bluuebunny/crossref_metadata_2025 huggingface dataset:
Catheter‐less robotic radical prostatectomy using a custom‐made synchronous anastomotic splint and vesical urinary diversion device: report of the initial series and perioperative outcomes
Authors: Tewari Ashutosh , Rao Sandhya , Mandhani Anil
Published: August 2008

OBJECTIVE

To study the feasibility of avoiding a urethral catheter after robotic radical prostatectomy by using suprapubic diversion with a urethral splint, as urethral catheterization is often a source of major discomfort and pain to the patient, and can cause more concern to the patient than the procedure; we present the outcomes of a pilot study.

PATIENTS AND METHODS

This pilot study involved 30 patients; in group 1 (the study group of 10 patients) we used a custom‐made suprapubic catheter which provided a small anastomotic splint, multiple holes for drainage and the ability to retract the splint to give a voiding trial before removing the drainage device. Group 2 was a control group of 20 patients who had standard urethral catheterization with an 18 F Silastic Foley catheter. Demographic, intraoperative and outcome data were measured and analysed. Urethral symptoms were recorded using a specially developed questionnaire.

RESULTS

The two groups were comparable in terms of age, serum prostate specific antigen level, body mass index, Gleason scores, tumour stage, operative duration, amount of bleeding, console times, anastomotic leakage and postoperative retention rates. The study group had significantly less penile shaft or tip pain and discomfort during walking or sleeping. No patient in either group had haematuria or clot retention requiring irrigation.

CONCLUSION

Urethral catheter‐less robotic radical prostatectomy is feasible. The advantages are decreased penile shaft and tip pain, and decreased patient discomfort and an earlier return of continence.
The accuracy of transrectal ultrasonography supplemented with computer‐aided ultrasonography for detecting small prostate cancers
Authors: Braeckman Johan , Autier Philippe , Soviany Cristina , Nir Rina , Nir Dror , Michielsen Dirk , Treurnicht Karien , Jarmulowicz Michael , Bleiberg Harry , Govindaraju Senthil , Emberton Mark
Published: August 2008

OBJECTIVE

To determine the extent to which computer‐aided ultrasonography of the prostate (HistoScanningTM, Advanced Medical Diagnostics, Waterloo, Belgium) can identify tumour foci that correspond to a volume of ≥0.50 mL.

PATIENTS AND METHODS

Between September 2004 and February 2006, 29 men were HistoScanned before scheduled radical prostatectomy. The three‐dimensional raw (grey‐scaled) data required for HistoScanning analysis were acquired by transrectal ultrasonography, and analysed using organ‐specific tissue‐characterization algorithms which form the core of the HistoScanning technology. The HistoScanning analysis results were compared with the histology of the whole‐mounted prostate, step‐sectioned sagittally at 5‐mm intervals, and each slide analysed by 5 × 5 mm grid analysis.

RESULTS

Of 29 patients, 13 had histology unknown to those evaluating the HistoScanning data. With 0.50 mL as the lower threshold for delineating and visualizing cancer volume, HistoScanning correctly predicted the presence of all 12 lesions that were subsequently confirmed to occupy ≥0.50 mL. In addition three lesions were predicted as being present and of ≥0.50 mL. These three lesions were subsequently confirmed to be present but were ≤0.50 mL on histopathological review. Thus, using the clinically accepted volume threshold of 0.50 mL, the sensitivity, specificity, positive and negative predictive value of HistoScanning were 12/12, 13/16 (82%), 12/15 (80%) and 12/12, respectively, for the cancer foci analysed.

CONCLUSIONS

In this preliminary study, HistoScanning accurately detected cancer foci of ≥0.50 mL; these encouraging results will need to be verified in a larger group of patients.
Auricular acupuncture: a novel treatment for vasomotor symptoms associated with luteinizing‐hormone releasing hormone agonist treatment for prostate cancer
Authors: Harding Christopher , Harris Andrea , Chadwick David
Published: August 2008

OBJECTIVES

To evaluate the role of auricular acupuncture (AA) in men receiving luteinizing‐hormone releasing hormone (LHRH) analogues for carcinoma of the prostate, as vasomotor symptoms can affect the quality of life in such men, and similar symptoms in postmenopausal women have been successfully treated with AA.

PATIENTS AND METHODS

In all, 60 consecutive patients with prostate cancer and on LHRH agonist treatment (median age 74 years, range 58–83) consented to weekly AA for 10 weeks. The validated ‘Measure Yourself Concerns and Well‐being’ questionnaire (a six‐point scale to assess symptom severity) was used to assess concerns and well‐being before and after treatment.

RESULTS

All men completed the treatment with no adverse events recorded, apart from transient exacerbation of symptoms in two men; 95% of patients reported a decrease in the severity of symptoms, from a mean 5.0 to 2.1 (Student’s t‐test, P < 0.01).

CONCLUSIONS

The symptomatic improvement was at levels comparable with that from pharmacotherapy, and cost analysis showed AA to be a viable alternative. Larger randomized studies are needed to fully evaluate AA against more conventional treatments, and these are planned.
Ureteric stents compromise stone clearance after shockwave lithotripsy for ureteric stones: results of a matched‐pair analysis
Authors: Argyropoulos Athanasios N. , Tolley David A.
Published: August 2008

OBJECTIVE

To identify the effect of the presence of a ureteric stent on the outcome of extracorporeal shockwave lithotripsy (ESWL), by comparing patients with ureteric stones with matched‐pair analysis.

PATIENTS AND METHODS

Patients undergoing ESWL with the Sonolith Vision lithotripter (Technomed Medical Systems, Vaulx‐en‐Velin, France) were identified from our prospectively maintained database. Only adult patients with a solitary, radio‐opaque, previously untreated ureteric stone were considered for further analysis. A follow‐up of ≥3 months with a plain abdominal film was used to identify residual fragments. Patients were exactly matched for gender, side, location in the ureter and size (in two dimensions, within ±2 mm). If both diameters could not be matched exactly, the size was extended to ±1 mm and then to ±2 mm of both diameters. An effort was finally made to match patients by age. The treatment outcome in terms of stone‐free rates was assessed and compared using McNemar’s test.

RESULTS

In all, 45 patients with a ureteric stent in place during ESWL were identified. The only patient who could not be adequately matched was a 40‐year‐old man with an 8 × 3 mm stone in the upper ureter. The best/closest match for age was selected. Most stones were in the upper ureter (77%); the mean stone size was 8.5 and 8.6 mm, respectively, with no statistical differences between the groups for age and size of stones (P = 0.41 and 0.86, Student’s t‐test). In 12 pairs, only patients with no stent were stone‐free, compared to two pairs where the patient with a stent was stone‐free. Using McNemar’s test, the odds ratio was 6.0 (95% confidence interval 1.3–55.2) and the difference between the groups was statistically significant (P = 0.016).

CONCLUSION

These results show that the presence of a stent is associated with a worse outcome after ESWL for ureteric stones. Ureteric stents should still be used in cases of obstruction, when there is a risk of sepsis, and in patients with intolerable pain or deteriorating renal function. However, their use in patients offered ESWL for ureteric stones should be considered with caution.
Efficacy, tolerability and satisfaction with sildenafil citrate 100‐mg titration compared with continued 50‐mg dose treatment in men with erectile dysfunction
Authors: Buvat Jacques , Hatzichristou Dimitrios , Maggi Mario , Farmer Ian , Martínez‐Jabaloyas Jose M. , Miller Paul J. , Schnetzler Gabriel
Published: August 2008

OBJECTIVE

To evaluate the efficacy, tolerability, and treatment satisfaction after initiating treatment with sildenafil 50 mg and later titrating to 100 mg, compared with continuing treatment with sildenafil 50 mg, in men with erectile dysfunction (ED).

PATIENTS AND METHODS

A multicentre, parallel‐group trial was conducted in two 4‐week periods. In period 1, patients received 50‐mg doses of sildenafil single‐blinded for 4 weeks. In period 2, patients were randomized to double‐blind, placebo‐controlled treatment with sildenafil 50 mg or sildenafil 100 mg for 4 weeks. All patients were aged ≥18 years with a documented clinical diagnosis of ED (score of ≤25 on the International Index of Erectile Function, IIEF, Erectile Function, EF, domain), and met the prescribing criteria for sildenafil 50 mg and 100 mg.

RESULTS

Of 492 enrolled patients (mean age 53 years, sd 11), 476 (97%) completed period 1 and 473 (96%) completed period 2. Patients receiving sildenafil 50 mg in period 1 had an increase in the mean (sd) baseline EF domain score from 12.8 (5.2) to 22.5 (6.6) (P < 0.001), and improved scores on the Quality of Erection Questionnaire (QEQ) and Sexual Experience Questionnaire (SEX‐Q). The IIEF EF domain scores were similar in the two groups at baseline and randomization. Patients titrated to the 100‐mg dose (237 men) showed a significantly greater improvement than those who continued on the 50‐mg dose (240; P < 0.001). There was a significant increase in QEQ and SEX‐Q scores in patients titrated to sildenafil 100 mg compared with patients continuing at sildenafil 50 mg. At either sildenafil dose, headache, flushing and hot flushes were the most common adverse events. Neither the frequency nor the severity of adverse events increased with titration to sildenafil 100 mg.

CONCLUSIONS

After initial treatment with sildenafil 50 mg, patients titrated to 100 mg showed further increases in efficacy and satisfaction with no increase in the number or severity of adverse events than in those remaining on the starting dose.
Kidney fusion anomalies revisited: clinical and radiological analysis of 209 cases of crossed fused ectopia and horseshoe kidney
Authors: Glodny Bernhard , Petersen Johannes , Hofmann Karin J. , Schenk Claudia , Herwig Ralf , Trieb Thomas , Koppelstaetter Christian , Steingruber Iris , Rehder Peter
Published: August 2008

OBJECTIVE

To analyse the morphological appearance of horseshoe kidneys (HKs) and crossed fused ectopia (CFE) and to assess the frequency and clinical significance of associated anomalies and diseases.

PATIENTS AND METHODS

The findings and images of 209 patients with fused kidneys (FKs) were reviewed; in all, 244 scans from computed tomography (CT), 233 ultrasonograms and 89 micturition cysto‐urethrograms, urograms, magnetic resonance images and angiograms were taken.

RESULTS

HKs (found in one of 474 abdominal CT scans) and CFEs (found in one of 3078 CT scans) showed a high variability of vasculature that could not be classified. However, some generalized conclusions were possible about the renal vasculature (430 arteries in 103 kidneys). Variants of the most cephalad artery of both sides were rare. The second artery on the right had a pre‐caval course. The origins of vessels located further caudal were more ventral. CFEs were anatomically different from HKs with respect to lower position, greater axial rotation, smaller pelvic width, more caudal origin, and fewer vessels, but not in accompanying anomalies. Severe anomalies or malformations were found in 23% of patients, with half of them in the urogenital system. Malformations were found considerably more often in children than in adults. There was no increased incidence of diseases such as stones or inflammation of the renal pelvis.

CONCLUSION

Concomitant anomalies and diseases were equally frequent for HK and CFE, but less frequent than generally assumed. Individual cases of complex anatomical situations require special examination strategies, and CT appears to be the most reliable imaging method.
Association of the ABCG2 C421A polymorphism with prostate cancer risk and survival
Authors: Gardner Erin R. , Ahlers Christoph M. , Shukla Suneet , Sissung Tristan M. , Ockers Sandra B. , Price Douglas K. , Hamada Akinobu , Robey Robert W. , Steinberg Seth M. , Ambudkar Suresh V. , Dahut William L. , Figg William D.
Published: August 2008

OBJECTIVE

To determine if the C421A single nucleotide polymorphism (SNP) in the ATP‐binding cassette transporter ABCG2 increases prostate cancer risk or affects survival.

PATIENTS, SUBJECTS AND METHODS

Numerous studies have suggested that dietary, hormonal and environmental factors all play a role in the initiation in prostate cancer; among these, the carcinogenic heterocyclic amine 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP), a known substrate of the ABCG2. A SNP of ABCG2, C421A, resulting in a glutamine to lysine change at amino acid 141, has been shown to result in decreased function of the protein. Due to the expression of ABCG2 in the prostate, together with the purported role of dietary carcinogens and steroids in the development and progression of prostate cancer, 311 individuals were genotyped for the ABCG2 C421A SNP, 170 patients with androgen‐independent prostate cancer (AIPC) and 141 ‘healthy’ controls. We also evaluated the effect of this SNP on the intracellular accumulation of PhIP and testosterone in vitro.

RESULTS

There were no significant differences in the prevalence of prostate cancer based on ABCG2 genetic variation in this population. However, survival was significantly longer for individuals with wild‐type ABCG2, as compared with those hetero‐ or homozygous for the C421A SNP (7.4 years vs 5.3 years, P = 0.044). Intracellular accumulation of PhIP was 80% higher in HEK293 cells transfected with Q141K ABCG2 than in wild‐type cells, confirming that this SNP decreases transport of PhIP. In contrast, testosterone was not transported by either wild‐type or variant transfected cells, nor did it act as in inhibitor of ABCG2 in subsequent transport assays.

CONCLUSION

Increased exposure to PhIP may decrease survival, but the ABCG2 C421A polymorphism does not appear to increase the risk of prostate cancer.
Holmium laser prostatic resection for patients presenting with acute urinary retention
Authors: Anderson Christopher B. , Helfand Brian T. , McVary Kevin T.
Published: August 2008

OBJECTIVE

To compare the outcomes of patients presenting with and without acute urinary retention (AUR) who were treated with 100‐W holmium laser resection of the prostate (HoLRP), as laser therapies, including HoLRP, have been used for treating lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH), but the effectiveness of HoLRP for patients with AUR has not been fully elucidated.

PATIENTS AND METHODS

The medical records of 87 patients who had HoLRP were reviewed, and prospective questionnaires aimed at determining patients’ American Urologic Association Symptom Index (AUA‐SI) and Quality‐of‐Life (QoL) scores and medication usage were also obtained. Statistical analyses were used to compare the clinical characteristics and outcomes between patients with and with no AUR for up to 2 years after HoLRP.

RESULTS

All patients had the catheter removed successfully by 1 month after surgery; those presenting with AUR tended to have a greater improvement in clinical outcomes than those with no AUR, including a mean AUA‐SI score decrease by ≈13 and ≈8 points, and a QoL score decrease by ≈2 and ≈1.4 points, respectively. These decreases were maintained throughout the study period. Patients with AUR had significantly greater decreases in their postvoid residual urine volume than those with no AUR. Serum prostate‐specific antigen levels also had a modest but sustained decrease (14%) in both groups. There were no significant decreases in the reported use of BPH‐related medications after surgery in either group.

CONCLUSIONS

HoLRP (100 W) is a safe and effective surgical therapy for patients presenting with AUR. The present results suggest that the short‐ and long‐term outcomes of these patients are similar between men presenting with and with no AUR.
Nephrectomy improves the survival of patients with locally advanced renal cell carcinoma
Authors: Zini Laurent , Perrotte Paul , Jeldres Claudio , Capitanio Umberto , Pharand Daniel , Arjane Philippe , Lapointe Steven , Montorsi Francesco , Patard Jean‐Jacques , Karakiewicz Pierre I.
Published: August 2008

OBJECTIVES

To examine the cancer‐specific survival of patients treated with nephrectomy and compared it to that of patients managed without surgery.

PATIENTS AND METHODS

Of 43 143 patients with renal cell carcinoma (RCC) identified in the 1988–2004 Surveillance, Epidemiology and End Results database, 7068 had locally advanced RCC and with no distant metastasis. These patients had a nephrectomy (6786, 96.0%) or no surgical therapy (282, 4.0%). Multivariable Cox regression models, and matched and unmatched Kaplan‐Meier survival analyses, were used to compare the effect of nephrectomy vs non‐surgical therapy on cancer‐specific survival. Also, competing‐risks regression models adjusted for the effect of other‐cause mortality. Covariates and matching variables consisted of age, gender, tumour size and year of diagnosis.

RESULTS

The 1‐, 2‐, 5‐ and 10‐year cancer‐specific survival of patients who had nephrectomy was 88.9%, 88.1%, 68.6% and 57.5%, vs 44.8%, 30.6%, 14.5% and 10.6% for non‐surgical therapy. In multivariable analyses, relative to nephrectomy, non‐surgical therapy was associated with a 5.8‐fold higher rate of cancer‐specific mortality (P < 0.001). Non‐surgical therapy was also associated with a 5.1‐fold higher rate of cancer‐specific mortality in matched analyses (P < 0.001). Finally, competing‐risks regression confirmed the statistical significance of the variable defining treatment type (nephrectomy vs non‐surgical therapy) in multivariable and matched analyses (P < 0.001).

CONCLUSION

Relative to non‐surgical treatment, nephrectomy improves the cancer‐specific survival of patients with locally advanced RCC; our findings await prospective confirmation.
Unilateral vs bilateral sacral neuromodulation in pigs with formalin‐induced detrusor hyperactivity
Authors: Kaufmann Sascha , Naumann Carsten M. , Hamann Morritz F. , Seif Christoph , Braun Peter M. , Jünemann Klaus P. , Van Der Horst Christof
Published: August 2008

OBJECTIVE

To investigate the efficacy of unilateral vs bilateral sacral neuromodulation (SNM) under standard experimental conditions by stimulating the dorsal sacral roots in pigs with formalin‐induced detrusor hyperactivity.

MATERIALS AND METHODS

After lumbosacral laminectomy in eight α‐chloralose‐anaesthetized Göttinger mini‐pigs, the dorsal roots of the nerve S3 were inserted into separate compartments of a size‐modified Brindley electrode. Detrusor hyperactivity was induced by intravesical instillation of a 0.25% formalin solution. Stimulation of the separated dorsal roots was performed on the unilateral right, respectively, the unilateral left side, as well as bilaterally and with stimulation off‐phases in a randomized pattern. A biphasic rectangular signal (impulse 200 µs, 20 Hz, 2.0 V) was used for SNM. The bladder pressure values were registered on a urodynamic unit and evaluated as contractions and amplitudes per minute.

RESULTS

During unilateral stimulation, the mean (sem) number of contractions was reduced significantly from 4.73 (0.66) to 2.73 (0.62). The amplitude was also reduced significantly from 12.86 (1.23) to 8.32 (0.66). By contrast, bilateral stimulation lowered the mean (sem) number of overactive detrusor contractions to 1.08 (1.02) and the amplitude to 3.08 (2.42), which are highly significant reductions.

CONCLUSION

In this porcine model, bilateral neurostimulation was a more effective method of SNM than unilateral stimulation. We assume that this is due to the additive effect of stimulating both sides, as well as the greater chance of stimulating the relevant dorsal roots of the sacral nerve fibres. By contrast, unilateral neuromodulation may be only partially effective by not being capable of influencing the entire bladder, or possibly by allowing new formation of neuronal pathophysiological pathways.
Contemporary imaging of patients with a renal mass: does size on computed tomography equal pathological size?
Authors: Kurta Jordan M. , Thompson R. Houston , Kundu Shilajit , Kaag Matthew , Manion M. Thomas , Herr Harry W. , Russo Paul
Published: August 2008

OBJECTIVE

To evaluate the difference between radiographic size on computed tomography (CT) and the pathological size of renal tumours, in contemporary patients.

PATIENTS AND METHODS

We retrospectively reviewed the records of 521 patients undergoing surgical resection of a renal mass between 2000 and 2007, who had tumour sizes recorded from both preoperative CT and pathological evaluation of the tumour specimen. Data on histological tumour type were also extracted. The paired Student’s t‐test was used to compare the mean radiographic size as measured on CT with the mean pathological size, with P < 0.05 considered to indicate statistical significance.

RESULTS

For all patients, the mean radiographic size and mean pathological size was 4.79 and 4.69 cm, respectively (P = 0.02). Therefore, on average, radiographic size overestimated pathological size by 1 mm. In patients with a tumour of 4–7 cm, radiographic size overestimated pathological size by 0.21 cm (P = 0.007). However, there was no significant difference in patients with a tumour of <4 cm or >7 cm.

CONCLUSIONS

Using contemporary patients, there was a statistically significant overestimation of renal tumour sizes by CT compared with the pathological assessment. However, the overall difference between radiographic and pathological tumour size was 1 mm, suggesting that CT provides an accurate method with which to estimate renal tumour size.
Growth, Expansion of Markets, and Income Elasticities in World Trade
Authors: Wu Yi
Published: August 2008

The Houthakker–Magee effect implies that a country facing unfavorable income elasticities in trade must either grow at a slower rate than its trading partners or experience a trend worsening of the current account and/or depreciation of the real exchange rate. Krugman (1989) first documented the existence of a “45‐degree rule” under which income elasticities are systematically related to growth rates. I develop a model which is a generalization of Krugman (1989) in several dimensions (including intertemporal). The intertemporal assumption of equal consumption growth for individuals across countries and the assumption of no intertemporal trade can be viewed as two extreme benchmarks. Empirical tests of the various 45‐degree rules suggest that it is misleading to treat income elasticities as structural, as is commonly done in forecasts of current account movements. The data also seem to be more consistent with the benchmark of no intertemporal trade than that of complete intertemporal trade.
The Credibility Problem Revisited: Thirty Years on from Kydland and Prescott*
Authors: Levine Paul , Pearlman Joseph , Yang Bo
Published: August 2008

Macroeconomics research has changed profoundly since the Kydland–Prescott seminal paper. In order to address the Lucas Critique, modeling is now based on micro‐foundations treating agents as rational utility optimizers. Bayesian estimation has produced models which are more data‐consistent than those based simply on calibration. With micro‐foundations and new linear‐quadratic techniques, normative policy based on welfare analysis is now possible. In the open economy, policy involves a “game” with policymakers and private institutions or private individuals as players. This paper attempts to reassess the Kydland–Prescott contribution in the light of these developments.
Different structural requirements for functional ion pore transplantation suggest different gating mechanisms of NMDA and kainate receptors
Authors: Villmann Carmen , Hoffmann Jutta , Werner Markus , Kott Sabine , Strutz‐Seebohm Nathalie , Nilsson Tanja , Hollmann Michael
Published: August 2008

Although considerable progress has been made in characterizing the physiological function of the high‐affinity kainate (KA) receptor subunits KA1 and KA2, no homomeric ion channel function has been shown. An ion channel transplantation approach was employed in this study to directly test if homomerically expressed KA1 and KA2 pore domains are capable of conducting currents. Transplantation of the ion pore of KA1 or KA2 into GluR6 generated perfectly functional ion channels that allowed characterization of those electrophysiological and pharmacological properties that are determined exclusively by the ion pore of KA1 or KA2. This demonstrates for the first time that KA1 and KA2 ion pore domains are intrinsically capable of conducting ions even in homomeric pore assemblies. NMDA receptors, similar to KA1‐ or KA2‐containing receptors, function only as heteromeric complexes. They are composed of NR1 and NR2 subunits, which both are non‐functional when expressed homomerically. In contrast to NR1, the homomeric NR2B ion pore failed to translate ligand binding into pore opening when transplanted into GluR6. Similarly, heteromeric coexpression of the ion channel domains of both NR1 and NR2 inserted into GluR6 failed to produce functional channels. Therefore, we conclude that the mechanism underlying the ion channel opening in the obligatorily heterotetrameric NMDA receptors differs significantly from that in the facultatively heterotetrameric α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionate and KA receptors.
PPARα and PPARγ effectively protect against HIV‐induced inflammatory responses in brain endothelial cells
Authors: Huang Wen , Rha Geun Bae , Han Min‐Joon , Eum Sung Yong , András Ibolya E. , Zhong Yu , Hennig Bernhard , Toborek Michal
Published: August 2008

Peroxisome proliferator‐activated receptors (PPARs) are nuclear receptors which down‐regulate inflammatory signaling pathways. Therefore, we hypothesized that alterations of PPAR functions can contribute to human immunodeficiency virus‐1 (HIV‐1)‐induced dysfunction of brain endothelial cells. Indeed, treatment with HIV‐1 transactivator of transcription (Tat) protein decreased PPAR transactivation in brain endothelial cells. We next stably over‐expressed PPARα and PPARγ in a newly developed cell line of human brain endothelial cells (hCMEC/D3 cells). Tat‐induced up‐regulation of inflammatory mediators, such as interleukin (IL)‐1β, tumor necrosis factor‐α, CCL2, and E‐selectin were markedly attenuated in hCMEC/D3 over‐expressing PPARα or PPARγ. These results were confirmed in CCL2 and E‐selectin promoter activity studies. Similar protective effects were observed in hCMEC/D3 after activation of PPARγ by exogenous PPAR agonists (dPGJ2 and rosiglitazone). PPAR over‐expression also prevented Tat‐induced binding activity and transactivation of nuclear factor‐κB. Importantly, increased PPAR activity attenuated induction of IL‐1β, tumor necrosis factor‐α, CCL2, and E‐selectin in hCMEC/D3 cells co‐cultured with HIV‐1‐infected Jurkat cells. The protective effects of PPAR over‐expression were reversed by the antagonists of PPARα (MK886) or PPARγ (GW9662). The present data suggest that targeting PPAR signaling may provide a novel therapeutic approach to attenuate HIV‐1‐induced local inflammatory responses in brain endothelial cells.
The lipopolysaccharide Parkinson’s disease animal model: mechanistic studies and drug discovery
Authors: Dutta Garima , Zhang Ping , Liu Bin
Published: August 2008

Research in the last two decades has unveiled an important role for neuroinflammation in the degeneration of the nigrostriatal dopaminergic (DA) pathway that constitutes the pathological basis of the prevailing movement disorder, Parkinson’s disease (PD). Neuroinflammation is characterized by the activation of brain glial cells, primarily microglia and astrocytes that release various soluble factors that include free radicals (reactive oxygen and nitrogen species), cytokines, and lipid metabolites. The majority of these glia‐derived factors are proinflammatory and neurotoxic and are particularly deleterious to oxidative damage‐vulnerable nigral DA neurons. As a proof of concept, various immunologic stimuli have been employed to directly induce glial activation to model DA neurodegeneration in PD. The bacterial endotoxin, lipopolysaccharide (LPS), has been the most extensively utilized glial activator for the induction of inflammatory DA neurodegeneration. In this review, we will summarize the various in vitro and in vivo LPS PD models. Furthermore, we will highlight the contribution of the LPS PD models to the mechanistic studies of PD pathogenesis and the search for neuroprotective agents for the treatment of PD.
Disposition of eslicarbazepine acetate in the mouse after oral administration
Authors: Alves Gilberto , Figueiredo Isabel , Castel‐Branco Margarida , Lourenço Nulita , Falcão Amílcar , Caramona Margarida , Soares‐da‐Silva Patrício
Published: August 2008

Eslicarbazepine acetate is a promising antiepileptic drug structurally related to carbamazepine and oxcarbazepine, which is in the final phase of clinical development. The metabolism of eslicarbazepine acetate is clearly species dependent and, in this case, among small laboratory animals, the mouse seems to be the most relevant species to humans. Hence, the aim of this study was to investigate the plasma, brain and liver disposition of eslicarbazepine acetate in mice to better understand its disposition in humans. Adult male CD‐1 mice were treated orally with a single dose of eslicarbazepine acetate 350 mg/kg. Blood samples, brain and liver tissues were taken at 0.25, 0.5, 0.75, 1, 2, 4, 6, 10, 16 and 24 h post‐dose. Plasma and tissue levels of eslicarbazepine acetate and its metabolites (S‐licarbazepine, R‐licarbazepine and oxcarbazepine) were assessed by using high‐performance liquid chromatography‐ultraviolet detection. Both eslicarbazepine acetate and R‐licarbazepine concentrations were below the limit of quantification of the assay in all matrices. Eslicarbazepine acetate was rapidly and extensively metabolized to S‐licarbazepine (major metabolite), which was oxidized to oxcarbazepine to a small extent. The brain/plasma ratios suggest that the brain exposure to S‐licarbazepine and oxcarbazepine was approximately 30% of their total systemic exposure. However, S‐licarbazepine crossed the blood–brain barrier (BBB) less efficiently than oxcarbazepine. On the other hand, the liver/plasma ratios support the notion that S‐licarbazepine undergoes hepatic accumulation, whereas oxcarbazepine appears to leave this compartment twice as fast as S‐licarbazepine. Thus, the diffusion through the BBB is favourable to oxcarbazepine and the liver acts like a deposit of the pharmacologically active metabolite of eslicarbazepine acetate (S‐licarbazepine).
Radiosensitivity of canine osteosarcoma cells transfected with wild‐type p53 in vitro*
Authors: Shiomitsu K. , Sajo E. , Xia X. , Hunley D. W. , Mauldin G. E. , Li S. , Mauldin G. N.
Published: August 2008

The p53 gene is one of the important tumour suppressor genes that are involved with the cell survival signal pathway. One of the major functions of the p53 protein is to organize cell cycle regulation and induction of apoptosis for cellular genetic stability. It has been documented that more than 50% of all human cancers include a p53 mutation. We evaluated the difference in radiosensitivity between upregulating the expression of canine wild‐type p53 (cp53) in cultured osteosarcoma (D17) cells and naive D17 cells in vitro. We found that upregulating transfected cp53 D17 cells increased their radiation sensitivity in vitro, and there was a significant decrease (P < 0.009) in survival between cp53‐transfected D17 cells and naive D17 cells. In this experiment, a p53 enhancement ratio (p53ER) reached approximately 3.0 at high doses. The transfected cp53 D17 cells were significantly more radiosensitive at all doses evaluated than naive D17 cells, except at 1 Gy where too few data points were available. The p53ER increased rapidly at doses less than 4 Gy, achieving a maximum of about 3.0 for doses of 4 Gy and above. This study shows the enhanced radiosensitivity of the transfected p53 at clinically relevant doses.
Effect of MMP‐1 promoter polymorphisms on GCF MMP‐1 levels and outcome of periodontal therapy in patients with severe chronic periodontitis
Authors: Pirhan Demet , Atilla Gül , Emingil Gülnur , Sorsa Timo , Tervahartiala Taina , Berdeli Afig
Published: August 2008

Aims: The aims of this study were to investigate (1) the matrix metalloproteinase‐1 (MMP‐1) promoter polymorphisms in severe chronic periodontitis (CP), (2) the relationship of periodontal therapy outcome with these genotypes, and (3) the gingival crevicular fluid (GCF) MMP‐1 levels–MMP‐1 genotype correlation.

Material and Methods: Genomic DNA was obtained from the peripheral blood of 102 patients with severe CP and 98 periodontally healthy subjects. MMP‐1 −519A/G and −1607 1G/2G polymorphisms were determined by the polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) method. Fifty‐eight CP patients received non‐surgical periodontal therapy and were followed for 6 months. Clinical periodontal parameters and GCF samples were collected at baseline and at 6 months. GCF MMP‐1 levels were analysed by enzyme‐linked immunosorbent assay (ELISA).

Results: The distribution of MMP‐1 genotypes did not significantly differ between the study groups. On the other hand, the −1607 2G allele frequency of severe CP patients was higher than that of healthy subjects. MMP‐1 −519G allele carriers had higher GCF MMP‐1 levels and percentage of sites with 4–6 mm clinical attachment level (CAL) compared with AA genotypes after non‐surgical periodontal therapy (p<0.05).

Conclusions: These data suggest that the −1607 2G polymorphic allele of the MMP‐1 gene could be associated with susceptibility to severe CP in the Turkish population. It seems that −519AG and GG genotypes could play a role in the outcome of periodontal therapy.
Anetodermic pilomatricoma
Authors: De Souza Elemir M. , Ayres Vallarelli Andrelou F. , Cintra Maria L. , Vetter‐Kauczok Claudia‐S. , Brocker Eva‐B.
Published: August 2008

A pilomatricoma, or Malherbe’s calcifying epithelioma, is an uncommon tumor originating from hair matrix cells. It is clinically characterized by a solitary, firm nodule. As the skin overlying the pilomatricoma may change in color and texture, its clinical presentation can vary. We report an unusual case of pilomatricoma with associated anetoderma on the lower extremity of a 12‐year‐old girl. Histology revealed a thinned dermis replaced by myxomatous tissue between the surface and a deep‐seated tumoral mass. This mass is formed of irregular islands of basaloid cells, shadow cells, calcified areas and discrete inflammatory and foreign‐body reactions surrounding it. Anetodermic cutaneous changes may occur in pilomatricomas without histological evidence of triggering factors.
Medication errors in a neonatal intensive care unit. Influence of observation on the error rate
Authors: Campino Ainara , Lopez‐Herrera Maria Cruz , Lopez‐de‐Heredia Ion , Valls‐i‐Soler Adolf
Published: August 2008

Aim: To study if medication error rate decreased as a consequence of a simple observation process of registering its occurrence.

Methods: Prescription and transcription processes were prospectively registered along two different period of time in a level III regional Neonatal Intensive Care Unit: a pilot phase, aimed to know the baseline drug error rate and a phase I, a pre‐intervention phase, both part of a study designed to determinate the effect of a preventive strategy in drug error rate. Random drug prescriptions by physicians and their transcriptions by nurses were reviewed and registered by a hospital pharmacist. A drug error episode was registered if dosage, units, route and administration interval were incorrect, illegible or not indicated.

Results: A significant reduction in the prescription error rate from 32.8% in the pilot phase to 19.2% in the pre‐intervention study phase was observed (p< 0.001). Rates of incorrect dosing (13.6% vs. 5%) and lack of dose specification in the medical prescriptions (3.3% vs. 0.5%) dropped significantly but transcription errors did not.

Conclusion: The presence of a person reviewing and registering the drug records apparently had by itself a substantial positive effect on the overall drug error rate. This phenomenon known as the Hawthorne effect should be taken in consideration when evaluating the efficacy of any preventive intervention aimed at improving patient safety.
Correlations between welfare initiatives and breastfeeding rates: a 10‐year follow‐up study
Authors: Mordini Bruno , Bortoli Elisa , Pagano Rossella , Barozzi Giulia , Ferrari Fabrizio
Published: August 2008

Aim: To evaluate the prevalence of full breastfeeding during the first 6 months of age and to discover if training programs for health caregivers and welfare initiatives at the community level could improve breastfeeding rates.

Methods: Newborn babies with gestational age ≥36 weeks and birth weight ≥2500 g, discharged from the hospital within the first week of life, without any underlying pathologies, were enrolled in 3‐month long sample periods between 1997 and 2006. A questionnaire was distributed to the mothers, to be completed and submitted before hospital discharge. Data were collected from phone interviews at 1, 3 and 6 months.

Results: Full breastfeeding rates at hospital discharge showed an oscillation between 69.9% and 87%. The rate decreased in the following months and reached very low levels at 6 months of age (<24%), with the exception of the last sample period in 2006 (44.9%).

Conclusion: A simple questionnaire, combined with standardized phone interviews, can be easily reproduced and may be used as an indicator for quality of neonatal care at hospital nurseries. A social and cultural change of the whole community towards breastfeeding promotion will result in increasing breastfeeding rates.
The change in ghrelin and obestatin levels in obese children after weight reduction
Authors: Zou Chao Chun , Liang Li , Wang Chun Lin , Fu Jun Fen , Zhao Zheng Yan
Published: August 2008

Aim: To investigate the role of ghrelin and obestatin in obesity mechanisms.

Methods: A total of 88 obese children and 25 normal children were enrolled. Moreover, 46 obese children took part in a summer camp for weight reduction. Fasting ghrelin, obestatin and other biochemical parameters were measured in all subjects and re‐measured in 45 obese children finishing the camp.

Results: The ghrelin levels in the control and obese groups were 67.26 ± 23.41 pmol/L and 56.53 ± 15.97 pmol/L with a significant difference (p = 0.039), while the obestatin levels (89.41 ± 23.63 vs. 83.13 ± 17.21 pmol/L) were not significantly different (p = 0.083). The ghrelin/obestatin ratio in the controls was significantly higher than that in the obese group (p = 0.014). In the latter, fasting insulin and alanine aminotransferase were independent factors for ghrelin; fasting insulin, weight and gender were independent factors for obestatin and alanine aminotransferase was an independent factor for ghrelin/obestatin. Moreover, ghrelin, obestatin and ghrelin/obestatin increased after weight reduction (p < 0.05, respectively), and the increment in ghrelin and obestatin was associated with a decrement in insulin resistance.

Conclusion: These data suggest that ghrelin, obestatin and/or the ghrelin/obestatin ratio are associated with obesity in childhood.
TEXTURAL CHARACTERISTICS OF FIVE MICROORGANISMS FOR RAPID DETECTION USING IMAGE PROCESSING
Authors: KUMAR S. , MITTAL G.S.
Published: August 2008

A rapid and cost‐effective technique for identification and classification of microorganisms was explored using fluorescence microscopy and image analysis. After staining the microorganisms with fluorescent dyes (diamidino‐2‐phenyl‐indole [DAPI] and acridine orange [AO], images of the microorganisms were captured using a charge‐coupled device camera attached to a light microscope. Textural features were extracted from the images. Fluorescence emission from Bacillus thuringiensis is the highest compared with other microbes, and the emission from Lactobacillus brevis is the lowest. Various microorganisms can be differentiated using various textural features from images using AO or DAPI dye. Many textural features of the images obtained from the two dyes were different.

PRACTICAL APPLICATIONS

Conventional microbial detection methods take considerable time and are laborious. Rapid methods are required so that pathogens and spoilage microorganisms in foods and water can be identified and counted in a much shorter time. This work investigates image processing techniques particularly based on textural properties of the images of microorganisms. Images of microorganisms in samples can be captured using light microscopes after concentrating using centrifuge or membrane separation devices. This work will assist in developing a commercial method for rapid detection of microbes in food samples.
EFFECTS OF INTERMOLECULAR INTERACTIONS AND MOLECULAR ORIENTATION ON THE FLUX BEHAVIOR OF XANTHAN GUM SOLUTIONS DURING ULTRAFILTRATION
Authors: LO Y.M. , ZIEGLER R.C. , ARGIN‐SOYSAL S. , HSU C.H. , WAGNER N.J.
Published: August 2008

Conformational changes of xanthan gum as a function of concentration were investigated to elucidate its unusual flux behavior during ultrafiltration (UF). The contribution of hydrogen bonding on structure formation and the molecular orientation of xanthan gum on the flow characteristics were studied rheomechanically and rheo‐optically. Known to affect xanthan structure at low concentrations, hydrogen bonding unexpectedly did not show significant influence on xanthan rheological properties up to 2 wt %. The ordered layers formed on the membrane surface proved responsible for the enhanced water removal during UF. This unique behavior could be attributed to the formation of aligned molecular orientation in addition to the viscosity increases during the biphasic region. Significant differences were observed between xanthan fermentation broth and solutions made of commercial xanthan, suggesting the need to control the salt concentration in fermentation broth in order to make UF an effective recovery process for xanthan gum after fermentation.

PRACTICAL APPLICATIONS

The knowledge gained from the present study strengthens fundamental understandings on the conformational changes of xanthan biopolymers during the recovery of xanthan gum from fermentation broth using ultrafiltration (UF). By taking advantage of the aligned molecular orientation, along with controlling the salt concentration in the fermentation broth, UF could be operated at elevated flux to speed up the removal of water from the viscous fermentation broth. The technology should find broad applications in the fermentation industry, especially where viscosity is of concern during the separation and purification of the product.
Hematological Toxicity Associated with Tissue Extract from Poisonous Fish Lagocephalus lagocephalus—Influence on Erythrocyte Function in Wistar Rats
Authors: Saoudi M. , Abdelmouleh A. , Jamoussi K. , Kammoun A. , El Feki A.
Published: August 2008

ABSTRACT:  The puffer fish Lagocephalus lagocephalus represents serious public health problems in the world. The relative toxicity of each organ (liver and flesh) was determined by the relation dose–death time “mouse bioassay.” The average liver toxicity of the puffer fish was the highest when compared with flesh giving 14.32 and 10.88 MU/g, respectively. A mouse unit is the amount of toxin (extract of fish organ) that kills a 20 g male mouse in 30 min after intraperitoneal injection. One mouse unit is equivalent to 0.22 μg of TTX. For the rat bioassay tests, Wistar rats were daily i.p. injected, for 10 d, with extracts of liver (LT) or flesh (FT) (muscles + skin) of L. lagocephalus. Control rats received injection of NaCl (0.9%). During the experiment, a significant reduction in red blood cell number (RBC), hemoglobin (HGB) concentration, and hematocrit (HCT) was observed essentially after 10 d of treatment in the FT and LT‐exposed groups. Consequently, treatment led to severe anemia and hemolytic action as indicated by a significant reduction in the total number of erythrocytes. In fact, our study revealed a significant increase in erythrocyte lipid peroxidation (LPO) in FT and LT groups compared with controls after experimental exposure. The flesh and liver tissue extracts also altered antioxidative enzymes activities: catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH‐Px). Histopathological alterations in the spleen occurred exclusively at the end of treatment. We marked also an increase in reticulo‐endothelial cells, which led to remove damaged erythrocytes.
Hematological features and molecular lesions of hemoglobin gene disorders in Taiwanese patients
Authors: LIN H.‐J. , SHIH M.‐C. , PENG C.‐T. , LIU T.‐C. , CHEN K.‐W. , SHIH H.‐C. , CHANG J.‐G.
Published: August 2008

Hemoglobin (Hb) gene disorders are one of the most common inherited diseases in Taiwan, which include α‐thalassemia, β‐thalassemia, and Hb variants. In this study, we collected and analyzed mutations found in 930 patients with Hb gene disorders except Hb Bart’s Hydrops and β‐thalassemia major. The patients included 650 cases of α‐thalassemia, 225 cases of β‐thalassemia, 9 cases of α‐thalassemia combined with β‐thalassemia, and 46 cases of Hb variants or Hb variants combined with α‐thalassemia or β‐thalassemia. The most common type of α0‐thalassemia and α++‐thalassemia mutations in our study were the SEA type deletion and the α3.7 deletion, respectively; the most common β‐thalassemia mutation was the IVS‐2 nt 654 C→T mutation; and the most common Hb variant was the HbE. We compared the relationships between genotype and hematological phenotypes of various Hb gene disorders and found that different genotypes of α0‐thalassemia have similar hematological features. In conclusion, the results of our study provide data of the complex interaction of thalassemias and Hb variants which might be useful for other researchers in this field.
Expression of small‐conductance calcium‐activated potassium channels (SK3) in skeletal muscle: regulation by muscle activity
Authors: Favero Morgana , Jiang De‐Jian , Chiamulera Christian , Cangiano Alberto , Fumagalli Guido Francesco
Published: August 2008

The type 3 small conductance calcium‐activated potassium channel (SK3) is expressed in embryonic and adult denervated skeletal muscles where it contributes to hyperexcitability. This study aimed at determining the role of muscle activity in regulating SK3 channels. Soleus muscles of adult rats were denervated by cutting the sciatic nerve. In reinnervation studies, the soleus nerve was crushed: in one group, muscles were reinnervated with electrically silent axons, by chronic sciatic nerve perfusion with tetrodotoxin. Several groups of denervated muscles were subjected to chronic direct electrical stimulation, using either fast (100 Hz) or slower patterns (20 or 30 Hz). The SK3 mRNA and protein levels in soleus muscle were determined by reverse transcriptional‐PCR, Western blot and immunofluorescence. Both denervated and reinnervated–paralysed soleus muscles displayed similar up‐regulation of SK3 mRNA and protein. Reinnervation with electrically active axons instead inhibited SK3 up‐regulation. Chronic muscle direct stimulation in vivo, irrespective of the pattern used, reversed the denervation‐induced up‐regulation of SK3 expression or prevented it when initiated at the time of denervation. Chronic electrical stimulation of denervated muscles also completely prevented the development of the after‐hyperpolarization (AHP) following the action potential, normally induced in the muscle fibres by denervation. We conclude that action potential activity evoked by motor neurones in muscle fibres is both necessary and sufficient to account for the physiological down‐regulation of SK3 channels in the non‐junctional membrane of skeletal muscle.