bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of Lactobacillus casei rhamnosus Lcr35 in restoring the normal vaginal flora after antibiotic treatment of bacterial vaginosis
Authors: Petricevic L , Witt A
Published: October 2008

Objective  To evaluate the efficacy of additional topical Lactobacillus casei rhamnosus (Lcr35) subsequent to antibiotic treatment of bacterial vaginosis (BV) to restore the normal vaginal flora.

Study design  Single‐centre, randomised, observerblinded study.

Setting  Population‐based study in Vienna over 1 year.

Sample  190 women were enrolled in the study.

Methods  Women with Nugent scores between 7 and 10 on initial vaginal swab were randomised to the one of two groups. All women were treated with standard antibiotic therapy for 7 days. Only women in the intervention group received vaginal capsules containing 109 colony‐forming units of live Lcr35 for 7 days after antibiotic treatment. Final vaginal swabs for Nugent scoring were taken 4 weeks after the last administration of the study medication.

Main outcome measures  The primary efficacy variable was a change in the Nugent score between the baseline and the end of the study of at least 5 grades in each individual woman.

Results  Sixty‐nine of the 83 women (83%) in the intervention group and 31 of the 88 women (35%) in the control group showed a reduction of the Nugent score by at least 5 grades. The difference in the number of women with improvement was highly significant (P < 0.001). The median difference in Nugent scores between initial and final swabs was 6.61 in the intervention group and 4.13 in the control group (P < 0.001).

Conclusion  Our data show that the restoration of the vaginal flora after antibiotic treatment of BV can be significantly enhanced by exogenously applied lactobacilli.
Placental protein 13 as an early marker for pre‐eclampsia: a prospective longitudinal study*
Authors: Gonen R , Shahar R , Grimpel YI , Chefetz I , Sammar M , Meiri H , Gibor Y
Published: October 2008

Objective  To assess the value of placental protein 13 (PP13) as an early marker of pre‐eclampsia.

Design  Sequential blood samples were obtained from women with singleton viable pregnancies at 6–10, 16–20 and 24–28 weeks of gestation. Samples were tested for PP13 using a solid‐phase sandwich enzyme‐linked immunosorbent assay. Levels were expressed as multiples of the medians (MoM) of the unaffected population. The slope or rate of change in PP13 concentration per week of gestation was also calculated.

Setting  Thirty‐five prenatal care community clinics.

Sample  In total, 1366 women were recruited, and subsequently, 20 were diagnosed with pre‐eclampsia, 41 with gestational hypertension and 1178 were unaffected.

Main outcome measures  Sensitivity and specificity of screening with PP13 at each gestational period and of PP13 level combined with the slope of PP13 between two testing periods.

Results  At 6–10 gestational weeks, PP13 levels were significantly lower among the pre‐eclampsia group with a median 0.28 MoM (95% CI 0.15–0.39, P < 0.004). Using a cutoff of 0.40 MoM, the sensitivity was 80%, false‐positive rate (FPR) was 20% and odds ratio was 16.0 (95% CI 5.3–48.4). Combining MoM of 6–10 weeks and slope between 6–10 and 16–20 weeks, the sensitivity was 78%, the FPR was 6% and odds ratio was 55.5 (95% CI 18.2–169.2). The gestational hypertension group was not different from the normal group.

Conclusions  PP13 in the first trimester alone or in combination with the slope between the first and the second trimesters may be a promising marker for assessing the risk of pre‐eclampsia.
Acupuncture as an adjunct to standard treatment for pelvic girdle pain in pregnant women: randomised double‐blinded controlled trial comparing acupuncture with non‐penetrating sham acupuncture
Authors: Elden H , Fagevik‐Olsen M , Ostgaard H‐C , Stener‐Victorin E , Hagberg H
Published: October 2008

Objective  To investigate whether acupuncture has a greater treatment effect than non‐penetrating sham acupuncture in women with pelvic girdle pain (PGP) during pregnancy.

Design  Randomised double‐blinded controlled trial.

Setting  East Hospital, Gothenburg, and 25 antenatal primary care units in the region of Västra Götaland, Sweden.

Population  A total of 115 pregnant women with a clinical diagnosis of PGP who scored ≥50 on a 100‐mm visual analogue scale (VAS).

Method  Women were randomly allocated to standard treatment plus acupuncture or to standard treatment plus non‐penetrating sham acupuncture for 8 weeks.

Main outcome measures  Main outcome measure was pain. Secondary outcomes were frequency of sick leave, functional status, discomfort of PGP, health‐related quality of life and recovery of severity of PGP as assessed by the independent examiner.

Results  After treatment, median pain decreased from 66 to 36 in the acupuncture group and from 69 to 41 in the non‐penetrating sham group (P = 0.493) as assessed on a VAS. Women in the acupuncture group were in regular work to a higher extent than women in the sham group (n = 28/57 versus 16/57, P = 0.041). The acupuncture group had superior ability to perform daily activities measured with the disability rating index (DRI) (44 versus 55, P = 0.001). There were no significant differences in quality of life, discomfort of PGP and recovery from severity of PGP between the groups.

Conclusions  Acupuncture had no significant effect on pain or on the degree of sick leave compared with non‐penetrating sham acupuncture. There was some improvement in performing daily activities according to DRI. The data imply that needle penetration contributes to a limited extent to the previously reported beneficial effects of acupuncture.
Morbidity outcomes of 78 577 hysterectomies for benign reasons over 23 years
Authors: Spilsbury K , Hammond I , Bulsara M , Semmens JB
Published: October 2008

Objective  To investigate the association of the method of hysterectomy for benign reasons with morbidity outcomes in Western Australia after taking other demographic, social and health‐related factors into account.

Design  Population‐based retrospective observational study.

Setting  All hospitals in Western Australia where hysterectomies were performed from 1981 to 2003.

Population  All women aged 20 years or older who underwent a hysterectomy for benign reasons.

Method  Logistic and zero‐truncated negative binomial regression analysis of record‐linked administrative health data.

Main outcome measures  Relative odds of experiencing complications during the hysterectomy admission or readmission and relative length of stay in hospital by type of hysterectomy.

Results  There were 78 577 hysterectomies performed for benign reasons from 1981 to 2003. Procedure‐related haemorrhage (2.4%) was the most commonly recorded complication, followed by genitourinary disorders (1.9%), infection (1.6%) and urinary tract infections (1.6%). Vaginal hysterectomy was associated with reduced odds of infection and haemorrhage compared with abdominal procedures during the hysterectomy admission. Readmission rates increased from 5.4% in 1981–84 to 7.2% in 2000–03 as average length of stay decreased by 53% over the same time period. Women who underwent laparoscopically assisted vaginal hysterectomies and vaginal hysterectomies had increased odds of readmission for haemorrhage and genitourinary disorders compared with abdominal hysterectomy. Young age, increasing number of co‐morbid conditions and having a complication at hysterectomy admission were also associated with increased odds of readmission.

Conclusion  These findings identify women at risk of readmission following hysterectomy and highlight an opportunity to modify early discharge and patient follow‐up practices to reduce this risk.
Management of threatened preterm delivery in France: a national practice survey (the EVAPRIMA study)
Authors: Parant O , Maillard F , Tsatsaris V , Delattre M , Subtil D , Goffinet F ,   the EVAPRIMA Group
Published: October 2008

Objectives  To describe the management of threatened preterm delivery (TPD) in France 3 years after publication of the French guidelines and to analyse the factors of variation of the practices observed.

Design  Population‐based study.

Setting  Representative sample of French maternity units. The study included 107 hospitals, accounting for 20% of all French maternity units.

Population  Women hospitalised for TPD during May 2005.

Methods  Cross‐sectional national practice survey.

Results  Of the 734 admissions for TPD, 12.1% involved premature rupture of membranes and 12.9% were in utero transfers. Women admitted for TPD accounted for roughly 6% of all annual deliveries, regardless of the unit’s level of care, and 42.4% of these women delivered preterm: none delivered before 32 weeks in level 1 maternity units, 11.6% in level 2 and 88.4% in level 3. Transvaginal cervical ultrasound was performed for 54.5% of the women with intact membranes. Tocolysis was administered in 87.1% of women with intact membranes, with 45.6% of such women receiving this intervention for longer than 48 hours. First‐line tocolytics used were calcium channel blockers (53.7%), beta‐agonists (34.7%) or atosiban (8.8%), but their distribution differed substantially according to level of care. Maintenance tocolysis was administered to 385 women (59.8%) with intact membranes. Of the women admitted before 34 weeks, 21.1% did not receive corticosteroids.

Conclusions  Practices for the management of TPD vary widely and appear to depend on the level of care. Some practices appear less than optimal, especially those related to duration of tocolysis, maintenance tocolysis, antenatal corticosteroid and use of cervical ultrasound.
Evidence‐based intrapartum care in Cali, Colombia: a quantitative and qualitative study
Authors: Conde‐Agudelo A , Rosas‐Bermudez A , Gülmezoglu AM
Published: October 2008

Objectives  To measure the rate of use of selected intrapartum obstetric practices and to explore the factors associated with their use.

Design  Prospective quantitative and qualitative study.

Setting  Fifteen public and private hospitals in Cali, Colombia.

Sample  Quantitative arm: 1767 low‐risk women delivering a single live baby; qualitative arm: 36 intrapartum care providers.

Methods  Quantitative analysis of women’s clinical charts for measuring the rates of obstetric practices. Qualitative analysis of audiotaped semi‐structured interviews with intrapartum care providers.

Main outcome measures  Rates of use of ten intrapartum obstetric practices and associated factors and intrapartum care providers’ views on evidence‐based obstetric practice.

Results  Rates for the ineffective practices of enema use, perineal/pubic shaving, and routine intravenous infusion during labour were around 75%. Episiotomy rates for primiparae and multiparae were 70 and 22%, respectively. Rates for the beneficial practices of active management of the third stage of labour and allowing women’s choice of position during the first stage of labour were around 45%. Companionship during labour, external cephalic version for breech presentation at term, and absorbable synthetic sutures for episiotomy showed rates of utilisation lower than 15%. Hospital characteristics, type of intrapartum care provider, and women’s medical insurance status were associated with use of selected practices. Barriers and opportunities for implementing evidence‐based practices in routine obstetric care were identified.

Conclusions  Intrapartum care in Cali, Colombia, is not guided by the best available evidence. Effective change strategies should be undertaken to encourage the adoption of obstetric practices clearly demonstrated as effective and to discard those that are ineffective.
Trends in maternal obesity and associated risks of adverse pregnancy outcomes in a population of Chinese women
Authors: Leung TY , Leung TN , Sahota DS , Chan OK , Chan LW , Fung TY , Lau TK
Published: October 2008

Objective  To assess the effect of increasing body mass index (BMI) on pregnancy outcome in a population of Chinese women.

Design  A retrospective study.

Setting  A university teaching hospital.

Population  Women delivering singleton babies between 1995 and 2005 who sought antenatal care before 20 weeks of gestation.

Methods  A total of 29 303 women were categorised into six BMI groups according to WHO’s classification. Univariate, multivariate and logistic regression analysis were performed to compare obstetric and perinatal outcomes between BMI groups.

Main outcome measures  Incidences of caesarean delivery, pre‐eclampsia, gestational diabetes, preterm delivery, small for gestational age (SGA) and large for gestational age (LGA), perinatal death, and the respective odd ratios in reference to the normal group with BMI ≥ 18.5 kg/m2 and <23 kg/m2.

Results  The median BMI increased with increasing maternal age, parity, gestation at the first visit, but decreased with year of delivery (P < 0.001). Concerning the obstetric outcomes, increasing BMI was associated with increasing incidence of caesarean section, pre‐eclampsia, gestational diabetes, preterm delivery, LGA, as well as SGA according to customised growth standards (P < 0.001). The odds ratios for most of these adverse outcomes are higher than those reported in Caucasian population. Increasing BMI was not associated with the rate of stillbirth, neonatal death or shoulder dystocia.

Conclusion  Increasing BMI is associated with increased risks of adverse obstetric outcomes. The impacts of high BMI on pre‐eclampsia, gestational diabetes and preterm delivery in Chinese women might be stronger than that in Caucasian. Hence, it may be appropriate to use a lower BMI cutoff for defining overweight in Chinese.
Does Low to Moderate Alcohol Intake Protect Against Cognitive Decline in Older People?
Authors: Stott David J. , Falconer Alison , Kerr Gillian D. , Murray Heather M. , Trompet Stella , Westendorp Rudi G. J. , Buckley Brendan , De Craen Anton J. M. , Sattar Naveed , Ford Ian
Published: October 2008

OBJECTIVES: To determine whether low to moderate alcohol intake is protective against cognitive decline in older people.

DESIGN: Prospective cohort study.

SETTING: Community‐based study in Ireland, the Netherlands, and Scotland.

PARTICIPANTS: Five thousand eight hundred four people (3,000 women) aged 70 to 82 and randomized to pravastatin or placebo in the Prospective Study of Pravastatin in the Elderly at Risk.

MEASUREMENTS: Alcohol consumption was determined at study baseline. Serial measures of cognitive function over 3.2 years mean follow‐up included Mini‐Mental‐State‐Examination (MMSE), speed of information processing (Stroop and Letter‐Digit Coding tests), and immediate and delayed memory (Picture‐Word Learning test).

RESULTS: Forty‐two percent of women and 71% of men were alcohol drinkers. Cognitive performance was better for female drinkers than nondrinkers for all cognitive domains over the 3.2‐year follow‐up; no significant effects were seen for men (linear mixed model, including adjusting for possible confounders). The rate of cognitive decline was similar for drinkers and nondrinkers for all cognitive domains, except for MMSE, which declined significantly less in female drinkers than nondrinkers (linear mixed model attenuated rate of decline=0.05 MMSE units per annum, P=.001).

CONCLUSION: Drinking low to moderate amounts of alcohol may delay age‐associated cognitive decline in older women (including slowing deterioration in global cognitive function), but these apparent benefits were not clearly seen in older men.
Voting by Mail: Turnout and Institutional Reform in Oregon*
Authors: Richey Sean
Published: October 2008

Objectives.I test the impact of Oregon's vote‐by‐mail system on voter turnout.

Methods.To determine the impact, I create a cross‐sectional time‐series regression model of state turnout in presidential elections from 1980 to 2004 and mid‐term elections from 1982 to 2006.

Results.I find that Oregon's turnout increases by around 10 percentage points of registered voters in both presidential and mid‐term elections due to the voting‐by‐mail reform.

Conclusions.These results suggest that one of the reasons that the United States has comparatively lower turnout is due to its more onerous voting procedures.
Diapause incidence of progeny in relation to parental geographic origin, host plant and rearing density in the cabbage beetle, Colaphellus bowringi
Authors: Lai Xi‐Ting , Yang Dong , Wu Shao‐Hui , Zhu Xing‐Fen , Xue Fang‐Sen
Published: October 2008

The cabbage beetle, Colaphellus bowringi Baly (Coleoptera: Chrysomelidae), which is widely distributed in China, undergoes an imaginal diapause in the soil. In this study, we investigated the influences of parental geographic origin, host plant, and rearing density on the diapause incidence of progeny in this beetle. In studies conducted at 25 °C and L12:D12 photoperiod, the proportions of adults entering diapause were significantly different among latitudes from which the parents had been collected. The incidence of diapause increased with increasing latitude. Reciprocal cross tests between post‐diapause adults from different latitudes showed that there were significant differences in diapause incidence between pure‐bred and hybrid adults, suggesting that diapause incidence among progeny was determined by both the female and male, although the female appeared to have a stronger effect than the male. These results revealed that parental origin has an important influence on progeny diapause. Parental host plant species not only affected diapause incidence of the current generation, but also affected the incidence of diapause in the progeny produced by the non‐diapause parents; yet, the parental host plant had no influence on the incidence of diapause in the progeny produced by the post‐diapause parents. Rearing density of the parental generation had no significant effect on the incidence of diapause in the progeny.
Caveolin‐1 is transported to multi‐vesicular bodies after albumin‐induced endocytosis of caveolae in HepG2 cells
Authors: Botos E. , Klumperman J. , Oorschot V. , Ígyártó B. , Magyar A. , Oláh M. , Kiss A. L.
Published: October 2008

Caveolae‐mediated endocytosis is a highly regulated endocytic pathway that exists in parallel to other forms of clathrin‐dependent and ‐independent endocytosis. Internalized caveolae accumulate in intermediate organelles called caveosomes. Here we addressed the further fate of internalized caveolae by inducing caveolae‐mediated uptake of albumin by HepG2 cells. We followed the route of internalized caveolin‐1 by immunogold labelling of ultrathin frozen sections and by Western blot analyses of purified membrane fractions. Long‐term (1 and 3 hrs) albumin treatment resulted in the appearance of albumin‐containing caveolae in special multi‐caveolar complexes (consisting of multiple caveolae clustered together) connected to the plasma membrane and caveosome‐like structures in the cytoplasm. In addition, numerous CD63 (LIMP‐1) positive late endosomes/multi‐vesicular bodies were found positive for caveolin‐1, suggesting that upon albumin incubation, caveolin‐1 is endocytosed and enters the degradative pathway. Surprisingly, the number of caveolae at the plasma membrane increased after addition of albumin. This increase was blocked by cycloheximide treatment, indicating that albumin internalization also stimulates de novo protein synthesis, which is necessary for new caveolae formation. Together, our results show that during long‐term albumin uptake, caveolin‐1 travels to late endosomes and is replaced by newly synthesized caveolin‐1 at the plasma membrane.
Epidermal growth factor increases insulin secretion and lowers blood glucose in diabetic mice
Authors: Lee H. Y. , Yea K. , Kim J. , Lee B. D. , Chae Y. C. , Kim H. S. , Lee D.‐W. , Kim S.‐H. , Cho J.‐H. , Jin C. J. , Koh D.‐S. , Park K. S. , Suh P.‐G. , Ryu S. H.
Published: October 2008

Epidermal growth factor (EGF) is synthesized in the pancreas and diabetic animals have low levels of EGF. However, the role of EGF in regulating the major function of the pancreas, insulin secretion, has not been studied. Here, we show that EGF rapidly increased insulin secretion in mouse pancreatic islets, as well as in a pancreatic β‐cell line. These events were dependent on a Ca2+influx and phospholipase D (PLD) activity, particularly PLD2, as determined using pharmacological blockers and molecular manipulations such as over‐expression and siRNA of PLD isozymes. In addition, EGF also increased plasma insulin levels and mediated glucose lowering in normal and diabetic mice. Here, for the first time, we provide evidence that EGF is a novel secretagogue that regulates plasma glucose levels and a candidate for the development of therapeutics for diabetes.
The ginsenoside metabolite compound K, a novel agonist of glucocorticoid receptor, induces tolerance to endotoxin‐induced lethal shock
Authors: Yang Chul‐Su , Ko Sung‐Ryong , Cho Byung‐Goo , Shin Dong‐Min , Yuk Jae‐Min , Li Shengjin , Kim Jin‐Man , Evans Ronald M. , Jung Jun‐Sub , Song Dong‐Keun , Jo Eun‐Kyeong
Published: October 2008

Compound K (C‐K), a protopanaxadiol ginsenoside metabolite, was previously shown to have immunomodulatory effects. Here, we describe a novel therapeutic role for C‐K in the treatment of lethal sepsis through the modulation of Toll‐like receptor (TLR) 4‐associated signallingviaglucocorticoid receptor (GR) binding. In mononuclear phagocytes, C‐K significantly repressed the activation of TLR4/lipopolysaccharide (LPS)‐induced NF‐κB and mitogen‐activated protein kinases (MAPKs), as well as the secretion of pro‐inflammatory cytokines. However C‐K did not affect the TLR3‐mediated expression of interferon‐β or the nuclear translocation of IRF‐3. C‐K competed with the synthetic glucocorticoid dexamethasone for binding to GR and activated glucocorticoid responsive element (GRE)‐containing reporter plasmids in a dose‐dependent manner. In addition, the blockade of GR with either the GR antagonist RU486 or a siRNA against GR substantially reversed the anti‐inflammatory effects of C‐K. Furthermore, TLR4‐dependent repression of inflammatory response genes by C‐K was mediated through the disruption of p65/interferon regulatory factor complexes. Importantly, pre‐ or post‐treatment with C‐K significantly rescued mice from Gram‐negative bacterial LPS‐induced lethal shock by lowering their systemic inflammatory cytokine levels and by reversing the lethal sequelae of sepsis. Collectively, these results demonstrate that C‐K, as a functional ligand of GR, regulates distinct TLR4‐mediated inflammatory responses, and suggest a novel therapy for Gram‐negative septic shock.
Homocysteine up‐regulates vascular transmembrane chemokine CXCL16 and induces CXCR6+ lymphocyte recruitment in vitro and in vivo
Authors: Postea O. , Koenen R. R. , Hristov M. , Weber C. , Ludwig A.
Published: October 2008

Objective: Hyperhomocysteinemia induces endothelial dysfunction and promotes atherosclerotic vascular disease. Infiltrates of activated macrophages and lymphocytes are observed in human and experimental atherosclerotic lesions, their emigration being guided by endothelial‐leukocyte adhesion molecules and chemoattractants. The CXC‐chemokine CXCL16 functions as an adhesion molecule by interacting with its receptor (CXCR6) and also as a scavenger for oxidized low density lipoprotein (oxLDL). We investigated the modulation of CXCL16 on cultured endothelial cells (EC) and the recruitment of CXCR6+ lymphocytes in response to homocysteine (Hcy), in vitro and in vivo. Methods and Results: Hcy‐stimulated EC show a significant increase in CXCL16 mRNA and protein expression. Incubation of EC with d,l‐Hcy and l‐Hcy significantly increased CXCR6+ lymphocyte adhesion to EC while l‐Cysteine (l‐Cys) had no effect. Furthermore, EC stimulation with Hcy increased uptake of DiI‐oxLDL. An anti‐CXCL16 monoclonal antibody, antioxidants (Tiron) and PPAR‐γ agonists (Pioglitazone) considerably reduced CXCR6+ lymphocyte adhesion and uptake of DiI‐oxLDL. Upon injection in the peritoneal cavities of mice, l‐Hcy and not l‐Cys, increased the number of CXCR6+ lymphocytes, which was reduced by coinjection with Pioglitazone or anti‐human CXCL16 antibody. Conclusions: Hyperhomocysteinemia up‐regulates CXCL16 leading to increased recruitment of CXCR6+ lymphocytes and scavenging of modified lipids via a potential involvement of a PPAR‐γ‐dependent mechanism. CXCL16 may therefore contribute to the formation and progression of atherosclerotic lesions under conditions of hyperhomocysteinemia.
Genetics, epigenetics and pharmaco‐(epi)genomics in angiogenesis
Authors: Buysschaert Ian , Schmidt Thomas , Roncal Carmen , Carmeliet Peter , Lambrechts Diether
Published: October 2008

Introduction

Angiogenesis is genetically pre‐determined

Mutations causing vascular anomalies

Translocations reveal novel angiogenic genes

Single nucleotide polymorphisms shape the angio‐genome

Copy number variability affects angiogenesis

Epigenetic regulation of angiogenesis

Micromanagers of angiogenesis

Perspectives

Angiogenesis is controlled by a balance between pro‐ and anti‐angiogenic factors. Studies in mice and human beings have shown that this balance, as well as the general sensitivity of the endothelium to these factors, is genetically pre‐determined. In an effort to dissect this genetic basis, different types of genetic variability have emerged: mutations and translocations in angiogenic factors have been linked to several vascular malformations and haemangiomas, whereas SNPs have been associated with complex genetic disorders, such as cancer, neurodegeneration and diabetes. In addition, copy number alterations of angiogenic factors have been reported in several tumours. More recently, epigenetic changes caused by aberrant DNA methylation or histone acetylation of anti‐angiogenic molecules have been shown to determine angiogenesis as well. Initial studies also revealed a crucial role for microRNAs in stimulating or reducing angiogenesis. So far, most of these genetic studies have focused on tumour angiogenesis, but future research is expected to improve our understanding of how genetic variants determine angiogenesis in other diseases. Importantly, these genetic insights might also be of important clinical relevance for the use of anti‐angiogenic strategies in cancer or macular degeneration.
Homeoprotein Cdx2 and nuclear PTEN expression profiles are related to gastric cancer prognosis
Authors: BAI ZHIGANG , YE YINGJIANG , CHEN DINGBAO , SHEN DANHUA , XU FENG , CUI ZHIRONG , WANG SHAN
Published: October 2008

The aim of the study was to analyze the expression of Cdx2 and nuclear PTEN in relation to clinicopathological features of gastric cancer tissue biopsies in order to determine the value of a combined analysis of Cdx2 and nuclear PTEN expression in distinguishing histological types and prognosis of gastric cancers. The expression of Cdx2 and nuclear PTEN was studied using immunohistochemistry of paraffin‐embedded tumor specimens from 99 patients who underwent radical D2 gastrectomy between 1999 and 2001. Cdx2 and nuclear PTEN expression were detected in 39.6% (36 of 91) and 70.3% (64 of 91) of gastric cancer cases, respectively. There was a negative correlation between Cdx2 expression and Lauren classification (p=0.032), and between nuclear PTEN expression and lymph node metastasis (p=0.049). Patients with Cdx2‐positive, or nuclear PTEN‐positive expression had higher survival rates than those with Cdx2‐negative or nuclear PTEN‐negative expression (p<0.001 and p=0.003, respectively). Co‐expression of Cdx2 and nuclear PTEN showed significantly lower levels in diffuse‐ or mixed‐type cancers than in intestinal‐type cancers (p=0.005). Multivariate analysis revealed that Cdx2 expression was an independent prognostic indicator of gastric cancer (p=0.014). These data suggest that combined analysis of Cdx2 and nuclear PTEN expression can have significant value in distinguishing histological types of gastric cancer and assessing prognosis in patients with gastric cancer.
Multiplex PCR amplification assay for the detection of blaSHV, blaTEM and blaCTX‐M genes in Enterobacteriaceae
Authors: MONSTEIN H.‐J. , ÖSTHOLM‐BALKHED Å. , NILSSON M. V. , NILSSON M. , DORNBUSCH K. , NILSSON L. E.
Published: October 2008

Extended‐spectrum β‐lactamases (ESBLs) are often mediated by bla‐SHV, blaTEM and blaCTX‐M genes in Enterobacteriaceae and other Gram‐negative bacteria. Numerous molecular typing methods, including PCR‐based assays, have been developed for their identification. To reduce the number of PCR amplifications needed we have developed a multiplex PCR assay which detects and discriminates between bla‐SHV, blaTEM and blaCTX‐M PCR amplicons of 747, 445 and 593 bp, respectively. This multiplex PCR assay allowed the identification of bla‐SHV, blaTEM and blaCTX‐M genes in a series of clinical isolates of Enterobacteriaceae with previously characterised ESBL phenotype. The presence of blaSHV, blaTEM and blaCTX‐M genes was confirmed by partial DNA sequence analysis. Apparently, the universal well‐established CTX‐M primer pair used here to reveal plasmid‐encoded blaCTX‐M genes would also amplify the chromosomally located K‐1 enzyme gene in all Klebsiella oxytoca strains included in the study.
Primary hepatic clear cell myomelanocytic tumor
Authors: LARBCHAROENSUB NOPPADOL , KARNSOMBUT PATCHAREE , JATCHAVALA JANJIRA , WASUTIT YODYING , NITIYANANT PRAWAT
Published: October 2008

A case of hepatic clear cell myomelanocytic tumor in a 31‐year‐old woman presenting clinically with abdominal pain is reported. Histopathologic examination showed a lesion characterized by a population of large epithelioid cells with clear or eosinophilic granular cytoplasm, rich in glycogen. Immunohistochemically, the tumor cells were positive for HMB‐45, Melan‐A and muscle‐specific actin, but negative for epithelial markers, desmin, S‐100 protein, and neuroendocrine markers. Ultrastructurally, the tumor cells had abundant glycogen, well‐developed rough endoplasmic reticulum, microtubules and aberrant melanosomes. Clinical and pathologic features with a brief review of the relevant literature for hepatic CCMMT as a variant of perivascular epithelioid cell tumor (PEComa) are discussed.
Cervical intraepithelial neoplasia grade 3 lesions can regress
Authors: MUNK ANE CECILIE , KRUSE ARNOLD‐JAN , VAN DIERMEN BIANCA , JANSSEN EMIEL A. M. , SKALAND IVAR , GUDLAUGSSON EINAR , NILSEN STEIN TORE , BAAK JAN P. A.
Published: October 2008

Up to 30% of cervical intraepithelial grades 2–3 (CIN2–3) lesions regress, but some believe that “regression” is due to “curative” punch biopsies. If this is true, CIN2–3 in the resection margins of the biopsies would be associated with more frequent “persistent” CIN2–3. If, however, immunology‐related regression exists, regression would increase with increasing biopsy‐cone interval. In 61 punch biopsies diagnosed as CIN3 at careful review by two independent gynaecological pathologists, CIN3 in the resection margins and duration of the biopsy‐cone interval was evaluated in relation to CIN2–3‐or‐not in the cones (again after independent review by expert pathologists). 10 of 61 (16%) patients with CIN3 showed CIN1 or less in the follow‐up cones. CIN3‐or‐not in the resection margins, size of the lesion in the punch biopsy, and presence or absence of CIN2–3 in the cones were not correlated with regression‐or‐not. However, the number of cones without CIN2–3 increased with longer biopsy‐cone interval, 5% in patients with a punch‐cone biopsy interval under 9 weeks and 38%≥9 weeks (p<0.001). These results favour the hypothesis that CIN3 can regress, and do not support the “curative punch biopsy” theory.
Performance of Bordetella pertussis IS481 real‐time PCR in a vaccine trial setting
Authors: GULLSBY KAROLINA , HALLANDER HANS O. , BONDESON KÅRE
Published: October 2008

A real‐time PCR method targeting the Bordetella pertussis IS481 gene fragment was evaluated in a vaccine trial setting in which real‐time PCR results could be validated against culture and serology results. Two commonly used DNA extraction methods, Amplicor® Respiratory Preparation kit and the QIAamp® DNA Mini Kit, were compared. An approximately 50‐fold higher sensitivity was achieved using the Amplicor kit. 89 of 276 aspirates analysed with the IS481 real‐time PCR were positive. Interestingly, six of these were culture negative and came from serology‐negative patients. Defining true positive cases either as culture‐positive or as PCR‐positive cases that had been confirmed with a serology‐positive result or verified with a newly constructed recA PCR, the sensitivity and specificity of the IS481 real‐time PCR were 89% and 98%, respectively. This study confirms the specificity and high diagnostic sensitivity of IS481‐based PCR methods for diagnosis of B. pertussis.
Localized lymphoid hyperplasia of the rectum representing progressive transformation of the germinal center
Authors: KOJIMA MASARU , IIJIMA MISA , SHIMIZU KAZUHIKO , HOSHI KAZUE
Published: October 2008

Histologically, benign lymphoid hyperplasia (BLH) of the rectum is usually characterized by large lymphoid follicles with active germinal centers, and a narrow surrounding mantle zone and marginal zone. We present two cases of BLH of the rectum demonstrating progressive transformation of the germinal center (PTGC). The patients were 50‐ and 71‐year‐old Japanese women. Colonoscopy demonstrated small sessile polyps in both cases. The resected specimen contained numerous lymphoid follicles with active germinal centers and a portion of the lymphoid follicles exhibited PTGC. The area showing PTGC contained a few large lymphoid cells resembling lymphocytic and histiocytic Reed‐Sternberg cells of nodular lymphocyte‐predominant Hodgkin lymphoma. These PTGC contained small‐ to‐medium clusters of epithelioid cells in both cases. In situ hybridization studies demonstrated scattered Epstein‐Barr virus (EBV)‐encoded small RNA‐positive medium and large lymphoid cells and crypt epithelium in both lesions. EBV may be involved in the etiology of a subset of BLH of the rectum. However, reactivity of lymphoid cells for EBV has been reported in lymphoid tissues in a high percentage of “normal” individuals. The etiology of BLH of the rectum remains unclear.
Frequency of the basal‐like phenotype in African breast cancer
Authors: NALWOGA HAWA , ARNES JARLE B. , WABINGA HENRY , AKSLEN LARS A.
Published: October 2008

Basal‐like breast carcinoma has been recognized as a subtype with specific prognostic implications. However, there is a lack of reports about this category of breast tumors in African women. The aim of this study was to explore the basal‐like phenotype in breast cancer patients in an African population, and a registry‐based series was included from the well‐defined Kyadondo County in Uganda (1.7 millions). We studied a total of 65 archival paraffin blocks of invasive breast cancer using antibodies against cytokeratin 5/6 and P‐cadherin, and these markers were expressed in 34% of all cases and in 52% of ER (estrogen receptor)‐negative tumors. All basal‐like tumors were ER negative (p<0.0005) and PR (progesterone receptor) negative (p=0.002). Basal‐like breast carcinomas were of a higher histologic grade (p=0.001), had high mitotic counts (p=0.002), and marked nuclear pleomorphism (p=0.002). P‐cadherin‐positive tumors had a high Ki‐67 proliferative rate (p=0.039). In conclusion, the basal‐like phenotype is frequent in this African series of breast cancer and is strongly associated with poor prognostic factors. Our findings might be significant in relation to clinical management of these patients, including novel targeted therapy.
Persistent expression of an unproductive immunoglobulin heavy chain allele with DH‐JH‐γ configuration in peripheral tissues
Authors: ONO MASAO , NOSE MASATO
Published: October 2008

Genomic recombination events, including VDJ recombination (VDJR) and class‐switch recombination (CSR), are indispensable for the adaptation and progression of the acquired immune system. These processes are completed by orderly, temporal onsets of the gene rearrangements along with B‐cell differentiation. The presence of various premature transcripts of immunoglobulin heavy chain (IgH) alleles has been demonstrated during B‐cell ontogeny. These include DH‐JH (DJ)‐μ, JH‐μ, and sterile transcripts of CH. Since these transcripts can be detected during the onset of VDJR and CSR, their presence is believed to reflect a structural change in the genome, favoring VDJR and CSR. This report presents evidence of persistent DJ transcription and onset of CSR on an unproductive IgH allele in peripheral tissues. Nucleotide sequence analysis revealed that these transcripts showed DJ‐γ (Dγ) configuration and that characteristics of the variable region were essentially the same as those of the DJ‐μ transcript previously described. It was noted that the small intestine abundantly expresses Dγtranscripts with γ2b and γ1 isotypes of the IgH constant region. The present findings indicate the onset of CSR preceding VH to DJ joining in an unproductive IgH allele of the peripheral B cell and the specificity for the gut‐associated condition for B‐cell differentiation in the small intestine.
Discohesive malignant melanoma simulating a bullous dermatoses
Authors: Kartono Francisca , Shitabata Paul K. , Magro Cynthia M. , Rayhan David
Published: October 2008

A variety of clinical and histological presentations can accompany the evolution of malignant melanoma. Unusual cytological variants of malignant melanoma include balloon cell, signet ring cell, myxoid and other metaplastic changes. With the exception of a case of pemphigus‐like changes associated with malignant melanoma in paraneoplastic pemphigus, acantholysis is not a common histopathological feature of malignant melanoma. We present two unique cases of malignant melanoma with varying degrees of extensive melanocytic discohesion in an acantholytic pattern mimicking pemphigus vulgaris, further referred to in this article as ‘discohesive melanoma’. Routine direct immunofluorescence studies for pemphigus‐related antibodies (IgG and C3) were negative. In one case, indirect immunofluorescence for desmoglein autoantibodies characteristic of pemphigus were negative, although positive antibodies to desmoglein 1 was detected using immunosorbent assay. The differential diagnoses and pitfalls in recognition of this unusual presentation of malignant melanoma along with possible pathogenetic mechanisms are discussed.
Clear (pale) cell acanthosis as an incidental finding
Authors: Ko Christine J. , Subtil Antonio
Published: October 2008

Different patterns of epidermal change, including epidermolytic hyperkeratosis and acantholytic dyskeratosis, may represent the predominant histopathologic finding in several localized and generalized processes. Occasionally, minute foci of these reaction patterns are identified as an incidental finding in a biopsy taken because of the presence of some other lesion. Clear (pale) cell acanthosis may occur as the main histologic alteration in clear (pale) cell acanthoma or incidentally, such as may be seen within a seborrheic keratosis. Two cases of incidental minute foci of clear (pale) cell acanthosis are described and put into the broader context of other epidermal histologic reaction patterns.
Stereologic estimation of the total numbers, the composition and the anatomic distribution of lymphocytes in cone biopsies from patients with stage I squamous cell carcinoma of the cervix uteri
Authors: NEDERGAARD BETTINA S. , NIELSEN KARSTEN , NYENGAARD JENS RANDEL , LADEKARL MORTEN
Published: October 2008

The aim of this study was to present a method to obtain basic biological data on the in situ cellular immune response towards cancer. Using stereology, we estimated the density and frequency of immune cells of 10 different phenotypes in cone biopsies from 20 patients with FIGO stage I cervical squamous cell carcinoma. The anatomic distribution of immune cells with respect to intraepithelial, periepithelial or stromal compartments was recorded in normal epithelium, dysplastic epithelium and carcinoma. We estimated the number of immune cells per cancer cell, and the 3D total number of immune cells, inside cancer tissue. The tumor volume was estimated in 3D and corrected for shrinkage occurring during tissue processing. We found more immune cells in cancer compared to dysplasia and normal epithelia. A median total number of 278 ? 103 CD3+, 69.1 ? 103 CD4+ and 113 ? 103 CD8+ cells were present in the cancers. A median number of 63 CD3+, 11 CD4+ and 29 CD8+ cells were present per cancer cell. The average volume of tumors in stage IA was significantly smaller than that of stage IB. This method was found to be usable and of potential value in clinical pathology research, and for development and evaluation of immunotherapy.
Ethical and Public Health Considerations in HIV Counseling and Testing: Policy Implications
Authors: Yeatman Sara E.
Published: October 2008

HIV counseling and testing is broadly considered a critical component of HIV transmission‐prevention and treatment efforts. Given the severity of the AIDS pandemic in sub‐Saharan Africa, the potential societal benefit of testing is invoked to call for its massive expansion and to justify a shift from voluntary to routine testing. Surprisingly little evidence has demonstrated, however, that such a shift will result in the intended benefits to communities, particularly that of reducing the horizontal transmission of HIV. This analysis addresses and critiques the assumptions underlying a serostatus‐based approach to behavior change and discusses the ethical consequences of transferring control of the decision to be tested from the individual to the provider. It concludes with a discussion of the implications for HIV counseling and testing policies and proposes alternatives to routine testing that have the potential to be effective while preserving the right to know one's HIV status.
Natural polyphenols as proteasome modulators and their role as anti‐cancer compounds
Authors: Bonfili Laura , Cecarini Valentina , Amici Manila , Cuccioloni Massimiliano , Angeletti Mauro , Keller Jeffrey N. , Eleuteri Anna M.
Published: October 2008

The purpose of this review is to discuss the effect of natural antioxidant compounds as modulators of the 20S proteasome, a multi‐enzymatic multi‐catalytic complex present in the cytoplasm and nucleus of eukaryotic cells and involved in several cellular activities such as cell‐cycle progression, proliferation and the degradation of oxidized and damaged proteins. From this perspective, proteasome inhibition is a promising approach to anticancer therapy and such natural antioxidant effectors can be considered as potential relevant adjuvants and pharmacological models in the study of new drugs.
Knockdown of integrin β4‐induced autophagic cell death associated with P53 in A549 lung adenocarcinoma cells
Authors: He Qiuxia , Huang Bin , Zhao Jing , Zhang Yun , Zhang Shangli , Miao Junying
Published: October 2008

Integrin β4 is a tissue‐specific protein, but its role in autophagy of lung adenocarcinoma cells is not clear. In this study, we used microtubule‐associated protein 1 light chain 3 processing and acridine orange staining to reveal that knockdown of integrin β4 by its specific siRNA induced autophagic cell death in A549 lung cancer cells. Next, we investigated the effects of siRNA‐mediated downregulation of integrin β4 on cell death and the level of p53. The proportion of dead cells and level of p53 were significantly increased. Inhibition of autophagy by the inhibitor 3‐methyladenine attenuated the cell death induced by integrin β4 knockdown. To further understand the relationship between p53 and integrin β4 in autophagic cell death, we inhibited the expression of integrin β4 by its specific siRNA in p53‐mutated H322 lung cancer cells. Knockdown of integrin β4 could not induce autophagic cell death in H322 cells. The data suggest that integrin β4 is implicated in and associated with p53 in autophagy of lung cancer cells.
Implementation of a guideline for computed tomography head imaging in head injury: A prospective study
Authors: Fong Christina , Chong Winston , Villaneuva Elmer , Segal Ahuva Yocheved
Published: October 2008

Objective:  To improve appropriate ordering of head computed tomography (CT) in patients presenting with a head injury by applying an evidence‐based head injury guideline.

Methods:  This was a comparison observational study of CT head ordering in the setting of head trauma between two groups of patients. There was a pre‐guideline implementation group and a post‐guideline implementation group. Our Southernhealth Head Injury Guideline was largely based on the Canadian CT Head Rule by Steill et al. 2001.We also applied the Canadian CT Head Rule to our post‐guideline implementation group.

Results:  CT ordering rate in the pre‐guideline group was 31.6% compared with 59% in the post‐guideline group with a relative risk of 1.88 (95% confidence interval [CI]: 1.56–2.27). Abnormal head CT were reported in 6.8% in the pre‐guideline group and 5% in the post‐guideline group (relative risk 0.88, 95% CI 0.44–1.51). When we applied the Canadian CT Head Rule to the prospective group, four patients with clinically significant abnormal head CT would not have been scanned. The sensitivity of the guideline was 100% (95% CI 79–100%), with a specificity of 43.22% (95% CI 37–48%) in diagnosing a significant head injury on CT.

Conclusion:  The Southernhealth Head Injury Guideline is safe and easy to apply to minor and major head injuries.
Rapid risk stratification in suspected acute coronary syndrome using serial multiple cardiac biomarkers: A pilot study
Authors: Macdonald Stephen PJ , Nagree Yusuf
Published: October 2008

Objective:  To determine the feasibility of using a biomarker panel of myoglobin, creatinine kinase MB (CK‐MB) and cardiac troponin I (cTnI) to identify patients with suspected acute coronary syndrome (ACS) who are suitable for discharge within 2 h.

Methods:  We took blood at presentation and at 2 h from patients with suspected ACS and non‐diagnostic electrocardiogram who were admitted to the ED short stay ward for serial electrocardiogram and troponin testing. We used a point‐of‐care device that gives rapid estimation of myoglobin, CK‐MB and cTnI (Triage cardiac panel). These results were compared with the results of our standard hospital cardiac troponin T assay. Patients were followed up by telephone at 30 days.

Results:  The study group comprised 100 patients (61 men) with mean age of 58 years. Six had a troponin‐positive ACS during their ED stay. One additional patient died of a myocardial infarction within the follow‐up period. The Triage panel at 2 h after presentation predicted 12‐h cardiac troponin T elevation (sensitivity 100%, negative predictive value 99%) and 30‐day events (sensitivity 86%, negative predictive value 97%). The majority of patients were ultimately suitable for discharge.

Conclusion:  Serial myoglobin, CK‐MB and cTnI have the potential to identify patients who are suitable for early discharge and outpatient work‐up. A large multicentre study is required.