bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of smoking cessation, acute re‐exposure and nicotine replacement in smokers on AIR® inhaled insulin pharmacokinetics and glucodynamics
Authors: Pan Alan X. , De La Peña Amparo , Yeo Kwee P. , Chan Clark , Loh Mei T. , Wise Stephen D. , Silverman Bernard L. , Muchmore Douglas B.
Published: October 2007

What is already known about this subject

• Only one other study (Becker et al.) has reported on the influence of smoking cessation and smoking resumption on inhaled insulin pharmacokinetics and glucodynamics, concluding that the rapid changes associated with smoking resumption carry the risk for hypoglycaemia and thus should not be used by active smokers.

What this study adds

• This is the first euglycaemic clamp study on the impact of smoking cessation, acute smoking re‐exposure and nicotine replacement on AIR® inhaled insulin pharmacokinetics and glucodynamics.

• We demonstrate clinically and statistically significant shifts in glucodynamic response to acute re‐exposure to a single cigarette, leading us to conclude that active smokers should be advised against inhaled insulin therapy until smoking abstinence is stable.

• Additionally, these results are also the first to demonstrate an apparent independent effect of nicotine replacement therapy on insulin exposure and glucodynamic response.

Aims

To explore the effects of smoking cessation and acute smoking re‐exposure on the pharmacokinetic (PK) and glucodynamic (GD) profiles of AIR® inhaled insulin (AIR Insulin) with or without nicotine replacement therapy (NRT).

Methods

Nondiabetic smokers (n = 24) with normal pulmonary function completed a two‐phase (four‐period), open‐label, randomized euglycaemic clamp study. During the initial study phase, subjects underwent glucose clamps following AIR Insulin dosing, shortly after smoking, 8–12 h after smoking, or following subcutaneous insulin lispro shortly after smoking. AIR Insulin PK and GD were again assessed during and after a 4‐week smoking‐cessation period with or without NRT. In the last study period, subjects smoked one cigarette shortly before final AIR Insulin dosing and glucose clamp, to study the effect of acute smoking re‐exposure on inhaled insulin PK and GD.

Results

Compared with the preceding active smoking phase, the administration of AIR Insulin in nondiabetic subjects undergoing a 4‐week period of smoking abstinence resulted in a decrease in PK and GD of approximately 25% (P = 0.008 for both), an effect which was greater in subjects using NRT. Following rechallenge with a single cigarette (without NRT), GD response to AIR Insulin increased significantly (P = 0.006) towards precessation levels, relative to smoking abstinence. In subjects using NRT, however, the increase in GD was less pronounced.

Conclusion

Smoking, smoking cessation and acute re‐exposure with a single cigarette are associated with clinically significant alterations in AIR Insulin pharmacokinetics and glucodynamics. AIR Insulin should not be used by smokers or those at risk for recidivism.
Chronic lymphocytic leukaemia and radiation: findings among workers at five US nuclear facilities and a review of the recent literature
Authors: Schubauer‐Berigan Mary K. , Daniels Robert D. , Fleming Donald A. , Markey Andrea M. , Couch James R. , Ahrenholz Steven H. , Burphy Jenneh S. , Anderson Jeri L. , Tseng Chih‐Yu
Published: October 2007

The aetiology of chronic lymphocytic leukaemia (CLL) is largely unknown. Despite compelling evidence for ionising radiation as a cause of most forms of leukaemia, CLL was not found to be radiogenic in early studies. Herein we describe the recent evidence for causation of CLL by ionising and non‐ionising radiation, including a nested case‐control study conducted within a cohort of 94 517 US workers at four nuclear weapons facilities and a nuclear naval shipyard. Forty‐three cases of CLL deaths and 172 age‐matched controls were identified with follow‐up up to between 1990 and 1996. Radiation exposure from external sources and plutonium (lagged 10 years) was assessed for each worker, based on monitoring records. The excess relative rate (ERR) was estimated for workers receiving elevated doses compared to unexposed workers, controlling for possible risk factors. The ERR per 10 mSv was −0·020 (95% confidence interval: <0, 0·14) based on all exposed workers. However, for workers receiving <100 mSv, the ERR per 10 mSv was 0·20 (−0·035, 0·96). Recent studies of uranium miners and other populations have shown elevations of CLL possibly associated with ionising and non‐ionising radiation. New studies should use incident cases and sufficient latency to account for the expected lengthy induction period for CLL.
TRAIL signals to apoptosis in chronic lymphocytic leukaemia cells primarily through TRAIL‐R1 whereas cross‐linked agonistic TRAIL‐R2 antibodies facilitate signalling via TRAIL‐R2
Authors: Natoni Alessandro , MacFarlane Marion , Inoue Satoshi , Walewska Renata , Majid Aneela , Knee Deborah , Stover David R. , Dyer Martin J. S. , Cohen Gerald M.
Published: October 2007

Tumour necrosis factor (TNF)‐related apoptosis‐inducing ligand (TRAIL), a member of the TNF family, which is being developed as an anti‐tumour agent due to its selective toxicity to tumour cells, induces apoptosis by binding to two membrane‐bound receptors, TRAIL‐R1 and TRAIL‐R2. Clinical trials have been initiated with various preparations of TRAIL as well as agonistic monoclonal antibodies to TRAIL‐R1 and TRAIL‐R2. Previously we reported that prior treatment of primary chronic lymphocytic leukaemia (CLL) cells with histone deacetylase inhibitors was required to sensitize CLL cells to TRAIL and, using various receptor‐selective TRAIL mutant ligands, we demonstrated that CLL cells signalled to apoptosis primarily through TRAIL‐R1. Some, but not all, agonistic TRAIL‐receptor antibodies require cross‐linking in order to induce apoptosis. The present study demonstrated that CLL cells can signal to apoptosis through the TRAIL‐R2 receptor, but only after cross‐linking of the agonistic TRAIL‐R2 antibodies, LBY135 and lexatumumab (HGS‐ETR2). In contrast, signalling through TRAIL‐R1 by receptor‐selective ligands or certain agonistic antibodies, such as mapatumumab (HGS‐ETR1), occurs in the absence of cross‐linking. These results further highlight important differences in apoptotic signalling triggered through TRAIL‐R1 and TRAIL‐R2 in primary tumour cells. Such information is clearly important for the rational optimisation of TRAIL therapy in primary lymphoid malignancies, such as CLL.
Increasing trend in atopy markers prevalence in a Croatian adult population between 1985 and 1999
Authors: Macan J. , Varnai V. M. , Maloča I. , Kanceljak‐Macan B.
Published: October 2007

Background
Reports about the increasing prevalence of atopy and atopic diseases are common, but recently they have been critically reviewed and the need for relevant research methods has been established.

Objectives
This study evaluated a 15‐year trend in the prevalence of atopy markers [elevated total IgE, positive skin prick test (SPT) to common aeroallergens and positive atopic symptoms] in Croatian adults, separately for women and men.

Methods
The study included 721 subjects (445 men and 276 women), 18–45 years old, examined for allergies within a pre‐employment preventive examination. All subjects underwent medical history, SPT with common inhalatory allergens and total serum IgE measurement. The trend analysis of atopy prevalence was performed after stratification of subjects into three consecutive 5‐year periods from 1985 to1999.

Results
The prevalence of concurrently elevated total IgE and positive atopic symptoms significantly increased during the studied period in men [odds ratio (OR) 2.44, 95% confidence interval (CI) 1.39–4.29, P=0.002]. Women showed an increased prevalence of positive SPT only, with borderline significance (OR 1.65, 95% CI 1.00–2.71, P=0.050). In women, rural residence was found to be a predictor of elevated total IgE (OR 5.36, 95% CI 2.41–11.93, P=0.000) and smoking to be a predictor of concurrently elevated total IgE and positive SPT (OR 6.20, 95% CI 1.67–23.07, P=0.006).

Conclusions
An increasing trend in the prevalence of concurrently elevated total IgE and positive atopic symptoms was found in the Croatian adult male population between 1985 and 1999, but not in the female population. Sex differences responsible for the production and regulation of IgE were suggested.
Radioiodine therapy after pretreatment with bexarotene for metastases of differentiated thyroid carcinoma
Authors: Liu Ying Y. , Stokkel Marcel P. , Morreau Hans A. , Pereira Alberto M. , Romijn Johannes A. , Smit Johannes W. A.
Published: October 2007

Objective  To evaluate the effects of pretreatment with the retinoid X receptor (RXR) agonist bexarotene on the efficacy of radioiodine therapy for metastases of differentiated thyroid carcinoma (DTC) with limited uptake of radioiodine (I‐131).

Design  An open prospective intervention study.

Methods  Eight patients with metastases of DTC, with insufficient uptake of I‐131 who showed increased uptake of radioiodine after previous treatment with bexarotene were treated with radioiodine (7400 MBq), preceded by 6 weeks of treatment with bexarotene 300 mg/day. Outcome parameters were serum thyroglobulin (Tg) levels and dimensions of metastases at computed tomography (CT), measured before and 6 months after therapy. Tissues of primary tumours were stained with antibodies against retinoic acid receptor (RAR) and RXR subtypes.

Results  Bexarotene pretreatment induced radioiodine uptake in metastases in all eight patients, although uptake was only discernable at single photon emission computed tomography (SPECT) and had incomplete matching with the metastases visualized by CT scanning. Six months after radioiodine therapy, six patients had progressive disease (defined as a > 10% increase in serum Tg and/or a > 25% increase in tumour dimensions), whereas two patients had stable disease. No relationship was observed between retinoid receptor staining pattern at immunohistochemistry and the outcome of therapy.

Conclusions  Bexarotene therapy did not result in restoration of susceptibility to radioiodine therapy.
Retinol‐binding protein in nonobese women with polycystic ovary syndrome
Authors: Lee Ji‐Won , Im Jee‐Aee , Lee Duk‐Chul , Lee Hye‐Ree , Shim Jae‐Yong
Published: October 2007

Objective  Although polycystic ovary syndrome (PCOS) is frequently associated with insulin resistance, cardiovascular disease and various metabolic diseases, the mechanisms linking PCOS to metabolic changes are not fully understood. Retinol‐binding protein (RBP) was recently reported as an adipocytokine that may link insulin resistance and lipid metabolism. The aim of this study was to investigate the potential role of RBP in women with PCOS.

Research design and methods  Fifty women with PCOS and 40 healthy women, all of whom were age‐ and weight‐matched, were studied. Blood was obtained to determine RBP levels as well as metabolic and hormonal parameters, and the homeostasis model assessment of insulin resistance (HOMA‐IR) was calculated for each subject.

Results  The RBP levels were higher (P < 0·01) in women with PCOS after adjusting for age, body mass index (BMI), mean blood pressure, triglyceride (TG), high density lipoprotein (HDL)‐cholesterol, low density lipoprotein (LDL)‐cholesterol, fasting glucose, fasting insulin, estimated glomerular filtration rate (GFR), LH/FSH, total testosterone and SHBG levels. PCOS status was the strongest predictor of elevated RBP levels. In both the PCOS and control groups, RBP levels were significantly correlated with HOMA‐IR (P = 0·03 in the PCOS group; P = 0·01 in controls). In addition, RBP levels were significantly correlated with total cholesterol, LDL‐cholesterol and TG levels in PCOS (P < 0·01, P < 0·01 and P = 0·01, respectively).

Conclusions  Higher RBP levels in the PCOS group, when compared to the non‐PCOS group, were observed, and this difference may play a role in the pathophysiology found in women with PCOS. Further studies are needed to clarify the role of RBP in these women.
Up‐regulation of SOX9 in human sex‐determining region on the Y chromosome (SRY)‐negative XX males
Authors: Kojima Yoshiyuki , Hayashi Yutaro , Mizuno Kentaro , Sasaki Shoichi , Fukui Yuko , Koopman Peter , Morohashi Ken‐Ichiro , Kohri Kenjiro
Published: October 2007

Background  In mammals, gonadal sex is normally determined by the presence or absence of the Y chromosome gene SRY. After expression of SRY in the sexually indifferent gonad, a number of genes encoding transcription factors and growth factors implicated in testis differentiation start to show male‐specific expression. However, in XX males, these genes must be up‐regulated in the absence of SRY, but the aetiology of SRY‐negative XX maleness remains unclear.

Aim and methods  We examined the expression of representative gonad marker genes in SRY‐negative XX male testes.

Results  RT‐PCR and immunohistochemical studies revealed that SOX9, DAX‐1, Ad4BP/SF‐1, WT‐1, GATA‐4 and MIS were expressed in testicular tissues of SRY‐negative XX males. Expression levels of SOX9 in testes of these patients averaged 1·9‐fold higher than in normal XY testes, while expression levels of Ad4BP/SF‐1, DAX‐1 and MIS were lower in the SRY‐negative XX testes than in XY testes. All XX patients were found to carry two copies of the SOX9 gene per diploid genome as do normal XX females and XY males. The XX male patients also carried two copies of the DAX‐1 gene as do normal XX females, while normal XY males carry a single DAX‐1 gene.

Conclusions  Our data suggest that lesions affecting SOX9 expression are the key factor in sex determination in SRY‐negative XX males, and that the decreased expression of Ad4BP/SF‐1, DAX‐1 and MIS contribute to their clinical features.
Myb proteins regulate expression of histone variant H2A.Z during thymocyte development
Authors: Hooper Joel , Maurice Diane , Argent‐Katwala Mary J. G. , Weston Kathleen
Published: October 2007

The c‐myb gene encodes a transcription factor required for the normal development of T cells in the thymus, and for subsequent peripheral T‐cell activation and survival. However, the profile of genes known to be transcriptionally regulated by c‐Myb in T cells does not adequately explain the pleiotrophic nature of the effects of c‐Myb. We present here a detailed molecular characterization of the regulation of a novel target gene, the histone variant H2A.Z. We show that c‐Myb is able to bind to and activate the H2A.Z promoter in T cells both in vitro and in vivo, and present evidence that perturbation of Myb activity during T‐cell development results in reduced H2A.Z expression. As H2A.Z is absolutely required for the early stages of mammalian development, and plays essential roles in the regulation of chromatin structure in gene promoters in yeast, its regulation by c‐Myb is likely to be of some importance during T‐cell development.
Neuropeptides activate human mast cell degranulation and chemokine production
Authors: Kulka Marianna , Sheen Cecilia H. , Tancowny Brian P. , Grammer Leslie C. , Schleimer Robert P.
Published: October 2007

During neuronal‐induced inflammation, mast cells may respond to stimuli such as neuropeptides in an FcεRI‐independent manner. In this study, we characterized human mast cell responses to substance P (SP), nerve growth factor (NGF), calcitonin gene‐related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) and compared these responses to human mast cell responses to immunoglobulin E (IgE)/anti‐IgE and compound 48/80. Primary cultured mast cells, generated from CD34+progenitors in the presence of stem cell factor and interleukin‐6 (IL‐6), and human cultured mast cells (LAD2) were stimulated with these and other stimuli (gastrin, concanavalin A, radiocontrast media, and mannitol) and their degranulation and chemokine production was assessed. VIP and SP stimulated primary human mast cells and LAD cells to degranulate; gastrin, concanavalin A, radiocontrast media, mannitol, CGRP and NGF did not activate degranulation. While anti‐IgE stimulation did not induce significant production of chemokines, stimulation with VIP, SP or compound 48/80 potently induced production of monocyte chemoattractant protein‐1, inducible protein‐10, monokine induced by interferon‐γ (MIG), RANTES (regulated on activation, normal, T‐cell expressed, and secreted) and IL‐8. VIP, SP and compound 48/80 also activated release of tumour necrosis factor, IL‐3 and granulocyte–macrophage colony‐stimulating factor, but not IL‐4, interferon‐γ or eotaxin. Human mast cells expressed surface neurokinin 1 receptor (NK1R), NK2R, NK3R and VIP receptor type 2 (VPAC2) but not VPAC1 and activation of human mast cells by IgE/anti‐IgE up‐regulated expression of VPAC2, NK2R, and NK3R. These studies demonstrate the pattern of receptor expression and activation of mast cell by a host of G‐protein coupled receptor ligands and suggest that SP and VIP activate a unique signalling pathway in human mast cells. These results are likely to have direct relevance to neuronally induced inflammatory diseases.
Quantitative method for pheromone delivery in studies of sensory adaptation of moth antennae
Authors: TRIMBLE R. M. , MARSHALL D. B.
Published: October 2007

Abstract A pheromone sprayer and an electroantennogram (EAG) are used to study sensory adaptation in the antennae of male obliquebanded leafrollers, Choristoneura rosaceana and oriental fruit moths, Grapholita molesta, to the main pheromone compounds (Z)‐11‐tetradecen‐1‐yl acetate (Z11‐14:Ac) and (Z)‐8‐dodecen‐1‐yl acetate (Z8‐12:Ac), respectively. The atomization of 0.125, 0.25, 0.5 or 1 μL ethanol min−1 into the EAG air delivery tube at an airflow rate of 2 L min−1, with resultant concentrations of 6.25, 12.5, 25 or 50 × 10−5μL ethanol mL air−1, respectively, does not affect the EAG response of C. rosaceana or C. molesta after a 30‐min exposure period. The atomization of 0.125 μL min−1 of a solution of 8 mg Z11‐14:Ac mL−1 ethanol into the EAG air delivery tube at an airflow rate of 2 L min−1, with a resultant concentration of 0.5 ng pheromone mL−1 air, reduces the EAG response of C. rosaceana by approximately 70% after a 15‐min exposure period. An additional 15 min of exposure to pheromone does not result in increased sensory adaptation. Antennae recover 32% of the lost responsiveness when exposed to pheromone‐free air for 15 min. The atomization of 0.125 μL min−1 of a solution of 8 mg Z8‐12:Ac mL−1 ethanol into the EAG air delivery tube at an airflow rate of 2 L min−1, with a resultant concentration of 0.5 ng pheromone mL−1 air, reduces the EAG response of C. molesta antenna by approximately 80% after a 15‐ or 30‐min exposure period. The antennae of this species do not recover responsiveness when exposed to pheromone‐free air for 15 min.
Pliocene extensional tectonics in the Eastern Central Patagonian Cordillera: geochronological constraints and new field evidence
Authors: Lagabrielle Yves , Suárez Manuel , Malavieille Jacques , Morata Diego , Espinoza Felipe , Maury René C. , Scalabrino Bruno , Barbero Luis , Cruz Rita de la , Rossello Eduardo , Bellon Hervé
Published: October 2007

Recent field work and review of radiometric data obtained from Neogene lavas and plutonic rocks exposed in the Eastern Central Patagonian Cordillera (46–48ºS), which overlie subducted segments of the South Chile Ridge, suggest important Late Miocene to Pleistocene morphological changes in relation to base level variations and/or tectonic events. We present new field observations from a region south of Lago General Carrera‐Buenos Aires, between the main Cordillera and the Meseta del Lago Buenos Aires, demonstrating that normal faulting controlled valley incisions and occurred during lava emplacement at 5–4 Ma and after 3 Ma. We also show that the 12 Ma basaltic flows of the Meseta del Lago Buenos Aires (∼2000 m a.s.l.) have been subjected to deep incision, with younger lavas dated at 1.2 Ma partially filling the valleys. These incisions are thought to reflect progressive eastward tilting of the entire meseta. Our new observations, together with additional features from Central Patagonia, strongly suggest that tectonic events led to a regional widespread morphological change after 5 Ma. The coincidence in time and space between the subduction of segments of the South Chile Ridge at 6 and 3 Ma causing opening of a slab window, and strong base level variations in the studied area, suggests a cause‐and‐effect relationship. In Central Patagonia, compressional tectonics ended well before extensional events reported here. Causes of uplift and further extension are probably completely disconnected. The uplift is purely tectonic in origin and occurred prior to the subduction of the South Chile Ridge. Extension should be a consequence of this subduction.
Effects of differentially fermentable carbohydrates on the microbial fermentation profile of the gastrointestinal tract of broilers
Authors: Rehman H. , Böhm J. , Zentek J.
Published: October 2007

The objective of the present study was to evaluate the effects of dietary inulin and sucrose on the fermentation profile of the gastrointestinal microflora in chicken. Day‐old broilers (n = 80) were assigned to four dietary treatments, either fed a basal diet or the same diet supplemented with sucrose (4%), inulin (1%) or sucrose and inulin. At day 35, birds were killed and pH, lactate, ammonia, short chain fatty acids (SCFA) and biogenic amines were determined in different parts of the digestive tract. Final body weights and the relative weights of liver, pancreas, crop, gizzard and small intestine were not influenced by treatment. The relative weights of the empty caeca and of the caecal digesta were higher with the diets containing inulin while caecal pH and ammonia were reduced. Lactate concentration was reduced in the crop (p ≤ 0.01) and gizzard (p ≤ 0.001) of sucrose‐fed groups, while it was increased (p ≤ 0.01) in the jejunum of inulin‐fed group. Ammonia in the crop (p = 0.089) and gizzard (p = 0.067) tended to be lower in the group receiving inulin plus sucrose. Amongst SCFA, only acetate was detected in the crop and gizzard contents that tended to be lower (p = 0.09) in the crop digesta of sucrose plus inulin‐fed group. N‐butyrate (mol %) was higher (p ≤ 0.001) in the caecal digesta of inulin‐supplemented groups without affecting total SCFA. Dietary inulin elevated the concentration of putrescine in the jejunal and caecal contents. In the caecal digesta, total biogenic amines were increased (p ≤ 0.001) in sucrose plus inulin‐fed group without affecting production of biogenic amines in the jejunum. In conclusion, inulin could reduce the pH in the lower gastrointestinal tract of broilers, while sucrose had no acidifying influence in the upper digestive tract. Inulin enhanced the concentration or metabolic activity of butyrate‐producing bacteria in the caecum. Further studies are needed to investigate the potential effect of inulin on the intestinal microbial composition.
Pretransplant laparoscopic nephrectomy in adult polycystic kidney disease: a single centre experience
Authors: Desai Mahesh R. , Nandkishore S. K. , Ganpule Arvind , Thimmegowda Manohar
Published: October 2007

OBJECTIVE

To report our experience with pretransplant laparoscopic nephrectomy in patients with autosomal dominant polycystic kidney disease (ADPKD), as ADPKD often progresses to end‐stage renal disease and most azotaemic patients with ADPKD have enlarged kidneys, making graft placement difficult.

MATERIAL AND METHODS

We retrospectively reviewed the medical records of 13 patients with renal failure attributable to ADPKD who underwent pretransplant laparoscopic nephrectomy (21 renal units) from August 2002 to December 2006. Five patients had a unilateral nephrectomy, seven had a staged bilateral nephrectomy, and one had a simultaneous bilateral nephrectomy. All patients underwent subsequent living‐related renal transplantation. The operative duration, haemoglobin decrease, blood transfusion, hospital stay, analgesic requirement and time to receipt of a transplant were compared with those of patients who underwent open pretransplant nephrectomy (14 patients) from 1984 to 2001.

RESULTS

Kidneys of a size to interfere with graft placement were the commonest indication for surgery (eight patients). In comparison with open surgery, the mean (sd) hospital stay at 9.26 (2.9) vs 4.86 (0.9) days, analgesic requirement at 320 (120) vs 221 (120.5) mg of tramadol, blood transfusion rate at 1.3 (0.5) vs 0.9 (0.6) units, period to receive a graft kidney at 29.77 (4.6) vs 9.14 (3.38) days, were significantly less with laparoscopy. The complications noted were single instances of splenic capsular tear, pleural tear, sub‐acute intestinal obstruction and vena caval injury.

CONCLUSION

Pretransplant laparoscopic nephrectomy in patients with ADPKD has all the benefits of minimally invasive surgery such as reduced intraoperative blood loss and minimal postoperative pain leading to early and faster convalescence. These benefits help in decreasing the period between nephrectomy and transplantation. The surgeon needs to have considerable experience in laparoscopy before embarking on laparoscopic pretransplant nephrectomy.
Urethral substitution using autologous lingual mucosal grafts: an experimental study
Authors: Song Lu‐Jie , Xu Yue‐Min , Hu Xiao‐Yong , Zhang Hui‐Zhen
Published: October 2007

OBJECTIVE

To investigate the feasibility of urethral substitution using free lingual mucosa grafts (LMGs) in a dog model.

MATERIALS AND METHODS

The study included 10 female mongrel dogs in which a 4 × 1 cm2 section of urethral mucosa was excised. The defect was immediately repaired with a size‐matched free LMG harvested from the inferior lateral surface of the tongue. A 12 F urethral catheter was kept inside the urethra for a mean of 7 days. At 3 months after the procedure, the patency of the urethra was assessed by both insertion of a 12 F catheter and by retrograde urethrography. Dogs were killed, the grafted areas excised, and evaluated by gross and histopathological examination.

RESULTS

All dogs survived the procedure and there were no tongue complications. One of the 10 dogs developed a slight urethral stricture near the proximal anastomosis. The remaining nine dogs voided spontaneously with no difficulty. Retrograde urethrography showed that no strictures or fistulas had formed. The LMGs shortened by 9.5% after surgery, from a mean (sd) of 4 (0.13) to 3.62 (0.11) cm (statistically significant, P < 0.05). Histological examination showed that the LMGs were well‐incorporated into the urethral walls and covered by a keratinized squamous epithelium. Neovascularization was evident beneath the grafts.

CONCLUSION

We successfully developed an dog model for free LMGs and showed the feasibility of this approach for urethral substitution.
Computer‐aided ultrasonography (HistoScanning): a novel technology for locating and characterizing prostate cancer
Authors: Braeckman Johan , Autier Philippe , Garbar Christian , Marichal Miriam Pipeleers , Soviany Cristina , Nir Rina , Nir Dror , Michielsen Dirk , Bleiberg Harry , Egevad Lars , Emberton Mark
Published: October 2007

OBJECTIVE

To assess the extent to which prostate HistoScanningTM (PHS), a new ultrasound‐based technology that uses computer‐aided analysis to quantify tissue disorganization induced by malignant processes, can identify and characterize foci of prostate cancer compared with step‐sectioned radical prostatectomy (RP) specimens.

PATIENTS AND METHODS

Between September 2004 and February 2006, 29 men had PHS before their scheduled RP. A three‐dimensional ultrasound raw‐data file was acquired, and PHS analysed regions of interest (ROI) corresponding to tissue volumes of ≈ 0.04 mL. In 13 men the histology was examined on sections of the whole‐mount prostate onto which a grid of 5 × 5 mm squares was applied. On a test set of 14 of the 29 patients, PHS analysis was used before knowing the histology results (blinded data), to predict the maximum tumour diameter, focality, laterality and extraprostatic extension (EPE).

RESULTS

Identification and characterization by PHS of the index tumour in the 14 patients in the test set correlated closely (r = 0.95, P < 0.001) with the reference test. The concordance in the attribution of multifocality (present/absent), unilateral/bilateral disease between PHS and histology was 100%. EPE as determined by PHS was attributed to all three pT3a pathological specimens in the blinded paired data. In the same set of data, EPE was attributed to one prostate cancer that on pathological inspection was deemed to be organ‐confined (pT2b).

CONCLUSIONS

PHS has the potential to identify and characterize prostate cancer foci noninvasively. The precision appears to be sufficient to suggest that PHS might be useful as a triage test for men deemed to be at risk of prostate cancer and who wish to avoid prostate biopsy.
Prevalence of renal cysts in a Middle‐Eastern population: an evaluation of characteristics and risk factors
Authors: Mosharafa Ashraf A.
Published: October 2007

OBJECTIVE

To assess the prevalence of renal cysts in a large Middle‐Eastern population presenting for a health‐screening programme, evaluating cyst characteristics and risk factors for their development.

PATIENTS AND METHODS

The reported prevalence of renal cysts detected by ultrasonography (US) in the general population is 5.0–20.8%, and their development has been linked to several factors. The electronic charts of 8551 patients (from eight nations, predominantly Egypt and Yemen) presenting for the ‘check‐up’ programme at the author’s institution during 2005 were retrospectively reviewed. The presence and characteristics of renal cysts on abdominal US were noted, as were any associated renal pathologies. Various risk factors were evaluated for renal cyst development, i.e. age, gender, hypertension, diabetes mellitus and serum creatinine levels, and hyperlipidaemia and a history of bilharziasis were also assessed.

RESULTS

The prevalence of renal cysts was 4.2%, ranging from 0.6% for patients in their third decade, to a third of those aged >80 years. Cysts were detected in 4.8% of men and 2.8% of women (P < 0.001). The mean serum creatinine level was 1.02 mg/dL in those with cysts and 0.88 mg/dL in those without (P < 0.001). On univariate analysis, hypertension, diabetes and hyperlipidaemia had a significant influence on the occurrence of renal cysts, but not in the multivariate model. Of the 361 patients with renal cysts, 58 (16.1%) had bilateral and 26 (7.2%) had multiple unilateral cysts, with a mean (range) size of 26 (4–104) mm. The vast majority of cysts were classified as Bosniak I simple cysts; seven were Bosniak II and there was one Bosniak IV cyst. Associated renal pathologies included renal stones in 39 patients, hydronephrosis in nine, increased parenchymal echogenicity in 18, small atrophic kidneys in three, haematuria (not associated with other imaging abnormalities) in six, and a renal mass in one patient.

CONCLUSIONS

The prevalence of renal cysts detected by US in a health‐screened population from the Middle East was 4.2%. Increasing age, male gender and a higher serum creatinine level were significant independent risk factors for cyst development. There was also a relatively high prevalence of associated renal pathologies (increased parenchymal echogenicity and stones).
Secondary hormonal therapy for prostate cancer: what lies on the horizon?
Authors: Sharifi Nima , Dahut William L. , Figg William D.
Published: October 2007

Androgen deprivation therapy with medical or surgical castration is generally the first‐line treatment against advanced prostate cancer. Almost invariably, metastatic prostate cancer overcomes testosterone depletion and grows, despite castrate levels of testosterone. Despite advances in cytotoxic chemotherapy, secondary hormonal therapies are often used after the development of castrate‐resistant prostate cancer. Secondary hormonal therapies either lower the androgen levels further or directly antagonize the androgen receptor in prostate cancer cells. We discuss novel secondary hormonal agents that are under development, which work by either inhibiting androgen synthesis or directly targeting the androgen receptor.
Glucose transporter‐1 expression in renal cell carcinoma and its correlation with hypoxia inducible factor‐1α
Authors: Lidgren Anders , Bergh Anders , Grankvist Kjell , Rasmuson Torgny , Ljungberg Börje
Published: October 2007

OBJECTIVE

To evaluate transcription factor hypoxia inducible factor‐1α (HIF‐1α) activity, by analysing a target gene for HIF‐1α, glucose transporter‐1 (GLUT‐1), using a tissue microarray (TMA) in different types of renal cell carcinoma (RCC, a tumour with a variable clinical course, partly due to angiogenic activity), as angiogenesis is important for tumour progression and metastatic spread, and is activated by hypoxia.

PATIENTS AND METHODS

GLUT‐1 and HIF‐1α expressions were semiquantitatively analysed using immunohistological staining of a prepared TMA, using samples from 187 patients, including 148 with conventional, 26 with papillary and 13 with chromophobe RCC.

RESULTS

GLUT‐1 staining was found mainly in the cytoplasm. The tumours were subdivided into GLUT −1LOW and GLUT‐1HIGH, based on staining intensity. There was a significant difference in GLUT‐1 expression between RCC types (P < 0.05). In conventional RCC, GLUT‐1 had no correlation with clinicopathological variables. By contrast there was a correlation with tumour stage in papillary RCC. There was an insignificant trend to better survival of patients with GLUT‐1LOW expression in both conventional and papillary RCC. GLUT‐1 correlated significantly (P = 0.008) with HIF‐1α.

CONCLUSIONS

Most patients with conventional RCC had GLUT‐1HIGH staining and there was a significant correlation with HIF‐1α. In papillary RCC, GLUT‐1 expression was associated with stage; GLUT‐1 expression was significantly higher in conventional RCC than in papillary and chromophobe RCC. GLUT‐1LOW in both papillary and conventional RCC appeared to correspond with a better prognosis.
FOURNIER'S Gangrene: The Development Of A Classical Pathology
Authors: Verit Ayhan , Verit Fatma Ferda
Published: October 2007

Necrotizing fasciitis, especially when termed Fournier’s gangrene (FG) when it initiates at the perineum, is a rare but rapidly progressive subcutaneous tissue infection characterized by extensive necrosis. Although it has been known for more than a century and considered as a cause of death, the basic medical principles have not changed for many years. We discuss what is new in the evaluation of this enigmatic pathology and speculate about its clinical metamorphosis. We reviewed reports of FG in the English language. The clinical characteristics of FG have been changing; atypical locations of necrotizing fasciitis, e.g. in the head and neck, and the incidence of patients with FG but no predisposing factors, has been increasing. While the role of anaerobic bacteria in FG is decreasing, that of atypical organisms is increasing, and thus hyperbaric oxygen therapy will probably cease to be a common treatment. We think that FG will not be as likely to cause death in future.
Prognostic significance of altered p120ctn expression in bladder cancer
Authors: Neto Brasil Silva , Smith Gjanje L. , Mandeville Jessica A. , Vanni Alex J. , Wotkowicz Chad , Rieger‐Christ Kimberly M. , Baumgart Egbert , Jacobs Micah A. , Cohen Michael S. , Zeheb Ron , Loda Massimo , Libertino John A. , Summerhayes Ian C.
Published: October 2007

OBJECTIVE

To identify the frequency of change in the expression and localization of p120ctn in bladder tumours and its association with clinical outcomes, and to investigate the potential role of p120ctn in the migratory and invasive behaviour of bladder carcinoma cells.

MATERIALS AND METHODS

In all, 425 superficial tumour specimens (Ta, Tis and T1) and 305 invasive (T2–T4) tumour specimens from 534 patients were assembled in 10 tissue microarrays. P120ctn immunostaining was scored for intensity and cellular localization and correlated with clinical variables and survival analysis. Knockdown of p120ctn was achieved using small‐interference RNA (siRNA) followed by the assessment of migration and invasion behaviour in standard in vitro assays.

RESULTS

The expression levels of p120 catenin inversely correlated with pathological tumour stage (P < 0.001), histological grade (P < 0.001), presence of lymphovascular invasion (P = 0.02) but not lymph node (LN) involvement (P = 0.17). Non‐membranous localization of p120ctn correlated with stage (P < 0.001), grade (P < 0.001), lymphovascular invasion (P = 0.04) and LN‐positive disease (P = 0.02). A low expression level of p120ctn was linked to a poor outcome in cancer‐specific survival analysis. Knockdown of p120ctn using siRNA resulted in a significant reduction in the migration and invasive potential of bladder carcinoma cells.

CONCLUSIONS

Our findings suggest that p120ctn acts as a prognostic factor in bladder tumours and has a primary role to play in the migratory and invasive behaviour of bladder carcinoma cells.
Trauma to male genital organs: a 10‐year review of 156 patients, including 118 treated by surgery
Authors: Lee Sung Hoon , Bak Chong Won , Choi Min Ho , Lee Han Sae , Lee Min Sung , Yoon Sang Jin
Published: October 2007

OBJECTIVE

To assess testicular rupture, scrotal haematoma, penile fracture and penile injury, comparing the prognoses of surgery and conservative management, as trauma to male external genital organs can cause devastating effects on patients and their partners.

PATIENTS AND METHODS

We reviewed the medical records of 156 male patients who presented to our emergency centre with trauma to the external genital organs between January 1996 and March 2006.

RESULTS

In all, 74 patients had testicular rupture, 32 penile fracture, 26 a penile injury and 24 a scrotal haematoma (mean age 27.8 years). The main cause of trauma was assault (52, 33%). Four of 14 patients with penile trauma who were managed conservatively had complications. Of 20 patients, 17 had a partial orchidectomy and were followed for a month after surgery; scrotal ultrasonography showed three cases of testicular atrophy. The mean hospital stay was less for patients with surgical intervention, at 6.4 days, than for those managed conservatively, at 8.7 days (P < 0.05). A visual analogue pain scale showed less pain in patients who were surgically treated (P < 0.05).

CONCLUSION

Prompt surgical intervention is crucial; it should be considered by urologists, and is strongly recommended. Ultrasonography was highly sensitive and specific, and should be used in all patients with trauma to the external genital organs, to aid diagnosis and evaluation before surgery.
Can non‐malignant biopsy features identify men at increased risk of biopsy‐detectable prostate cancer at re‐screening after 4 years?
Authors: Wolters Tineke , Roobol Monique J. , Schröder Fritz H. , Van Der Kwast Theodorus H. , Roemeling Stijn , Van Der Cruijsen‐Koeter Ingrid W. , Bangma Chris H. , Van Leenders Geert J.L.H. ,   (ERSPC Rotterdam section)
Published: October 2007

OBJECTIVES

To identify pathological features in non‐malignant sextant prostate needle biopsies and assess their predictive value for detecting prostate cancer on biopsy 4 years later.

PATIENTS AND METHODS

We selected and reviewed the biopsy specimens of 121 men that were diagnosed as non‐malignant during the first screening round of the European Randomized Study of Screening for Prostate Cancer (ERSPC), Rotterdam section. Of these 61 (50.4%) were positive for cancer during the second round (the result of a matched random sample). The biopsies were indicated by prostate‐specific antigen levels of ≥ 3.0 ng/mL. Specimens were scored for high‐grade prostatic intraepithelial neoplasia (HGPIN), active and chronic inflammation, biopsy core length and glandular core length. The predictive value of the pathological features for detecting prostate cancer after 4 years was assessed.

RESULTS

In the first‐round biopsies the incidence of HGPIN was 7.1%; there was active inflammation in 22.4% and chronic inflammation in 51.0%. The mean core length was 9.3 mm and mean glandular core length 7.4 mm; the mean total biopsy length (sum of core lengths) was 56.3 mm and mean total glandular length (sum of glandular core lengths) was 44.6 mm. None of the pathological features in the initial round was significantly related to the detection of cancer in the second round.

CONCLUSIONS

In this study of non‐malignant prostate biopsy specimens from a screened population, no pathological features could be identified that were predictive for detecting prostate cancer on biopsy 4 years later.
Impact of prostate‐specific antigen testing on the clinical and pathological outcomes after radical prostatectomy for Gleason 8–10 cancers
Authors: Boorjian Stephen A. , Karnes R. Jeffrey , Rangel Laureano J. , Bergstralh Eric J. , Frank Igor , Blute Michael L.
Published: October 2007

OBJECTIVE

To investigate whether the clinical and pathological outcomes after radical retropubic prostatectomy (RRP) have changed since the advent of prostate‐specific antigen (PSA) testing for patients with Gleason 8–10 cancers.

PATIENTS AND METHODS

We identified 584 men treated with RRP between 1988 and 2001 for pathological Gleason 8–10 tumours. Patients were divided for analysis by year of surgery, i.e. early (1988–93), mid (1994–97) and late PSA era (1998–2001). Survival rates after RRP were estimated using the Kaplan‐Meier method, and the effect of clinicopathological factors on outcome was analysed using Cox proportional hazard regression models.

RESULTS

The median preoperative PSA level decreased from 15 ng/mL in the early to 10 ng/mL in the late PSA era (P < 0.001), while the rate of organ‐confined disease increased from 22.9% to 35.1% (P = 0.007). However, the 7‐year biochemical recurrence‐free (37% vs 45%, P = 0.087) and cancer‐specific survival (89% to 91%, P = 0.73) did not change significantly from the early to the late PSA era. Increased preoperative PSA level (P < 0.001), seminal vesicle invasion (P < 0.001) and positive lymph nodes (P = 0.02) were associated with biochemical recurrence. Seminal vesicle invasion (P = 0.005), positive nodes (P < 0.001) and positive surgical margins (P = 0.03) predicted death from cancer.

CONCLUSION

Although the pathological features of Gleason 8–10 cancers have become more favourable over the PSA era, survival has not changed. This lack of improvement in clinical outcome probably reflects the inherent biological aggressiveness of these cancers. While RRP provides long‐term cancer control in a subset of these patients, continued investigation of multi‐modal treatment options is warranted.
STATE‐LEVEL BASIC WAGES IN AUSTRALIA DURING THE DEPRESSION, 1929–35: INSTITUTIONS AND POLITICS OVER MARKETS
Authors: Sheldon Peter
Published: October 2007

State wage‐fixation tribunals developed quite particular patterns of basic wage fixation during the Depression. They declined to follow the Commonwealth Court's 10 per cent wage cut, thereby confining its effect to about half the workforce and creating distinctly different State and Commonwealth basic wage patterns in each capital city. Further, tribunals' uneven patterns of basic wage adjustment to deflation meant that in some states, the real State basic wage increased. Patterns of state institutional behaviour and state politics therefore help explain the stickiness of real average wage levels during the Depression.
BIG QUESTIONS IN AUSTRALIAN ECONOMIC HISTORY: FROM THE OUTSIDE LOOKING IN1
Authors: Dick Howard
Published: October 2007

The conventional story of Australian economic history is worth challenging. Rather than just assuming a national economy with conventional turning points such as Federation, economic historians would do well to investigate more complex processes like the interplay between regions, races and development, and the changing patterns of interaction with the outside world. The big question for economic historians is whether in the future they can undertake economic research which informs history and so contributes to the national debate.
Redistributive Taxation under Ethical Behaviour*
Authors: Boadway Robin , Marceau Nicolas , Mongrain Steeve
Published: October 2007

We consider the implications of ethical behaviour on the effect of a redistributive tax‐transfer system. In choosing their labour supplies, individuals take into account whether their tax liabilities correspond to what they view as ethically acceptable. If tax liabilities are viewed as ethically acceptable, a taxpayer behaves ethically, does not distort her behaviour, and chooses to work as if she were not taxed. On the other hand, if ethical behaviour results in tax liabilities that exceed those that are ethically acceptable, she behaves egoistically (partially or fully), distorts her behaviour, and chooses her labour supply taking into account the income tax. We establish taxpayers' equilibrium behaviour and obtain that labour supply is less elastic when taxpayers may behave ethically than when they act egoistically. We characterise and compare the egoistic voting equilibrium linear tax schedules under potentially ethical and egoistic behaviour. We also compare our results to those obtained under altruism, an alternative benchmark.
Comparisons of regression constants fitted by maximum likelihood to four common transformations of binomial data*
Authors: NAYLOR A. F.
Published: October 2007

An electronic computer was used to fit regression constants of arcsine, logit, log‐log and inverse normal (probit) transforms of binomial data. The data ranged over a variety of types, biologically and mathematically, but were ‘complex’(with several independent variables). This empirical study leads one to assume, very unequivocally, that there is no practical difference in analyses using these four transformations.

I thank Drs Daphne Trasler and Dorothy Warburton for permission to quote unpublished data and the McGill Computing Centre for advice and assistance.
Genetic studies of the syndrome of congenital deafness and simple goitre
Authors: THOULD A. K. , SCOWEN E. F.
Published: October 2007

Twenty‐six pedigrees containing thirty examples of the syndrome of congenital deafness and sporadic goitre are presented. Evidence is put forward to support our conclusion that the mode of inheritance is that of a recessive character. There were insufficient data, due to the small numbers involved, for us to obtain any significant evidence of linkage to the ABO blood groups and other marker genes.

We would like to thank Dr C. F. Harris for enabling us to investigate family no. 22, and Dr H. W. Balme for family no. 20. Thanks are also due to the Biochemical, Haematological, Isotope and Statistical Departments of St Bartholomew's Hospital for their assistance. Particularly, we would like to thank Professor H. Harris for his help and advice.