Effect of aspirin and NSAIDs on colorectal adenomas. Protective effect may be spurious.
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Biomedical subjects
Publications and source records attributed to R Lyons.
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Complexity in the retinoid signaling system arises from a combination of several forms of retinoic acid which possess differential activities, multiple cytoplasmic binding proteins and nuclear receptors that have distinct ligand specificities and functional properties, and the existence of polymorphic retinoic acid response elements. Additional diversity appears to be generated by heterodimeric interactions between the two classes of nuclear retinoic acid receptors and between retinoic acid receptors and some other members of the nuclear receptor superfamily. Thus, a complex array of combinatorial effects is beginning to emerge that may account for the pleiotropic effects of retinoids.
The aim of this study was to determine the extent to which variation in socioeconomic factors derived from the 1986 census could "explain" variation in standardised mortality ratio (SMR) between the 322 electoral wards and district electoral divisions (DEDs) in Dublin. Factors examined included percentage of population in the various Irish social class groupings, percentage of male unemployment, number of cars per private household and number of persons per car. Regression analysis between SMR and each of these factors individually showed a significant relationship in every case. The explanatory variables studied were all highly correlated and stepwise forward multiple regression was used to identify factors which had an independent effect. Two factors emerged as significant--percentage of persons in social classes 5 & 6 (semiskilled and unskilled) and number of cars per private household. This model explained 27.4% of the variance in SMR. We conclude that the variation of SMRs between DEDs in Dublin can partly be explained by variation in socioeconomic factors.
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We have purified and cloned a HeLa cell nuclear protein that strongly stimulates binding of retinoic acid and thyroid hormone receptors (RARs and TRs) to response elements. The purified protein is a human retinoid X receptor beta (hRXR beta). Three murine members of the RXR family (mRXR alpha, beta, and gamma) have also been cloned, and their interactions with RARs and TRs have been investigated. Under conditions where RAR, RXR, and TR bound poorly as homodimers to various response elements, strongly cooperative RAR-RXR and TR-RXR binding was observed. The binding efficiency was dependent on the sequence, relative orientation, and spacing of the repeated motifs of response elements. We show also that unstable RAR-RXR heterodimers were formed in solution, and that C-terminal sequences and the DNA-binding domains of both receptors were required for efficient formation of stable heterodimers on response elements. These findings suggest a convergence of the signaling pathways of some members of the nuclear receptor superfamily.
A community-based cross-sectional survey of behavioural risk factors for premature mortality was carried out on a group of 354 adults aged 25-44 from previously identified high-mortality 'black-spots' in Dublin who were compared with 333 others from low-mortality areas. In the black-spot areas, 50.9% of respondents were current smokers versus 28.5% in low-mortality areas and 14.6% took 'sufficient' exercise versus 31.4% in low-mortality areas. People living in black spots were also less likely to make 'healthy' dietary choices than those in low-mortality areas. There is a higher prevalence of behavioural risk factors for premature mortality among young adults living in electoral wards/district electoral divisions (DEDs) with high standardized mortality ratios (SMRs) from all causes than among those in areas with low SMRs. A health promotion programme aimed at increasing exercise levels, reducing smoking and encouraging healthy eating should be aimed at young adults in DEDs with high SMRs.
Seventy-seven children (mean age 44.2 months) were entered in a randomised double blind study to find out if two commonly used measles, mumps, and rubella (MMR) vaccines (Pluserix and MMR II) caused pain on injection. Pain was judged by the amount of crying. Infants given MMR II were 2.31 times more likely to cry than those given Pluserix.
The conversion of latent transforming growth factor beta (LTGF-beta) to the active species, transforming growth factor beta (TGF-beta), has been characterized in heterotypic cultures of bovine aortic endothelial (BAE) cells and bovine smooth muscle cells (SMCs). The formation of TGF-beta in co-cultures of BAE cells and SMCs was documented by a specific radioreceptor competition assay, while medium from homotypic cultures of BAE cells or SMCs contained no active TGF-beta as determined by this assay. The concentration of TGF-beta in the conditioned medium of heterotypic co-cultures was estimated to be 400-1,200 pg/ml using the inhibition of BAE cell migration as an assay. Northern blotting of poly A+ RNA extracted from both homotypic and heterotypic cultures of BAE cells and SMCs revealed that BAE cells produced both TGF-beta 1 and TGF-beta 2, while SMCs produced primarily TGF-beta 1. No change in the expression of these two forms of TGF-beta was apparent after 24 h in heterotypic cultures. Time course studies on the appearance of TGF-beta indicated that most of the active TGF-beta was generated within the first 12 h after the establishment of co-cultures. The generation of TGF-beta in co-cultures stimulated the production of the protease inhibitor plasminogen activator inhibitor-1 (PAI-1). The inclusion of neutralizing antibodies to TGF-beta in the co-culture medium blocked the observed increase in PAI-1 levels. The increased expression of PAI-1 subsequent to TGF-beta formation blocked the activation of the protease required for conversion of LTGF-beta to TGF-beta as the inclusion of neutralizing antibodies to PAI-1 in the co-culture medium resulted in prolonged production of TGF-beta. This effect was lost upon removal of the PAI-1 antibodies. Thus, the activation of LTGF-beta appears to be a self-regulating system.
The effect of different temporal patterns of calorie intake on plasma glucose, serum insulin, and insulin secretion rates was examined in six patients with moderately well controlled non-insulin-dependent diabetes mellitus (NIDDM). Patients were studied on three separate occasions over 26 h. Total calories and food composition (50% carbohydrate, 15% protein, and 35% fat) were kept constant, but the pattern of calorie intake was varied. In study A (similar meal size), calories were distributed as 30, 40, and 30% at breakfast, lunch, and dinner, respectively. In study B (3 snacks, 3 meals), each subject ate three meals of 20, 20, and 30% of calories for breakfast, lunch, and dinner, respectively, and three snacks, each comprising 10% of calories, presented 2.5 h after the meal. In study C (large dinner), 10% of calories were consumed at breakfast, 20% at lunch, and 70% at dinner. Glucose, insulin, and C-peptide concentrations were measured at 15- to 30-min intervals. Insulin secretion rates were calculated from C-peptide levels with individually derived C-peptide clearance parameters. The different eating patterns were associated with only modest differences in overall levels of glucose and insulin secretion. Daytime insulin secretion was lowest when most of the daily calorie intake occurred in the form of a large dinner. Overnight levels of glucose and insulin secretion rates did not differ for the three eating patterns, and the morning glucose levels were also unaffected by the pattern of calorie intake on the previous day. A morning rise of glucose of greater than 0.28 mM occurred consistently only when dinner was of moderate size (30% of total calories).(ABSTRACT TRUNCATED AT 250 WORDS)
The efficacy of total body showering and incision site scrub with disinfectant agents was evaluated in a randomized, prospective study of 575 patients undergoing selected surgical procedures. Patients who showered twice with 4% chlorhexidine gluconate had lower mean colony counts of skin bacteria at the surgical incision site in the operating room prior to the final scrub than patients who showered twice with povidone-iodine solution or medicated bar soap. Patients in the chlorhexidine group had no growth on 43% of the incision site skin cultures compared with 16% in the povidone-iodine group and 6% in the soap and water group. Patients who showered and who were scrubbed with chlorhexidine also had lower rates of intraoperative wound contamination. Bacteria were recovered from the wounds of 4% of patients using this regimen compared with 9% for patients who used povidone-iodine and 15% for patients who showered with medicated soap and water and were scrubbed with povidone-iodine. We noted no difference in surgery-specific infection rates among patients in the three treatment groups; however, our sample sizes were too small to evaluate this outcome parameter adequately. These data suggest that preoperative showering and scrubbing with chlorhexidine is an effective regimen to reduce extrinsic intraoperative contamination of the surgical wound from skin bacteria. The efficacy of this regimen to prevent postoperative wound infection needs to be evaluated in a well-designed, carefully controlled prospective trial with adequate numbers of patients to achieve statistically valid conclusions.
TGF beta has been identified in normal human urine specimens from five individuals studied for five consecutive days. The peptide was extracted from urine using Sepralyte C1 beads. Detectable levels of [125I]TGF beta competing activity as measured by radioreceptor assay was found in about half of the specimens studied. The protein isolated from urine using C1 Sepralyte beads was further purified using Biogel P-60 column chromatography. Fractions were tested for TGF beta and EGF competing activity using radioreceptor assays. TGF beta and EGF extracted from urine are clearly separated by column chromatography. Two distinct EGF peaks and a single TGF beta peak were observed. Fractions having [125I]TGF beta competing activity were pooled and further purified using reverse-phase HPLC. HPLC fractions having [125I]TGF beta competing activity were tested for bioactivity using a soft agar assay. The fractions were capable of stimulating soft agar growth of AKR-2B (clone 84A) cells and cross reacted with a TGF beta antibody in a radioimmunoassay. The presence of TGF beta in normal human urine was also demonstrated by immunoblotting. These results also suggest that C1 bead extraction of urine specimens can be used as a rapid first step in purification of TGF beta.
This study compared the histology, biochemistry, and tensile strength of laser-welded and sutured canine venotomies, arteriotomies, and arteriovenous fistulas. Twelve animals had bilateral femoral vessels studied, with one repair (control) closed with interrupted 6-0 polypropylene sutures, and the contralateral repair (experimental) welded with the argon laser. Specimens were examined at weekly intervals from 1 to 4 weeks (four animals for each type of repair), and were evaluated histologically by hematoxylin and eosin, elastin, and trichrome stains; biochemically by the formation of [3H]hydroxyproline as an index of collagen synthesis; and mechanically by tensile strength determinations. At removal, all experimental closures were patent without hematomas, aneurysms, or luminal dilatation. Histologic and biochemical examination and tensile strength determinations suggest that laser welding may be an alternative to sutures for repair of large-diameter venotomies, arteriotomies, and arteriovenous fistulas, as healing is comparable to that seen with suture repairs up to 4 weeks postoperatively.
This study compared the histology and tensile strength of Nd:YAG laser welded and sutured small bowel enterotomies in Sprague-Dawley rats. Enterotomies (0.5 cm long) were either welded with the Nd:YAG laser (1 W and 10.6 sec pulses) or repaired with interrupted, simple 6-O silk sutures. Group I consisted of seven animals; five with enterotomies repaired by laser welding and two repaired by suturing. Group II consisted of eight animals with each having both laser and suture repairs. Animals were killed and specimens were removed and examined at 1 day, and at 1, 2, and 3 weeks postoperatively to compare the progression of healing. On macroscopic examination the laser welded enterotomies were closed 84% of the time and only 23% had adhesion formation while 90% of sutured repairs were closed and 100% had adhesion formation. Histologic examination of both suture and laser welded enterotomies demonstrated active healing at 1 week with minimal collagen bridging the enterotomies. At 2 and 3 weeks the sutured enterotomies had granulomatous reaction around the sutures while the laser welded enterotomies had minimal inflammatory response and near normal small bowel histology. The tensile strength of the 3-week specimens from both the suture and laser welded enterotomies were 50% of normal bowel. These findings suggest that the laser welding of small bowel enterotomies is comparable in closure and tensile strength to suture repair. The time required to repair the enterotomy is significantly decreased, the procedure is easily performed, and there is a marked decrease in adhesion formation following laser repair.
This study compared the healing of laser-welded and sutured canine femoral arteriovenous anastomoses. Arteriovenous fistulas 2 cm in length were created bilaterally in the femoral vessels of 10 dogs and were studied at 1 (n = 2), 2 (n = 2), 4 (n = 3), and 8 (n = 3) weeks. In each animal, one anastomosis (control) was closed with running 6-0 polypropylene sutures, and the contralateral anastomosis (experimental) was sealed with an argon laser (0.5 watt, 4 minutes of exposure, 1830 J/cm2/1 cm length of anastomosis). At removal all experimental anastomoses were patent without hematomas, aneurysms, or luminal narrowing. Histologic examination at 4 weeks revealed that laser-welded anastomoses had less inflammatory response and almost normal collagen and elastin reorientation. At 8 weeks sutured anastomoses had significant intimal hyperplasia whereas laser repairs had normal luminal architecture. Tensile strength and collagen production, measured by the synthesis of hydroxyproline and the steady-state levels of type I and type III procollagen messenger ribonucleic acids, at the anastomoses and in adjacent vein and artery specimens were similar in sutured and laser-welded repairs at 2, 4, and 8 weeks. We conclude that argon laser welding of anastomoses is an acceptable alternative to suture techniques, with the advantage of improved healing without foreign body response and possible diminished intimal hyperplasia at the anastomotic line.
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We compared the histologic features, tensile strength, and collagen synthesis of laser-welded and sutured arteriotomies. Four bilateral canine femoral or carotid arteries, 2 cm long, were studied at one through four weeks postoperatively, with one vessel (control) closed with interrupted 6-0 polypropylene sutures and the contralateral vessel (experimental) welded with an argon laser (0.5 W [1417 J/cm2], four-minute exposure per 1-cm length of incision). Histologic examination revealed that laser-welded arteriotomies had less inflammatory reaction, more normal collagen and elastin reorientation, and similar endothelial continuity when compared with the control, sutured wounds. The tensile strength of the one- and two-week laser-welded specimens was less than that of sutured wounds and became approximately equal to sutured repairs at three and four weeks. There were no significant differences in the rate of collagen synthesis. There was no evidence of abnormal healing in the laser-welded specimens, suggesting that argon laser welding may be an alternative to suture repair of arteriotomies.
The feasibility of welding thin-walled microvessels by laser has been established. This report summarizes our experience using laser welding to repair thick-walled, high-pressure, 4 to 8-mm canine arteries using CO2, Nd:YAG, and argon lasers. The CO2 laser did not produce seals that could withstand arterial pressure. Nd:YAG laser welds were initially successful, but the majority failed within 20 to 40 minutes. The argon laser uniformly sealed 2-cm-length arteriotomies that healed rapidly within 4 to 6 weeks and had less foreign body response compared to sutured controls. Laser welding may represent an alternative for repair of small- and large-diameter vessels with several advantages compared to conventional suture techniques.