this relationship between MLC phosphorylation andV _o is altered. A decrease in temperature from 37° to 23°C results in a similar magnitude of stress maintenance in response to 110 mM KCl and similar levels of MLC phosphorylation, but a reduction inV _o by approximately 50%. This differential effect of temperature onV _o and MLC phosphorylation results in a downward shift in the slope of the regression line describing the relationship between these two parameters. Decreasing [KCl] to 40 mM in the stimulating solution results again in similar magnitudes of miantained stress. MLC phosphorylation levels are not transient, but maintained at a constant value andV _o is transient at levels approximately 50% of those at 110 mM KCl at 37°C. This results in a complete lack of correlation between MLC phosphorylation andV _o. Thus stress can be developed to equal magnitudes under differing activation conditions with dissimilar patterns of MLC phosphorylation andV _o. Therefore, there is not a strict relationship between MLC phosphorylation andV _o in all cases.     

Primary retroperitoneal myxoid/round cell liposarcoma is a nonexisting disease: an immunohistochemical and molecular biological analysis

Almost all primary retroperitoneal liposarcomas can be classified as well-/dedifferentiated liposarcoma. Rarely, however, primary retroperitoneal liposarcoma is classified as myxoid/round cell liposarcoma, based on the presence of myxoid areas and vascular crow's feet pattern, which has resulted in a debate on the classification of liposarcoma in the retroperitoneum. Genetically, myxoid/round cell liposarcoma and well-/dedifferentiated liposarcoma are different diseases. Myxoid/round cell liposarcoma is characterized by a translocation causing FUS-CHOP or EWSR1-CHOP fusion, whereas well-/dedifferentiated liposarcoma is characterized by an amplification of the 12q13-15 region, including MDM2 and CDK4 genes. As myxoid/round cell liposarcoma is highly radio- and chemosensitive, differentiation between subtypes is important to optimize treatment. We studied whether primary retroperitoneal liposarcomas diagnosed as myxoid/round cell liposarcoma represent molecularly true myxoid/round cell liposarcoma or are histopathological mimics and represent well-/dedifferentiated liposarcoma. Primary retroperitoneal myxoid/round cell liposarcoma (n=16) were compared to primary extremity myxoid/round cell liposarcoma (n=20). Histopathological and immunohistochemical features were studied. Amplification status of the 12q13-15 region was studied using a multiplex ligation-dependent probe amplification analysis, and FUS-CHOP or EWS-CHOP translocations were studied using RT-PCR. In primary retroperitoneal myxoid/round cell liposarcoma, MDM2 and CDK4 staining was both positive in 12 of 15 cases. In primary extremity myxoid/round cell liposarcoma, MDM2 was negative in 18/20 and CDK4 was negative in all cases. Multiplex ligation-dependent probe amplification showed the amplification of 12q13-15 region in 16/16 primary retroperitoneal myxoid/round cell liposarcomas and in 1/20 primary extremity myxoid/round cell liposarcomas. Translocation was present in all (18/18) primary extremity myxoid/round cell liposarcomas, but absent in all primary retroperitoneal myxoid/round cell liposarcomas. On the basis of immunohistochemical and molecular characteristics, apparent primary retroperitoneal myxoid/round cell liposarcoma can be recognized as well-/dedifferentiated liposarcoma with morphological features mimicking myxoid/round cell liposarcoma. In these cases, treatment should probably be specifically designed as for well-/dedifferentiated liposarcoma. Moreover, finding of myxoid/round cell liposarcoma translocations in a retroperitoneal localization is highly suggestive of metastasis and should prompt search for a primary localization outside the retroperitoneum.     

Quantitative assessment of commercial filter ‘aids’ for red‐green colour defectives

The claims made for 43 commercial filter ‘aids’, that they improve the colour discrimination of red‐green colour defectives, are assessed for protanomaly and deuteranomaly by changes in the colour spacing of traffic signals (European Standard EN 1836:2005) and of the Farnsworth D15 test. Spectral transmittances of the ‘aids’ are measured and tristimulus values with and without ‘aids’ are computed using cone fundamentals and the spectral power distributions of either the D15 chips illuminated by CIE Illuminant C or of traffic signals. Chromaticities (l,s) are presented in cone excitation diagrams for protanomaly and deuteranomaly in terms of the relative excitation of their long (L), medium (M) and short (S) wavelength‐sensitive cones. After correcting for non‐uniform colour spacing in these diagrams, standard deviations parallel to the l and s axes are computed and enhancement factors E_l and E_s are derived as the ratio of ‘aided’ to ‘unaided’ standard deviations. Values of E_l for traffic signals with most ‘aids’ are <1 and many do not meet the European signal detection standard. A few ‘aids’ have expansive E_l factors but with inadequate utility: the largest being 1.2 for traffic signals and 1.3 for the D15 colours. Analyses, replicated for 19 ‘aids’ from one manufacturer using 658 Munsell colours inside the D15 locus, yield E_l factors within 1% of those found for the 16 D15 colours.