Archive of Medical Research

Rate of bilirubin regression after stenting in malignant biliary obstruction for the initiation of chemotherapy: how soon should we repeat endoscopic retrograde cholangiopancreatography?

BACKGROUND.: This study was conducted to evaluate the rate of regression of bilirubin after stent placement for malignant biliary obstruction. METHODS.: Records were reviewed from October 2002 to September 2005 for patients who underwent endoscopic retrograde cholangiopancreatography with stent placement. The time to achieve a bilirubin level </=2 mg/dL was the primary endpoint because this is the level required by most chemotherapy protocols. Patient variables included type of cancer, liver metastasis, recent chemotherapy, baseline creatinine, and international normalized ratio (INR). Stent variables included type, dimension, stricture location, and sphincterotomy. RESULTS.: In total, 156 patients were included in the analysis: Ninety-three patients achieved a poststent bilirubin level </=2 mg/dL, 29 patients failed because of stent failure, and 34 patients failed because of inadequate follow-up. The time required for 80% of patients to achieve normalization was more than doubled in those who had prestent bilirubin levels >/=10 mg/dL (6 weeks) compared with those who had prestent bilirubin levels <10 mg/dL (3 weeks). The following variables were identified as statistically significant: prestent bilirubin level, stricture location, liver metastasis, and INR. The cancer type, recent chemotherapy, stent type and diameter, and sphincterotomy were not statistically significant variables. CONCLUSIONS.: The rate of bilirubin normalization after biliary stenting was highly dependent on the prestent bilirubin level. Endoscopic intervention should be considered in patients who fail to achieve adequate normalization of serum bilirubin in 6 weeks if prestent bilirubin level was >/=10 mg/dL and in 3 weeks if their prestent bilirubin level was <10 mg/dL. Independent variables, such as diffuse liver metastases, stricture outside the common bile duct, and elevated INR had predictive value for bilirubin normalization. Cancer 2008. (c) 2008 American Cancer Society.

Weston BR, Ross WA, Wolff RA, Evans D, Lee JE, Wang X, Xiao LC, Lee JH.

Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.

Pygopus and the Wnt signaling pathway: A diverse set of connections.

Identification of Pygopus in Drosophila as a dedicated component of the Wg (fly homolog of mammalian Wnt) signaling cascade initiated many inquiries into the mechanism of its function. Surprisingly, the nearly exclusive role for Pygopus in Wg signal transduction in flies is not seen in mice, where Pygopus appears to have both Wnt-related and Wnt-independent functions. This review addresses the initial findings of Pygopus as a Wg/Wnt co-activator in light of recent data from both fly and mammalian studies. We compare and contrast the developmental phenotypes of pygopus mutants to those characterized for known Wg/Wnt transducers and explore the data regarding a role for mammalian Pygopus 2 in tumorigenesis. We further analyze the roles of the two conserved domains of Pygopus proteins in transcription, and propose a model for the molecular mechanism of Pygopus function in both Wg/Wnt signaling and Wnt-independent transcriptional regulation. BioEssays 30:448-456, 2008. (c) 2008 Wiley Periodicals, Inc.

Jessen S, Gu B, Dai X.

Department of Biological Chemistry, University of California, Irvine, CA.

Metabolic syndrome and prostate cancer.

Glode LM.

Department of Medicine, University of Colorado Health Science Center, Denver, Colorado.

Treatment options for muscle-invasive urothelial cancer for patients who were not eligible for cystectomy or neoadjuvant chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin: report of Southwest Oncology Group Trial 8733.

BACKGROUND.: Many patients with invasive urothelial cell cancer are poor candidates for cisplatin-based chemotherapy, and many are high risk for cystectomy. Southwest Oncology Group Trial 8733 was designed to address treatment for such patients. METHODS.: Eligible patients had primary or recurrent muscle-invasive disease with transitional cell or squamous cell histology, a performance status from 0 to 2, no extrapelvic disease, a life expectancy >3 months, and adequate hematologic function. The treating clinician assigned patients to operable or inoperable groups. All patients received 2 cycles of 5-fluorouracil (5-FU) at a dose of 1000mg/m(2) per day x 4 starting concurrently with radiation at a dose of 200 centigrays per day x 10 each cycle. After 2 cycles, operable patients with positive biopsies underwent cystectomy, and patients with negative biopsies received a third cycle of chemoradiotherapy. Patients in the inoperable group received 3 cycles without interim biopsy. RESULTS.: Eighteen of 24 eligible patients in the operable group were evaluable for response. Five patients had a complete response (CR), 9 patients had stable disease, 1 patient had progressive disease, and 3 patients were not assessable. The median progression-free survival was 10 months (95% confidence interval [95% CI], 4-14 months), and the median overall survival was 18 months (95% CI, 7-28 months). In the inoperable group, 35 of 37 eligible patients were evaluable for response with 17 CRs (49%; 95% CI, 31%-66%). The median progression-free survival was 13 months (95% CI, 10-17 months), and the median overall survival was 20 months (95% CI, 11-53 months). There were no episodes of grade 4 toxicity. CONCLUSIONS.: In the current study, the combination of 5-FU and radiation was found to be tolerated well by patients with numerous comorbidities who could not tolerate cisplatin-based therapy or cystectomy. Cancer 2008. (c) 2008 American Cancer Society.

Higano CS, Tangen CM, Sakr WA, Faulkner J, Rivkin SE, Meyers FJ, Hussain M, Baker LH, Russell KJ, Crawford ED.

Department of Medicine, Division of Oncology, University of Washington, Seattle, Washington.

On the origins of novelty in development and evolution.

The origin of novel traits is what draws many to evolutionary biology, yet our understanding of the mechanisms that underlie the genesis of novelty remains limited. Here I review definitions of novelty including its relationship to homology. I then discuss how ontogenetic perspectives may allow us to move beyond current roadblocks in our understanding of the mechanics of innovation. Specifically, I explore the roles of canalization, plasticity and threshold responses during development in generating a reservoir of cryptic genetic variation free to drift and accumulate in natural populations. Environmental or genetic perturbations that exceed the buffering capacity of development can then release this variation, and, through evolution by genetic accommodation, result in rapid diversification, recurrence of lost phenotypes as well as the origins of novel features. I conclude that, in our quest to understand the nature of innovation, the nature of development deserves to take center stage. BioEssays 30:432-447, 2008. (c) 2008 Wiley Periodicals, Inc.

Moczek AP.

Department of Biology, Indiana University, 915 E. Third Street, Myers Hall 150, Bloomington IN 47405‐7107.

Visualizing new dimensions in Drosophila myoblast fusion.

Over several years, genetic studies in the model system, Drosophila melanogastor, have uncovered genes that when mutated, lead to a block in myoblast fusion. Analyses of these gene products have suggested that Arp2/3-mediated regulation of the actin cytoskeleton is crucial to myoblast fusion in the fly. Recent advances in imaging in Drosophila embryos, both in fixed and live preparations, have led to a new appreciation of both the three-dimensional organization of the somatic mesoderm and the cell biology underlying myoblast fusion. BioEssays 30:423-431, 2008. (c) 2008 Wiley Periodicals, Inc.

Richardson B, Beckett K, Baylies M.

Program in Developmental Biology, Sloan Kettering Institute.

Keeping your vascular integrity: What can we learn from fish?

The cardiovascular system has the life-providing task of delivering oxygen and any flaw in this system can be life-threatening. This has encouraged extensive studies to elucidate the mechanisms behind cardiovascular development/homeostasis. The zebrafish has emerged as a formidable tool to speed up this quest, as illustrated in a recent issue of Nature Genetics.1 Baculovirus IAP repeat c2 (BIRC2), also termed cellular inhibitor of apoptosis (cIAP)-1, was found to specifically prevent endothelial cells (ECs, lining the inside of vessels) from going into suicide mode (\’apoptosis\’) and so preserve vessel integrity. Here, we summarize the factors determining vascular integrity and elaborate on the suitability of the zebrafish to study this phenomenon. BioEssays 30:418-422, 2008. (c) 2008 Wiley Periodicals, Inc.

Luttun A, Verhamme P.

Center for Molecular and Vascular Biology, KULeuven, Leuven, Belgium.

Embryonic pattern formation without morphogens.

One of the earliest and most-fundamental pattern- formation events in embryonic development is endoderm and mesoderm specification. In sea urchin embryos, this process begins with blimp1 and wnt8 gene expression at the vegetal pole as soon as embryonic transcription begins. Shortly afterwards, wnt8/blimp1 expression spreads to the adjacent ring of mesoderm progenitor cells and is extinguished in the vegetal-most cells. A little later, the ring of wnt8/blimp1 activity moves out of the mesoderm progenitors and into the neighboring endoderm cells. Remarkably, this moving ring of gene expression has now been shown to be controlled entirely by transcriptional cis-regulatory logic.1. BioEssays 30:412-417, 2008. (c) 2008 Wiley Periodicals, Inc.

Bolouri H.

Institute for Systems Biology, Seattle, 1441 N 34th St, Seattle WA 98103.

Phylogeographic and conservation genetic analysis of the black caiman (Melanosuchus niger).

We assessed the spatial distribution of the genetic variability of Melanosuchus niger from 11 localities in South America using 1,027 base pairs of the mitochondrial cytochrome b gene. Screening 132 animals, we found 41 haplotypes, high values of genetic diversity, low values of nucleotide diversity and significant deviations from neutral expectation of allelic frequencies in some localities. Mantel test and nested-clade analysis indicated that isolation-by-distance was an important population dynamic for the species as a whole. Wright\’s fixation indexes analyses showed that hydrogeographically separated populations from French Guiana together with Amapá state population in Brazil are genetically differentiated from all other populations that are found in the Amazon drainage basin. These indexes also disclosed that the population from Ecuador is genetically differentiated in relation to the populations from Brazil, Peru and French Guiana. Within the Amazon Basin little differentiation exists, and genetic and geographic distances are not correlated. Demographic data as well as population genetic data suggest that M. niger is recovering in some protected regions. However, part of this apparent recovery may be owing to the movement of animals into protected regions. J. Exp. Zool. 309A, 2008. (c) 2008 Wiley-Liss, Inc.

Vasconcelos WR, Hrbek T, Da Silveira R, Da Thoisy B, Ruffeil LA, Farias IP.

Departamento de Ciências Biológicas, Laboratório de Evolução e Genética Animal, Universidade Federal do Amazonas (UFAM), Manaus, AM, Brazil.

Musculoskeletal symptoms of the neck and upper extremities among Iowa dairy farmers.

BACKGROUND: The prevalence of musculoskeletal symptoms (MSS) among U.S. dairy farmers is relatively unknown. The purpose of this study was to assess the prevalence of neck and upper extremity MSS, and to examine associations between symptoms and dairy operation activities among dairy farmers. METHODS: Questionnaires were mailed to randomly selected dairy farmers in the State of Iowa, USA. Demographic, site specific MSS, and dairy operation activity information was obtained. Odds ratios and 95% confidence intervals were estimated with logistic regression adjusting for potential confounders. RESULTS: Among the participants (N = 341), shoulder MSS were reported most frequently (54%). Neck MSS were significantly associated with manually feeding (OR(adj) = 2.29; 95% CI = 1.09-4.80) and tractors use (OR(adj) = 2.17; 95% CI = 1.05-4.50). Also, wrist/hand MSS were associated with manually cleaning animal stalls (OR(adj) = 1.96; 95% CI = 1.06-3.63). CONCLUSIONS: Neck and upper extremity MSS were common and associated with common dairy farming practices. Future studies need to more accurately assess exposures to physical risk factors for MSS so ergonomic interventions can be developed. Am. J. Ind. Med. (c) 2008 Wiley-Liss, Inc.

Nonnenmann MW, Anton D, Gerr F, Merlino L, Donham K.

Department of Occupational Health Sciences, University of Texas Health Science Center at Tyler, Tyler, Texas.