Value of image-guided needle aspiration cytology in the assessment of thoracolumbar and sacrococcygeal masses

We have used a primary cloning assay to determine the frequency of 6-thioguanine (TG)-resistant tubular epithelial cells in kidney tissue from 72 human donors ranging in age from 2 to 94 years. The frequency of TG-resistant mutants ranged from approximately 5 x 10(-5) for donors in the first decade of life to approximately 2.5 x 10(-4) for donors in the eighth and later decades of life. Two different statistical analyses indicated that this increase in mutant frequency is exponential with age. We also observed a 2-fold higher TG-resistant mutant frequency in nephrectomy kidneys containing a coincident renal carcinoma. DNA sequence analyses revealed HPRT gene mutations in each of 14 TG-resistant mutants from seven unrelated donors. Thirteen of these 14 mutants resulted from independent mutational events. These results suggest that somatic mutations are common in renal--and perhaps in other human--epithelia, and thus could play an important role in the genesis of age-associated disease.     

Prognostic evaluation of early indicators in fulminant hepatic failure by multivariate analysis

Results of eight multicenter, randomized, placebo-controlled, double-blind, parallel-group studies were pooled to assess the efficacy of the angiotensin II-receptor blocker irbesartan over the dose range of 1 to 900 mg. A total of 2955 adults with a seated diastolic blood pressure of 95 to 110 mm Hg were randomized to treatment with oral irbesartan once daily or placebo for 6 to 8 weeks. Office blood pressure was measured at trough (24+/-3 hours after the last dose) and peak (3+/-1 hours after the last dose) by mercury sphygmomanometry. Demographic characteristics (mean blood pressure; 151/101 mm Hg; mean age, 54 years; 63% male; and 82% white) were similar across all dose groups. After the groups were pooled, antihypertensive efficacy was assessed by therapeutic response (trough seated diastolic blood pressure <90 mm Hg or a reduction from baseline of > or = 10 mm Hg) and by modeling of the maximum reductions in trough and peak seated diastolic and systolic blood pressure. Antihypertensive effects increased with increasing doses and reached a plateau at > or = 300 mg. Irbesartan 150 mg provided placebo-subtracted reductions in trough seated systolic and diastolic blood pressure of approximately 8 and approximately 5 mm Hg, respectively, with 56% of patients displaying a favorable response. In conclusion, irbesartan provides clinically significant blood pressure lowering, with a clear relationship between (log) dose and antihypertensive effect.     

Down-regulation of glial fibrillary acidic protein expression during acute lytic varicella-zoster virus infection of cultured human astrocytes

The effects of the varicella-zoster virus (VZV) OKA vaccine strain in producing morphologic and antigenic changes in dissociated cultures of human fetal brain was investigated. Cultures containing 80% glial acidic fibrillary protein (GFAP), GFAP+ (positive) astrocytes and 20% GFAP- (negative) fibroblastic-like cells were infected with cell-free VZV OKA at a multiplicity of infection of 0.1 plaque-forming units per cell. Cytopathic effects and significant viral antigen labeling with antibodies against VZV gpl and immediate-early (IE) protein 62 were first detected 6 to 7 days postinfection. Several observations indicated that astrocyte GFAP expression was altered and diminished as a result of VZV infection itself, thereby raising doubts about the utility of combining cell markers and viral antigenic labeling in assessing the susceptibility of neural cell types to viral infection. The down-regulation of GFAP expression by VZV appears to be mediated by early rather than late events in the viral replication cycle and may not be the result of virally induced global shut-off of host cell protein synthesis. Similar observations were made using VZV Ellen, a multipassaged, nonvaccine strain. These observations have potential in vivo implications related to histologic analysis of VZV-infected tissues and disease pathogenesis.     

Ultrasonically activated shears in thyroid surgery

BACKGROUND: Ultrasonically activated shears (UAS) have been documented to be both safe and fast devices in laparoscopic surgery. We studied whether the use of UAS would have some advantage in thyroid surgery. METHODS: Thyroidectomies, performed by one senior endocrine surgeon between December 1996 and February 1997, were retrospectively matched, with patients operated on by the same surgeon using the conventional method. RESULTS: Six pairs of total thyroidectomies and one pair of lobectomies could be matched. Mean operating time was 100 minutes for the patients operated on with the UAS and 154 minutes for the patients operated on with the conventional method. The mean operating time with the UAS was thus on average 64.6% of the operation time with the conventional method, with a 95% confidence interval from 50.1% to 83.5% (t = 4.00, 6 df, P = 0.007). CONCLUSIONS: In this material the use of UAS reduced significantly operating time in thyroidectomies.     

Numerical simulation of annular-phased arrays of dipoles forhyperthermia of deep-seated tumors

We have used the finite-difference time domain (FDTD) method to calculate the SAR distributions from an annular-phased array of eight dipole antennas coupled through water "boluses" in anatomically based three-dimensional models of the human body. We evaluated the effect of tapered bolus chambers, frequency (100-120 MHz), dipole length (17-30 cm), and phase and amplitude of power to the various dipoles on the ability to focus energy in the region of deep-seated tumors in the prostate and the liver. Assuming tumor conductivity and permittivity to be similar or slightly higher than surrounding normal tissues, calculations indicate that adjustment of the noted parameters should result in considerable improvement in focusing of SAR distributions in tumor-bearing regions. If such calculations can be shown to correctly predict empirical measurements from complex inhomogeneous (although not necessarily anatomically correct) phantoms, they may be useful for hyperthermia treatment planning based on patient-specific anatomic models.     

Improved corrosion protection of aluminum alloys by electrodeposited silanes

Organofunctional silanes recently have emerged as outstanding, environmentally friendly corrosion protectors for metal substrates, compared with conventional chromate treatments. A simple immersion technique is typically used to coat the metal surface with silane films. However, the thickness and uniformity of the films are uncontrolled in this process. This paper proposes a new deposition technique for the silane films on the metal surface, i.e., by electrodeposition. Hydrolyzed silanes are water-soluble, ionized molecules, so they can be deposited on metals by electrodeposition. Various combinations of silane mixtures were tested at different voltages, pH values, bath concentrations, and exposure times on panels of alloy aluminum and mirror-polished ferro-plate. The surface structure was characterized by scanning electron microscopy (SEM) and ellipsometry. The resistance of the film to corrosion was investigated by direct current (DC) polarization and electrochemical impedance spectroscopy (EIS) techniques. Electrodeposition results in a more organized and uniform film with fewer pores, compared with immersed or dipped films. This paper was presented at the 2nd International Surface Engineering Congress sponsored by ASM International, on September 15–17, 2003, in Indianapolis, Indiana, and appears on pp. 320–26 of the Proceedings.     

The influence of sulfur dioxide on propane oxidation activity over supported platinum and palladium

Earlier studies have shown that sulfur dioxide and metal-support interaction can strongly influence propane oxidation over platinum. In particular, oxidation activity is enhanced when platinum is supported on sulfated -alumina or zirconia compared to -alumina. Therefore, it is of interest to compare the performance of palladium under the same experimental conditions. Four model catalysts were examined: Pt/-alumina, Pt/zirconia, Pd/-alumina and Pd/zirconia. The metal loading was kept at or below 0.05 wt% to emphasize changes in activity attributable to metal-support interaction. Reaction rates were measured with and without sulfur dioxide. Surface sulfation was analyzed by measuring acid strength and evaluating spectra obtained by Fourier-transform infrared spectroscopy. In contrast to platinum, sulfation does not promote propane oxidation on Pd/-alumina, and Pd/zirconia is less active than Pd/-alumina.     

Effects of cellular pharmacology on drug distribution in tissues

The efficacy of targeted therapeutics such as immunotoxins is directly related to both the extent of distribution achievable and the degree of drug internalization by individual cells in the tissue of interest. The factors that influence the tissue distribution of such drugs include drug transport; receptor/drug binding; and cellular pharmacology, the processing and routing of the drug within cells. To examine the importance of cellular pharmacology, previously treated only superficially, we have developed a mathematical model for drug transport in tissues that includes drug and receptor internalization, recycling, and degradation, as well as drug diffusion in the extracellular space and binding to cell surface receptors. We have applied this "cellular pharmacology model" to a model drug/cell system, specifically, transferrin and the well-defined transferrin cycle in CHO cells. We compare simulation results to models with extracellular diffusion only or diffusion with binding to cell surface receptors and present a parameter sensitivity analysis. The comparison of models illustrates that inclusion of intracellular trafficking significantly increases the total transferrin concentration throughout much of the tissue while decreasing the penetration depth. Increasing receptor affinity or tissue receptor density reduces permeation of extracellular drug while increasing the peak value of the intracellular drug concentration, resulting in "internal trapping" of transferrin near the source; this could account for heterogeneity of drug distributions observed in experimental systems. Other results indicate that the degree of drug internalization is not predicted by the total drug profile. Hence, when intracellular drug is required for a therapeutic effect, the optimal treatment may not result from conditions that produce the maximal total drug distribution. Examination of models that include cellular pharmacology may help guide rational drug design and provide useful information for whole body pharmacokinetic studies.