bluuebunny/crossref_metadata_2025 huggingface dataset:
Post‐mortem clinical pharmacology
Authors: Ferner R. E.
Published: May 2008

Clinical pharmacology assumes that deductions can be made about the concentrations of drugs from a knowledge of the pharmacokinetic parameters in an individual; and that the effects are related to the measured concentration. Post‐mortem changes render the assumptions of clinical pharmacology largely invalid, and make the interpretation of concentrations measured in post‐mortem samples difficult or impossible. Qualitative tests can show the presence of substances that were not present in life, and can fail to detect substances that led to death. Quantitative analysis is subject to error in itself, and because post‐mortem concentrations vary in largely unpredictable ways with the site and time of sampling, as a result of the phenomenon of post‐mortem redistribution. Consequently, compilations of ‘lethal concentrations’ are misleading. There is a lack of adequate studies of the true relationship between fatal events and the concentrations that can be measured subsequently, but without such studies, clinical pharmacologists and others should be wary of interpreting post‐mortem measurements.
Neuro‐mediators as predictors of paediatric atopic dermatitis
Authors: Wang I. J. , Hsieh W. S. , Guo Y. L. , Jee S. H. , Hsieh C. J. , Hwang Y. H. , Chen P. C.
Published: May 2008

Background
Attempts to identify predictors of atopic dermatitis (AD) have focused on genetic and immunologic factors. However, the role of neuro‐mediators remains to be elucidated.

Objective
To evaluate nerve growth factor (NGF) and vaso‐active intestinal peptide (VIP) in predicting paediatric AD and assess their correlation with intrinsic and extrinsic types of AD.

Methods
We performed a nested case–control study in the prospective Taiwan birth panel cohort study. Cord and maternal plasma and questionnaires were gathered at birth. During follow‐up, we identified 40 available AD cases, which were matched to 80 unaffected controls chosen from this cohort. The concentrations of IgE, NGF, and VIP in cord and maternal plasma of these subjects were performed by ELISA. Receiver‐operating characteristic (ROC) curves were generated to see how well each biomarker could predict AD.

Results
The NGF levels were significantly higher in AD patients than controls (mean±SD: 65.47±44.45 vs. 49.21±12.18 pg/mL for cord plasma and 89.68±41.04 vs. 66.96±23.05 pg/mL for maternal plasma) (P<0.05). VIP levels were also higher but not statistically significant. Plasma NGF may be a better biomarker than IgE in detecting paediatric AD (area under the ROC curve=0.65 vs. 0.61 for cord plasma and 0.69 vs. 0.61 for maternal plasma). Maternal NGF levels were significantly higher in patients with both intrinsic (96.18±48.15 pg/mL) and extrinsic (86.18±37.23 pg/mL) types of AD compared with controls (66.96±23.05 pg/mL) (P<0.05). We assessed a significant correlation between self‐reported stress during pregnancy and maternal NGF levels (r=0.22, P=0.02).

Conclusion
Our results suggest that NGF is a good alternative biomarker in predicting children with a risk of AD.
Multiple controls for the variability of hydrogen isotopic compositions in higher plant n‐alkanes from modern ecosystems
Authors: LIU WEIGUO , YANG HONG
Published: May 2008

We performed a global scale analysis of available leaf wax n‐alkane δD data compiled from our new results, as well as from the literature and expressed as average values of D/H ratios from three common lipids of n‐alkanes with odd carbon numbers (n‐C27, n‐C29, and n‐C31) from living higher plants. Our results clearly indicate multiple controls of hydrogen isotope composition and its variability in plants leaf wax. (1) At the global scale, precipitation δD values play a dominating factor that exercises the first order of control for hydrogen isotopic compositions in plant leaf wax. The hydrogen isotopic composition of plant leaf wax tracks the decreasing trend of precipitation δD with increasing latitude. (2) Because of different water acquisition systems, plant life form influences the hydrogen isotopic composition of leaf wax n‐alkanes with woody plants and grasses having different responses to the change of global precipitation δD. (3) Physiological difference, due to different photosynthesis pathways or different water usage strategies, can leave an imprint on δD patterns of plant leaf waxes, causing δD variations among plants using the same source water. While these results better explain the variability of hydrogen isotope composition in leaf wax, they also have important implications for the interpretation of n‐alkane δD data from fossils and ancient sediments.
Biological functions and clinical implications of oestrogen receptors alfa and beta in epithelial tissues
Authors: Morani A. , Warner M. , Gustafsson J.‐Å.
Published: May 2008

For the past 10 years it is known that oestrogen functions through the activation of two oestrogen receptors (ERα and ERβ). To the great surprise of endocrinologists, ERβ was found to be widely distributed in tissues throughout the body including tissues previously considered as ‘oestrogen insensitive’. The epithelium of the ventral prostate and lung as well as ovarian granulosa cells are ERα‐negative but ERβ‐positive and in these tissues ERβ seems to be involved in important physiological processes, like differentiation, extracellular matrix organization and stromal–epithelial communication. In tissues where both ERs are expressed, the two receptors seem to counteract each other. In the uterus, mammary gland and immune system, ERα promotes proliferation whereas ERβ has pro‐apoptotic and pro‐differentiating functions. The challenge of the future will be to develop specific agonists, which can selectively activate/inactivate either ERα or ERβ. These pharmaceuticals are likely to be of clinical importance in the prevention or treatment of various diseases.
Central nervous system involvement in severe congenital neutropenia: neurological and neuropsychological abnormalities associated with specific HAX1 mutations
Authors: Carlsson G. , Van’t Hooft I. , Melin M. , Entesarian M. , Laurencikas E. , Nennesmo I. , Trębińska A. , Grzybowska E. , Palmblad J. , Dahl N. , Nordenskjöld M. , Fadeel B. , Henter J‐I
Published: May 2008

Objectives.  Homozygous mutations in the HAX1 gene were recently identified in severe congenital neutropenia patients belonging to the original Kostmann family in northern Sweden. Our observations suggested that these patients also develop neurological and neuropsychological symptoms.

Methods.  Detailed clinical studies and mutation analyses were performed in the surviving patients belonging to the Kostmann kindred and in two patients not related to this family, along with studies of HAX1 splice variant expression in normal human tissues.

Results.  Five of six Kostmann family patients and one other patient from northern Sweden harboured homozygous HAX1 mutations (568C→T, Q190X) and one carried a heterozygous ELA2 gene mutation. One Swedish patient of Kurdish extraction carried alternative homozygous HAX1 mutations (131G→A, W44X). All the three patients with Q190X mutations who were alive and available for evaluation developed neurological disease with decreased cognitive function, and three of four patients who reached 10 years developed epilepsy. In contrast, the patients with the ELA2 and W44X HAX1 mutations, respectively, showed no obvious neurological abnormalities. Moreover, two alternative HAX1 splice variants were identified in normal human tissues, including the brain. Both transcripts contained exon 5, harbouring the Q190X mutation, whereas the 5′ end of exon 2 containing the W44X mutation was spliced out from the second transcript.

Conclusions.  We describe neurological and neuropsychological abnormalities for the first time in Kostmann disease patients. These central nervous system symptoms appear to be associated with specific HAX1 mutations.
A common haplotype of the C‐C chemokine receptor 2 gene and HLA‐DRB1*0301 are independent genetic risk factors for Löfgren’s syndrome
Authors: Spagnolo P. , Sato H. , Grunewald J. , Brynedal B. , Hillert J. , Mañá J. , Wells A. U. , Eklund A. , Welsh K. I. , Du Bois R. M.
Published: May 2008

Aim.  Sarcoidosis is a heterogeneous disorder with a strong genetic influence. Genetic factors are also thought to influence disease severity and outcome. We sought to determine whether polymorphisms within CCR2 gene predispose to Löfgren’s syndrome – a clinically and genetically distinct sarcoidosis phenotype – and, importantly, whether this association is independent of the known association with the HLA‐DRB1*0301 allele.

Methods.  We investigated 5 CCR2 variants and HLA‐DRB1*0301 by sequence‐specific primer (SSP) polymerase chain reaction (PCR) in 176 Spanish (76 Löfgren’s syndrome, 100 controls) and 387 Swedish subjects (126 Löfgren’s syndrome, 77 non‐Löfgren sarcoidosis, 184 controls).

Results.  One of the deduced haplotypes (CCR2 haplotype 2) was associated with Löfgren’s syndrome in both Spanish (OR: 2.03, uncorrected P = 0.02; permuted P = 0.041 vs. controls) and Swedish patients (OR: 3.02, uncorrected P = 0.0007; permuted P = 0.0027 vs. non‐Löfgren sarcoidosis; OR: 2.46, uncorrected P = 0.0005; permuted P = 0.0031 vs. controls). HLA‐DRB1*0301 allele frequency was also increased in Spanish (OR: 3.52, P = 0.0004 vs. controls) and Swedish patients with Löfgren’s syndrome (OR: 10.98, P < 0.0001 vs. non‐Löfgren sarcoidosis, OR: 7.71, P < 0.0001 vs. controls). Finally, multivariate analysis revealed that the CCR2 association was independent of HLA‐DRB1*0301 in both Spanish (P = 0.02 vs. controls) and Swedish cohorts (P = 0.002 vs. non‐Löfgren sarcoidosis, P = 0.001 vs. controls).

Conclusions.  This study confirms that CCR2 haplotype 2 and HLA‐DRB1*0301 are independent genetic risk factors for Löfgren’s syndrome.
Combined effects of obesity and physical activity in predicting mortality among men
Authors: Orsini N. , Bellocco R. , Bottai M. , Pagano M. , Michaelsson K. , Wolk A.
Published: May 2008

Objective.  We evaluated the hypothesis that higher levels of total daily physical activity can eliminate the increased mortality rate associated with overweight and obesity.

Design.  Population‐based prospective cohort study.

Setting.  Central Sweden.

Subjects.  A total of 37 633 men at baseline 45–79 years of age and free of known cancer and cardiovascular disease and diabetes completed a self‐administered life‐style questionnaire, which included questions on body‐mass index (BMI) and physical activity. During 9.7 years of follow‐up, we identified a total of 4086 deaths.

Main outcome measures.  Mortality rate ratios (RRs).

Results.  Compared to men who were lean (BMI < 25 kg m−2) and active (top tertile of total physical activity level) the multivariable adjusted RRs (95% confidence interval) of death from all causes were 1.44 (1.11–1.86) for obese (BMI ≥ 30 kg m−2) and active men, 1.54 (1.34–1.77) for lean (BMI < 25 kg m−2) but inactive (bottom tertile) men, and 1.81 (1.48–2.23) for obese‐inactive men. After excluding the first 3 years of follow‐up, current and former smokers, those who had lost weight from age 20 years to age at baseline, and heavy manual workers, the adjusted RRs of death from all causes were 1.65 (1.20–2.27) for overweight‐to‐obese and active men, 2.15 (1.59–2.91) for lean‐inactive men, and 2.04 (1.52–2.74) for overweight‐to‐obese and inactive men compared to lean‐active men.

Conclusions.  We conclude that both overweight and physical inactivity are important predictors of mortality. Our findings do not support the hypothesis that a higher level of physical activity compensates the excess mortality associated with overweight and obesity.
Introduction of a real‐time based blood group genotyping approach
Authors: Polin H. , Danzer M. , Pröll J. , Hofer K. , Heilinger U. , Zopf A. , Gabriel C.
Published: May 2008

Background and Objective  Genotyping may be applied for rare blood group polymorphisms in a high‐throughput mode as well for the molecular determination of blood groups due to unclear serological results.

Material and Methods  We developed and validated a DNA typing method for the determination of KEL1/2, JK1/2, FY1/2, FY0, MNS1/2, MNS3/4, DO1/2, CO1/2 and LU1/2 alleles using a melting curve analysis downstream from a fully automated DNA extraction. All assays were validated in terms of specificity, sensitivity, assay variability and robustness. The usability was proven by a batch of 200 blood samples with partially known phenotype.

Results  Assays for all blood groups were within the range of specificity (100%), assay variability and robustness (coefficient of variance < 3%). Genotypes of 200 random platelet donors were fully consistent with existing phenotype data. The obtained genotype distribution is in complete concordance with existing data for the European population underlined by a complete absence of CO2 homozygous donors and the FY0 allele among the cohort.

Conclusion  We introduce an approach for blood group genotyping of particular samples or gene loci in glass capillary format and for medium‐throughput analysis in 96/384‐well format. The advantages of this real‐time polymerase chain reaction method are its automation potential, the flexibility regarding hardware and the rapid cycling time.
Inflammatory pain is enhanced in delta opioid receptor‐knockout mice
Authors: Gavériaux‐Ruff Claire , Karchewski Laurie A. , Hever Xavier , Matifas Audrey , Kieffer Brigitte L.
Published: May 2008

To examine the involvement of opioid receptors in inflammatory pain, we compared Complete Freund’s Adjuvant‐induced hyperalgesia in mice lacking mu, delta or kappa receptors under the same experimental conditions. Mechanical allodynia and thermal hyperalgesia were measured using von Frey filaments and the plantar test, respectively. All three receptor‐knockout mice, as well as wild‐type animals, developed inflammatory hyperalgesia following Complete Freund’s Adjuvant administration. Mu‐receptor mutants showed similar hyperalgesia to wild‐types in the two tests. Kappa‐receptor mutants exhibited enhanced mechanical allodynia compared with wild‐type mice but similar thermal hyperalgesia. In contrast, mechanical allodynia and thermal hyperalgesia were both markedly augmented in delta‐receptor mutants, indicating a role for an endogenous delta‐receptor tone in the control of inflammatory pain. Treatment with the delta‐selective agonist SNC80 produced antihyperalgesia, and this effect was abolished in the delta‐receptor knockout mice. Altogether, these data demonstrate that delta receptors inhibit inflammatory pain when activated either endogenously or exogenously. We have previously shown enhanced neuropathic pain in delta‐receptor knockout mice. The delta receptor definitely represents a promising target for treating chronic pain conditions.
Changes in nucleus accumbens dopamine transmission associated with fixed‐ and variable‐time schedule‐induced feeding
Authors: Richardson Nicole R. , Gratton Alain
Published: May 2008

We examined the changes in nucleus accumbens (NAcc) dopamine (DA) transmission associated with non‐contingent meal presentations under conditions of high (fixed time‐, FT‐schedule) and low (variable time‐, VT‐schedule) predictability. Of interest were the changes in NAcc DA transmission associated with discrepancies between the time food is expected and when it is actually presented. We used in vivo voltammetry to monitor NAcc DA levels as rats received, on the first and second test days, 30‐s meals of condensed milk on a VT‐52 schedule (inter‐meal intervals of 32, 35, 40, 45, 52, 64, and 95 s). On the third and subsequent days meals were presented first on a VT‐52 s schedule and then on an FT‐52 s schedule. On day 1, monotonic increases in NAcc DA signals were observed during both meal consumption and the intervals between VT meal presentations. By day 2, however, meal presentations on the VT schedule elicited biphasic DA signal fluctuations; DA signals increased prior to each meal presentation but then started to decline during the feeding bout that followed. Fixed‐time meal presentations on day 3 disrupted this pattern, resulting in a concurrent escalation of DA signal fluctuations upon subsequent VT meal presentations. These findings provide further evidence that, in trained animals, NAcc DA transmission is activated by conditioned incentive cues rather than by primary rewards. They also suggest that the increases in NAcc DA transmission associated with reward expectancy are sensitive to temporal cues (e.g. interval timing) and to discrepancies between expected and actual outcomes.
Endomorphin‐2 is released from newborn rat primary sensory neurons in a frequency‐ and calcium‐dependent manner
Authors: Scanlin Heather L. , Carroll Elizabeth A. , Jenkins Victoria K. , Balkowiec Agnieszka
Published: May 2008

Recent evidence indicates that endomorphins, endogenous mu‐opioid receptor (MOR) agonists, modulate synaptic transmission in both somatic and visceral sensory pathways. Here we show that endomorphin‐2 (END‐2) is expressed in newborn rat dorsal root ganglion (DRG) and nodose‐petrosal ganglion complex (NPG) neurons, and rarely co‐localizes with brain‐derived neurotrophic factor (BDNF). In order to examine activity‐dependent release of END‐2 from neurons, we established a model using dispersed cultures of DRG and NPG cells activated by patterned electrical field stimulation. To detect release of END‐2, we developed a novel rapid capture enzyme‐linked immunosorbent assay (ELISA), in which END‐2 capture antibody was added to neuronal cultures shortly before their electrical stimulation. The conventional assay was effective at reliably detecting END‐2 only when the cells were stimulated in the presence of CTAP, a MOR‐selective antagonist. This suggests that the strength of the novel assay is related primarily to rapid capture of released END‐2 before it binds to endogenous MORs. Using the rapid capture ELISA, we found that stimulation protocols known to induce plastic changes at sensory synapses were highly effective at releasing END‐2. Removal of extracellular calcium or blocking voltage‐activated calcium channels significantly reduced the release. Together, our data provide the first evidence that END‐2 is expressed by newborn DRG neurons of all sizes found in this age group, and can be released from these, as well as from NPG neurons, in an activity‐dependent manner. These results point to END‐2 as a likely mediator of activity‐dependent plasticity in sensory pathways.
Seasonal pheromone response byIps piniin northern Arizona and western Montana, U.S.A.
Authors: Steed Brytten E. , Wagner Michael R.
Published: May 2008

1 Populations ofIps pini(Say) in northern Arizona and western Montana, U.S.A., were studied to determine regional pheromone response and to evaluate seasonal shifts in that response. A range of enantiomeric blends of the attractant ipsdienol, alone and in the presence of the synergist lanierone, were tested during spring and summer seasons over several years.

2 Both populations were most attracted to high levels of (R)‐(–)‐ipsdienol, and lanierone was highly synergistic.

3 A significant seasonal shift in pheromone response between spring and summer seasons was found in both regions in both years. Shifts resulted in a more specific preference for the pheromone treatment of 97% (R)‐(–)‐ipsdienol with lanierone.

4 Several coleopteran insect associates ofI. pinialso displayed responses to the ipsdienol and lanierone treatments.Temnochila chlorodia(Mannerheim) (Trogositidae),Enoclerus sphegeus(F.) (Cleridae) and, to a limited extent,Lasconotus laqueatus(LeConte) (Colydiidae) were attracted to higher proportions of (R)‐(–)‐ipsdienol with no apparent reaction to the presence of lanierone.Orthotomicus latidens(LeConte) (Curculionidae: Scolytinae) was strongly attracted to (S)‐(+)‐ipsdienol withEnoclerus lecontei(Wolcott) (Cleridae),Pityogenes carinulatus(LeConte) (Curculionidae: Scolytinae) andHylurgops porosus(LeConte) (Curculionidae: Scolytinae) demonstrating some preferences for the (S)‐(+)‐enantiomer. However, lanierone was synergistic forE. leconteiandP. carinulatus, inhibitory forO. latidens, and produced no significant reaction forH. porosus.Elacatissp. (Salpingidae, previously Othniidae) was attracted to the presence of ipsdienol but displayed no preference to the enantiomeric ratios of ipsdienol or the presence of lanierone.
The fate of anastomotic sinuses after total mesorectal excision for rectal cancer
Authors: Arumainayagam N. , Chadwick M. , Roe A.
Published: May 2008

Objective  Chronic anastomotic sinus is a recognized complication of total mesorectal excision (TME) surgery. We observed two patients who developed new tumours within chronic anastomotic sinuses 6 and 19 years after initial surgery. The aim of this study was therefore to report the incidence and outcome of anastomotic sinuses, thus identifying those at potential risk of malignant change.

Method  We retrospectively reviewed patient records and radiology reports to identify potentially curative rectal cancer cases between 1998 and 2005.

Results  In a consecutive series of 100 TMEs with ileostomy, there were 70 males and 30 females, aged 66 (33–88) years. Anastomosis was by double staple technique. A policy of instant enema was used prior to ileostomy closure. Eighty‐six patients had instant enemas. Of the 14 that did not, four died prior to enema, one returned to theatre for sepsis, three had their anastomoses assessed by sigmoidoscopy alone. Six had incomplete records. Of the 86 patients, eight presacral sinuses were identified. Three sinuses closed spontaneously. Five persisted of whom two required further surgery.

Conclusion  Persistent anastomotic sinuses occurred in 5% after curative TME. Malignant transformation can occur. Active treatment for chronic sinuses should, therefore, be considered.
Preoperative staging of rectal cancer: pelvic MRI plus abdomen and pelvic CT. Does extrahepatic abdomen imaging matter? A case for routine thoracic CT
Authors: Adeyemo D. , Hutchinson R.
Published: May 2008

Objective  To assess the quality of preoperative magnetic resonance imaging (MRI) staging of rectal cancer, and the clinical significance of abdomen and pelvic computed tomogram (CT) scans in preoperative staging of rectal cancer in a district general hospital. We postulated that the ‘metastatic yield’ of extrahepatic abdominal imaging is poor, and rarely altered management of rectal cancer.

Methods  This is a retrospective study of preoperative MRI, CT scans and postoperative histology results of patients who had definitive surgery for rectal cancer at the Mid‐Staffordshire General Hospitals NHS Trust over a 36‐month period. Preoperative multiplanar pelvic MRI locoregional staging was compared with eventual histology. The incidence of and significance of abdomen and pelvic CT detected pathology (including metastasis) in the management of rectal cancers was also assessed.

Results  Preoperative pelvic MRI correctly predicted ‘clear’ Circumferential resection margins, in 28 of 29 patients who had primary surgery. This is comparable with many published studies. Significant CT detected pathology (including metastasis) on preoperative abdomen and pelvic CT scans was uncommon, and did not influence management of any rectal cancer patient in our study.

Discussion  Given that exclusive CT detected significant pathology caudal to the liver (extrahepatic abdomen) is rare, can full abdomen and pelvic CT scans be justified for preoperative staging of rectal cancers? – especially where chest X rays are employed for lung staging. Preoperative thoracic and upper abdomen CT scan may be a more productive use of resources. Full abdominal scans may be more appropriate for selection of rectal cancer patients with isolated liver metastasis for metastasectomy.
The double‐spouted loop ileostomy
Authors: Courtney E. D. , Callaghan C. J. , Ilett H. , Schrader D. , Brown K.
Published: May 2008

Objective  A functional improvement to a conventional loop ileostomy is described with both proximal and distal limbs spouted reducing the number of patients with problematic ileostomies.

Method  The results of the National Prospective Audit of Stoma Complications for the hospital showed 14/15 of the traditional single loop ileostomies were identified as problematic. 21 patients were then studied prospectively, who underwent formation of a new type of loop stoma, in which both the proximal and distal limbs were spouted.

Results  In the group of 21 patients with a double spouted loop ileostomy 3/21 had a problematic stoma. The number of appliances needed was significantly less than the single spouted group. The number of home visits by the stoma nurse and outpatient visits to the stoma therapy team at the hospital were also significantly less in the double spouted group.

Conclusion  This modification of the loop ileostomy, with both the proximal and distal ends of the bowel spouted has several advantages. The danger of spouting the wrong limb is eliminated, it can be created very easily via a trephine technique and spouting the distal limb reduces the leakage of mucus under the flange of the stoma bag, reducing the problems of poor appliance adhesion.
Comparison of carcinoembryonic antigen prognostic value in serum and tumour tissue of patients with colorectal cancer
Authors: Li M. , Li J.‐Y. , Zhao A.‐L. , He J.‐S. , Zhou L.‐X. , Li Y.‐A. , Gu J.
Published: May 2008

Objective   Carcinoembryonic antigen (CEA) in the serum and the tumour tissue of colorectal cancer (CRC) patients is the most commonly used tumour marker for the diagnosis and evaluation of prognosis or recurrence after treatment, but the role remains controversial. The objective of this study was to compare the prognostic value of CEA both in serum and tumour tissue in CRC.

Method  A total of 173 patients with CRC in stages I–III were retrospectively assessed with the endpoint of recurrence or metastasis after curative operation. CEA was assessed both in serum and tumour tissue.

Results  37.0% (64/173) patients had a high level of CEA in serum (S‐CEA) while 39.3% (68/173) had high CEA in tumour tissue (T‐CEA). There were no significant differences in clinico‐pathological features between the low and high S‐CEA or T‐CEA groups. The high S‐CEA group had a worse prognosis than the low S‐CEA group but the difference was not significant. The high T‐CEA group had a significantly poorer prognosis than the low T‐CEA group (P = 0.028) in the univariate analysis. The multivariate analysis demonstrated that the T‐CEA was an independent prognosis factor in CRC. Because many factors would affect the concentration of S‐CEA, there was no correlation between S‐CEA and T‐CEA directly.

Conclusion  Our study suggests that a high T‐CEA concentration may be a useful and independent predictor for poor outcome after surgery in CRC patients. It may be stronger than a high preoperative serum CEA level.
Postoperative course and long term follow up after colectomy for slow transit constipation – is surgery an appropriate approach?
Authors: Riss S. , Herbst F. , Birsan T. , Stift A.
Published: May 2008

Objective  Patients with slow transit constipation who do not respond satisfactorily to common medical treatment are considered candidates for colectomy. The present observational long term study was designed to assess outcome after surgery.

Method  Twenty consecutive patients were treated by colectomy for slow transit constipation between 1996 and 2004. Preoperative and postoperative data were reviewed by using our institutional database. A questionnaire including validated scoring systems and questions about complications and subsequent surgical interventions was sent to all available patients.

Results  Three patients (15%) died perioperatively. Median long term follow up was 84 months. Ten patients (50%) needed further operations after colectomy: Three patients (15%) had surgery during the early postoperative period, seven patients (35%) during follow up. A total of 31 operations had to be performed in these patients. Twelve patients (86%) responded to the questionnaires. Their median Wexner constipation score was 11.5 (range 8–23). Six patients fulfilled the Rome II criteria for constipation. The median Vaizey incontinence score was 7.5 (range 0–22). The median GIQLI showed 80 points (range 32–129).

Conclusion  Morbidity and mortality rate after colectomy were inadmissibly high. Taking into account the poor functional results, we cannot recommend colectomy for slow transit constipation.
Endoscopic decompression using a transanal drainage tube for acute obstruction of the rectum and left colon as a bridge to curative surgery
Authors: Xu M. , Zhong Y. , Yao L. , Xu J. , Zhou P. , Wang P. , Wang H.
Published: May 2008

Objective  The aim of this study was to clarify the usefulness of the management of acute left colon and rectum obstruction because of colorectal carcinoma using a transanal ileus drainage tube before curative surgery.

Method  Forty‐six patients (24 males and 22 females, aged 24–94 years, mean = 56.2) treated between September 2005 and March 2007 for acute left colon and rectal obstruction were identified in a colorectal obstruction database, and their clinical and radiological features were reviewed. After a cleaning enema was administered, urgent colonoscopy was performed. Subsequently, endoscopic decompression using a ileus tube was attempted.

Results  Endoscopic decompression using the ileus tube was technically successful in 45 of 46 patients (97.8%). Perforation occurred in one patient 3 days later and emergent operation was performed. The site of obstruction was the rectum in 15 patients, the sigmoid colon in 18, the descending colon in 13. Following adequate cleansing of the colon, patients’ abdominal girth were decreased from 91 ± 4 cm before drainage to 82 ± 2 cm 7 days later, and one‐stage surgery after 8 ± 1 days (SD; range 7–10 days) were performed. No anastomotic leakage or postoperative stenosis occurred after operation.

Conclusion  Management of acute left colon and rectum obstruction because of colorectal carcinoma using the ileus tube was found to be effective and safe, considered as a bridged method before curative surgery.
Abusive Supervision in Advising Relationships: Investigating the Role of Social Support
Authors: Hobman Elizabeth V. , Restubog Simon Lloyd D. , Bordia Prashant , Tang Robert L.
Published: May 2008

The present study examines the consequences of abusive supervision in an educational setting. The study contrasts the cross‐domain stress‐buffering hypothesis with the within‐domain stress exacerbation hypothesis in examining the moderating role of advisor and team member support on the relationship between abusive supervision and student outcomes in student–advisor relationships. Using a temporal research design, results provided support for both hypotheses. In support of the stress exacerbation hypothesis, in the presence of high advisor support, there was a significant positive relationship between abusive supervision and anxiety, and a significant negative association between abusive supervision and psychological well‐being. Consistent with the stress‐buffering hypothesis, in the presence of high team member support, there was a negligible association between abusive supervision and satisfaction and anxiety.
Dorothy Hodgkin Lecture 2008 Gastric inhibitory polypeptide (GIP) revisited: a new therapeutic target for obesity–diabetes?
Authors: Flatt P. R.
Published: May 2008

There is increasing realization that gastric inhibitory polypeptide (GIP) has actions outside of the pancreas and gastrointestinal tract. Most significant is the presence of functional GIP receptors on adipocytes and the appreciation that GIP, secreted strongly in response to fat ingestion, plays a role in the translation of excessive amounts of dietary fat into adipocyte tissue stores. Such effects open up the possibility of exploiting GIP receptor antagonism for the treatment of obesity and insulin resistance. This is borne out by studies in high‐fat‐fed mice or ob/ob mice with either genetic knockout of GIP receptor or chemical ablation of GIP action using the GIP receptor antagonist, (Pro3)GIP. By causing preferential oxidation of fat, blockade of GIP signalling clears triglyceride deposits from liver and muscle, thereby respectively restoring mechanisms for suppression of hepatic glucose output and cellular glucose uptake. Further studies are needed to determine the applicability of this research to human obesity–diabetes. However, proof of concept is provided by emerging evidence that rapid cure of diabetes in grossly obese subjects undergoing Roux‐en‐Y bypass surgery is mediated in part by surgical bypass of GIP‐secreting K‐cells in the upper small intestine.
Relationship between autonomic neuropathy and hypertension—are we underestimating the problem?
Authors: Istenes I. , Keresztes K. , Hermányi Z. , Putz Z. , Vargha P. , Gandhi R. , Tesfaye S. , Kempler P.
Published: May 2008

Background  Cardiac autonomic neuropathy (CAN) is associated with significant morbidity and mortality in diabetes and the risk is even greater in those with hypertension.

Aims  The aim of our study was to investigate the relationship between CAN and 24‐h blood pressure profile in normoalbuminuric patients with Type 2 diabetes mellitus.

Methods  Seventy patients with Type 2 diabetes (31 without CAN, 39 with CAN), who had no history of hypertension, and 29 healthy volunteers underwent five standard cardiovascular reflex tests to assess autonomic function and 24‐h ambulatory blood pressure monitoring.

Results  Twenty‐four‐hour mean systolic blood pressure, blood pressure load and hyperbaric impact values were significantly higher in diabetic patients with CAN compared with control subjects and diabetic patients without CAN (P < 0.05). In spite of normal clinic blood pressures, 54% of diabetic subjects with CAN and 29% without CAN were hypertensive (systolic blood pressure load > 20%, P < 0.05). In the diabetes group as a whole, Valsalva ratio, postural systolic blood pressure changes and diastolic blood pressure responses during sustained handgrip correlated significantly and negatively with 24‐h mean systolic blood pressure (P < 0.01, P < 0.001, P < 0.05) and blood pressure load (P < 0.05, P < 0.001, P < 0.05).

Conclusions  Cardiovascular autonomic neuropathy is independently associated with hypertension in normoalbuminuric Type 2 diabetic patients with no history of hypertension. Relying on clinic blood pressures in subjects with CAN could lead to a failure to diagnose hypertension in over half of cases. All normotensive patients with CAN should be screened for hypertension using ambulatory blood pressure monitoring in order to institute early aggressive interventions to improve their long‐term outlook.
Prevalence of HNF1A (MODY3) mutations in a Norwegian population (the HUNT2 Study)
Authors: Eide S. Å. , Ræder H. , Johansson S. , Midthjell K. , Søvik O. , Njølstad P. R. , Molven A.
Published: May 2008

Aims  Previous reports have indicated that maturity‐onset diabetes of the young (MODY) caused by hepatocyte nuclear factor 1A (HNF1A) mutations (MODY3) is the most common MODY subtype in Northern Europe, but population‐based prevalence estimates are lacking. We sought to determine the prevalence of HNF1A‐MODY in diabetic subjects of a defined Norwegian population (the HUNT2 Study).

Methods  Of the 1972 diabetic HUNT2 subjects, we identified a subgroup of 43 suspected MODY cases based on information on family history, disease onset and anti‐glutamic acid decarboxylase autoantibody status. These cases were considered a discovery group for HNF1A mutations and underwent full DNA sequencing. Subsequently, the entire cohort of diabetic HUNT2 subjects was screened for three selected HNF1A mutations. Possible founder effects were examined using the Norwegian MODY Registry.

Results  Three subjects from the discovery group harboured HNF1A mutations. Two subjects had the previously described R229Q mutation, one had a novel S6N alteration, whereas the HNF1A hot‐spot mutation P291fsinsC was not identified. Genotyping the cohort of diabetic HUNT2 subjects identified five additional R229Q‐positive subjects. Microsatellite analysis performed for all R229Q‐positive probands of the Norwegian MODY Registry and those found in the HUNT2 population revealed that 17 of 18 (94%) had genotypes consistent with a common haplotype.

Conclusions  Clinical MODY criteria were fulfilled in 2.2% of diabetic HUNT2 subjects. The minimum prevalence of HNF1A‐MODY among diabetic HUNT2 subjects was 0.4%. Because of founder effects, registry‐based prevalence studies probably need to be very large and they should also include prospectively collected phenotypes and extensive mutation screening to establish the true prevalence of MODY.
Psychological distress and risk of pre‐diabetes and Type 2 diabetes in a prospective study of Swedish middle‐aged men and women
Authors: Eriksson A.‐K. , Ekbom A. , Granath F. , Hilding A. , Efendic S. , Östenson C.‐G.
Published: May 2008

Aims  To determine the role of psychological distress as a predictor of pre‐diabetes and Type 2 diabetes.

Methods  This cohort study comprised 2127 Swedish middle‐aged men and 3100 women with baseline normal glucose tolerance measured by oral glucose tolerance test. At follow‐up 8–10 years later, 245 men and 177 women had pre‐diabetes [impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and IFG + IGT] and Type 2 diabetes was detected in 103 men and 57 women. Baseline psychological distress was measured by an index of five questions concerning anxiety, apathy, depression, fatigue and insomnia. Odds ratios (ORs) were estimated for pre‐diabetes and Type 2 diabetes in association with total psychological distress. In addition, ORs of the single‐item questions were calculated.

Results  In men, adjusted ORs (95% confidence interval) in the highest index group of psychological distress compared with the lowest group were 1.9 (1.2–2.8) and 2.2 (1.2–4.1) for pre‐diabetes and Type 2 diabetes, respectively. Corresponding estimates in women were 1.2 (0.7–2.1) and 0.5 (0.2–1.2). In the middle symptoms groups, adjusted ORs in men were 1.1 (0.8–1.4) for pre‐diabetes and 1.2 (0.7–2.0) for Type 2 diabetes and in women 1.8 (1.1–3.0) and 0.7 (0.3–1.4). When analysed separately, the associations with each of the five single factors were similar.

Conclusions  The results indicate that psychological distress, including symptoms of anxiety, apathy, depression, fatigue and insomnia, increases the risk of pre‐diabetes and Type 2 diabetes in Swedish middle‐aged men. Increased risks were not present in women, except for pre‐diabetes in the middle index group.
Can complement factors 5 and 8 and transthyretin be used as biomarkers for MODY 1 (HNF4A‐MODY) and MODY 3 (HNF1A‐MODY)?
Authors: Karlsson E. , Shaat N. , Groop L.
Published: May 2008

Aims  Genetic testing is needed for the formal diagnosis of maturity‐onset diabetes of the young (MODY), but this is not widely available. If any MODY biomarkers were known, these could possibly be used as an alternative. Hepatocyte nuclear factor (HNF)‐1α and HNF‐4α regulate transcription of genes encoding complement 5 (C5), complement 8 (C8) and transthyretin (TTR), suggesting that these could be potential biomarkers for the disease. We therefore set out to determine whether serum concentrations of C5, C8 and TTR can be used as biomarkers for patients with HNF4A‐MODY and HNF1A‐MODY.

Methods  The serum concentrations of C5, C8 and TTR were analysed in patients with mutations in the HNF‐1α (n = 29) and ΗΝF‐4α (n = 13) genes. Type 2 diabetic (n = 14) and healthy subjects (n = 20), matched for body mass index (BMI), served as diabetic and non‐diabetic control groups, respectively.

Results  Type 2 diabetic patients had markedly increased levels of C5 and C8 compared with healthy control subjects. Levels of C5 and C8 correlated with glycated haemoglobin (C5: r = 0.48, P = 0.019). After adjustment for BMI, glycated haemoglobin, age and gender, HNF4A‐MODY and HNF1A patients had reduced levels of C5 and C8 compared with Type 2 diabetic patients (C5: P = 0.001; C8: P = 0.004). In addition, patients with HNF4A‐MODY, but not those with HNF1A‐MODY, had decreased TTR compared with diabetic patients (P = 0.038).

Conclusions  Serum concentrations of C5 and C8 seem to distinguish HNF4A and HNF1A‐MODY from other forms of diabetes. However, hyperglycaemia per se increases the serum concentrations, thereby attenuating their potential role as biomarkers for MODY.
A New Era for Think Tanks in Public Policy? International Trends, Australian Realities
Authors: Hart Paul 't , Vromen Ariadne
Published: May 2008

Although the powerful have always sought advice from the knowledgeable, it took the appeal of the policy sciences movement of the late 1940s and onward to build and consolidate a veritable industry of policy analysis and advice.1One of the hallmarks of this development was the advent of institutes that were exclusively devoted to produce research‐based policy arguments and to inject these into the policy‐making process. These organisations were referred to as ‘think tanks’. Half a century later, the project of the policy sciences movement has been amply criticised, and has mutated into various philosophies of policy analysis, each harbouring distinct and often conflicting perspectives on the nature and role of (scientific) knowledge in the battle of arguments that is public policy‐making. The first wave of the policy sciences movement's privileging of science‐based policy has not disappeared. In fact it is currently experiencing a revival under the banner of ‘evidence‐based policy’. But it has to compete with other views of public policy‐making which deconstruct the authority claim of scientific knowledge, emphasising instead its contestability. Yet there are now more organisations that refer to themselves, or can be labelled, as ‘think tanks’ than ever before. Why? And what does it mean to be a ‘think tank’ in the post‐positivist era and in the increasingly boundary‐less, highly networked societies of today? This article first surveys recent developments in the world of think tanks as reported by the international literature on the subject, and then examines the implications for understanding the nature and role of Australian think tanks.
Gender Analysis and Community Consultation: The Role of Women's Policy Units
Authors: Osborne Katy , Bacchi Carol , Mackenzie Catherine
Published: May 2008

Community consultation has become a widely accepted part of policy development in Australia. In this article, we consider how, in an Australian context, consultation can be incorporated within gender analysis processes. Gender analysis refers to systematic procedures to detect and correct gender bias in the full range of government programs, projects and policies. We draw upon insights from a qualitative case study to argue that policy workers located within women's policy units could play a key role in designing and coordinating meaningful and inclusive consultation. We conclude that well‐resourced women's policy offices within Australian governments are essential to ensuring effective, equitable consultation exercises are included within gender analysis processes.
Cooperative Federalism?: The Case of the Ministerial Council on Education, Employment, Training and Youth Affairs
Authors: Jones Stephen
Published: May 2008

New Federalism reforms introduced in Australia in the early 1990s were expected to improve efficiency and reduce duplication through new cooperative intergovernmental arrangements. The reforms were also an attempt to reduce the continuing trend of Commonwealth intrusion in state powers. As well as establishing the Council of Australian Governments (COAG), the reforms created the Ministerial Council on Education, Employment, Training and Youth Affairs (MCEETYA) to promote a more coordinated and cooperative approach to the delivery of education. MCEETYA provides the quintessential example of the difficulties of establishing a national approach when the function, education, is squarely within the power of the states. This article investigates the operation of MCEETYA from its inception to 2006.
The Impact of Enterprise Size on Employment Tribunal Incidence and Outcomes: Evidence from Britain
Authors: Saridakis George , Sen‐Gupta Sukanya , Edwards Paul , Storey David J.
Published: May 2008

Employment Tribunals are the formal means of adjudicating disputes over individual employment rights in the UK. This article hypothesizes that, because small firms favour informality over formality, they are more likely (i) to experience employee claims than large firms; (ii) to be subject to different types of claims; (iii) to settle prior to reaching a formal Tribunal; and (iv) to lose at a Tribunal. Data from the 2003 Survey of Employment Tribunal Applications are used to examine these hypotheses. They are generally supported, although in relation to the third there was no size effect. Furthermore, our results show that firms that have procedures and follow them are more likely to win than those firms that do not have any procedures. Recognizing the benefits of informality, while also ensuring that small firms follow proper standards of procedural fairness, is a policy dilemma that has yet to be resolved.
Knowledge, Legitimation and the Politics of Risk: The Functions of Research in Public Debates on Migration
Authors: Boswell Christina
Published: May 2008

There is a striking lack of research on the utilisation of expert knowledge in public policy debates and party political mobilisation. Existing contributions in related fields of scholarship generate rather contradictory expectations. On the one hand, political communications literature points to the dumbing down of political debate, implying a limited role for expert knowledge. On the other hand, a number of prominent sociologists have noted the centrality of science in political debate on the politics of risk. This article suggests that the two theses are not necessarily incompatible. For knowledge to be reported in the media, it clearly needs to conform to criteria of novelty, drama and scandal, but scientific findings can and often do meet these criteria, especially in areas of risk, where there is enormous potential to scandalise government actions or omissions. The article illustrates these tendencies through an analysis of the use of expert knowledge in UK debates on migration from 2002 to 2004. It explores how research was used in parliamentary debates, speeches and newspaper coverage of three prominent episodes in the politics of migration. The examples demonstrate well how the mass media utilises research to expose political scandal. The analysis also suggests the ambivalence of political actors and especially incumbents in drawing on research. While governments are keen to utilise research to legitimise policies, they are also aware of the limitations of science in underpinning risky decisions. The article concludes with a discussion of how politics has responded to this dilemma.
Making Justice Sensitive to Responsibility
Authors: Stemplowska Zofia
Published: May 2008

When, if at all, can the fact that a person is responsible for his or her disadvantage justify leaving him or her to bear that disadvantage? Possibly no other question has caused more controversy among political theorists of egalitarianism in the last two decades. This article aims to show that it is possible to move beyond the answer to this question that is usually (rightly or wrongly) attributed to luck egalitarians without accepting the conclusion that a concern with responsibility is only marginal to theories of egalitarian justice. I identify the conditions under which disadvantage brought about through the exercise of responsibility should be accepted as just and show why egalitarians concerned with fair shares must sometimes accept as just even grave disadvantages.