Correlation between transformation potential and inducible enzyme levels of hamster embryo cells

When benzo(a)pyrene was used to evaluate the transformabilityof 129 hamster embryo cell preparations from pooled or individualembryos, approximately 50% of the cultures were transformable.A transformable and a non-transformable cell culture were furthertested with other carcinogens (3-methylcholanthrene [MCA], benzylchloride, ethyl-p-toluenesulfonate, 2-naphthylamine, and aflatoxinB₁). The transformable culture responded to all of the carcinogenswhile the non-transformable culture always gave negative results.Aryl hydrocarbon hydroxylase (AHH) and epoxide hydrase (EH)levels were compared in the two cell cultures using ß-naphthoflavone(BNF), benz(a)anthracene (BA), sodium phenobarbital (PB) orMCA as microsomal enzyme-inducing agents. It was found thatAHH levels and the degree of induction following treatment ofthe cells with BNF or BA were consistently higher in the transformablethan in the non-transformable cell culture. EH levels were greaterin the transformable cells following treatment with either BNF,BA, PB or MCA. Inducible AHH and EH levels might, therefore,be useful as predictors of the transformation potential of hamsterembryo cell cultures.     

Selective use of blood cultures in emergency department pneumonia patients

Our objectives were to identify factors associated with positive blood cultures and to evaluate blood culture use in the management of hospitalized pneumonia patients to limit their use. A retrospective chart review was conducted at a community teaching hospital. Emergency Department patients with an admission diagnosis of pneumonia during calendar years 2001-2002 were included. Patients younger than age 18 years and those with a non-pneumonia discharge diagnosis were excluded. Of 684 eligible patients, 23 (3.4%) had true positive blood cultures. All organisms were sensitive to empiric antibiotics. Three risk factors were associated with positive blood cultures: oxygen saturation < 90%, serum sodium < 130 and respiratory rate > 30 breaths/min. No patient had antibiotic coverage broadened based on blood culture results. Positive blood culture rates were low and did not affect the clinical management of pneumonia patients. We recommend eliminating blood cultures in community-acquired pneumonia (CAP) patients, but obtaining blood cultures in patients at risk for multi-drug resistant pathogens, such as health-care-associated pneumonia (HCAP) patients.     

The IBD international genetics consortium provides further evidence for linkage to IBD4 and shows gene-environment interaction

BACKGROUND AND AIMS: The inflammatory bowel diseases (IBDs) Crohn's disease (CD) and ulcerative colitis are complex disorders with an important genetic determinant. One gene associated with CD has been identified: NOD2/CARD15. Two independent genome-wide scans found significant evidence (logarithm of odds [LOD] 3.6) and suggestive evidence (LOD 2.8) for linkage on locus 14q11-12, also known as the IBD4 locus. To further characterize this locus, we assessed gene-environment interaction (IBD4 x smoking) and phenotypic heterogeneity in a large cohort of IBD-affected sibling pairs as part of an ongoing international collaborative effort. PATIENTS AND METHODS: A total of 733 IBD families, comprising 892 affected sibling pairs, were genotyped for microsatellites D14S261, D14S283, D14S972, and D14S275, spanning the IBD4 locus. Information on gender, ethnicity, age at onset, smoking at diagnosis, extraintestinal manifestations, and disease location was available. RESULTS: A significant distortion in the mean allele sharing (MAS) between affected siblings was observed for CD patients only at each of the four markers (54.6%, 52.8%, 50.4%, and 53.3%, respectively). Maximum linkage for CD was observed at marker D14S261 (multipoint nonparametric linkage score 2.36; P 相似文献   

Fecal incontinence severity index after fistulotomy: a predictor of quality of life

PURPOSE: The purpose of this study was to use the Fecal Incontinence Severity Index to assess fecal incontinence after fistulotomy and to correlate the Fecal Incontinence Severity Index score with quality-of-life measures. METHODS: A retrospective chart review was performed on consecutive patients undergoing fistulotomy by a single colon and rectal surgeon at a university hospital from 1991 to 1999. Demographics, fistula anatomy, surgical technique, and length of follow-up were recorded. Mailed questionnaires and telephone interviews were conducted to determine the Fecal Incontinence Severity Index score, pad usage, lifestyle restriction, and psychosocial factors. A linear regression model was used to determine the relationship of clinical factors with Fecal Incontinence Severity Index. One-way ANOVA was used to correlate Fecal Incontinence Severity Index with quality-of-life measures. RESULTS: Of 110 patients who underwent fistulotomy, 96 (88 percent) had complete follow-up. Mean age was 48 (range, 17–84) years, and 68 percent were male. Follow-up was less than two years in 26 percent, two to five years in 39 percent, and more than five years in 35 percent. Of these patients, 41 percent had intersphincteric fistulas, whereas 59 percent had transsphincteric fistulas. Median Fecal Incontinence Severity Index score was 6, with a mean of 13 (maximum Fecal Incontinence Severity Index = 61); 36 percent had a Fecal Incontinence Severity Index score of zero. Linear regression revealed that only the amount of external sphincter divided correlated with Fecal Incontinence Severity Index score (P = 0.05). Quality-of-life measures strongly correlated with Fecal Incontinence Severity Index by analysis of variance (P < 0.01 for pad usage, lifestyle restriction, depression, and embarrassment), with substantial quality-of-life drop-off documented with Fecal Incontinence Severity Index >30. CONCLUSION: The Fecal Incontinence Severity Index is an excellent tool to gauge quality of life after fistulotomy. Fecal Incontinence Severity Index scores >30 predict a detrimental effect on quality of life.     

Neurophysiological and biomechanical characterization of goat cervical facet joint capsules.

Cervical facet joints have been implicated as a major source of pain after whiplash injury. We sought to identify facet joint capsule receptors in the cervical spine and quantify their responses to capsular deformation. The response of mechanosensitive afferents in C5-C6 facet joint capsules to craniocaudal stretch (0.5 mm/s) was examined in anaesthetized adult goats. Capsular afferents were characterized into Group III and IV based on their conduction velocity. Two-dimensional strains across the capsules during stretch were obtained by a stereoimaging technique and finite element modeling. 17 (53%) Group III and 14 (56%) Group IV afferents were identified with low strain thresholds of 0.107+/-0.033 and 0.100+/-0.046. A subpopulation of low-strain-threshold afferents had discharge rate saturation at the strains of 0.388+/-0.121 (n=9, Group III) and 0.341+/-0.159 (n=9, Group IV). Two (8%) Group IV units responded only to high strains (0.460+/-0.170). 15 (47%) Group III and 9 (36%) Group IV units could not be excited even by noxious capsular stretch. Simple linear regressions were conducted with capsular load and principal strain as independent variables and neural response of low-strain-threshold afferents as the dependent variable. Correlation coefficients (R2) were 0.73+/-0.11 with load, and 0.82+/-0.12 with principal strain. The stiffness of the C5-C6 capsules was 16.8+/-11.4 N/mm. Our results indicate that sensory receptors in cervical facet joint capsules are not only capable of signaling a graded physiological mechanical stimulus, but may also elicit pain sensation under excessive deformation.     

Randomized, double-blind, placebo-controlled phase IIb trial of the cyclooxygenase inhibitor ketorolac as an oral rinse in oropharyngeal leukoplakia.

PURPOSE: Nonselective cyclooxygenase (COX) inhibitors have been reported to decrease the frequency of upper aerodigestive cancers. Ketorolac tromethamine oral rinse has been shown to resolve another COX-dependent process, periodontal disease, without incurring gastrointestinal side effects. This trial evaluated if a topically delivered oral rinse containing ketorolac was as safe as and more effective than oral rinse alone in reducing the area of oral leukoplakia. EXPERIMENTAL DESIGN: 57 patients were randomized (2:1 ratio) in a double-blind, placebo-controlled study of ketorolac (10 ml of a 0.1% ketorolac rinse solution; n = 38) or placebo (10 ml of rinse solution; n = 19) given twice daily for 30 s over 90 days. Primary end point was evaluated visually obtaining bidimensional measurement of the size of leukoplakia lesion(s) at entry and at 90 days. Secondary end point was histological assessment of the leukoplakia as sampled by serial punch biopsy and independently reviewed by three pathologists. RESULTS: The patients included 67% males, 11% non-Caucasian, and 86% used tobacco with no significant differences between the two arms. Both rinses were well tolerated with good compliance, and there was no significant difference in adverse events (P = 0.27). Major response rate (complete response and partial response) was 30% for ketorolac and 32% for the placebo arm. There was no significant difference in change in histology between the two arms. CONCLUSION: Local delivery of a COX-containing oral rinse was well tolerated but produced no significant reduction in the extent of leukoplakia compared with the placebo. However, the favorable response rate to placebo arm remains unexplained and additional investigation of the tissue penetration with ketorolac is warranted.     

Neurofibromatosis and neural crest neoplasms: primary acquired melanosis and malignant melanoma of the conjunctiva

With an occurrence of approximately 1 in 3000 births, von Recklinghausen neurofibromatosis (NF) is one of the most common inherited human disorders. NF is considered a neurocristopathy, a disorder of neural crest derived cells. One of the complications of NF is the development of neural crest derived malignancies such as malignant schwannoma, pheochromocytoma, and malignant melanoma of the skin and choroid. The case history of a patient with NF and conjunctival malignant melanoma which developed in an eye with primary acquired melanosis is yet another example of a neural crest malignancy developing in a NF patient.