bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating the Use of Reflective Counseling Group Supervision for Military Counselors in Taiwan
Authors: Jen der Pan Peter , Deng Liang-Yu F. , Tsai Shiou-Ling
Published: February 2008

The purpose of this study is to examine the effects of reflective counseling group supervision (RCGS) for military counselors. A convenience sampling method is adopted. Twenty-two military counselors participate in this study. Both qualitative and quantitative research methods are used for collecting and analyzing data. The results support our hypothesis that participants who received the RCGS would show a significant increase in their counseling competences. Four primary categories related to supervisory style, supervisory alliance, self-assessment, and supervising outcomes emerge as prominent and consistent from participants' learning experiences. RCGS can be an effective supervision model for participants. Implications of the findings for group supervision and further research are discussed.
Depression and Family Relationships
Authors: Marshall Amy J. , Harper-Jaques Sandy
Published: February 2008

Like a pebble that creates ripples when dropped into still water, depression is a health problem with an impact that reaches beyond the individual to touch family members. This health problem can limit the individual's ability to function and can create distress for loved ones. In this article, the authors present a clinical vignette about maternal depression to highlight the reciprocal nature of depression and family functioning. Family focused interventions based on the Calgary Family Intervention Model and the Illness Beliefs Model are presented and include psychoeducation, circular pattern diagrams, and therapeutic letters. The authors conclude the article with a discussion of implications for nursing practice.
Classical Marxism and the Second Law of Thermodynamics
Authors: Bellamy Foster John , Burkett Paul
Published: February 2008

Today's understanding of the significance of Karl Marx and Frederick Engels's work for the development of both ecological economics in particular and ecology in general has been hindered by persistent claims that Engels (and by imputation Marx) rejected the second law of thermodynamics. It is demonstrated here through textual analysis that Engels criticized not the entropy law itself but the extrapolation of this into the “heat death theory of the universe” hypothesis. The historical debate surrounding this hypothesis is examined, showing that Engels and Marx remained consistent with the natural science of their day. This opens the way to the recognition that Marx's political economy was unique in the 19th century in incorporating thermodynamics into the core of its analysis, thus providing the foundations for an ecological economics. The materialist-dialectical view of classical Marxism led to a dynamic, open, contingent approach to the earth system, reflecting a general evolutionary perspective.
Circulating neutrophils maintain physiological blood pressure by suppressing bacteria and IFNγ-dependent iNOS expression in the vasculature of healthy mice
Authors: Morton Jonathan , Coles Barbara , Wright Kate , Gallimore Awen , Morrow Jason D. , Terry Erin S. , Anning Peter B. , Morgan B. Paul , Dioszeghy Vincent , Kühn Hartmut , Chaitidis Pavlos , Hobbs Adrian J. , Jones Simon A. , O'Donnell Valerie B.
Published: February 2008

Whether leukocytes exert an influence on vascular function in vivo is not known. Here, genetic and pharmacologic approaches show that the absence of neutrophils leads to acute blood pressure dysregulation. Following neutrophil depletion, systolic blood pressure falls significantly over 3 days (88.0 ± 3.5 vs 104.0 ± 2.8 mm Hg, day 3 vs day 0, mean ± SEM, P < .001), and aortic rings from neutropenic mice do not constrict properly. The constriction defect is corrected using l-nitroarginine-methyl ester (L-NAME) or the specific inducible nitric oxide synthase (iNOS) inhibitor 1400W, while acetylcholine relaxation is normal. iNOS- or IFNγ-deficient mice are protected from neutropenia-induced hypotension, indicating that iNOS-derived nitric oxide (NO) is responsible and that its induction involves IFNγ. Oral enrofloxacin partially inhibited hypotension, implicating bacterial products. Roles for cyclooxygenase, complement C5, or endotoxin were excluded, although urinary prostacyclin metabolites were elevated. Neutrophil depletion required complement opsinization, with no evidence for intravascular degranulation. In summary, circulating neutrophils contribute to maintaining physiological tone in the vasculature, at least in part through suppressing early proinflammatory effects of infection. The speed with which hypotension developed provides insight into early changes that occur in the absence of neutrophils and illustrates the importance of constant surveillance of mucosal sites by granulocytes in healthy mice.
Genetic analysis of the two zebrafish patched homologues identifies novel roles for the hedgehog signaling pathway
Authors: Koudijs Marco J , den Broeder Marjo J , Groot Evelyn , van Eeden Fredericus JM
Published: February 2008

Background

Aberrant activation of the Hedgehog (Hh) signaling pathway in different organisms has shown the importance of this family of morphogens during development. Genetic screens in zebrafish have assigned specific roles for Hh in proliferation, differentiation and patterning, but mainly as a result of a loss of its activity. We attempted to fully activate the Hh pathway by removing both receptors for the Hh proteins, called Patched1 and 2, which are functioning as negative regulators in this pathway.

Results

Here we describe a splice-donor mutation in Ptc1, calledptc1hu1602, which in a homozygous state results in a subtle eye and somite phenotype. Since we recently positionally cloned aptc2mutant, aptc1;ptc2double mutant was generated, showing severely increased levels ofptc1,gli1andnkx2.2a, confirming an aberrant activation of Hh signaling. As a consequence, a number of phenotypes were observed that have not been reported previously usingShhmRNA overexpression. Somites ofptc1;ptc2double mutants do not express anteroposterior polarity markers, however initial segmentation of the somites itself is not affected. This is the first evidence that segmentation and anterior/posterior (A/P) patterning of the somites are genetically uncoupled processes. Furthermore, a novel negative function of Hh signaling is observed in the induction of the fin field, acting well before any of the previously reported function of Shh in fin formation and in a way that is different from the proposed early role of Gli3 in limb/fin bud patterning.

Conclusion

The generation and characterization of theptc1;ptc2double mutant assigned novel and unexpected functions to the Hh signaling pathway. Additionally, these mutants will provide a useful system to further investigate the consequences of constitutively activated Hh signaling during vertebrate development.
Parthenogenetic activation of bovine oocytes using bovine and murine phospholipase C zeta
Authors: Ross Pablo J , Beyhan Zeki , Iager Amy E , Yoon Sook-Young , Malcuit Christopher , Schellander Karl , Fissore Rafael A , Cibelli Jose B
Published: February 2008

Background

During natural fertilization, sperm fusion with the oocyte induces long lasting intracellular calcium oscillations which in turn are responsible for oocyte activation. PLCZ1 has been identified as the factor that the sperm delivers into the egg to induce such a response. We tested the hypothesis that PLCZ1 cRNA injection can be used to activate bovine oocytes.

Results

Mouse and bovine PLCZ1 cRNAs were injected into matured bovine oocytes at different concentrations. Within the concentrations tested, mouse PLCZ1 injection activated bovine oocytes at a maximum rate when the pipette concentration of cRNA ranged from 0.25 to 1 μg/μL, while bovine PLCZ1 was optimal at 0.1 μg/μL. At their most effective concentrations, PLCZ1 induced parthenogenetic development at rates similar to those observed using other activation stimuli such as Ionomycin/CHX and Ionomycin/DMAP. Injection of mouse and bovine PLCZ1 cRNA induced dose-dependent sperm-like calcium oscillations whose frequency increased over time. Injection of bovine and mouse PLCZ1 cRNA also induced IP3R-1 degradation, although bovine PLCZ1 cRNA evoked greater receptor degradation than its mouse counterpart.

Conclusion

Injection of PLCZ1 cRNA efficiently activated bovine oocytes by inducing a sperm-like calcium oscillatory pattern. Importantly, the high rate of aneuploidy encountered in parthenogenetic embryos activated by certain chemical means was not observed in PLCZ1 activated embryos.
Expression and protein localisation of IGF2in the marsupial placenta
Authors: Ager Eleanor I , Pask Andrew J , Shaw Geoff , Renfree Marilyn B
Published: February 2008

Background

In eutherian mammals, genomic imprinting is critical for normal placentation and embryo survival. Insulin-like growth factor 2 (IGF2) is imprinted in the placenta of both eutherians and marsupials, but its function, or that of any imprinted gene, has not been investigated in any marsupial. This study examines the role of IGF2 in the yolk sac placenta of the tammar wallaby, Macropus eugenii.

Results

IGF2 mRNA and protein were produced in the marsupial placenta. Both IGF2 receptors were present in the placenta, and presumably mediate IGF2 mitogenic actions. IGF2 mRNA levels were highest in the vascular region of the yolk sac placenta. IGF2 increased vascular endothelial growth factor expression in placental explant cultures, suggesting that IGF2 promotes vascularisation of the yolk sac.

Conclusion

This is the first demonstration of a physiological role for any imprinted gene in marsupial placentation. The conserved imprinting of IGF2 in this marsupial and in all eutherian species so far investigated, but not in monotremes, suggests that imprinting of this gene may have originated in the placenta of the therian ancestor.
Abnormal skeletal and cardiac development, cardiomyopathy, muscle atrophy and cataracts in mice with a targeted disruption of the Nov (Ccn3) gene
Authors: Heath Emma , Tahri Dalal , Andermarcher Elisabetta , Schofield Paul , Fleming Stewart , Boulter Catherine A
Published: February 2008

Background

Signals from the extracellular environment control many aspects of cell behaviour including proliferation, survival, differentiation, adhesion and migration. It is increasingly evident that these signals can be modulated by a group of matricellular proteins called the CCN family. CCN proteins have multiple domains through which they regulate the activities of a variety of signalling molecules including TGFβ, BMPs and integrins, thereby influencing a wide range of processes in development and disease. Whilst the developmental roles of CCN1 and CCN2 have been elucidated, very little is known about the function of CCN3 (NOV). To investigate this, we have generated mice carrying a targeted mutation in the Nov gene (Nov

del3
) which reveal for the first time its diverse functions in embryos and adults.

Results

By replacing Nov exon 3 with a TKneomycin cassette, we have generated Nov

del3
-/- mice which produce no full length NOV protein and express at a barely detectable level a mutant NOV protein that lacks the VWC domain. In Nov

del3
-/- embryos, and to a lesser extent in Nov

del3
+/- embryos, development of the appendicular and axial skeleton was affected with enlarged vertebrae, elongated long bones and digits, delayed ossification, increased bone mineralization and severe joint malformations. Primary embryo fibroblasts from Nov

del3
-/- mutant embryos showed enhanced chondrogenesis and osteogenesis. Cardiac development was also influenced leading to enlargement and abnormal modelling of the endocardial cushions, associated with septal defects and delayed fusion. In adults, cardiomyopathy was apparent, with hypertrophy and calcification of the septum and left ventricle dilation. Muscle atrophy was seen by 5 months of age, associated with transdifferentiation to fat. Premature tissue degeneration was also seen in the lens, with cataracts present from 6 months.

Conclusion

We have generated the first mice with a mutation in the Nov gene (Nov

del3
). Our data demonstrate that NOV is a regulator of skeletal and cardiac development, and implicates NOV in various disease processes including cardiomyopathy, muscle atrophy and cataract formation. Nov

del3
mutants represent a valuable resource for studying NOV's role in the modulation and co-ordination of multiple signalling pathways that underpin organogenesis and tissue homeostasis.
A haplotype of polymorphisms in ASE-1, RAI and ERCC1and the effects of tobacco smoking and alcohol consumption on risk of colorectal cancer: a danish prospective case-cohort study
Authors: Hansen Rikke D , Sørensen Mette , Tjønneland Anne , Overvad Kim , Wallin Håkan , Raaschou-Nielsen Ole , Vogel Ulla
Published: February 2008

Background

Single nucleotide polymorphisms (SNPs) are the most frequent type of genetic variation in the human genome, and are of interest for the study of susceptibility to and protection from diseases. The haplotype at chromosome 19q13.2-3 encompassing the three SNPs ASE-1 G-21A, RAI IVS1 A4364G and ERCC1 Asn118Asn have been associated with risk of breast cancer and lung cancer. Haplotype carriers are defined as the homozygous carriers of RAI IVS1 A4364GA, ERCC1 Asn118AsnT and ASE-1 G-21AG. We aimed to evaluate whether the three polymorphisms and the haplotype are associated to risk of colorectal cancer, and investigated gene-environment associations between the polymorphisms and the haplotype and smoking status at enrolment, smoking duration, average smoking intensity and alcohol consumption, respectively, in relation to risk of colorectal cancer.

Methods

Associations between the three individual polymorphisms, the haplotype and risk of colorectal cancer were examined, as well as gene-environment interaction, in a Danish case-cohort study including 405 cases and a comparison group of 810 persons. Incidence rate ratio (IRR) were estimated by the Cox proportional hazards model stratified according to gender, and two-sided 95% confidence intervals (CI) and p-values were calculated based on robust estimates of the variance-covariance matrix and Wald's test of the Cox regression parameter.

Results

No consistent associations between the three individual polymorphisms, the haplotype and risk of colorectal cancer were found. No statistically significant interactions between the genotypes and the lifestyle exposures smoking or alcohol consumption were observed.

Conclusion

Our results suggest that the ASE-1 G-21A, RAI IVS1 A4364G and ERCC1 Asn118Asn polymorphisms and the previously identified haplotype are not associated with risk of colorectal cancer. We found no evidence of gene-environment interaction between the three polymorphisms and the haplotype and smoking intensity and alcohol consumption, respectively, in relation to the risk of colorectal cancer.
An investigation of the smoking behaviours of parents before, during and after the birth of their children in Taiwan
Authors: Shih Shu-Fang , Chen Likwang , Wen Chi Pang , Yang Wei-Chih , Shih Yaw-Tang
Published: February 2008

Background

Although many studies have investigated the negative effects of parental smoking on children and Taiwan has started campaigns to promote smoke-free homes, little is known about the smoking behaviours of Taiwanese parents during the childbearing period. To help fill the gap, this study investigated Taiwanese parents' smoking behaviours before, during and after the birth of their children, particularly focusing on smoking cessation during pregnancy and relapse after childbirth.

Methods

We used data from the Survey of Health Status of Women and Children, conducted by Taiwan's National Health Research Institutes in 2000. After excluding survey respondents with missing information about their smoking behaviours, our sample consisted of 3,109 women who were married at the time of interview and had at least one childbearing experience between March 1, 1995 and February 28, 1999. Data on parental smoking behaviour in the six months before pregnancy, during pregnancy, and in the first year after childbirth were extracted from the survey and analysed by descriptive statistics as well as logistic regression.

Results

Four percent of the mothers and sixty percent of the fathers smoked before the conception of their first child. The educational attainment and occupation of the parents were associated with their smoking status before the first pregnancy in the family. Over 80% of smoking mothers did not quit during pregnancy, and almost all of the smoking fathers continued tobacco use while their partners were pregnant. Over two thirds of the women who stopped smoking during their pregnancies relapsed soon after childbirth. Very few smoking men stopped tobacco use while their partners were pregnant, and over a half of those who quit started to smoke again soon after their children were born.

Conclusion

Among Taiwanese women who had childbearing experiences in the late 1990s, few smoked. Of those who smoked, few quit during pregnancy. Most of those who quit relapsed in the first year after childbirth. The smoking prevalence was high among the husbands of these Taiwanese women, and almost all of these smoking fathers continued tobacco use while their partners were pregnant. It is important to advocate the benefits of a smoke-free home to Taiwanese parents-to-be and parents with young children, especially the fathers. The government should take advantage of its free prenatal care and well-child care services to do this. In addition to educational campaigns through the media, the government can request physicians to promote smoke-free homes when they deliver prenatal care and well-child care. This could help reduce young children's health risks from their mothers' smoking during pregnancy and second-hand smoke at home.
Amplification of multiple genomic loci from single cells isolated by laser micro-dissection of tissues
Authors: Frumkin Dan , Wasserstrom Adam , Itzkovitz Shalev , Harmelin Alon , Rechavi Gideon , Shapiro Ehud
Published: February 2008

Background

Whole genome amplification (WGA) and laser assisted micro-dissection represent two recently developed technologies that can greatly advance biological and medical research. WGA allows the analysis of multiple genomic loci from a single genome and has been performed on single cells from cell suspensions and from enzymatically-digested tissues. Laser micro-dissection makes it possible to isolate specific single cells from heterogeneous tissues.

Results

Here we applied for the first time WGA on laser micro-dissected single cells from stained tissue sections, and developed a protocol for sequentially performing the two procedures. The combined procedure allows correlating the cell's genome with its natural morphology and precise anatomical position. From each cell we amplified 122 genomic and mitochondrial loci. In cells obtained from fresh tissue sections, 64.5% of alleles successfully amplified to ~700000 copies each, and mitochondrial DNA was amplified successfully in all cells. Multiplex PCR amplification and analysis of cells from pre-stored sections yielded significantly poorer results. Sequencing and capillary electrophoresis of WGA products allowed detection of slippage mutations in microsatellites (MS), and point mutations in P53.

Conclusion

Comprehensive genomic analysis of single cells from stained tissue sections opens new research opportunities for cell lineage and depth analyses, genome-wide mutation surveys, and other single cell assays.
Human articular chondrocytes produce IL-7 and respond to IL-7 with increased production of matrix metalloproteinase-13
Authors: Long David , Blake Simon , Song Xiao-Yu , Lark Michael , Loeser Richard F
Published: February 2008

Introduction

Fibronectin fragments have been found in the articular cartilage and synovial fluid of patients with osteoarthritis and rheumatoid arthritis. These matrix fragments can stimulate production of multiple mediators of matrix destruction, including various cytokines and metalloproteinases. The purpose of this study was to discover novel mediators of cartilage destruction using fibronectin fragments as a stimulus.

Methods

Human articular cartilage was obtained from tissue donors and from osteoarthritic cartilage removed at the time of knee replacement surgery. Enzymatically isolated chondrocytes in serum-free cultures were stimulated overnight with the 110 kDa α5β1 integrin-binding fibronectin fragment or with IL-1, IL-6, or IL-7. Cytokines and matrix metalloproteinases released into the media were detected using antibody arrays and quantified by ELISA. IL-7 receptor expression was evaluated by flow cytometry, immunocytochemical staining, and PCR.

Results

IL-7 was found to be produced by chondrocytes treated with fibronectin fragments. Compared with cells isolated from normal young adult human articular cartilage, increased IL-7 production was noted in cells isolated from older adult tissue donors and from osteoarthritic cartilage. Chondrocyte IL-7 production was also stimulated by combined treatment with the catabolic cytokines IL-1 and IL-6. Chondrocytes were found to express IL-7 receptors and to respond to IL-7 stimulation with increased production of matrix metalloproteinase-13 and with proteoglycan release from cartilage explants.

Conclusion

These novel findings indicate that IL-7 may contribute to cartilage destruction in joint diseases, including osteoarthritis.
MyD88 is necessary for neutrophil recruitment in hypersensitivity pneumonitis
Authors: Nance Stephanie C , Yi Ae-Kyung , Re Fabio C , Fitzpatrick Elizabeth A
Published: February 2008

Hypersensitivity pneumonitis is an interstitial lung disease that is characterized by alveolitis, granuloma formation, and in some patients, fibrosis. Using the Saccharopolyspora rectivirgula animal model of Farmer’s lung disease, our laboratory has demonstrated that neutrophils play a critical role in IFN-γ production during the acute phase of the disease. As IFN-γ is necessary for granuloma formation, it is important to identify the factors that lead to neutrophil recruitment during disease. To begin to identify the pattern recognition receptors (PRRs) that initiate chemokine production, leading to neutrophil recruitment following S. rectivirgula exposure, we examined the role of MyD88 and TLR2. Our results demonstrate that neutrophil recruitment, as measured by flow cytometry and the myeloperoxidase assay, was abolished in the absence of MyD88 following S. rectivirgula exposure. The decrease in neutrophil recruitment was likely a result of a significant decrease in production of neutrophil chemokines MIP-2 and keratinocyte-derived chemokine. These results suggest that S. rectivirgula interacts with PRRs that are upstream of the MyD88 pathway to initiate cytokine and chemokine production. In vitro studies suggest that S. rectivirgula can interact with TLR2, and stimulation of adherent cells from TLR2 knockout (KO) mice with S. rectivirgula resulted in a significant decrease in MIP-2 production. However, TLR2 KO mice did not have a reduction in neutrophil recruitment compared with wild-type mice following S. rectivirgula exposure. The results from our studies suggest that one or more PRR(s) upstream of MyD88 are necessary for neutrophil recruitment following S. rectivirgula exposure.
Lovastatin inhibits formation of AA amyloid
Authors: van der Hilst J C H , Kluve-Beckerman B , Bodar E J , van der Meer J W M , Drenth J P H , Simon A
Published: February 2008

Amyloid A (AA) amyloidosis is a severe complication of many chronic inflammatory disorders, including the hereditary periodic fever syndromes. However, in one of these periodic fever syndromes, the hyper IgD and periodic fever syndrome, amyloidosis is rare despite vigorous, recurring inflammation. This hereditary syndrome is caused by mutations in the gene coding for mevalonate kinase, an enzyme of the isoprenoid pathway. In this study, we used a cell culture system with human monocytes to show that inhibition of the isoprenoid pathway inhibits amyloidogenesis. Inhibition of the isoprenoid pathway by lovastatin resulted in a dose-dependent reduction of amyloid formed [53% at 10 μM (P=0.01)] compared with mononuclear cells that are exposed only to serum AA. The inhibitory effects of lovastatin are reversible by addition of farnesol but not geranylgeraniol. Farnesyl transferase inhibition also inhibited amyloidogenesis. These results implicate that the isoprenoid metabolism could be a potential target for prevention and treatment of AA amyloidosis.
Phase III Comparison of Vitespen, an Autologous Tumor-Derived Heat Shock Protein gp96 Peptide Complex Vaccine, With Physician's Choice of Treatment for Stage IV Melanoma: The C-100-21 Study Group
Authors: Testori Alessandro , Richards Jon , Whitman Eric , Mann G. Bruce , Lutzky Jose , Camacho Luis , Parmiani Giorgio , Tosti Giulio , Kirkwood John M. , Hoos Axel , Yuh Lianng , Gupta Renu , Srivastava Pramod K.
Published: February 2008

Purpose

To assess the antitumor activity of vitespen (autologous, tumor- derived heat shock protein gp96 peptide complexes) by determining whether patients with stage IV melanoma treated with vitespen experienced longer overall survival than patients treated with physician's choice.

Patients and Methods

Patients (N = 322) were randomly assigned 2:1 to receive vitespen or physician's choice (PC) of a treatment containing one or more of the following: dacarbazine, temozolomide, interleukin-2, or complete tumor resection. This open-label trial was conducted at 71 centers worldwide. Patients were monitored for safety and overall survival.

Results

Therapy with vitespen is devoid of significant toxicity. Patients randomly assigned to the vitespen arm received variable number of injections (range, 0 to 87; median, 6) in part because of the autologous nature of vitespen therapy. Intention-to-treat analysis showed that overall survival in the vitespen arm is statistically indistinguishable from that in the PC arm. Exploratory landmark analyses show that patients in the M1a and M1b substages receiving a larger number of vitespen immunizations survived longer than those receiving fewer such treatments. Such difference was not detected for substage M1c patients.

Conclusion

These results are consistent with the immunologic mechanism of action of vitespen, indicating delayed onset of clinical activity after exposure to the vaccine. The results suggest patients with M1a and M1b disease who are able to receive 10 or more doses of vitespen as the candidate population for a confirmatory study.
Indium-111–Pentetreotide Scintigraphy and Somatostatin Receptor Subtype 2 Expression: New Prognostic Factors for Malignant Well-Differentiated Endocrine Tumors
Authors: Asnacios Amani , Courbon Frédéric , Rochaix Philippe , Bauvin Eric , Cances-Lauwers Valérie , Susini Christiane , Schulz Stefan , Boneu Andrée , Guimbaud Rosine , Buscail Louis
Published: February 2008

Purpose

Well-differentiated metastatic endocrine carcinomas are difficult to manage because of variable disease outcome. New prognostic factors are required. These tumors overexpress somatostatin receptors (sst), implying the use of somatostatin analogs for tumor localization by somatostatin receptor scintigraphy using indium-111–pentetreotide (111In-pentetreotide) and for medical treatment. The aim of the present study was to evaluate the correlation between 111In-pentetreotide scintigraphy, sst receptor expression, and prognosis.

Patients and Methods

Between 1994 and 2002, 48 consecutive patients with well-differentiated endocrine carcinomas and a negative 111In-pentetreotide scintigraphy were retrospectively paired according to sex, age, and tumor localization with 50 patients with well-differentiated endocrine carcinomas and a positive tracer uptake at 111In-pentetreotide scintigraphy. Overall survival and expression of sst1 to sst5 receptors by immunohistochemistry were assessed.

Results

The lack of tracer uptake at the 111In-pentetreotide scintigraphy seemed to be a poor prognostic factor (P = .007) for overall survival by Kaplan-Meier test and in multivariate analysis; age and absence of clinical secretory syndrome also seemed to be poor prognostic factors. The tracer uptake (positive 111In-pentetreotide scintigraphy) correlated with the tumor expression of somatostatin receptor sst2 (P < .001) but not with that of sst1, sst3, sst4, or sst5. In a bivariate analysis, lack of sst2 expression also significantly correlated with poor prognosis.

Conclusion

We demonstrate the prognostic value of 111In-pentetreotide scintigraphy in well-differentiated malignant endocrine tumors. In these tumors, sst2 somatostatin receptor expression correlates with both tracer uptake and a better prognosis.
Full-Dose Gemcitabine With Concurrent Radiation Therapy in Patients With Nonmetastatic Pancreatic Cancer: A Multicenter Phase II Trial
Authors: Small William , Berlin Jordan , Freedman Gary M. , Lawrence Theodore , Talamonti Mark S. , Mulcahy Mary F. , Chakravarthy A. Bapsi , Konski Andre A. , Zalupski Mark M. , Philip Philip A. , Kinsella Timothy J. , Merchant Nipun B. , Hoffman John P. , Benson Al B. , Nicol Steven , Xu Rong M. , Gill John F. , McGinn Cornelius J.
Published: February 2008

Purpose

Gemcitabine is effective in the treatment of pancreatic cancer and is a potent radiosensitizer. This study assessed safety and efficacy of full-dose gemcitabine administered before and during concurrent three-dimensional conformal radiation (3D-CRT) in patients with nonmetastatic pancreatic cancer.

Patients and Methods

During cycles 1 and 3, patients received gemcitabine at 1,000 mg/m2on days 1 and 8 of each 21-day cycle. Cycle 2 included the same dose of gemcitabine on days 1, 8, and 15 of a 28-day cycle with concurrent 3D-CRT at 36 Gy, administered in 15 fractions of 2.4 Gy, over 3 weeks. Resectable patients underwent surgery 4 to 6 weeks after treatment. The primary objective was evaluation of toxicity. Tumor response, CA 19-9, and 1-year survival were also assessed.

Results

Forty-one patients enrolled at six institutions between April 2002 and October 2003. Among the 39 treated patients, the most common toxicities were grade 3 neutropenia (12.8%), grade 3 nausea (10.3%), and grade 3 vomiting (10.3%). The response rate was 5.1% and disease control rate was 84.6%. Mean post-treatment CA 19-9 levels (228 ± 347 U/mL) were significantly (P = .006) reduced compared with pretreatment levels (1,241 ± 2,124 U/mL). Thirteen (81%) of 16 patients initially judged resectable, three (33%) of nine borderline-resectable patients, and one (7%) of 14 unresectable patients underwent resection after therapy. One-year survival rates were 73% for all patients, 94% for resectable patients, 76% for borderline-resectable patients, and 47% for unresectable patients.

Conclusion

Full-dose gemcitabine with concurrent radiotherapy was well tolerated and active. Evaluation of this regimen in a larger, randomized trial for patients with resectable or borderline-resectable disease may be warranted.
Sentinel Node Dissection Is Safe in the Treatment of Early-Stage Vulvar Cancer
Authors: Van der Zee Ate G.J. , Oonk Maaike H. , De Hullu Joanne A. , Ansink Anca C. , Vergote Ignace , Verheijen René H. , Maggioni Angelo , Gaarenstroom Katja N. , Baldwin Peter J. , Van Dorst Eleonore B. , Van der Velden Jacobus , Hermans Ralph H. , van der Putten Hans , Drouin Pierre , Schneider Achim , Sluiter Wim J.
Published: February 2008

Purpose

To investigate the safety and clinical utility of the sentinel node procedure in early-stage vulvar cancer patients.

Patients and Methods

A multicenter observational study on sentinel node detection using radioactive tracer and blue dye was performed in patients with T1/2 (< 4 cm) squamous cell cancer of the vulva. When the sentinel node was found to be negative at pathologic ultrastaging, inguinofemoral lymphadenectomy was omitted, and the patient was observed with follow-up for 2 years at intervals of every 2 months. Stopping rules were defined for the occurrence of groin recurrences.

Results

From March 2000 until June 2006, a sentinel node procedure was performed in 623 groins of 403 assessable patients. In 259 patients with unifocal vulvar disease and a negative sentinel node (median follow-up time, 35 months), six groin recurrences were diagnosed (2.3%; 95% CI, 0.6% to 5%), and 3-year survival rate was 97% (95% CI, 91% to 99%). Short-term morbidity was decreased in patients after sentinel node dissection only when compared with patients with a positive sentinel node who underwent inguinofemoral lymphadenectomy (wound breakdown in groin: 11.7% v 34.0%, respectively; P < .0001; and cellulitis: 4.5% v 21.3%, respectively; P < .0001). Long-term morbidity also was less frequently observed after removal of only the sentinel node compared with sentinel node removal and inguinofemoral lymphadenectomy (recurrent erysipelas: 0.4% v 16.2%, respectively; P < .0001; and lymphedema of the legs: 1.9% v 25.2%, respectively; P < .0001).

Conclusion

In early-stage vulvar cancer patients with a negative sentinel node, the groin recurrence rate is low, survival is excellent, and treatment-related morbidity is minimal. We suggest that sentinel node dissection, performed by a quality-controlled multidisciplinary team, should be part of the standard treatment in selected patients with early-stage vulvar cancer.
Dissociation between the Insulin-Sensitizing Effect of Rosiglitazone and Its Effect on Hepatic and Intestinal Lipoprotein Production
Authors: Duez Hélène , Lamarche Benoît , Uffelman Kristine D. , Valéro René , Szeto Linda , Lemieux Simone , Cohn Jeffrey S. , Lewis Gary F.
Published: February 2008

Context: Despite its potent, well-documented insulin-sensitizing effects, rosiglitazone (RSG) does not effectively ameliorate the hypertriglyceridemia of insulin-resistant or diabetic individuals and has even been shown to slightly but significantly increase triglyceride-rich lipoproteins (TRL) in some studies. The mechanism of this effect is currently not known.

Objective: We investigated the effect of RSG treatment on TRL metabolism.

Design: This was a 12-wk, single-sequence, cross-over study of rosiglitazone vs. placebo for 6 wk.

Participants: Participants included 17 nondiabetic men with a broad range of insulin sensitivity.

Intervention: Intervention included rosiglitazone 8 mg/d vs. placebo for 6 wk.

Main Outcome Measure: TRL metabolism (concentration, production and catabolic rates) was assessed in a constant fed state with a 12-h primed constant infusion of [D3]l-leucine and multicompartmental modeling.

Results: RSG treatment resulted in significant insulin sensitization with no change in body weight. Fasting plasma triglyceride (TG) concentration, however, was higher with RSG vs. placebo (P = 0.0006), as were fasting and fed TRL-TG, TRL-apoB-48, and TRL-apoB-100 (fed TRL-apoB-48: 0.93 ± 0.08 vs. 0.76 ± 0.07 mg/dl, P =0.017, and fed TRL-apoB-100: 15.57 ± 0.90 vs. 13.71 ± 1.27 mg/dl, P = 0.029). This small but significant increase in plasma TRL concentration was explained by a tendency for RSG to increase TRL production and reduce particle clearance, as indicated by the significantly increased production to clearance ratios for both apoB-48-containing (0.43 ± 0.03 vs. 0.34 ± 0.03, P = 0.048) and apoB-100-containing (7.0 ± 0.4 vs. 6.2 ± 0.6, P = 0.029) TRL.

Conclusion: These data indicate dissociation between the insulin-sensitizing effects of RSG and absence of anticipated reductions in production rates of apoB-100- and apoB-48-containing-TRL particles, which may explain the absence of TG lowering seen in humans treated with this agent.
The Impact of Risk Factors and More Stringent Diagnostic Criteria of Gestational Diabetes on Outcomes in Central European Women
Authors: Kautzky-Willer A. , Bancher-Todesca D. , Weitgasser R. , Prikoszovich T. , Steiner H. , Shnawa N. , Schernthaner G. , Birnbacher R. , Schneider B. , Marth Ch. , Roden M. , Lechleitner M.
Published: February 2008

Objectives: In the face of the ongoing discussion on the criteria for the diagnosis of gestational diabetes (GDM), we aimed to examine whether the criteria of the Fourth International Workshop Conference of GDM (WC) select women and children at risk better than the World Health Organization (WHO) criteria.

Design and Setting: This was a prospective longitudinal open study in five tertiary care centers in Austria.

Patients and Outcome Measures: The impact of risk factors, different thresholds (WC vs. WHO), and numbers of abnormal glucose values (WC) during the 2-h, 75-g oral glucose tolerance test on fetal/neonatal complications and maternal postpartum glucose tolerance was studied in 1466 pregnant women. Women were treated if at least one value according to the WC (GDM-WC1) was met or exceeded.

Results: Forty-six percent of all women had GDM-WC1, whereas 29% had GDM-WHO, and 21% of all women had two or three abnormal values according to WC criteria (GDM-WC2). Eighty-five percent of the GDM-WHO were also identified by GDM-WC1. Previous GDM [odds ratio (OR) 2.9], glucosuria (OR 2.4), preconceptual overweight/obesity (OR 2.3), age 30 yr or older (OR 1.9), and large-for-gestational age (LGA) fetus (OR 1.8) were the best independent predictors of the occurrence of GDM. Previous GDM (OR 4.4) and overweight/obesity (OR 4.0) also independently predicted diabetes postpartum. GDM-WC1 had a higher rate of obstetrical complications (LGA neonates, neonatal hypoglycemia, cesarean sections; P < 0.001) and impaired postpartum glucose tolerance (P < 0.0001) than GDM-WHO.

Conclusion: These results suggest the use of more stringent WC criteria for the diagnosis of GDM with the initiation of therapy in case of one fasting or stimulated abnormal glucose value because these criteria detected more LGA neonates with hypoglycemia and mothers with impaired postpartum glucose metabolism than the WHO criteria.
Increased Androgen Response to Follicle-Stimulating Hormone Administration in Women with Polycystic Ovary Syndrome
Authors: Wachs Deborah S. , Coffler Mickey S. , Malcom Pamela J. , Shimasaki Shunichi , Chang R. Jeffrey
Published: February 2008

Context: In women with polycystic ovary syndrome (PCOS), excess ovarian androgen production is driven by increased LH secretion. Studies conducted in animals suggest that the granulosa cell may influence LH-stimulated theca cell androgen production.

Objective: The objective of this study was to determine whether FSH enhances androgen production in women with PCOS compared with that of normal women.

Design: A prospective study was conducted to compare androgen production in response to FSH in two groups of women.

Setting: The study was conducted in a General Clinical Research Center in a tertiary academic medical center.

Patients: Women with PCOS, 18–35 yr (n = 20), and normal ovulatory controls, 18–35 yr (n = 10), were recruited for study.

Interventions: Serial blood samples were obtained over a 24-h period after an iv injection of recombinant human FSH (150 IU).

Main Outcome Measures: The main outcome measures were serum 17-hydroxyprogesterone (17-OHP), androstenedione (A), dehydroepiandrosterone (DHEA), testosterone (T), and inhibin B (Inh B) responses after FSH administration.

Results: Basal serum 17-OHP, A, and T levels were markedly increased in women with PCOS compared with that observed in normal women. Basal DHEA and Inh B levels were similar to those of normal controls. After FSH injection, PCOS women demonstrated enhanced production of 17-OHP, A, DHEA, and Inh B, whereas in normal women no increases were observed. T levels declined slightly in both groups.

Conclusions: These findings provide evidence that, in PCOS women, theca cell androgen production is enhanced by FSH administration and suggest a granulosa-theca cell paracrine mechanism.
Patient responses to an integrated service, initiated by community pharmacists, for the prevention of osteoporosis
Authors: Crockett Judith A , Taylor Susan J , McLeod Lynette J
Published: February 2008

Objective

This study aimed to develop, implement and evaluate an integrated service provided by pharmacists to consumers based on the results of a risk-assessment survey carried out by the pharmacist and testing of bone mineral density (BMD) by a radiographer. It also investigated whether measurement of BMD in the pharmacy increased the effectiveness of the service and pharmacist referral in terms of adherence to advice and uptake of referral compared with the same service offered without BMD testing.

Setting

Community pharmacists in urban and rural settings in New South Wales, Australia, delivered the service.

Method

The adherence to advice or referral given by 12 community pharmacists during 2003 to 217 participants about the prevention of osteoporosis following screening with either a BMD test plus risk-assessment questionnaire or a risk-assessment questionnaire only was compared.

Key findings

No significant between-group differences in adherence to advice or referral were found. However, participants valued the BMD service significantly more highly than the non-BMD service as measured by satisfaction scores.

Conclusions

Consumers were interested in receiving information about osteoporosis and their own risk of it and even greater interest in BMD testing in the pharmacy. There was no difference in uptake of referral or advice following either questionnaire only or questionnaire plus BMD testing. Low uptake of referral and advice overall by those deemed to be at high risk is of concern. Far greater education and encouragement for consumers to follow through is required.
The adoption of dispensing technology: an occasion for restructuring hospital pharmacy work
Authors: Oborn Eivor , Barrett Michael
Published: February 2008

Objective

To understand the ways in which hospital dispensary work is being restructured following the implementation of dispensing technology. We examine the evolving role of pharmacists, technicians and assistants in their use of the technology.

Setting

The implementation of dispensing robots in two hospital dispensaries in a metropolitan region of the UK were examined over a 2-year period.

Method

A qualitative case-study design was used. Non-participant observation, interviews and organisational documentary sources were the primary data sources. Analysis of first-order themes identified common issues. Drawing on literature within organisational studies, second-order themes were developed iteratively.

Key findings

Pharmacists render the dispensary less dependent on their physical presence by inscribing key dispensary practices into the robot, enabling them to move into more cognitive work roles. Technicians quickly adapt to the new dispensing process, gaining technical skills and competences through training on the robot and daily maintenance. This modernises the role of technicians and improves their visibility in the dispensary and within the pharmacy profession. Assistants become users of technology and become increasingly dependent on others for technical support. They lose autonomy as their work becomes more interdependent. The robot takes on the role as a team member, christened with a name, and referred to in anthropomorphising terms.

Conclusion

Dispensary workers and managing pharmacists should go beyond viewing the adoption of new technology at a functional level of efficiency and error rates. Rather, the findings highlight the changing nature of tasks and roles that are evolving with the restructuring of dispensing work. These need to be considered by those managing change processes associated with the implementation of these technologies, as they are shaped by workers' perception of the technology in use.
The Balkans: In the Era of Peace and Stability
Authors: Mallias Alexandros P.
Published: February 2008

The author, the Greek ambassador to the United States, argues that the Balkan countries have made significant strides in economic and security stabilization over the past decade but points to particular challenges, notably in Kosovo and the Former Yugoslav Republic of Macedonia (FYROM). He argues that conditions in both countries remain volatile and that any solutions must come in the context of relations with European neighbors and within the frameworks of existing treaties and policies. He describes how Greece has contributed to economic development in the region in hopes of stabilizing the it as part of the wider European and international communities and argues that actions by FYROM jeopardize its relationship with international organizations and thus pose a threat to stability in the region.
Turkey and the Threat of Kurdish Nationalism
Authors: Giraldi Philip
Published: February 2008

The US-led invasion of Iraq in 2003 has resulted in a resurgence in Kurdish nationalism. There has also been a revival of the terrorist threat directed against Turkey coming from the Kurdistan Workers' Party based in northern Iraq. The inability of the United States to curb the terrorism problem and the increasing instability of the region as a whole have put pressure on the Turkish government to act decisively. Much of this pressure comes from secularists and the army itself, both of which criticize the ruling AK Party because of its failure to provide security. The decision whether to invade northern Iraq will depend on exactly how Prime Minister Recep Tayyip Erdogan chooses to respond to that pressure.
Nation Building in a War Zone: The US Record in Iraq, 2003–2007
Authors: El-Khawas Mohamed A.
Published: February 2008

The essay examines Bush's strategies to democratize Iraq. Failure to draft a plan for Iraq's stabilization led to costly mistakes that drove many Sunnis to join insurgent groups, fueling sectarian strife. Holding multiparty elections was a major accomplishment, but it did not lead to national reconciliation. Meanwhile, Bush has given Prime Minister Nouri al-Maliki governmental benchmarks to meet, has sent more troops to drive insurgents out of Baghdad, and has armed Sunni tribes to fight al Qaeda. After reviewing key events, the essay assesses the prospects for the future of democracy in a country where there is neither security nor the rule of law.
Approaching Albania
Authors: Binder David
Published: February 2008

It took twenty-seven years and the ending of the Cold War for former New York Times correspondent David Binder to obtain permission to enter Communist Albania. Once there, in 1990, the author was introduced to both suspicion and traditionally warm hospitality. He found Albania impoverished, as it had been throughout its history, but also rich in talented and thoughtful people. Images of Stalin and of Enver Hoxha, Stalin's Albanian imitator, were still omnipresent. “We are a terrorized people,” one student commented. Rebellion was in the air.