PubMed Health⌕ Search

Biomedical subjects

Michael O'Brien

Publications and source records attributed to Michael O'Brien.

At least 19 recordsLinked to original sources
PubMed2006

Interleukin-6 genetic ablation protects from trinitrobenzene sulfonic acid-induced colitis in mice. Putative effect of antiinflammatory cytokines.

BACKGROUND: Interleukin (IL)-6 is a proinflammatory cytokine implicated in the pathogenesis of inflammatory bowel disease. IL-6 is locally upregulated in inflammatory bowel disease patients and in murine models of experimental colitis. Treatment with anti-IL-6 receptor antibody ameliorates intestinal inflammation. OBJECTIVE: It was the aim of this study to investigate the role of genetic IL-6 deficiency in trinitrobenzene sulfonic acid (TNBS)-mediated colitis, an experimental model inflammation that shares several features with Crohn's disease in humans. METHODS: Acute colitis was induced in wild-type and IL-6-deficient (Il-6(-/-)) mice by intracolonic administration of TNBS. Forty-eight hours after treatment, the local and systemic features of inflammation, i.e. food intake, weight loss, histological markers of colitis, cytokine expression by real-time PCR, food intake and body weight changes, were assessed. RESULTS: In wild-type mice, TNBS administration increased both IL-6 serum levels and local expression of IL-6 by 36 and 9 fold, respectively, compared with control, vehicle-injected mice. Compared with the wild-type mice, the Il-6(-/-) mice had significantly reduced intestinal inflammation as evidenced by epithelial damage, neutrophil infiltration, colon thickness and proinflammatory cytokine expression, following treatment with TNBS. Moreover, baseline levels of the antiinflammatory cytokines IL-10 and tumor growth factor-beta were significantly elevated in Il-6(-/-)compared with the wild-type mice. CONCLUSIONS: Our results demonstrate that Il-6(-/-)are partially protected from the development of TNBS-induced acute experimental colitis, most likely via their significantly elevated baseline levels of antiinflammatory cytokines.

Animals↗
PubMed2006

Radiation exposure during pedicle screw placement in adolescent idiopathic scoliosis: is fluoroscopy safe?

STUDY DESIGN: With institutional review board approval, prospective data were collected during fluoroscopically guided pedicle screw placement. OBJECTIVE: To estimate a surgeon's radiation exposure with all screw constructs during surgery to repair idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: To our knowledge, there is no established consensus regarding the safety of radiation exposure during fluoroscopically guided procedures. METHODS: A surgeon was outfitted intraoperatively with a thermoluminescent dosimeter to estimate radiation exposure to his whole body and thyroid gland. RESULTS: The index surgeon is projected to receive 13.49 mSv of whole body ionizing radiation and 4.31 mSv of thyroid gland irradiation annually. The National Council on Radiation Protection's current recommendations set lifetime dose equivalent limits for classified workers (radiologists) at 10 mSv per year of life and at 3 mSv for nonclassified workers (spinal surgeons). At the levels estimated, a surgeon beginning his/her career at age 30 years would exceed the lifetime limit for nonclassified workers in less than 10 years. The National Council on Radiation Protection limits the single-year maximum safe dosage to the thyroid to 500 mSv; the yearly exposure estimated here is significantly less. CONCLUSIONS: The spinal surgeon's intraoperative radiation exposure may be unacceptable. Spinal surgeons should be considered classified workers and monitored accordingly. Methods to lower radiation dosage seem strongly indicated.

Adolescent↗
PubMed2006

Corticotropin-releasing hormone receptor 2-deficient mice have reduced intestinal inflammatory responses.

Corticotropin-releasing hormone (CRH) and urocortins (Ucn) bind with various affinities to two G-protein-coupled receptors, CRHR1 and CRHR2, which are expressed in brain and in peripheral tissues, including immune cells. CRHR2-deficient mice display anxiety-like behavior, hypersensitivity to stress, altered feeding behavior and metabolism, and cardiovascular abnormalities. However, the phenotype of these mice in inflammatory responses has not been determined. In the present study we found that compared with wild-type CRHR2-null mice developed substantially reduced intestinal inflammation and had lower intestinal mRNA expression of the potent chemoattractants keratinocyte chemokine and monocyte chemoattractant protein 1 following intraluminal exposure to Clostridium difficile toxin A, a potent enterotoxin that mediates antibiotic-associated diarrhea and colitis in humans. This effect was recapitulated by administration of astressin 2B, a selective CRHR2 antagonist, before toxin A exposure. Moreover, Ab array analysis revealed reduced expression of several inflammatory chemokines, including keratinocyte chemokine and monocyte chemoattractant protein 1 in toxin A-exposed mice pretreated with astressin 2B. Real-time RT-PCR of wild-type mouse intestine showed that only UcnII, but not other Ucn, was significantly up-regulated by ileal administration of toxin A at 4 h compared with buffer exposure. We also found that human colonic epithelial HT-29 cells express CRHR2alpha mRNA, whereas expression of beta and gamma spliced variants was minimal. Moreover, treatment of HT-29 cells with UcnII, which binds exclusively to CRHR2, stimulated expression of IL-8 and monocyte chemoattractant protein 1. Taken together, these results provide direct evidence that CRHR2 mediates intestinal inflammatory responses via release of proinflammatory mediators at the colonocyte level.

Animals↗
PubMed2006

Saccharomyces boulardii inhibits ERK1/2 mitogen-activated protein kinase activation both in vitro and in vivo and protects against Clostridium difficile toxin A-induced enteritis.

Saccharomyces boulardii (Sb), a probiotic yeast, protects against intestinal injury and inflammation caused by a wide variety of enteric pathogens, including Clostridium difficile. Given the broad range of protective effects of Sb in multiple gastrointestinal disorders, we hypothesize that Sb modulates host signaling pathways involved in intestinal inflammatory responses. In this study, we found that Sb culture supernatant (SbS) inhibits interleukin-8 production induced by C. difficile toxin A or IL-1beta in human colonocyte NCM460 cells in a dose-dependent fashion. Furthermore, SbS inhibited IL-1beta and toxin A induced Erk1/2 and JNK/SAPK but not p38 activation in NCM460 cells. To test whether this inhibition also occurs in vivo, we used a previously established mouse ileal loop model. On its own, SbS had no significant effect on basal fluid secretion or intestinal histology. However, Erk1/2 activation was significantly inhibited by SbS in toxin A exposed mouse ileal mucosa. In control loops, toxin A increased fluid secretion (2.2-fold), histological score (3.3-fold), and levels of the chemokine KC (4.5-fold). SbS pretreatment completely normalized toxin A mediated fluid secretion (p < 0.01), and histopathologic changes (p < 0.01) and substantially inhibited toxin A-associated KC increases (p < 0.001). In summary, the probiotic yeast S. boulardii inhibits C. difficile toxin A-associated enteritis by blocking the activation of Erk1/2 MAP kinases. This study indicates a new mechanism whereby Sb protects against intestinal inflammation and supports the hypothesis that Sb modulates host inflammatory signaling pathways to exert its beneficial effects.

Animals↗
PubMed2006

Induction of colitis causes inflammatory responses in fat depots: evidence for substance P pathways in human mesenteric preadipocytes.

Intracolonic administration of trinitrobenzene sulfonic acid in mice causes inflammation in the colon that is accompanied by increased expression of proinflammatory cytokines and of the substance P (SP), neurokinin 1 receptor (NK-1R) in the proximal mesenteric fat depot. We also investigated whether human mesenteric preadipocytes contain NK-1R and examined the functional consequences of exposure of these cells to SP as it relates to proinflammatory signaling. We found that human mesenteric preadipocytes express NK-1R both at the mRNA and protein levels. Exposure of human mesenteric preadipocytes to SP increased NK-1R mRNA and protein expression by 3-fold, and stimulated IL-8 mRNA expression and protein secretion. This effect was abolished when these cells were pretreated with the specific NK-1R antagonist CJ 012,255. Moreover, human mesenteric preadipocytes transfected with a luciferase promoter/reporter system containing the IL-8 promoter with a mutated NF-kappaB site lost their ability to respond to SP, indicating that SP-induced IL-8 expression is NF-kappaB-dependent. This report indicates that human mesenteric preadipocytes contain functional SP receptors that are linked to proinflammatory pathways, and that SP can directly increase NK-1R expression. We speculate that mesenteric fat depots may participate in intestinal inflammatory responses via SP-NK-1R-related pathways, as well as other systemic responses to the presence of an ongoing inflammation of the colon.

Abdominal Fat↗
PubMed2006

End organ effects of high-dose human equivalent methylprednisolone in a spinal cord injury rat model.

STUDY DESIGN: Interventional study. OBJECTIVE: To analyze the histologic effects of high-dose human equivalent methylprednisolone on the pulmonary, cardiac, intestinal, renal, hepatic, and splenic tissues in a spinal cord injury rat model. SUMMARY OF BACKGROUND DATA: There are numerous investigations of various medical interventions for the treatment of acute spinal cord trauma. Currently, the only generally accepted medical intervention in an acute spinal cord trauma is the intravenous administration of high doses of methylprednisolone. Although it has been nearly 2 decades since the first National Acute Spinal Cord Injury Study investigated the role high-dose steroids might play in the treatment of acute spinal cord trauma, controversy still exists regarding the efficacy of this treatment. To our knowledge, no study has examined the role of high-dose methylprednisolone in organ systems other than the spinal cord in an acute spinal cord injury model at the histologic level. This study attempts to characterize end organ histologic response to human dose equivalent (HDE) intravenous methylprednisolone administration in a rodent model of acute spinal cord injury. METHODS: A total of 48 Sprague-Dawley rats were divided equally into control and experimental groups. Each group was subdivided into 6 sets of 4 animals each, according to intervals after injury. Groups 1-6 consisted of animals euthanized at 0, 4, 8, 16, 24, and 48 hours after spinal cord injury. Paraplegia after lower thoracic laminectomy was achieved using a standardized Allen weight drop technique. Within 1 hour of injury, experimental animals were treated with HDE methylprednisolone, infused for 23 hours continuously. Liver, kidney, lung, intestine, spleen, and heart were harvested at variable intervals after injury and prepared for histologic examination. These slides were analyzed with microscopic staining techniques and compared in a blinded manner by a qualified pathologist. RESULTS: Of all the end organs analyzed, the spleens were most affected. Lymphocytic depletion was seen in as little as 4 hours after methylprednisolone infusion and continued until 48 hours. Pulmonary tissues variably showed interstitial congestion and eosinophilic alveolar collections. Intestinal mucosal tissues showed edema and autolyzed mucosa from 16 hours onwards. Cardiac, kidney, and hepatic tissue did not differ significantly from controls. CONCLUSIONS: Histologically, HDE methylprednisolone caused significant splenic lymphocytic depletion changes in as little as 4 hours. This trend of end organ lymphocytopenia continued to progress until 48 hours. Pulmonary eosinophilic infiltrates were seen from 8 until 24 hours. Intestinal mucosal edema and necrosis were seen in samples at 16 hours throughout 48 hours. This study was designed to evaluate end organ changes seen in an animal model of an acute spinal cord injury treated with HDE methylprednisolone. Study animals were infused with HDE methylprednisolone given according to the National Acute Spinal Cord Injury Study II protocol. The kidney, lung, cardiac, intestinal, splenic, and hepatic tissues from the aforementioned animals were then sectioned and analyzed using histologic staining techniques by a qualified pathologist.

Animals↗
PubMed2006

Design principles for developing an efficient clinical anatomy course.

The exponential growth of medical knowledge presents a challenge for the medical school curriculum. Because anatomy is traditionally a long course, it is an attractive target to reduce course hours, yet designing courses that produce students with less understanding of human anatomy is not a viable option. Faced with the challenge of teaching more anatomy with less time, we set out to understand how students employ instructional media to learn anatomy inside and outside of the classroom. We developed a series of pilot programs to explore how students learn anatomy and, in particular, how they combine instructional technology with more traditional classroom and laboratory-based learning. We then integrated what we learned with principles of effective instruction to design a course that makes the most efficient use of students' in-class and out-of-class learning. Overall, we concluded that our new anatomy course needed to focus on transforming how medical students think, reason, and learn. We are currently testing the hypothesis that this novel approach will enhance the ability of students to recall and expand their base of anatomical knowledge throughout their medical school training and beyond.

Anatomy↗
PubMed2006

A new transcription factor that regulates TNF-alpha gene expression, LITAF, is increased in intestinal tissues from patients with CD and UC.

BACKGROUND: The proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) plays a key role in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC). Recently, a new transcription factor termed LITAF (lipopolysaccharide-induced TNF-alpha factor) was shown to mediate TNF-alpha expression in human macrophages by direct binding to specific sequences in the promoter region of the TNF-alpha gene. METHODS: In this report, we identified LITAF in resected ileal and colonic tissues from patients with CD and UC by immunohistochemistry, real-time polymerase chain reaction, and Western blot analysis. LITAF expression in inflamed and noninflamed areas of the tissues was compared. RESULTS: This is the first demonstration of LITAF, a newly discovered transcription factor that regulates TNF-alpha gene transcription in ileal and colonic tissues from patients with either CD or UC. LITAF immunostaining was localized to lamina propria macrophages and was markedly increased relative to tissues from controls without inflammatory bowel disease. In patients with CD, a 5-fold increase in LITAF mRNA was measurable in noninflamed colonic tissues compared with controls without inflammatory bowel disease. LITAF mRNA in tissues from inflamed areas of the colon was increased by an additional 60% compared with noninflamed tissues. In patients with UC, LITAF mRNA levels in colonic tissues resected from noninflamed areas were elevated 15-fold above nondisease controls, but they were not different in tissues resected from inflamed areas. Western blot analysis showed that in patients with CD, there was a marked increase in LITAF protein in inflamed areas compared with noninflamed areas. LITAF protein levels were not different between noninflamed and inflamed tissues obtained from patients with UC. TNF-alpha mRNA and protein levels paralleled LITAF. Similarly, in inflamed ileal tissues from patients with CD, LITAF is also localized to lamina propria macrophages. LITAF mRNA and LITAF protein were significantly increased in inflamed ileal tissues compared with noninflamed areas. CONCLUSIONS: LITAF is readily detectable in ileal and colonic tissues from patients with either CD or UC, is significantly elevated above controls, and is localized to macrophages, a major source of TNF-alpha. These data provide strong evidence of a role for LITAF in the pathophysiological regulation of the TNF-alpha gene and underscore the potential value of anti-LITAF strategies in the clinical management of these diseases.

Colitis, Ulcerative↗
PubMed2006

The effects of goal setting on rugby performance.

Goal-setting effects on selected performance behaviors of 5 collegiate rugby players were assessed over an entire competitive season using self-generated targets and goal-attainment scaling. Results suggest that goal setting was effective for enhancing task-specific on-field behavior in rugby union.

Adult↗
PubMed2005

HIV infection does not affect the performance of noninvasive markers of fibrosis for the diagnosis of hepatitis C virus-related liver disease.

BACKGROUND: Noninvasive markers of hepatic fibrosis hold great promise to stage liver fibrosis and to monitor disease progression. To date, few studies have assessed the performance of the currently available markers of hepatic fibrosis in HIV-infected cohorts. The aim of the current study was to compare the diagnostic performance and characteristics of a number of noninvasive markers of hepatic fibrosis in populations of hepatitis C virus (HCV)-infected patients with and without HIV infection. METHODS: A sample of 97 subjects (40 HCV/HIV-coinfected, 57 HCV-infected) undergoing liver biopsy as part of an ongoing prospective cohort study was evaluated. Liver biopsies were assessed by a single hepatopathologist and scored according to Ishak criteria. Noninvasive markers of fibrosis studied included international normalized ratio, platelet count, aspartate aminotransferase (AST)/alanine aminotransferase ratio, AST platelet ratio index (APRI), Forns index, procollagen III N peptide, hyaluronic acid, and YKL-40. RESULTS: The correlations between fibrosis markers with the stage of fibrosis and the diagnostic performance of each of the tests were similar in the groups with and without HIV infection. Although a trend to improved diagnostic performance in the HCV/HIV-coinfected group was observed, this may be related to the small sample size. CONCLUSIONS: The diagnostic performance of the evaluated noninvasive markers of liver fibrosis is equivalent in HCV/HIV-coinfected and HCV-infected subjects. These tests may be of value for the clinical evaluation of HCV/HIV-coinfected patients and warrant further study.

Adult↗
PubMed2005

Pedicle screw fixation of the thoracic spine: an in vitro biomechanical study on different configurations.

STUDY DESIGN: An in vitro biomechanical study of different pedicle screw configuration usage on the thoracic spine using a cadaveric model. OBJECTIVES: To investigate the degree of motion afforded different pedicle screw configurations in the thoracic spine using a cadaveric model with 2 different degrees of intrinsic stability. SUMMARY OF BACKGROUND DATA: Recently, thoracic pedicle screws have become an alternative to hook and wire fixation, and have gained popularity. Clinically, pedicle screw use has ranged from application to every segment, to skipping every other level. There exists no clear consensus as to which strategy is most appropriate. METHODS: The load-displacement behavior of 6 different constructs was determined on 8 fresh frozen cadaver spine specimens (T4-T12). Each construct was evaluated on 2 destabilization models, including minimum destabilization (bilateral facetectomy) and maximum destabilization (facetectomy and annulotomy). Pure moments were applied, and the resultant range of motion for each scenario was determined. RESULTS: Facetectomy did not significantly destabilize the thoracic spine. Annulotomy and facetectomy created gross instability that rendered testing of this destabilization model impossible. All constructs significantly reduced the range of motion compared to intact or facetectomized specimens (P < or = 0.001). When different constructs were compared to each other, a pattern of continuously increasing stability emerged, with the "maximum" construct being the most stable and "minimum" configuration being the least, with varying degrees of statistical significance. CONCLUSIONS: Our results suggest that the most important factor for the acute postoperative stability of spinal fixation is the degree of preoperative or iatrogenic destabilization. The minimum amount of pedicle screws provides adequate stability when there is minimal destabilization of the spine. On the other hand, when anterior column release has been performed or instability exists before surgery, segmental pedicle screw fixation may be necessary to achieve adequate stability.

Aged↗
PubMed2005

Control of joint rotations in overarm throws of different speeds made by dominant and nondominant arms.

We tested the hypothesis that dominant and nondominant overarm throws of different speeds are made by time-scaling of joint rotations, i.e., by joint rotations that have the same positions and amplitudes but that are scaled in time. Eight skilled subjects stood and made overarm throws with both their dominant and nondominant arms. Six joint rotations were computed from recordings of arm segments made with the search-coil technique. Throws made with nondominant arms were less accurate and had lower ball speeds. In contrast to the hypothesis, dominant arms showed large and consistent differences between fast and slow throws in six-dimensional angular position joint space. These same throws showed similar hand angular paths when these were time-scaled based on ball speed. Nondominant arms showed only small differences in angular position joint space in fast and slow throws. It is concluded that a joint space pattern resembling that predicted by time-scaling occurs in nondominant arm throwing when it is unskilled. However, time-scaling does not occur in dominant arm throwing, i.e., a skilled fast throw is not simply a skilled slow throw whose joint positions and amplitudes remain constant but whose joint velocities are sped-up. We hypothesize for future study that, when subjects first learn to throw at different speeds with their dominant arms, they use time-scaling of joint rotations that involves compensating for interaction torques; then as they become skilled at throwing fast, time-scaling is superseded by a more complex pattern of interjoint coordination that involves exploiting interaction torques.

Adult↗
PubMed2005

The importance of spino-pelvic balance in L5-s1 developmental spondylolisthesis: a review of pertinent radiologic measurements.

STUDY DESIGN: A review article. OBJECTIVES: The purpose of this article is to review pertinent radiologic measurements for the evaluation of spino-pelvic balance in developmental spondylolisthesis, based on the experience of the Spinal Deformity Study Group. SUMMARY OF BACKGROUND DATA: Over the past decade, pelvic morphology has been shown to significantly influence spino-pelvic balance of the human trunk in normal and pathologic conditions. This finding has important implications for the evaluation and treatment of developmental spondylolisthesis and has fostered a renewed interest in the radiologic evaluation of spino-pelvic balance in this condition. METHODS: The lateral standing radiographs of the spine and pelvis of subjects with developmental L5-S1 spondylolisthesis were analyzed with a dedicated software allowing the calculation of the following parameters: pelvic incidence, sacral slope, pelvic tilt, L5 incidence angle, lumbosacral angle, lumbar lordosis, thoracic kyphosis, and grade of spondylolisthesis. All measurements were done by the same individual and compared to those of an adult and child reference population. RESULTS: The pelvic shape, best quantified by the pelvic incidence angle, determines the position of the sacral endplate. The spine reacts to this position by adapting through lumbar lordosis, the amount of lordosis increasing as the sacral slope increases in order to balance the trunk in the upright position. Pelvic incidence, sacral slope, pelvic tilt, and lumbar lordosis are found to be significantly greater in subjects with developmental spondylolisthesis, while thoracic kyphosis is significantly lower when compared to a reference population. Furthermore, the differences between the two populations increase in a direct linear fashion as the severity of the spondylolisthesis increases, suggesting that pelvic anatomy has a direct influence on the development of a spondylolisthesis. Studies also indicate that pelvic incidence is unaffected by surgical reduction and instrumentation. Pelvic tilt, sacral slope, and thoracic kyphosis are slightly affected, while grade, L5 incidence angle, lumbosacral angle, and shape of the lumbar spine are significantly improved after surgery. A postoperative improvement in L5 incidence angle and lumbosacral angle appears correlated with a better outcome while subjects with a poor outcome have a higher preoperative grade. CONCLUSIONS: Spino-pelvic balance in the sagittal plane can be considered as an open linear chain linking the head to the pelvis where the shape and orientation of each successive anatomic segment are closely related and influence the adjacent segment. Pelvic morphology and spino-pelvic balance are abnormal in developmental spondylolisthesis. These abnormalities should be quantified on lateral standing radiographs of the spine and pelvis and have important implications for the evaluation and treatment of this pathologic condition.

Humans↗
PubMed2005

NF-kappaB activation precedes increases in mRNA encoding neurokinin-1 receptor, proinflammatory cytokines, and adhesion molecules in dextran sulfate sodium-induced colitis in rats.

Nuclear factor kappa B (NF-kappa B) plays a key role in initiating inflammation associated with colitis. A systematic study was conducted in the rat DSS colitis model to determine the temporal relationship between NF-kappa B activation and expression of substance P (SP), neurokinin-1 receptor (NK-1R), proinflammatory cytokines, and adhesion molecules. Rats were given 5% DSS in their water and sacrificed daily for 6 days. Colon tissue was collected for assessment of histological changes, NF-kappa B activation, myeloperoxidase (MPO) activity, and expression of NK-1R, SP, TNFalpha, IL-1beta, VCAM-1, ICAM-1, E-selectin, CINC-1, MIP-1alpha, and iNOS. NF-kappa B activation increased, biphasically, on Day 1 and again on Days 4-6. The mRNA levels for ICAM-1, CINC-1, IL-1beta, TNFalpha, VCAM-1, and NK-1R rose significantly (P < 0.05) by 2-4 days. Increased iNOS mRNA levels, MPO activity, and mucosal damage occurred on Day 6. These data demonstrate that NF-kappa B activation substantially precedes the onset of physical disease signs and active inflammation.

Analysis of Variance↗
PubMed2005

Information literacy: developing lifelong skills through nursing education.

The amount and complexity of information nurses are expected to manage continues to increase exponentially. Support has grown for integrated curriculum approaches that include appropriate content on the use of a variety of information formats and instruction using resource-based and process methods. Such teaching-learning approaches demand a major shift in educational paradigms and encompass resource-based learning, undergraduate research, service learning, inquiry learning, and problem-based learning. The implementation of an integrated curriculum promises advanced information skills, access, and use of available evidence to support clinical decision making and a foundation for lifetime learning. In this article, we argue that for information literacy to be enhanced, collaboration between teaching faculty and librarians must be fostered in meaningful ways. We report on the rationale of an integrated curriculum, changes to nursing education, and obstacles to the development and application of advanced information skills that exist within higher education and clinical settings.

Computer Literacy↗
PubMed2004

Spondylolisthesis, pelvic incidence, and spinopelvic balance: a correlation study.

STUDY DESIGN: A retrospective study of the sagittal alignment in developmental spondylolisthesis. OBJECTIVES: To investigate the role of pelvic anatomy and its effect on the global balance of the trunk in developmental spondylolisthesis. SUMMARY OF BACKGROUND DATA: Pelvic incidence (PI) is a fundamental anatomic parameter that is specific and constant for each individual, and independent of the three-dimensional orientation of the pelvis. Recent studies have suggested an association between a high PI and patients with isthmic spondylolisthesis. METHODS: The lateral standing radiographs of the spine and pelvis of 214 subjects with developmental L5-S1 spondylolisthesis were analyzed with a dedicated software allowing the calculation of the following parameters: pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), lumbar lordosis (LL), thoracic kyphosis (TK), and grade of spondylolisthesis. All measurements were done by the same individual and compared to those of a cohort of 160 normal subjects. Student's tests were used to compare the parameters between the curve types and Pearson's correlation coefficients were used to investigate the association between all parameters (alpha = 0.01). RESULTS: PI, SS, PT, and LL are significantly greater (P < 0.01) in subjects with spondylolisthesis, while TK is significantly decreased. PI has a direct linear correlation (0.41-0.65) with SS, PT, and LL. Furthermore, the differences between the two populations increase in a direct linear fashion as the severity of the spondylolisthesis increases. CONCLUSIONS: Since PI is a constant anatomic pelvic variable specific to each individual and strongly determines SS, PT, and LL, which are position-dependent variables, this study suggests that pelvic anatomy has a direct influence on the development of a spondylolisthesis.Study participants with an increased pelvic incidence appear to be at higher risk of presenting a spondylolisthesis, and an increased PI may be an important factor predisposing to progression in developmental spondylolisthesis.

Adolescent↗
PubMed2004

Corticotropin-releasing hormone (CRH) requirement in Clostridium difficile toxin A-mediated intestinal inflammation.

Clostridium difficile, the causative agent of antibiotic-associated colitis, mediates inflammatory diarrhea by releasing toxin A, a potent 308-kDa enterotoxin. Toxin A-induced inflammatory diarrhea involves many steps, including mucosal release of substance P (SP) corticotropin-releasing hormone (CRH) and neutrophil transmigration. Here we demonstrate that, compared with wild type, mice genetically deficient in CRH (Crh(-/-)) have dramatically reduced ileal fluid secretion, epithelial cell damage, and neutrophil transmigration 4 h after intraluminal toxin A administration. This response is associated with diminished mucosal activity of the neutrophil enzyme myeloperoxidase compared with that of wildtype mice. In wild-type mice, toxin A stimulates an increase in intestinal SP content compared with buffer administration. In contrast, toxin A administration in Crh(-/-) mice fails to result in an increased SP content. Moreover, immunohistochemical experiments showed that CRH and SP are colocalized in some enteric nerves of wild-type mice, and this colocalization is more evident after toxin A administration. These results provide direct evidence for a major proinflammatory role for CRH in the pathophysiology of enterotoxin-mediated inflammatory diarrhea and indicate a SP-linked pathway.

Animals↗