The effect of PGI2 and theophylline on the response of platelets subjected to shear stress

A specially designed rotational viscometer was used to investigate the effects of the antiplatelet agent PGI2 in combination with theophylline on the response of human platelets subjected to shear stress. Samples of citrated platelet-rich plasma (PRP) were exposed to shear stress in the viscometer for a period of 5 min at 23 degrees C. The levels of stress studied ranged from 50 to 300 dynes/sq cm. Pretreatment of the platelets with 0.01 microM PGI2 and 500 microM theophylline before exposure to shear stress caused a large reduction in shear-induced platelet aggregation. However, it was also observed that the PGI2-- theophylline pretreatment concomitantly caused a large increase in shear-induced platelet lysis and serotonin release at stress levels equal to or greater than 150 dynes/sq cm. This observed increase in platelet fragility may have important implications for clinical applications of PGI2. The results are discussed and compared to those obtained in prior work in which platelets were pretreated with acetylsalicylic acid or with PGE1.     

Gamma-carboxylated isoforms of recombinant human protein S with different biologic properties

Human protein S (HPS), a regulator of hemostasis, is a vitamin K- dependent plasma protein with potential clinical utility. We have obtained high-level expression of the cDNA for HPS in two mammalian cell lines. Both cell lines secreted single chain recombinant HPS (rHPS) in serum-free medium as determined by Western blot analysis. The ability of the rHPS from both cell lines to act as a cofactor for human protein C (HPC) was determined; the rHPS secreted from the human 293 cell line had an activity six times that of the rHPS from the AV12-664 Syrian hamster cell line. Furthermore, the relative specific cofactor activity of rHPS from the 293 cell line was actually 2.5-fold higher than that of single-chain human plasma-derived HPS. Essentially all of the rHPS secreted from the 293 cell line exhibited a calcium-dependent elution profile on anion exchange chromatography, whereas only 25% to 35% of the hamster cell-derived rHPS exhibited this profile. However, the calcium-eluted rHPS from the AV12 cell line had a high specific cofactor activity, equivalent to that of the 293-derived rHPS. A NaCl- elutable rHPS fraction (calcium nondependent) was isolated from the recombinant AV12-664 cell line, further purified, and found to have reduced activity, only 40% that of the calcium-dependent rHPS. The only observable difference in the calcium-dependent and nondependent rHPS molecules was in the content of gamma-carboxyglutamic acid (Gla); the calcium-dependent material contained approximately 10 mol Gla/mol protein whereas the calcium-nondependent material contained only approximately 8 mol Gla/mol of protein. In addition, the calcium- nondependent rHPS had reduced ability to interact with phospholipid vesicles as evidenced by an eightfold increase in the apparent kd. Our data demonstrate the isolation of rHPS with high specific activity, and show that a reduction in as few as two Gla residues dramatically decreases its functional cofactor activity for HPC, due to a reduction in ability to interact with the phospholipid bilayer.     

Pulmonary histiocytosis X: comparison of radiographic and CT findings

The authors retrospectively evaluated radiographs, computed tomographic (CT) scans, and results of pulmonary function tests (when available) for 17 patients with biopsy-proved pulmonary histiocytosis X. In 11 patients, high-resolution CT was used. In 12 patients, CT demonstrated cystic air spaces, usually less than 10 mm in diameter. In three of these 12, cysts were the only abnormality, but in six others, nodules (usually less than 5 mm in diameter) were also present. Two patients had only nodules and one, only emphysema. CT showed that many lesions that appeared reticular on plain radiographs were actually cysts. CT showed no central or peripheral concentration of lesions, but it did reveal that many small nodules were distributed in the centers of secondary lobules around small airways. CT findings correlated better with the diffusing capacity (rho = -0.71) than did the plain radiographic findings (rho = -0.57). Thus, CT was better than radiography at showing the morphology and distribution of lung abnormalities.     

Quantitative measurement of lead in paint by XRF analysis without manual substrate correction

X-ray fluorescence analysis has been used for measurement of lead in paint for more than a decade. The early systems provided a nondestructive alternative technology to laboratory-based technologies, but were somewhat time consuming and often led to inconclusive results. The procedure required manual substrate correction, multiple measurements, operator's discretion in validating a measurement due to interfering elements and laboratory analysis of inconclusive samples. A new instrument, the RMD LPA-1 system, has been developed based on X-ray fluorescence technology that addresses all of the drawbacks to the older systems. This new system uses a carefully designed and controlled geometry and modern microprocessor technology to automatically provide a rapid quantitative measurement of lead in paint with a 95% confidence level. The improved precision and accuracy achieved with this system are due to geometric enhancements and a mathematical approach which incorporates corrections for both random and systematic errors such as matrix effects and Compton scatter. This technology has been incorporated in a hand-held X-ray fluorescence lead paint analyzer system. A key design philosophy for this system was to maintain a very narrow, task-specific focus, the system was not designed to be an all purpose XRF analyzer, rather it is optimized to meet regulatory requirements of lead paint testing in the most efficient manner. The development of the LPA-1 system is an example of what can be accomplished by listening to the needs and desires of the users, rethinking the design of an existing technique and incorporating modern microprocessor technology.     

Socio-demographic factors and their impact on the number of resections for patients with recurrent glioblastoma

Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumour. Having a second or subsequent operation at recurrence may be a positive prognostic factor for survival. Recent studies suggest that socio-demographic variables may influence survival, raising the question whether surgical care differs based on these variables. We examined the relationship between selected socio-demographic variables and the number of repeat operations undergone by patients with recurrent GBM. Data from all patients diagnosed with GBM between 2001 and 2011 was obtained from a clinical database maintained across two institutions (one public, one private). The clinical and socio-demographic factors for patients who received one operation were compared to those who had two or more operations, using chi-squared analyses to determine statistical differences between groups. Socioeconomic status was measured using the Index of Relative Socioeconomic Advantage and Disadvantage scores. Of 553 patients, 449 (81%) had one operation and 104 (19%) had ?2 operations. Patients who had ?2 operations were significantly younger (median 55 years versus 64 years, p < 0.001), less likely to have multifocal (p = 0.043) or bilateral (p = 0.037) disease and more likely to have initial macroscopic resection (p = 0.006), than those who had only one operation. Socioeconomic status did not significantly differ between the groups (p = 0.31). Similarly, there was no significant difference between the number of operations in patients from regional versus city residence and public versus private hospital. This is reassuring as it suggests similar surgical management options are available for patients regardless of socio-demographic background.     

Porous Ba Ferrite Prepared from Wood Template

Ba ferrite materials with porous microstructures were prepared from a natural cedar wood template in order to investigate new electromagnetic shielding materials. The wood templates were infiltrated with barium nitrate and iron nitrate solutions (molar ratio = 1:12) and dried to form ferrite gel, then, they were sintered in air at a temperature between 800 °C and 1400 °C. The 1-dimensional porous structures were retained after sintering and the pore size was approximately 10–20 μm. These ferrites show large coercive force and anisotropy field. The largest coercive force was obtained for the specimen sintered at 800 °C.     

Postinflammatory ossicular fixation: CT analysis with surgical correlation

Postinflammatory ossicular fixation is a common problem encountered by the otologic surgeon upon exploration because of conductive hearing loss in patients with chronic otitis media. These nonotosclerotic noncongenital lesions take three pathologic forms: fibrous tissue fixation (chronic adhesive otitis media), hyalinization of collagen (tympanosclerosis), and new bone formation (fibro-osseous sclerosis). Fibrous tissue fixation appears on CT as nonbony, noncalcific soft-tissue debris encasing some or all of the ossicular chain. Tympanosclerosis appears as unifocal or multifocal punctate or weblike calcifications in the middle ear cavity or on the tympanic membrane. This debris may be in direct apposition to the ossicular chain or may replace the suspensory ligaments in symptomatic patients. New bone formation has been identified only in the attic and is the least common manifestation. Thick bony webs or generalized bony encasement may be present at CT. More than 300 patients with the clinical diagnosis of chronic otitis media have been examined. This study encompasses 23 proved cases.     

Identification and characterization of novel uroporphyrinogen decarboxylase gene mutations in a large series of porphyria cutanea tarda patients and relatives

Porphyria cutanea tarda (PCT) arises from decreased hepatic activity of uroporphyrinogen decarboxylase (UROD). Both genetic and environmental factors interplay in the precipitation of clinically overt PCT, but these factors may vary between different geographic areas. Decreased activity of UROD in erythrocytes was used to identify patients with UROD mutations among a group of 130 Spanish PCT patients. Nineteen patients (14.6%) were found to harbor a mutation in the UROD gene. Eight mutations were novel: M1I, 5del10, A22V, D79N, F84I, Q116X, T141I and Y182C. Five others were previously described: F46L, V134Q, R142Q, P150L and E218G. The new missense mutations and P150L were expressed in Escherichia coli. D79N and P150L resulted in proteins that were localized to inclusion bodies. The other mutations produced recombinant proteins that were purified and showed reduced activity (range: 2.3–73.2% of wild type). These single amino acid changes were predicted to produce complex structural alterations and/or reduced stability of the enzyme. Screening of relatives of the probands showed that 37.5% of mutation carriers demonstrated increased urinary porphyrins. This study emphasizes the role of UROD mutations as a strong risk factor for PCT even in areas where environmental factors (hepatitis C virus) have been shown to be highly associated with the disease.