bluuebunny/crossref_metadata_2025 huggingface dataset:
GLUTEAL COMPARTMENT SYNDROME
Authors: Hayden Georgina , Leung Michael , Leong James
Published: June 2006

Gluteal compartment syndrome is uncommon and is often diagnosed late, resulting in muscle necrosis and sciatic nerve palsy. The mainstay of treatment is prompt diagnosis and early surgery. A high index of suspicion is essential, especially in the setting of major bleeding and excessive pain. Embolization and hyperbaric oxygen may be considered as adjuncts to surgery.
Neuropeptide Y in the olfactory microvillar cells
Authors: Montani Giorgia , Tonelli Simone , Elsaesser Rebecca , Paysan Jacques , Tirindelli Roberto
Published: June 2006

This paper examines a possible role of microvillar cells in coordinating cell death and regeneration of olfactory epithelial neurons. The olfactory neuroepithelium of mammals is a highly dynamic organ. Olfactory neurons periodically degenerate by apoptosis and as a consequence of chemical or physical damage. To compensate for this loss of cells, the olfactory epithelium maintains a lifelong ability to regenerate from a pool of resident multipotent stem cells. To assure functional continuity and histological integrity of the olfactory epithelium over a period of many decades, apoptosis and regeneration require to be precisely coordinated. Among the factors that have been implicated in mediating this regulation is the neuropeptide Y (NPY). Knockout mice that lack functional expression of this neurogenic peptide show defects in embryonic development of the olfactory epithelium and in its ability to regenerate in the adult. Here we show that, in postnatal olfactory epithelia, NPY is exclusively expressed by a specific population of microvillar cells. We previously characterized these cells as a novel type of putative chemosensory cells, which are provided with a phosphatidyl‐inositol‐mediated signal transduction cascade. Our findings allow for the first time to suggest that microvillar cells are involved in connecting apoptosis to neuronal regeneration by stimulus‐induced release of NPY.
Negative cross‐talk between presynaptic adenosine and acetylcholine receptors
Authors: Shakirzyanova A. V. , Bukharaeva E. A. , Nikolsky E. E. , Giniatullin R. A.
Published: June 2006

Functional interactions between presynaptic adenosine and acetylcholine (ACh) autoreceptors were studied at the frog neuromuscular junction by recording miniature end‐plate potentials (MEPPs) during bath or local application of agonists. The frequency of MEPPs was reduced by adenosine acting on presynaptic adenosine A1 receptors (EC50 = 1.1 µm) or by carbachol acting on muscarinic M2 receptors (EC50 = 1.8 µm). However, carbachol did not produce the depressant effect when it was applied after the action of adenosine had reached its maximum. This phenomenon implied that the negative cross‐talk (occlusion) had occurred between A1 and M2 receptors. Moreover, the occlusion was receptor‐specific as ATP applied in the presence of adenosine continued to depress MEPP frequency. Muscarinic antagonists [atropine or 1‐[[2‐[(diethylamino)methyl)‐1‐piperidinyl]acetyl]‐5,11‐dihydro‐6H‐pyrido [2,3‐b][1,4]benzodiazepine‐6‐one) (AFDX‐116)] had no effect on the inhibitory action of adenosine and adenosine antagonists [8‐(p‐sulfophenyl)theophylline (8‐SPT) or 1,3‐dipropyl‐8‐cyclopentylxanthine (DPCPX)] had no effect on the action of carbachol. These data suggested that membrane–delimited interactions did not occur between A1 and M2 receptors. Both carbachol and adenosine similarly inhibited quantal release triggered by high potassium, ionomycin or sucrose. These results indicated a convergence of intracellular pathways activated by M2 and A1 receptors to a common presynaptic effector located downstream of Ca2+ influx. We propose that the negative cross‐talk between two major autoreceptors could take place during intense synaptic activity and thereby attenuate the presynaptic inhibitory effects of ACh and adenosine.
Ethanol withdrawal induces hyperalgesia mediated by PKCε
Authors: Dina Olayinka A. , Messing Robert O. , Levine Jon D.
Published: June 2006

Symptoms of ethanol withdrawal include heightened responses to sensory stimuli, as well as tremors and convulsions. We tested the hypothesis that repeated episodes of ethanol intake and withdrawal exacerbate the symptoms of alcohol‐induced peripheral neuropathy. In contrast to the hyperalgesia produced when an alcohol (6.5%)‐containing diet was fed continuously to male rats which took 4 weeks to develop (Dinaet al., 2000), feeding alcohol (6.5%) in repeated cycles of 4 days of alcohol followed by 3 days without alcohol resulted in a withdrawal‐induced hyperalgesia that began at the end of one weekly cycle and reached a maximum during the fourth cycle. For ethanol withdrawal to produce hyperalgesia, ethanol consumption needed to be terminated for a period of 2 days. Paradoxically, as the amount of alcohol consumed decreased, the hyperalgesia induced by withdrawal developed more rapidly, being maximal between 1.4 and 1.6% ethanol. These results suggest that continued exposure to ethanol also has a neuroprotective effect. Withdrawal‐induced hyperalgesia, similar to the hyperalgesia induced by continuous, chronic alcohol intake, was inhibited reversibly by intrathecal administration of an antisense oligodeoxynucleotide to protein kinase C (PKC)ε.
TRPV1, but not P2X3, requires cholesterol for its function and membrane expression in rat nociceptors
Authors: Liu Min , Huang Wenlong , Wu Dongsheng , Priestley John V.
Published: June 2006

We examined the importance of membrane cholesterol for the function and expression of TRPV1 (vanilloid receptor subtype 1) and P2X3in adult rat dorsal root ganglion (DRG) neurons. Cholesterol, an essential component of lipid rafts, was depleted using methyl β‐cyclodextrin (MCD). We found that MCD significantly reduced TRPV1‐mediated capsaicin‐ and proton‐activated currents. By contrast, inward currents activated by α,β‐methylene ATP (α,β‐meATP), a non‐hydrolysable ATP analogue, were not altered. Immunoreactivity for TRPV1, but not P2X3, in the plasma membrane was markedly reduced by MCD. A reduction of TRPV1 protein in membrane fractions was found following cholesterol depletion. Our data show that the level of cholesterol determines the activity and the amount of membrane TRPV1, suggesting that TRPV1 might be localized in cholesterol‐rich microdomains in nociceptors. The differential dependence on the membrane cholesterol of TRPV1 and P2X3may have physiological significance in nociception during inflammation.
Blood–CSF barrier function in the rat embryo
Authors: Johansson P. A. , Dziegielewska K. M. , Ek C. J. , Habgood M. D. , Liddelow S. A. , Potter A. M. , Stolp H. B. , Saunders N. R.
Published: June 2006

Blood–cerebrospinal fluid (CSF) barrier function and expansion of the ventricular system were investigated in embryonic rats (E12–18). Permeability markers (sucrose and inulin) were injected intraperitoneally and concentrations measured in plasma and CSF at two sites (lateral and 4th ventricles) after 1 h. Total protein concentrations were also measured. CSF/plasma concentration ratios for endogenous protein were stable at ∼ 20% at E14–18 and subsequently declined. In contrast, ratios for sucrose (100%) and inulin (40%) were highest at the earliest ages studied (E13–14) and then decreased substantially. Between E13 and E16 the volume of the lateral ventricles increased over three‐fold. Decreasing CSF/plasma concentration ratios for small, passively diffusing molecules during embryonic development may not reflect changes in permeability. Instead, increasing volume of distribution appears to be important in this decline. The intracellular presence of a small marker (3000 Da biotin–dextranamine) in plexus epithelial cells following intraperitoneal injection indicates a transcellular route of transfer. Ultrastructural evidence confirmed that choroid plexus tight junctions are impermeable to small molecules at least as early as E15, indicating the blood–CSF barrier is morphologically and functionally mature early in embryonic development. Comparison of two albumins (human and bovine) showed that transfer of human albumin (surrogate for endogenous protein) was 4–5 times greater than bovine, indicating selective blood‐to‐CSF transfer. The number of plexus epithelial cells immunopositive for endogenous plasma protein increased in parallel with increases in total protein content of the expanding ventricular system. Results suggest that different transcellular mechanisms for protein and small molecule transfer are operating across the embryonic blood–CSF interface.
Hemodynamic changes during acute elevation of intra‐abdominal pressure in rabbits
Authors: SÜMPELMANN ROBERT , SCHUERHOLZ TOBIAS , MARX GERNOT , JESCH NATALIE K. , OSTHAUS WILHELM A. , URE BENNO M.
Published: June 2006

Background:  The intra‐abdominal pressure (IAP) may be increased during pneumoperitoneum for minimally invasive surgery, after high tension repairs of congenital abdominal wall defects, major abdominal surgery, liver transplantation, abdominal trauma, peritonitis or ileus. The aim of this study was to investigate hemodynamic changes during elevation of IAP using an experimental setting, which mirrors anatomical and physiological conditions of neonates and small infants as closely as possible.

Methods:  In five fasted, anesthetized, mechanically ventilated and multicatheterized New Zealand rabbits, the IAP was gradually increased by intra‐abdominal infusion of normal saline (total volume 1000 ml). At baseline and after each infusion of 100 ml normal saline cardiac output (CO, transcardiopulmonary thermodilution), pressure in the superior (SVCP) and inferior vena cava (IVCP), mean arterial pressure (MAP), peak airway pressure (PAP) and IAP was recorded.

Results:  During the study, IAP, SVCP and IVCP increased significantly. IVCP was significantly higher than SVCP from timepoint 200 ml to study end. After abdominal decompression IAP, SVCP and IVCP decreased to baseline levels. Changes in MAP were not significant. CO increased significantly from baseline to timepoint 200 ml (peak value), remained nearly constant until timepoint 800 ml and decreased thereafter until the abdominal infusion ceased. After abdominal decompression CO returned to baseline level. SVCP, IVCP and PAP correlated significantly with IAP (SVCP, r = 0.73; IVCP, r = 0.97; PAP, r = 0.94; P < 0.0001).

Conclusions:  The hemodynamic changes caused by increased IAP cannot be recognized by routine monitoring of arterial blood pressure and transcutaneous oxygen saturation. The increase in central venous pressure may be misinterpreted as an elevation of cardiac preload. One major effect of a prolonged increase in IAP is a decreased CO.
Transpulmonary thermodilution hemodynamic monitoring for pheochromocytoma surgery in a child with complex congenital heart disease
Authors: CHERQAOUI IMANE , RAUX OLIVIER , DEHOUR LAURENCE , ROCHETTE ALAIN , DADURE CHRISTOPHE , CAPDEVILA XAVIER
Published: June 2006

Hemodynamic alterations related to pheochromocytoma surgery may lead to decompensation with an associated cardiac malformation. Moreover, they are incompletely described in children because of potential hazards of invasive monitoring. We report transpulmonary thermodilution hemodynamic monitoring during pheochromocytoma surgery in a child with a complex congenital heart malformation. Comprehensive analysis of hemodynamic events was obtained that guided therapeutic decisions. Cardiac function was preserved and no complication occurred.
Isoflurane is associated with a similar incidence of emergence agitation/delirium as sevoflurane in young children – a randomized controlled study
Authors: MEYER ROLAND RICHARD , MÜNSTER PETER , WERNER CHRISTIAN , BRAMBRINK ANSGAR MARIA
Published: June 2006

Background:  Children may be agitated or even delirious especially when recovering from general anesthesia using volatile anesthetics. Many trials have focused on the newer agents sevoflurane and desflurane but for the widely used isoflurane little is known about its potential to generate agitation. We investigated the emergence characteristics of small children after sevoflurane or isoflurane with caudal anesthesia for postoperative pain control.

Methods:  After institutional approval and parental consent, anesthesia was randomly performed with sevoflurane (n = 30) or isoflurane (n = 29) in children at the age of 3.8 ± 1.8 years during surgical interventions on the lower part of the body. After induction, all children received caudal anesthesia with bupivacaine (0.25%, 0.8 ml·kg−1). Postoperatively, the incidences of emergence agitation (EA) and emergence delirium (ED) were measured by a blinded observer using a ten point scale (TPS; EA = TPS > 5 ED = TPS > 7) as well as vigilance, nausea/vomiting and shivering.

Results:  The two groups were comparable with respect to demographic data, duration of surgery and duration of anesthesia. There were also no differences in the period of time from the end of surgery until extubation, duration of stay in the PACU, postoperative vigilance and vegetative parameters. Incidence of EA was 30% (9/30) for sevoflurane and 34% (10/29) for isoflurane during the first 60 min in the PACU (P = 0.785). Likewise, the incidence of ED was not different between the groups (20% and 24%, respectively).

Conclusions:  In our randomized controlled study, we found no difference in the incidence of EA or ED between sevoflurane and isoflurane. Therefore, the decision to use one or the other should not be based upon the incidence of EA or ED.
Hemodynamic differences between propofol–remifentanil and sevoflurane anesthesia for repair of cleft lip and palate in infants
Authors: STEINMETZ JACOB , HOLM‐KNUDSEN ROLF , SØRENSEN MARTIN KRYSPIN , ERIKSEN KIRSTEN , RASMUSSEN LARS S.
Published: June 2006

Background:  Propofol–remifentanil anesthesia is widely used in adults but few studies are available in infants. We aimed at comparing the hemodynamic effects of propofol–remifentanil vs sevoflurane–fentanyl anesthesia. In addition, we sought to investigate recovery and whether remifentanil induced acute opioid tolerance.

Methods:  In total, 39 infants 4–6 months old were prospectively enrolled and randomized to receive either a combination of remifentanil and propofol (n = 17) or a sevoflurane–fentanyl anesthesia (n = 22) for surgical repair of cleft lip and palate. In both groups, sevoflurane was used for induction of anesthesia and fentanyl was administered before tracheal extubation. Mean arterial blood pressure and heart rate were recorded every 5 min after induction. We also recorded time from termination of surgery to tracheal extubation, postoperative behavior and the need for analgesia for the first 24 h after surgery. Postoperative observations were blinded.

Results:  In the remifentanil–propofol group, the mean arterial blood pressure was higher [58 (51–65) vs 51 (45–55), P = 0.02] and the mean heart rate was lower [111 (108–113) vs 128 (122–143), P < 0.0001]. There were no differences in recovery time or behavior after surgery. In the remifentanil group, a median fentanyl dose of 4 μg·kg−1 was required to insure a smooth recovery, but there was no difference in morphine consumption during the first 24 h after surgery.

Conclusions:  A high‐dose remifentanil–propofol infusion was associated with a higher blood pressure and lower heart rate than sevoflurane–fentanyl anesthesia in infants. Postoperative morphine consumption, recovery time and quality were similar.
Prevention of hypothermia in children under combined epidural and general anesthesia: a comparison between upper‐ and lower‐body warming
Authors: SHORRAB AHMED A. , EL‐SAWY MOHAMED E. , OTHMAN MAHMOUD M. , HAMMOUDA GOLINAR E.
Published: June 2006

Background:  Children receiving combined epidural and general anesthesia may be at greater risk of hypothermia. Active warming should be undertaken to combat heat loss. With combined epidural and general anesthesia heat loss from the lower body may be greater than from the upper body because of shift of blood towards the vasodilated lower body. We assumed that application of the warming blanket to the lower body might provide better protection against hypothermia. To test this hypothesis, lower‐body warming (LBW) was compared with upper‐body warming (UBW) in a randomized comparative study.

Methods:  Children subjected to open urologic surgery under combined epidural and general anesthesia were randomly allocated to either UBW n = 38 or LBW n = 35 using a forced‐air warming blanket. Core and peripheral skin temperatures were monitored. Temperature gradients between forearm and fingertip during LBW and between leg and toe during UBW were calculated. The warmer was set at 32°C, room temperature was around 22°C and fluids were infused at ambient room temperature.

Results:  The changes in core temperature were comparable and parallel in both groups. Core temperature decreased significantly in each group at 1 h after induction compared with basal values. Temperature gradients at forearm‐fingertip and at leg‐toe were also comparable in both groups. Recovery was uneventful and no patient shivered in the recovery room.

Conclusions:  Lower body warming is as effective as UBW in prevention of hypothermia in children subjected to combined epidural and general anesthesia.
Motion sickness as a predictor of postoperative vomiting in children aged 1–16 years
Authors: THOMAS MARK , WOODHEAD GREG , MASOOD NADIA , HOWARD RICHARD
Published: June 2006

Background:  Motion sickness (MS) may be a risk factor for postoperative vomiting (POV), but its independent predictive value in children is not known.

Methods:  A convenience sample of 70 consecutive patients aged 1–16 years scheduled for elective surgery were questioned, a history of MS was sought and patients were observed for the subsequent development of POV.

Results:  The overall incidence of POV was 29%. Fourteen children (20%) had a history of MS; MS‐positive children were more likely to vomit than those who were MS‐negative (P < 0.01). The type of surgery, use of opioids or prophylactic antiemetics did not differ significantly between the groups. The sensitivity of MS as a predictor of POV is 45% and the specificity 90%, giving a positive predictive value of 64.3% and a negative predictive value of 80.4%.

Conclusion:  Motion sickness is associated with POV in this group of children, but its positive predictive value is fairly low.
Study of nitrogen fixation in microbial communities of oil‐contaminated marine sediment microcosms
Authors: Musat Florin , Harder Jens , Widdel Friedrich
Published: June 2006

Aerobic microbial degradation of pollutant oil (petroleum) in aquatic environments is often severely limited by the availability of combined nitrogen. We therefore studied whether the microbial community enriched in marine sediment microcosms with an added oil layer and exposure to light harboured nitrogenase activity. The acetylene reduction (AR) assay indeed indicated active nitrogenase; however, similar activity was observed in oil‐free control microcosms. In both microcosms, the AR rate was significantly reduced upon a dark shift, indicating that enriched cyanobacteria were the dominant diazotrophs. Analysis of structural dinitrogenase reductase genes (nifH) amplified from both microcosms indeed revealed NifH sequences related mostly to those of heterocystous cyanobacteria. NifH sequences typically affiliating with those of heterotrophic bacteria were more frequently retrieved from the oil‐containing sediment. Expression analyses showed that mainly nifH genes similar to those of heterocystous cyanobacteria were expressed in the light. Upon a dark shift, nifH genes related to those of non‐heterocystous cyanobacteria were expressed. Expression of nifH assignable to heterotrophs was apparently not significant. It is concluded that cyanobacteria are the main contributors of fixed nitrogen to oil‐contaminated and pristine sediments if nitrogen is a limiting factor and if light is available. Hence, also the oil‐degrading heterotrophic community may thus receive a significant part of combined nitrogen from cyanobacteria, even though oil vice versa apparently does not stimulate an additional nitrogen fixation in the enriched community.
Late results of treatment of anal fistulas
Authors: Sygut A. , Zajdel R. , Kędzia‐Budziewska R. , Trzciński R. , Dziki A.
Published: June 2006

Objective  The aim of this paper was to analyse the results of treatment of anal fistulas retrospectively.

Methods  Between 1992 and 2004, 407 patients were operated on for perianal fistula. In the follow‐up period, 107 patients were lost, so 300 patients were analysed in the study. The mean follow‐up time was 4.2 years. Analysed parameters included: types of surgical procedures in different kinds of fistulas and postoperative complications. Various types of surgical procedures and their effectiveness were described. Late results were assessed taking into account healing time, duration of sick leave, recurrence rate and incidence of anal sphincter dysfunction. Severity of gas and stool incontinence was assessed according to the Cleveland Clinic Incontinence Score.

Results  In our study, subcutaneous fistula was diagnosed in 23.3%, inter‐sphincteric in 18%, trans‐sphincteric in 37.7%, supra‐sphincteric in 16% and extra‐sphincteric in 5% of patients. Single‐tract fistulas were present in 88.7% and multi‐tract fistulas were present in 11.3%. Overall, 242 patients had primary fistulas and 58 patients had recurrent fistulas. The most frequently performed procedures were cutting seton (139 patients) and radical fistulectomy (104 patients). Recurrent fistulas developed in 14.3%. Postoperative gas and/or stool incontinence was noticed in 10.7%. The recurrence rate was 5.4% in patients with primary fistula and in 51.7% patients presenting with a recurrent fistula. Gas and stool incontinence developed in 3.7% of patients with primary fistulas and in 39.7% of patients presenting with recurrent fistulas. Recurrence rate was 12% in the patients of single‐tract fistulas and 32.4% in the patients of multi‐tract fistulas. Postoperative gas and/or stool incontinence occurred in 8.3% of patients of single‐tract fistulas and in 29.4% of patients of multi‐tract fistulas.

Conclusions  The complication rate was 10‐fold higher in patients presenting with a recurrent fistula than in those with primary fistulas and threefold higher in patients with multi‐tract fistulas than in those with single‐tract fistulas.
Validation of a nomogram predicting the probability of lymph node invasion based on the extent of pelvic lymphadenectomy in patients with clinically localized prostate cancer
Authors: Briganti Alberto , Chun Felix K‐H. , Salonia Andrea , Gallina Andrea , Farina Elena , Da Pozzo Luigi F. , Rigatti Patrizio , Montorsi Francesco , Karakiewicz Pierre I.
Published: June 2006

OBJECTIVE

To develop a multivariate nomogram to predict the rate of lymph node invasion (LNI) in patients with clinically localized prostate cancer according to the extent of extended pelvic lymphadenectomy (PLND), which is associated with significantly higher rate of LNI.

PATIENTS AND METHODS

The study comprised 781 consecutive patients (median age 66.6 years, range 45–85) treated with PLND and radical retropubic prostatectomy (RRP) for clinically localized prostate cancer. Their median (range) prostate‐specific antigen (PSA) level was 7 (1.03–49.91) ng/mL, and their clinical stages were T1c in 433 (55.4%), T2 in 328 (42%) and T3 in 20 (2.6%). Biopsy Gleason sums were ≤ 6 in 514 (65.8%), 7 in 204 (26.1%) and 8–10 in 63 (8.1%). Multivariate logistic regression models were used to test the association between predictors including PSA level, biopsy Gleason sum, clinical stage, number of nodes removed and the rate of LNI. Finally, regression coefficients were used to develop a nomogram, which was internally validated with 200 bootstrap re‐samples.

RESULTS

The median (range) number of lymph nodes removed was 14 (2–40); LNI was detected in 71 patients (9.1%). The univariate predictive accuracy for total PSA level, clinical stage, biopsy Gleason sum and number of total nodes removed and examined was 64.2%, 59.8%, 74% and 62.9%, respectively. Except for PSA (P = 0.2), all variables were statistically significant multivariate predictors of LNI at RRP (P ≤ 0.001). A nomogram based on clinical stage, PSA level, biopsy Gleason sum and the number of total lymph nodes removed was 78.6% accurate, and 1.8% more accurate than a nomogram without the number of removed lymph nodes.

CONCLUSIONS

The extent of PLND is directly related to the probability of LNI. The risk of LNI increases linearly, and is proportional to the number of nodes removed and examined. The effect of the increased probability of LNI is weighted more heavily in men with more advanced clinical stage and grade.
The effect of intracavernosal growth differentiation factor‐5 therapy in a rat model of cavernosal nerve injury
Authors: FANDEL THOMAS M. , BELLA ANTHONY J. , TANTIWONGSE KAVIRACH , GARCIA MAURICE , NUNES LORA , THüROFF JOACHIM W. , TANAGHO EMIL A. , POHL JENS , LUE TOM F.
Published: June 2006

OBJECTIVE

To determine whether the intracavernosal application of growth differentiation factor‐5 (GDF‐5) influences nerve regeneration and erectile function after cavernosal nerve injury in a rat model.

MATERIALS AND METHODS

Thirty‐two male Sprague‐Dawley rats were randomly divided into four equal groups: eight had a sham operation (uninjured controls), while 24 had bilateral cavernosal nerve crush. The crush‐injury groups were treated at the time of injury with an impregnated collagen sponge implanted into the right corpus cavernosum. The sponge contained no GDF‐5 (injured controls), 2 µg (low concentration), or 20 µg GDF‐5 (high concentration). Erectile function was assessed by cavernosal nerve electrostimulation at 8 weeks. Midshaft penile tissue samples were histochemically evaluated for neuronal nitric oxide synthase (nNOS)‐containing fibres in the dorsal penile nerve.

RESULTS

There was no erectile dysfunction in the uninjured control group, as shown by a mean (sem) maximal increase in intracavernosal pressure (ICP) of 149.5 (17.0) cmH2O on stimulation. By comparison, the ICP decreased in the injured control group, by 21.3 (6.7) cmH2O. After cavernosal nerve injury, the recovery of erectile function was greatest in the low‐concentration GDF‐5 group; the maximum ICP increase was 40.8 (13.3) cmH2O, vs 24.3 (5.9) cmH2O for 20 µg GDF‐5. Histologically, the low‐concentration group had significantly more nNOS‐containing nerve fibres, at 163 (24.7), than the high‐concentration group, at 76 (17.3), or injured controls, at 67 (23.8). By contrast, the uninjured controls had a mean of 538 (40.6) nerve fibres in the dorsal nerve.

CONCLUSION

Bilateral cavernosal nerve crush resulted in erectile dysfunction with accompanying neurological changes in the rat. The intracavernosal application of GDF‐5 enhanced the recovery of erectile function and n‐NOS nerve preservation, with a 2‐µg dose giving the most promising results.
Trends in the operative management of renal tumours over a 14‐year period
Authors: Permpongkosol Sompol , Bagga Herman S. , Romero Frederico R. , Solomon Stephen B. , Kavoussi Louis R.
Published: June 2006

OBJECTIVE

To review the trends in the operative management of renal tumours over a 14‐year period at a university hospital, as the therapeutic options available for treating renal tumours have increased over the past decade.

PATIENTS AND METHODS

The study was a retrospective chart review of 1621 consecutive patients undergoing treatment for renal tumours from January 1991 to March 2005. The characteristics assessed included patient demographics, tumour size, operative duration and treatment.

RESULTS

During the study period, 624 (38.6%) open, 883 (54.6%) laparoscopic and 111 (6.7%) percutaneous approaches were performed. The number of renal tumours treated increased annually, as did the use of minimally invasive techniques (93.4% in 2005). Conversely, the number of open surgical treatments used declined both absolutely and proportionally. Over the study period, for tumours of ≤ 4 cm, laparoscopic partial nephrectomy was the most common approach (41.0%). Percutaneous ablation has also made an impact as a treatment method for small tumours (13.8% in 2005). For tumours of >7 cm, open radical nephrectomy (ORN) was the most common method of treatment over all years. However, since 2002, laparoscopic radical nephrectomy (LRN) surgery has been increasingly used over ORN for treating this tumour group (73% LRN vs 19.2% ORN in 2004).

CONCLUSION

The available treatment options for renal tumours have increased significantly since the early 1990s. At a university hospital in which there are physicians with a specific interest in minimally invasive surgery and ablative treatments, minimally invasive approaches have become the standard treatment.
Prevalence and associations of low plasma erythropoietin in patients with Type 2 diabetes mellitus
Authors: Mojiminiyi O. A. , Abdella N. A. , Zaki M. Y. , El Gebely S. A. , Mohamedi H. M. , Aldhahi W. A.
Published: June 2006

Aims  Low plasma erythropoeitin (EPO) is a key causal factor in the anaemia of diabetic patients. The aim of this study was to investigate the prevalence of anaemia in relation to EPO in patients with Type 2 diabetes.

Methods  In a clinic‐based cross‐sectional study of 161 Type 2 diabetes patients, we measured EPO, ferritin and full blood count. The patients were classified on the basis of the urine albumin:creatinine excretion ratio as normo‐, micro‐ or macroalbuminuric. Serum creatinine, cystatin C and glomerular filtration rate (GFR) calculated from cystatin C were used as markers of renal function. All the patients were assessed for symptoms and signs of diabetic complications, including diabetic peripheral sensory neuropathy (PSN).

Results  Twenty‐one (13.0%) patients were anaemic; 80 patients (49.7%) had low EPO (< 5 mU/ml), of whom 28.8% had a GFR < 60 ml/min per 1.73 m2; 57.5% were normoalbuminuric, 33.7% were microalbuminuric and 8.8% macroalbuminuric. Although EPO was significantly higher in anaemic patients compared with non‐anaemic patients, the EPO response was inappropriate for the degree of anaemia. Of patients with PSN, 66.7% had low EPO but there was no significant difference in EPO between patients with and without PSN. Log EPO correlated significantly with urine microalbumin:creatinine ratio and logistic regression analysis showed that haemoglobin, age and urine microalbumin: creatinine ratio were the main determinants of EPO.

Conclusions  The degree of microalbuminuria is the most significant determinant of plasma EPO, which is often low or inappropriately normal in diabetic patients with and without anaemia.
GAD antibodies in probands and their relatives in a cohort clinically selected for Type 2 diabetes
Authors: Castleden H. A. J. , Shields B. , Bingley P. J. , Williams A. J. K. , Sampson M. , Walker M. , Gibson J. M. , McCarthy M. I. , Hitman G. A. , Levy J. C. , Hattersley A. T. , Vaidya B. , Pearson E. R.
Published: June 2006

Aims  A subset of patients who present as if they have Type 2 diabetes have positive pancreatic autoantibodies, and have been referred to as having latent autoimmune diabetes in adults (LADA). We assessed the prevalence and clinical characteristics of patients with glutamic acid decarboxylase antibodies (GADA) in a cohort clinically selected for Type 2 diabetes and determined the presence of diabetes and GADA in their first‐degree relatives.

Methods  GADA were measured in 2059 subjects, not known to be related, and clinically selected as having Type 2 diabetes for genetic studies. Clinical characteristics were compared in GADA positive and GADA negative subjects. Diabetes and GAD antibody status were compared in 208 first‐degree relatives of GADA positive and GADA negative probands.

Results  Of the subjects, 136 (7%) were GADA positive. Compared with the GADA negative subjects, they were slimmer (P < 0.001), diagnosed at a younger age (P = 0.011) and progressed to insulin faster (P < 0.001). Thirty‐three per cent of GADA positive subjects had a first‐degree relative with diabetes compared with 42% of GADA negative subjects (P = 0.034). The overall prevalence of GADA was similar in the first‐degree relatives of GADA positive and GADA negative probands (4 v 5%), and 19 of 22 (86%) diabetic relatives of GADA positive probands were GADA negative.

Conclusion  Despite clinically selecting a Type 2 diabetes cohort, 7% were GADA positive with an altered phenotype. These GADA positive patients had a strong family history of non‐autoimmune diabetes. This suggests that, in this subgroup of patients, autoimmune pancreatic β‐cell destruction occurs on a background of Type 2 diabetes genetic susceptibility.
Strategies and students: beginning teachers' early encounters with national policy
Authors: Rosowsky Andrey
Published: June 2006

The 1‐year Postgraduate Certificate in Education Secondary English method course at the University of Sheffield's School of Education has, since 2001, asked its students to write an essay of around 4000 words on their initial understanding and experience of the National Strategies promoted by the United Kingdom's Department for Education and Skills. The essay expects a critical, reflective and analytical piece of writing that records the student teacher's developing views on the place, role and value of the National Strategies in the classroom. Using grounded theory and content analysis techniques, this small‐scale study of the 2005 cohort identifies common perceptions regarding the National Strategies among student teachers of English and seeks to categorise these to account for their developing identities as future English teachers. Drawing on Twiselton's identification of teacher types, Task Manager, Curriculum Deliverer and Concept/Skill Builder, and Shulman's classification of knowledges necessary for teaching, this article will argue that the National Strategies and their respective Frameworks, while successful in moving teachers on from the role of ‘Task Managers’, runs the risk of locking teachers into being ‘Curriculum Deliverers’, and not developing the pedagogical content knowledge necessary for teaching English expertly.
Transformations in learning and teaching through Initial Teacher Education
Authors: Stevens David , Hodges Gabrielle Cliff , Gibbons Simon , Hunt Philippa , Turvey Anne
Published: June 2006

In England, little research has been carried out into how pre‐service secondary English teachers transform what they know as they learn to teach. They are seldom asked to reflect explicitly on the connections between the pedagogy of their undergraduate studies and their pedagogical experiences as student teachers. The initial teacher education committee of the National Association for the Teaching of English decided to explore these connections by asking student teachers on English Postgraduate Certificate in Education (PGCE) courses in five different university departments of education to respond to a series of questions at the start and end of the academic year 2004–2005. The questions fall into four broad areas: student teachers' experiences as learners at undergraduate level and developing ideas about teaching; the nature of the subject English; tensions encountered during the PGCE course; new learning about teaching. The purpose of this article is to discuss some patterns emerging from the research. The most prominent of these is student teachers' realisation that good teaching comes from teachers seeing themselves as learners. We argue that ‘reflexivity’ (Moore, 2004) is a valuable way to help student teachers begin to understand this transformation from learner into learning teacher.
“Too many theories and not enough instruction”: perceptions of preservice teacher preparation for literacy teaching in Australian schools
Authors: Louden William , Rohl Mary
Published: June 2006

In this paper, we describe part of an Australian national research project that aimed to find out how well prepared beginning teachers are to teach literacy. A majority of beginning teachers participating in a series of national surveys and focus group meetings were confident about their personal literacy skills, their conceptual understandings of literacy, their understanding of curriculum documents and assessment strategies and their broad preparation to teach. Fewer beginning teachers were confident about their capacity to teach specific aspects of literacy such as viewing, spelling, grammar and phonics, or about their capacity to meet the challenges of student diversity. Senior staff working with beginning teachers were generally sceptical about the quality of teacher preparation for teaching literacy and were less confident than the beginning teachers about personal literacy skills. We discuss these findings in relation to the relative importance placed on particular substantive and structural issues by the study participants and in terms of previous findings.
Identification of potential target genes for RFX4_v3, a transcription factor critical for brain development
Authors: Zhang Donghui , Stumpo Deborah J. , Graves Joan P. , DeGraff Laura M. , Grissom Sherry F. , Collins Jennifer B. , Li Leping , Zeldin Darryl C. , Blackshear Perry J.
Published: June 2006

Regulatory factor X4 variant transcript 3 (Rfx4_v3) gene disruption in mice demonstrated that interruption of a single allele (heterozygous, +/–) prevented formation of the subcommissural organ, resulting in congenital hydrocephalus, while interruption of two alleles (homozygous, –/–) caused fatal failure of dorsal midline brain structure formation. To identify potential target genes for RFX4_v3, we used microarray analysis to identify differentially expressed genes in Rfx4_v3‐deficient mouse brains at embryonic day 10.5, before gross structural changes were apparent. Of 109 differentially expressed transcripts, 24 were chosen for validation and 22 were confirmed by real‐time PCR. Many validated genes encoded critical proteins involved in brain morphogenesis, such as the signaling components in the Wnt, bone morphogenetic protein (BMP) and retinoic acid (RA) pathways. Cx3cl1, a CX3C‐type chemokine gene that is highly expressed in brain, was down‐regulated in the Rfx4_v3‐null mice. Both human and mouse Cx3cl1 proximal promoters contained highly conserved X‐boxes, known cis‐acting elements for RFX protein binding. Using the Cx3cl1 promoter as an example of a target gene, we demonstrated direct binding of RFX4_v3 to the Cx3cl1 promoter, and trans‐acting activity of RFX4_v3 protein to stimulate gene expression. These data suggest that RFX4_v3 may act upstream of critical signaling pathways in the process of brain development.
Proteomic analysis of rat hippocampal plasma membrane: characterization of potential neuronal‐specific plasma membrane proteins
Authors: Chen Ping , Li Xuanwen , Sun Yalan , Liu Zhen , Cao Rui , He Quanyuan , Wang Meichi , Xiong Jixian , Xie Jinyun , Wang Xianchun , Liang Songping
Published: June 2006

The hippocampus is a distinct brain structure that is crucial in memory storage and retrieval. To identify comprehensively proteins of hippocampal plasma membrane (PM) and detect the neuronal‐specific PM proteins, we performed a proteomic analysis of rat hippocampus PM using the following three technical strategies. First, proteins of the PM were purified by differential and density‐gradient centrifugation from hippocampal tissue and separated by one‐dimensional electophoresis, digested with trypsin and analyzed by electrospray ionization (ESI) quadrupole time‐of‐flight (Q‐TOF) tandem mass spectrometry (MS/MS). Second, the tryptic peptide mixture from PMs purified from hippocampal tissue using the centrifugation method was analyzed by liquid chromatography ion‐trap ESI‐MS/MS. Finally, the PM proteins from primary hippocampal neurons purified by a biotin‐directed affinity technique were separated by one‐dimensional electrophoresis, digested with trypsin and analyzed by ESI‐Q‐TOF‐MS/MS. A total of 345, 452 and 336 non‐redundant proteins were identified by each technical procedure respectively. There was a total of 867 non‐redundant protein entries, of which 64.9% are integral membrane or membrane‐associated proteins. One hundred and eighty‐one proteins were detected only in the primary neurons and could be regarded as neuronal PM marker candidates. We also found some hypothetical proteins with no functional annotations that were first found in the hippocampal PM. This work will pave the way for further elucidation of the mechanisms of hippocampal function.
Calpain inhibitors and antioxidants act synergistically to prevent cell necrosis: effects of the novel dual inhibitors (cysteine protease inhibitor and antioxidant) BN 82204 and its pro‐drug BN 82270
Authors: Pignol Bernadette , Auvin Serge , Carré Denis , Marin Jean‐Grégoire , Chabrier Pierre‐Etienne
Published: June 2006

Cell death is a common feature observed in neurodegenerative disorders, and is often associated with calpain activation and overproduction of reactive oxygen species (ROS). This study investigated the use of calpain inhibitors and antioxidants in combination to protect cells against necrosis. Maitotoxin (MTX), which induces a massive influx of calcium, was used to provoke neuronal cell death. This toxin increased, in a concentration‐dependent manner, both calpain activity and ROS formation. Calpain inhibitors or antioxidants inhibited MTX‐induced necrosis only marginally (below 20%), whereas their association protected against cell death by 40–66% in a synergistic manner. BN 82204, which possesses both calpain–cathepsin L inhibitory and antioxidant properties, and its acetylated pro‐drug BN 82270, totally protected cells at 100 µm. The pro‐drug BN 82270, which had better cell penetration, was twice as effective as the active principle BN 82204 in protecting glioma C6 or neuroblastoma SHSY5Y cells against death. These results suggest the potential therapeutic relevance of using a single molecule with multiple activities (cysteine protease inhibitor/antioxidant), and warrant further in vivo investigations in models of neuronal disorders.
Ceramide is the key mediator of oxidative stress‐induced apoptosis in retinal photoreceptor cells
Authors: Sanvicens Nuria , Cotter Thomas G.
Published: June 2006

Nitric oxide and reactive oxygen species play a critical role in photoreceptor apoptosis. However, the exact molecular mechanisms triggered by oxidative stress in photoreceptor cell death remain undefined. Here, we demonstrate that the sphingolipid ceramide is the key mediator of oxidative stress‐induced apoptosis in 661W retinal photoreceptor cells. Treatment of 661W cells with the nitric oxide donor, sodium nitroprusside, activates acid sphingomyelinase. As a result, sphingomyelin is hydrolysed, which leads to an increase in the concentration of ceramide. We also show that ceramide is responsible for the activation of the mitochondrial apoptotic pathway in 661W photoreceptor cells and subsequent activation of the caspase cascade. Furthermore, we show for the first time that ceramide is responsible for the increased Ca2+ levels in the mitochondria and cytosol that precedes activation of the calpain‐mediated apoptotic pathway. Additionally, we provide evidence that ceramide also activates the endolysosomal protease cathepsin D pathway. In summary, our findings show that ceramide controls the cell death decisions in photoreceptor cells and highlight the relevance of acid sphingomyelinase as a potential therapeutic target for the treatment of retinal pathologies.
REVIEW: Pin1 in Alzheimer's disease
Authors: Butterfield D. Allan , Abdul Hafiz Mohmmad , Opii Wycliffe , Newman Shelley F. , Joshi Gururaj , Ansari Mubeen Ahmad , Sultana Rukhsana
Published: June 2006

Proteolytic processing and phosphorylation of amyloid precursor protein (APP), and hyperphosphorylation of tau protein, have been shown to be increased in Alzheimer's disease (AD) brains, leading to increased production of β‐amyloid (Aβ) peptides and neurofibrillary tangles, respectively. These observations suggest that phosphorylation events are critical to the understanding of the pathogenesis and treatment of this devastating disease. Pin‐1, one of the peptidyl‐prolyl isomerases (PPIase), catalyzes the isomerization of the peptide bond between pSer/Thr‐Pro in proteins, thereby regulating their biological functions which include protein assembly, folding, intracellular transport, intracellular signaling, transcription, cell cycle progression and apoptosis. A number of previous studies have shown that Pin1 is co‐localized with phosphorylated tau in AD brain, and shows an inverse relationship to the expression of tau. Pin1 protects neurons under in vitro conditions. Moreover, recent studies demonstrate that APP is a target for Pin1 and thus, in Aβ production. Furthermore, Pin1 was found to be oxidatively modified and to have reduced activity in the hippocampus in mild cognitive impairment (MCI) and AD. Because of the diverse functions of Pin1, and the discovery that this protein is one of the oxidized proteins common to both MCI and AD brain, the question arises as to whether Pin1 is one of the driving forces for the initiation or progression of AD pathogenesis, finally leading to neurodegeneration and neuronal apoptosis. In the present review, we discuss the role of Pin1 with respect to Alzheimer's disease.
Microtubules are required for NF‐κB nuclear translocation in neuroblastoma IMR‐32 cells: modulation by zinc
Authors: Mackenzie Gerardo G. , Keen Carl L. , Oteiza Patricia I.
Published: June 2006

The relevance of a functional cytoskeleton for Nuclear Factor‐κB (NF‐κB) nuclear translocation was investigated in neuronal cells, using conditions that led to a disruption of the cytoskeleton [inhibition of tubulin (vinblastine, colchicine), or actin (cytochalasin D) polymerization and zinc deficiency]. We present evidence that an impairment in tubulin polymerization can inhibit the formation of the complex tubulin‐dynein‐karyopherin α‐p50 that is required for neuronal retrograde and nuclear NF‐κB transport. Cells treated with vinblastine, colchicine or cytochalasin D, and zinc deficient cells, all showed a low nuclear NF‐κB binding activity, and low nuclear concentrations of RelA and p50. The altered nuclear translocation was reflected by a decreased transactivation of NF‐κB‐driven genes. The immunocytochemical characterization of cellular RelA showed that cytoskeleton disruption can lead to an altered distribution of RelA resulting in the formation of peripheral accumuli. These results support the concept that cytoskeleton integrity is necessary for the transport and translocation of NF‐κB required for synapse to nuclei communication. We suggest that during development, as well as in the adult brain, conditions such as zinc deficiency, that affect the normal structure and function of the cytoskeleton can affect neuronal proliferation, differentiation, and survival by altering NF‐κB nuclear translocation and subsequent impairment of NF‐κB‐dependent gene regulation.