Effect of polytetrafluoroethylene covering of Palmaz stents on the development of intimal hyperplasia in human iliac arteries

PURPOSE: The occurrence of neointimal hyperplasia within a stent may result in restenosis with recurrent symptoms of end-organ ischemia. This study evaluated the potential of a nonporous covering of a stent to function as a barrier to the formation of intrastent neointimal hyperplasia. MATERIALS AND METHODS: Twelve endovascular stent grafts were used to treat 12 high-risk patients with limb-threatening ischemia secondary to long-segment iliac artery occlusion. A 6-mm, thin-walled polytetrafluoroethylene graft was inserted and anchored to the common iliac artery with use of Palmaz stents. Each stent was covered by graft material over one-half of its length. Control angiograms obtained immediately after graft insertion were compared with follow-up angiograms obtained between 4 and 6 months after the initial procedure. On each angiogram, the region of the stent was magnified by 20x to permit computerized luminal diameter measurements. RESULTS: The mean luminal diameter within the stent was significantly greater on the covered (7.7 mm +/- 0.33 standard deviation) compared with the uncovered (6.7 mm +/- 0.85 standard deviation) portions (P < .01). CONCLUSIONS: Partially covered stents are a unique model for assessing the effects of an extrinsic stent covering on arterial healing and myointimal hyperplasia. These data suggest that a relatively nonporous covering of polytetrafluoroethylene may inhibit stent-related restenosis in iliac arteries.     

Closed treatment of displaced middle-third fractures of the clavicle gives poor results

We evaluated 242 consecutive fractures of the clavicle in adults which had been treated conservatively. Of these, 66 (27%) were originally in the middle third of the clavicle and had been completely displaced. We reviewed 52 of these patients at a mean of 38 months after injury. Eight of the 52 fractures (15%) had developed nonunion, and 16 patients (31%) reported unsatisfactory results. Thirteen patients had mild to moderate residual pain and 15 had some evidence of brachial plexus irritation. Of the 28 who had cosmetic complaints, only 11 considered accepting corrective surgery. No patient had significant impairment of range of movement or shoulder strength as a result of the injury. We found that initial shortening at the fracture of > or = 20 mm had a highly significant association with nonunion (p < 0.0001) and the chance of an unsatisfactory result. Final shortening of 20 mm or more was associated with an unsatisfactory result, but not with nonunion. No other patient variable, treatment factor, or fracture characteristic had a significant effect on outcome. We now recommend open reduction and internal fixation of severely displaced fractures of the middle third of the clavicle in adult patients.     

Discrimination of complex patterns: orientation information is integrated across spatial scale; spatial-frequency and contrast information are not

Real-world objects are complex, containing information at multiple orientations and spatial scales. It is well established that at initial cortical stages of processing, local information about an image is separately represented at multiple spatial scales. However, it is not yet established how these early representations are later integrated across scale to signal useful information about complex stimulus features, such as edges and textures. In the studies reported here, we investigate the scale-integration processes involved in distinguishing among complex patterns. We use a concurrent-response paradigm in which observers simultaneously judge two components of compound gratings that differ widely in spatial frequency. In different experiments, each component takes one of two slightly different values along the dimensions of spatial frequency, contrast, or orientation. Using analyses developed within the framework of a multivariate extension of signal-detection theory, we ask how information about the frequency, contrast, or orientation of the components is or is not integrated across the two grating components. Our techniques permit us to isolate and identify interactions due to excitatory or inhibitory processes from effects due to noise, and to separately assess any attentional limitations that might occur in processing. Results indicate that orientation information is fully integrated across spatial scales within a limited orientation band and that decisions are based entirely on the summed information. Information about spatial frequency and contrast is not summed over spatial scale; cross-scale results show sensory independence. However, our results suggest that observers cannot simultaneously use information about frequency or contrast when it is presented at different spatial scales. Our results provide direct evidence for the existence of a higher-level summing circuit tailored to signal information about orientation. The properties of this mechanism differ substantially from edge-detector mechanisms proposed by Marr and others.     

Mechanisms of isoniazid resistance in Mycobacterium tuberculosis: enzymatic characterization of enoyl reductase mutants identified in isoniazid-resistant clinical isolates

Hepatocyte growth factor (HGF) decreases transforming growth factor beta1 (TGFbeta1) levels in the liver and attenuates hepatic fibrosis caused by dimethylnitrosamine in rats. In the liver, HGF is presumed to act predominantly on parenchymal cells, and TGFbeta1 is produced mainly by mesenchymal cells. In hepatic fibrosis, stellate cells play a central role with undergoing activation, which also occurs when the cells are cultured on plastic. Thus, we wondered if HGF could act directly on stellate cells. c-Met was detected in rat stellate cells activated by culture for 10 days, but not in the cells cultured for 3 days. Specific binding of HGF to the activated cells was determined, and Scatchard analysis indicated an apparent Kd of 1.5 nM. c-Met mRNA was detected in freshly isolated stellate cells from rats treated with carbon tetrachloride for 8 weeks, but not in those cells from normal rats. These results indicate that stellate cells express c-met when activated in vitro and in vivo. HGF enhanced TGFbeta1 production and DNA synthesis in the activated cells.     

Sabotaging one''s own medical care. Prevalence in a primary care setting

Treatment of washed boar sperm with hypotonic phosphate buffer removed the acrosome, disrupted the cytoplasmic membrane and almost completely separated the heads from the mid piece-tail segment. As assessed by oxygen uptake studies and their ability to oxidize 14C-labelled substrates to 14CO2, hypotonically-treated cells exhibit low glycolytic activity yet mitochondrial activity remains high. Both lactate and glycerol 3-phosphate underwent oxidation and these substrates continued to be metabolized by this preparation which had been stored for up to 10 days at 4 degrees C. Such preparations may be of assistance in the investigation of the biochemistry of boar sperm mitochondria.     

Hammerhead ribozymes targeted to the FBN1 mRNA can discriminate a single base mismatch between ribozyme and target

Hammerhead ribozymes are catalytic RNA molecules that can act in trans, with ribozyme and substrate being two different oligoribonucleotides with regions of complementarity. Mutations in the gene for fibrillin-1 (FBN1) cause Marfan syndrome. The majority of mutations are single-base changes, many of which exert their effect via a dominant-negative mechanism. Previously we have shown that an antisense hammerhead ribozyme, targeted to the FBN1 mRNA can reduce deposition of fibrillin to the extracellular matrix of cultured fibroblasts, suggesting it may be possible to utilize ribozymes to down regulate the production of mutant protein and thus restore normal fibrillin function. This might be achieved by the mutation creating a ribozyme cleavage site that is not present in the normal allele, however this is likely to limit the number of mutations that could be targeted. Alternatively, it might be possible to target the mutant allele via the ribozyme binding arms. To determine the potential of ribozymes to preferentially target mutant FBN1 alleles via the latter approach, the effect of mismatches in helix I of a hammerhead ribozyme, on the cleavage of fibrillin (FBN1) mRNA was investigated. A single base mismatch significantly reduced ribozyme cleavage efficiency both in vitro and in vivo. The discrimination between fully-matched and mismatched ribozyme varied with the length of helix I, with the discrimination being more pronounced in ribozymes with a shorter helix. These data suggest that it should be possible to design hammerhead ribozymes that can discriminate between closely related (mutant and normal) target RNAs varying in as little as a single nucleotide, even if the mutation does not create a ribozyme cleavage site.     

Adenovirus vector-based purging of multiple myeloma cells

Adenoviruses are efficient gene delivery agents for a variety of neoplasms. In the present study, we have investigated the use of adenoviruses for the delivery of the thymidine kinase (tk) gene into multiple myeloma (MM) cells. We first demonstrated that MM cell lines and MM patient cells express both adenovirus receptors as well as the DF3/MUC1 protein, thus providing a rationale for using adenoviruses to selectively deliver genes under the control of the DF3 promoter. By using an adenoviral construct containing beta-galactosidase (beta-gal) gene driven by the DF3 promoter (Ad. DF3-betagal), we demonstrate greater than 80% transduction efficiency in OCI-My5 and RPMI 8226 MM cell lines at a multiplicity of infection of 1 to 100. Importantly, transduction with the tk gene driven by the DF3 promoter (Ad.DF3-tk) followed by treatment with 50 micromol/L ganciclovir (GCV) purged >/=6 log of contaminating OCI-My5 and RPMI 8226 MM cells within bone marrow mononuclear cells. In contrast, normal human hematopoietic progenitor cell number was unaffected under these conditions. Selectivity of DF3/MUC1 promoter was further confirmed, because Ad.DF3-betagal or Ad.DF3-tk did not transduce MUC1-negative HeLa cervical carcinoma cells. In addition, GCV treatment of Ad.DF3-tk-transduced RPMI 8226 MM cells did not induce a significant bystander effect. These findings demonstrate that transduction with Ad vectors using a tumor-selective promoter provides a highly efficient and selective approach for the ex vivo purging of MM cells.     

Male-female differences in the relationship between obesity and lipids/lipoproteins

OBJECTIVE: To examine the effect of gender on the relationship between obesity measures and lipids/lipoproteins. DESIGN: Cross-sectional, matched observational study of adult men and women. SUBJECTS: 225 spousal pairs from Cincinnati, Ohio (age range, 28-66 years; mean +/- SD (yr), 44.0 +/- 6.7 (men), 42.1 +/- 5.9 (women). MEASUREMENTS: Body mass measures, lipids, lipoproteins, apolipoproteins, physical activity levels, cigarette use and dietary variables. RESULTS: Correlations between the lipids/lipoproteins and body mass index (BMI) were stronger in women than in men for cholesterol (r = 0.24 vs 0.10), LDL-c (r = 0.27 vs 0.12), triglycerides (TG) (r = 0.48 vs 0.23) and the ratio cholesterol/HDL-c (r = 0.47 vs 0.28). Utilizing statistical regression models which included potentially confounding environmental factors, BMI and WHR both contributed significant information to describe cholesterol, HDL-c, TG and cholesterol/HDL-c values in women, whereas WHR alone provided information for these lipids/lipoproteins in men. CONCLUSION: The association between BMI and lipids/lipoproteins appears to be stronger in women than in men. In women, in contrast to men, BMI and WHR, measures which are easily attainable in the clinical setting, provide separate, independent information in the explanation of these lipid/lipoprotein levels.     

Oligoclonality of Vdelta1 and Vdelta2 cells in human peripheral blood mononuclear cells: TCR selection is not altered by stimulation with gram-negative bacteria

Despite the enormous potential repertoire of gammadelta T cells, there are several observations which suggest that the expressed gammadelta repertoire in the periphery of normal individuals is often quite restricted. To assess selective expansions among gammadelta T cells from both adult and newborn blood samples, PBMC from 12 normal adults and cord blood from 15 normal newborns were analyzed for TCRDV1 and TCRDV2 junctional diversity by CDR3 size spectratyping and single-strand conformational polymorphism. Although TCRBV usage showed extensive heterogeneity in adults and newborns, both populations often showed CDR3 region restriction for TCRDV1 and TCRDV2. Analysis of the CDR3 spectratype patterns of newborn twins suggested that clonal selection for TCRDV is independent of genetic background. The possible role of Gram-negative bacteria in driving selective responsiveness of gammadelta T cells in PBMCs from adults was examined by in vitro stimulation with Escherichia coli and Pseudomonas aeruginosa. Donors whose TCRDV repertoire was highly clonal in the unstimulated blood cells showed the same predominant clones among the bacteria-stimulated cultures. In individuals whose gammadelta T cells were less restricted, in vitro stimulation did not select for clonality; rather, the TCRDV repertoires were similar before and after bacterial stimulation. Together, these data indicate that gammadelta T cells are often clonally restricted in adults as well as in newborns and suggest that the prominent stimulatory activity of Gram-negative bacteria does not by itself account for the restriction or diversity of the gammadelta T cell repertoire.     

Prevalence of sexual assault history among women with common gynecologic symptoms

OBJECTIVE: The purpose of this study was to evaluate the prevalence of a sexual assault history among women with and without 3 common gynecologic complaints: dysmenorrhea, menorrhagia, and sexual dysfunction. STUDY DESIGN: Data came from 3 surveys of women randomly selected from general populations: 2 United States regional samples (n = 1428 and n = 1703) and 1 national sample (n = 963). Prevalence rates and adjusted odds ratios were calculated and combined across the 3 samples with a meta-analysis. RESULTS: The prevalence of an assault history ranged from 6% to 26% among women with 1 symptom to 13% to 40% among women with 3 symptoms. Symptoms were associated with increased odds of an assault history for women 18 to 34 years old (odds ratio 1.90, 95% confidence interval 1.56 to 2.32), 35 to 44 years old (odds ratio 1.99, 95% confidence interval 1.57 to 2.53), and >54 years old (odds ratio 1.37, 95% confidence interval 1.04 to 1.80). Symptoms were unrelated to sexual assault history for women in the perimenopausal (45 to 54 years) age group (odds ratio 0.94, 95% confidence interval 0.71 to 1.24). Symptom level was unrelated to having disclosed assaults to a physician (odds ratio 1.17, 95% confidence interval 0.85 to 1.62). CONCLUSIONS: Women in the general population with common gynecologic complaints are at a substantially increased risk of having a history of sexual assault.