bluuebunny/crossref_metadata_2025 huggingface dataset:
CTLA‐4 expression in T cells of patients with atopic dermatitis
Authors: Choi Sung Yon , Sohn Myung Hyun , Kwon Byoung Chul , Kim Kyu‐Earn
Published: August 2005

Cytotoxic T lymphocyte‐associated antigen‐4 (CTLA‐4; CD152) is a surface molecule of activated T cells with sequence homologous to CD28, and may act as a negative regulator of T‐cell activation. In murine animal models, cross‐linkage of CTLA‐4 molecules on the cell surface results in decreased T‐cell proliferation, accompanied by increased interleukin (IL)‐2 production and apotosis. To clarify the activation of peripheral blood T cells, we studied the CTLA‐4 expression in 32 patients with atopic dermatitis who visited our institution, and 19 normal children who visited for pre‐operative laboratory examination were used as normal controls. Whole blood was obtained from all subjects and stained with anti‐CD3, anti‐CD4, anti‐CD8 monoclonal antibodies (mAb). After erythrocyte lysis with lysing solution, the cells were stained with anti‐CTLA‐4 mAb, and stained cells were analysed by fluorescence‐activated cell sorter (FACScan) flow cytometer. Intracellular expression of CTLA‐4 was significantly upregulated in peripheral blood CD3+ T cells (36.8%), CD4+ T cells (21.7%) and CD8+ T cells (18.7%) of patients with atopic dermatitis, compared with normal control (18.3%, 9.7%, 9.8%; respectively). Furthermore, CTLA‐4‐positive CD3+ T cells in patients with severe atopic dermatitis were significantly higher compared with milder group (42.8% vs. 32.2%). However, no significant difference was obtained in CD4+ and CD8+ T cells. Mean percentage of T cells expressing CTLA‐4 in patients with atopic dermatitis was higher than the control group. These observations suggest the possibility that the disease activity can be correlated with the CTLA‐4 level.
The efficacy and safety of heat‐killed Lactobacillus paracasei for treatment of perennial allergic rhinitis induced by house‐dust mite
Authors: Peng Guei‐Cheng , Hsu Ching‐Hsiang
Published: August 2005

Live Lactobacillus paracasi 33 (LP33) may effectively improve the quality of life for patients with perennial allergic rhinitis. It has been demonstrated that heat‐killed lactic acid bacteria (LAB) suppress specific immunoglobulin E synthesis and stimulate interleukin‐12 production in animals. The aim of this study was, therefore, to evaluate the efficacy of heat‐killed LP33 in the treatment of allergic rhinitis induced by house‐dust‐mite in human subjects. A total of 90 patients were enrolled in a randomized, double blind, placebo‐controlled trial and assigned to three treatment groups. Patients in groups A and B received two capsules per day of live or heat‐killed LAB (5 × 109 colony‐forming units/capsule), respectively, over a period of 30 days while those in Group C received placebo capsules. A modified questionnaire on pediatric rhinoconjunctivitis‐related quality of life was administered to all subjects or their parents during each clinical visit. The overall quality of life score decreased for groups A and B, as compared with the placebo group, in terms of both frequency (9.47 ± 2.89, 6.30 ± 2.19, vs. −3.47 ± 1.53, respectively; p < 0.0001) and level of bother (5.91 ± 3.21, 6.04 ± 2.44, vs. −2.80 ± 1.64, respectively; p = 0.004) after the 30‐day treatment. The efficacy of the heat‐killed LP33 was not inferior to the live variant. No obvious side effects were reported for either active treatment group during the study period. Our results suggest that heat‐killed LP33 can effectively improve the overall quality of life for patients with allergic rhinitis, and that it may be efficacious as an alternative treatment.
Sensitization to common indoor allergens and its association with allergic diseases in Thai female high‐school students
Authors: Prasarnphanich Thanong , Sindhurat Sintra
Published: August 2005

Allergic sensitization is generally agreed to be an important risk factor for allergic diseases. It has been demonstrated in most of the children attending allergy clinics in Thailand but has never been studied in Thai general populations. The objectives were (i) to describe the prevalence of sensitization to common indoor allergens in Thai female‐high‐school students and (ii) to evaluate the association of allergic sensitization to allergic diseases in these students. cross‐sectional analytic study was designed. Seven hundred and six schoolgirls were enrolled during May–June 2002. Written ISAAC questionnaires were completed by the students and skin prick tests were performed in 344 (48.7%) students with a battery of seven common allergens including Dermatophagoides pteronyssinus, Dermatophagoides farinae, American cockroach, Cat, Cladosporium, Penicillium, and Aspergillus. Positive test was defined as a mean wheal diameter of at least 3 mm at the 15 min reading. The adjusted odds ratios (OR) and 95% confidence intervals (CI) were obtained from multiple regression analysis for the independent effect of sensitization to each allergen on allergic diseases. A total of 154 (44.8%) students had evidence of allergic sensitization on skin prick tests. The prevalence rates of sensitization to various groups of allergens were as follows; mites 43.0%, cockroach 12.8%, cat 4.1%, and molds 1.2%. The independent effect of allergic sensitization on allergic diseases was observed only in mite sensitization on nose problem (OR = 1.73, CI = 1.07–2.78 for nose problem ever and OR = 1.85, CI = 1.13–3.02 for nose problem in 12 months). The risk of nose problem was also increased with the number of positive reactons. Conclusion: We found that sensitization to the four common allergen groups were weakly associated with the presence of allergic diseases in Thai schoolgirls. This confirms the observation that the development of allergic diseases is not solely attributable to allergic sensitization.
Increased IFN‐γ secretion from duodenal biopsy samples in delayed‐type cow's milk allergy
Authors: Paajanen Laura , Vaarala Outi , Karttunen Riitta , Tuure Tuula , Korpela Riitta , Kokkonen Jorma
Published: August 2005

A delayed and local gastrointestinal hypersensitivity to cow's milk (CM) protein is difficult to diagnose and there are limited data on this disorder. The aim of this study was to investigate local intestinal cytokine secretion in the upper small intestine in children with delayed‐type cow's milk allergy (CMA). Duodenal biopsy samples from 31 children with delayed CMA, 14 with celiac disease (CD), and 14 healthy controls were studied for the spontaneous release of IFN‐γ, TNF‐α, IL‐2, IL‐4, IL‐5, and IL‐10, measured by cytometric bead array, and of TGF‐β and IL‐6 measured by ELISA. The children with delayed CMA secreted more IFN‐γ than the controls (p = 0.006) and the children with CD (p = 0.006). The children with CD secreted more IL‐6 compared to the controls (p = 0.008) and the children with delayed CMA (p = 0.002). The children with delayed CMA who had continuously been exposed to CM secreted less TGF‐β than the children with delayed CMA who avoided CM (p = 0.050), and showed a tendency towards lower secretion compared to the controls (p = 0.078). Secretions of TNF‐α, IL‐2, IL‐4, IL‐5, and IL‐10 were low in general; however, the children with delayed CMA who did not avoid CM secreted more IL‐4 and IL‐10 than the controls (p = 0.016, 0.059). In conclusion, the children with delayed CMA showed up‐regulation of IFN‐γ. Interestingly, TGF‐β secretion was up‐regulated in those children with delayed CMA who avoided CM suggesting recovery of regulation mechanisms.
Effect of prolonged mechanical ventilation on diaphragm muscle mitochondria in piglets
Authors: Fredriksson K. , Radell P. , Eriksson L. I. , Hultenby K. , Rooyackers O.
Published: August 2005

Background:  Respiratory muscle weakness is a common problem in the intensive care unit and could be involved in difficulties in weaning from the ventilator after prolonged mechanical ventilation. Animal models have shown that mechanical ventilation itself impairs diaphragm muscle function. In this study we investigated whether diaphragm contractile impairment caused by mechanical ventilation and immobilization in piglets is associated with a derangement in diaphragm mitochondria.

Methods:  Seven piglets received controlled mechanical ventilation during 5 days. A control group of eight piglets were anaesthetized and surgically manipulated in the same way, but were mechanically ventilated for 4–6 h. After mechanical ventilation, diaphragm muscle biopsies were taken for measurements of mitochondria content, mitochondrial respiratory enzymes and markers of oxidative stress.

Results:  Diaphragm mitochondrial content, as assessed by citrate synthase activities and volume density, was not different between the control and ventilated piglets. Activity of complex IV of the mitochondrial respiratory chain decreased by 21% (P = 0.02) when expressed per muscle weight and by 11% (P = 0.03) when expressed per citrate synthase activity. There were no changes in the markers of oxidative stress between the two groups.

Conclusion:  Five days of mechanical ventilation and immobilization decreased the activity of complex IV of the mitochondrial respiratory chain in the diaphragm muscle of the piglets.
Respiration can be monitored by photoplethysmography with high sensitivity and specificity regardless of anaesthesia and ventilatory mode
Authors: Nilsson L. , Johansson A. , Kalman S.
Published: August 2005

Background:  Photoplethysmography (PPG) is a non‐invasive optical technique used, for instance, in pulse oximetry. Beside the pulse synchronous component, PPG has a respiratory synchronous variation (PPGr). Efforts have been made to utilize this component for indirect monitoring of respiratory rate and volume. Assessment of the clinical usefulness as well as of the physiological background of PPGr is required. We evaluated if anaesthesia and positive‐pressure ventilation would affect PPGr.

Methods:  We recorded reflection mode PPGr, at the forearm, and the respiratory synchronous changes in central venous pressure (CVP), peripheral venous pressure (PVP) and arterial blood pressure (ABP) in 12 patients. Recordings for each patient were made on three occasions: awake with spontaneous breathing; anaesthetized with spontaneous breathing; and anaesthetized with positive‐pressure ventilation. We analyzed the sensitivity, specificity, coherence and time relationship between the signals.

Results:  PPGr sensitivity for breath detection was [mean (SD)] >86(21)% and specificity >96(12)%. Respiratory detection in the macrocirculation (CVP, PVP and ABP) showed a sensitivity >83(29)% and specificity >93(12)%. The coherence between signals was high (0.75–0.99). The three measurement situations did not significantly influence sensitivity, specificity or time shifts between the PPGr, PVP, ABP, and the reference CVP signal despite changes in physiological data between measurements.

Conclusion:  A respiratory synchronous variation in PPG and all invasive pressure signals was detected. The reflection mode PPGr signal seemed to be a constant phenomenon related to respiration regardless of whether or not the subject was awake, anaesthetized or ventilated, which increases its clinical usefulness in respiratory monitoring.
McArdle's disease and anaesthesia: Case reports. Review of potential problems and association with malignant hyperthermia
Authors: Bollig G. , Mohr S. , Ræder J.
Published: August 2005

Background: McArdle's disease of isolated deficiency in glycogen degradation in skeletal muscles has the potential of creating perioperative anaesthesiological problems; such as hypoglycaemia, rhabdomyolysis, myoglobinuria, acute renal failure and possibly malignant hyperthermia.

Methods: Eight patients with McArdle's disease were asked about previous surgery, anaesthesia and perioperative problems, and available hospital records were reviewed. Existing literature was reviewed for reports on McArdle's disease and anaesthesia.

Results: The eight patients had 35 anaesthesias (23 general anaesthesias, three regional anaesthesias and nine local anaesthesias). Perioperative problems of a non‐specific nature were mentioned in three cases of general anaesthesia: two with postoperative nausea/vomiting, and one with an episode of tachycardia and low blood pressure. Three patients were tested for malignant hyperthermia (MH) using thein vitrocontracture test (IVCT); two of them with a positive result. The literature search revealed seven case reports of McArdle's disease and anaesthesia. Apart from one report of hyperthermia, pulmonary oedema and rhabdomyolysis; probably not associated with MH, no problems were encountered from the literature search.

Conclusion: McArdle's disease does not seem to cause severe perioperative problems in routine anaesthetic care. However, measures for preventing muscle ischaemia and rhabdomyolysis should be kept in mind, as well as the potential for these patients to develop postoperative fatigue, myoglobinuria and renal failure. Although no clinical association with malignant hyperthermia has been established, many of these patients can have a positivein vitrocontracture test, and simple prophylactic measures, as with malignant hyperthermia, may be recommended if otherwise not contraindicated.
Venous oxygen saturation during normovolaemic haemodilution in the pig
Authors: Krantz T. , Warberg J. , Secher N. H.
Published: August 2005

Background:  Hypovolaemia may be considered to represent a volume‐restricted cardiac output (CO), but CO varies inversely with the haemoglobin concentration (Hb) and a maximal mixed venous oxygen saturation (SvO2) may be a better target for volume administration than a maximal CO.

Methods:  In 10 anaesthetized pigs, volume loading with 6% hydroxyethyl starch was performed to obtain a maximal SvO2 followed by normovolaemic haemodilution with 6% hydroxyethyl starch.

Results:  Volume loading increased SvO2 from 55.0 ± 5.2% to 64.8 ± 9.0% (mean ± SD) associated with an increase in CO (2.3 ± 0.4 to 3.5 ± 0.9 l/min) and central venous oxygen saturation (ScvO2; 68.2 ± 9.3% to 79.4 ± 7.2%; P < 0.05). Heart rate (HR), mean arterial (MAP), central venous (CVP), pulmonary arterial mean (PAMP), and occlusion pressures (PAOP) increased as well (P < 0.05). In contrast, during progressive haemodilution, SvO2 and ScvO2 remained statistically unchanged until the haemoglobin concentration had decreased from 5.5 ± 0.4 to 2.9 ± 0.2 mM, while CO and HR increased at a haemoglobin value of 4.4 ± 0.4 and 4.0 ± 0.4 mM and CVP and PAOP decreased at a haemoglobin of 4.0 ± 0.4 and 2.9 ± 0.2 mM, respectively (P < 0.05) leaving MAP unaffected.

Conclusion:  This study found that volume loading increased cardiac output and mixed and central venous oxygen saturations in parallel, but during normovolaemic haemodilution an increase in cardiac output left mixed and central venous oxygen saturations statistically unchanged until haemoglobin concentration was reduced by ∼50%. Accordingly, volume therapy should be directed to maintain a high venous oxygen saturation rather than a change in cardiac output.
Single‐dose dexmedetomidine attenuates airway and circulatory reflexes during extubation
Authors: Guler G. , Akin A. , Tosun Z. , Eskitascoglu E. , Mizrak A. , Boyaci A.
Published: August 2005

Background:  The alpha agonist dexmedetomidine, a sedative and analgesic, reduces heart rate and blood pressure dose‐dependently. We investigated whether it also has the ability to attenuate airway and circulatory reflexes during emergence from anaesthesia.

Methods:  Sixty ASA I–III patients received a standard anaesthetic. Five minutes before the end of surgery, they were randomly allocated to receive either dexmedetomidine 0.5 µg/kg (Group D) (n = 30) or saline placebo (Group P) (n = 30) intravenously (i.v.) over 60 s in a double‐blind design. The blinded anaesthetist awoke all the patients, and the number of coughs per patient was continuously monitored for 15 min after extubation; coughing was evaluated on a 4‐point scale. Any laryngospasm, bronchospasm or desaturation was recorded. Heart rate (HR) and systolic and diastolic blood pressure (SAP, DAP) were measured before, during and after tracheal extubation. The time from tracheal extubation and emergence from anaesthesia were recorded.

Results:  Median coughing scores were 1 (1–3) in Group D and 2 (1–4) in Group P (P < 0.05), but there were no differences between the groups in the incidence of breath holding or desaturation. HR, SAP and DAP increased at extubation in both groups (P < 0.05), but the increase was less significant with dexmedetomidine. The time from tracheal extubation and emergence from anaesthesia were similar in both groups.

Conclusion:  These findings suggest that a single‐dose bolus injection of dexmedetomidine before tracheal extubation attenuates airway‐circulatory reflexes during extubation.
Pre‐operative fasting guidelines: an update
Authors: Søreide E. , Eriksson L. I. , Hirlekar G. , Eriksson H. , Henneberg S. W. , Sandin R. , Raeder J. ,   (Task Force on Scandinavian Pre‐operative Fasting Guidelines, Clinical Practice Committee Scandinavian Society of Anaesthesiology and Intensive Care Medicine)
Published: August 2005

Liberal pre‐operative fasting routines have been implemented in most countries. In general, clear fluids are allowed up to 2 h before anaesthesia, and light meals up to 6 h. The same recommendations apply for children and pregnant women not in labour. In children <6 months, most recommendations now allow breast‐ or formula milk feeding up to 4 h before anaesthesia. Recently, the concept of pre‐operative oral nutrition using a special carbohydrate‐rich beverage has also gained support and been shown not to increase gastric fluid volume or acidity. Based on the available literature, our Task Force has produced new consensus‐based Scandinavian guidelines for pre‐operative fasting. What is still not clear is to what extent the new liberal fasting routines should apply to patients with functional dyspepsia or systematic diseases such as diabetes mellitus. Other still controversial areas include the need for and effect of fasting in emergency patients, women in labour and in association with procedures done under ‘deep sedation’. We think more research on the effect of various fasting regimes in subpopulations of patients is needed before we can move one step further towards completely evidence‐based pre‐operative fasting guidelines.
Neuroprotective effect of mivazerol, an α2‐agonist, after transient forebrain ischemia in rats*
Authors: Kimura T. , Sato M. , Nishikawa T. , Tanaka M. , Tobe Y. , Masaki Y.
Published: August 2005

Background:  We examined whether mivazerol, an α2‐agonist, had neuroprotective effects after transient forebrain ischemia in rats.

Methods:  Male Sprague‐Dawley rats, anesthetized with halothane, were assigned to one of four groups (n = 10 each): control (C, normal saline) and mivazerol 10 µg/kg (M10), 20 µg/kg (M20) and 40 µg/kg (M40) groups. Thirty minutes after drug administration, forebrain ischemia was induced with hemorrhagic hypotension and bilateral carotid artery occlusion for 10 min, and then the brain was reperfused. The neurologic outcome was evaluated 24 h, 48 h and 7 days after ischemia, followed by histologic evaluation.

Results:  The survival rate during 7 days was significantly lower in group M40 than in groups M10 and M20 (P < 0.05). The neurologic outcome was significantly better in groups M10 and M20 than in group M40 7 days after ischemia (P < 0.05). The number of intact neurons in hippocampal CA1 was significantly greater in group M20 than in the other groups (P < 0.05). Neuronal injury in the neocortex was significantly less in group M20 than in groups C and M40 (P < 0.05).

Conclusions:  Our results suggest that mivazerol, up to 20 µg/kg, provides neuroprotective effects, whereas 40 µg/kg may exaggerate neuronal injury after transient forebrain ischemia in rats.
Ventilatory management and weaning in a patient with central hypoventilation caused by a brainstem cavernoma
Authors: Rao G. S. U. , Ramesh V. J. , Lalla R. K.
Published: August 2005

We describe a patient with a brainstem cavernoma who was dependent on hypoxic respiratory drive initially. After excision of the lesion, the patient developed severe hypoventilation unresponsive to both hypoxia and hypercapnia. Weaning from mechanical ventilation could be achieved through central respiratory stimulation by acetazolamide. Problems associated with respiratory management of central hypoventilation due to a brainstem lesion are described.
Beneficial effects of hypertonic saline/dextran on early survival in porcine endotoxin shock
Authors: Somell A. , Sollevi A. , Suneson A. , Riddez L. , Hjelmqvist H.
Published: August 2005

Background:  Hypertonic saline/dextran (HSD) has been shown to have beneficial effects in haemorrhagic shock. These effects, with improved haemodynamics and organ perfusion, would in theory also be of benefit in septic shock. However, this is less studied. We have therefore further evaluated the effect of additional treatment with HSD in a porcine endotoxin shock model.

Methods:  Sixteen anaesthetized pigs were used. A continuous infusion of endotoxin (LPS EC) was increased stepwise during 30 min to a rate of 5 µg/kg/h. The infusion was discontinued after 3 h and the animals were observed for another 2 h. The animals received continuous basal fluid resuscitation with isotonic Ringer's glucose 2.5% at a rate of 20 ml/kg/h throughout the experiment. After 1 h of endotoxin infusion, the animals were randomized to additional treatment with HSD, 4 ml/kg over 5 min, or the same volume of isotonic saline. Every 30 min, haemodynamics and mixed venous saturation (SvO2) were measured via a pulmonary artery catheter. Regional blood flow rates were measured continuously by perivascular ultrasonic flow probes. The metabolic response was measured by arterial blood gas analysis.

Results:  The endotoxin put all animals into a progressive hypodynamic circulatory shock during the experiment. Treatment with HSD improved survival rate to 8/8 compared with controls 3/8. There was a transient circulatory recovery with improved central and regional haemodynamics, accompanied by stabilized metabolic response.

Conclusion:  Treatment with additional HSD improves survival in an early phase of endotoxin shock. Generally improved haemodynamics and oxygenation of peripheral tissues are suggested as possible mechanisms.
Bispectral Index™ values are higher during halothane vs. sevoflurane anesthesia in children, but not in infants
Authors: Edwards J. J. , Soto R. G. , Bedford R. F.
Published: August 2005

Background:  Previously, we have shown in adult patients that bispectral index score (BIS) values are significantly higher during halothane anesthesia (53–61 units) as compared with those observed during equipotent concentrations of sevoflurane (39–43 units). Because halothane is frequently used in the pediatric setting, we tested the hypothesis that BIS values observed in children might also be higher during general anesthesia with halothane than with sevoflurane.

Methods:  Forty‐one healthy, unpremedicated pediatric patients scheduled for elective operations received either halothane or sevoflurane titrated as appropriate for surgical stimulation.

Results:  During maintenance sevoflurane anesthesia (n = 20), the mean BIS values and percent end‐tidal concentrations were 44 ± 14 and 2.1 ± 0.6, respectively, whereas for the halothane group (n = 21) the corresponding values were 61 ± 7 and 1.1 ± 0.4, respectively.

Conclusion:  These findings suggest that BIS values are higher during halothane vs. sevoflurane anesthesia in children, but not in infants
The role of the medial temporal lobe in autistic spectrum disorders
Authors: Salmond C. H. , Ashburner J. , Connelly A. , Friston K. J. , Gadian D. G. , Vargha‐Khadem F.
Published: August 2005

The neural basis of autistic spectrum disorders (ASDs) is poorly understood. Studies of mnemonic function in ASD suggest a profile of impaired episodic memory with relative preservation of semantic memory (at least in high‐functioning individuals). Such a pattern is consistent with developmental hippocampal abnormality. However, imaging evidence for abnormality of the hippocampal formation in ASD is inconsistent. These inconsistencies led us to examine the memory profile of children with ASD and the relationship to structural abnormalities. A cohort of high‐functioning individuals with ASD and matched controls completed a comprehensive neuropsychological memory battery and underwent magnetic resonance imaging for the purpose of voxel‐based morphometric analyses. Correlations between cognitive/behavioural test scores and quantified results of brain scans were also carried out to further examine the role of the medial temporal lobe in ASD. A selective deficit in episodic memory with relative preservation of semantic memory was found. Voxel‐based morphometry revealed bilateral abnormalities in several areas implicated in ASD including the hippocampal formation. A significant correlation was found between parental ratings reflecting autistic symptomatology and the measure of grey matter density in the junction area involving the amygdala, hippocampus and entorhinal cortex. The data reveal a pattern of impaired and relatively preserved mnemonic function that is consistent with a hippocampal abnormality of developmental origin. The structural imaging data highlight abnormalities in several brain regions previously implicated in ASD, including the medial temporal lobes.
Graded classes of cortical connections: quantitative analyses of laminar projections to motion areas of cat extrastriate cortex
Authors: Grant Simon , Hilgetag Claus C.
Published: August 2005

Current hierarchical models of the cerebral cortex are mainly based on qualitative connection studies. From wheatgerm‐agglutinin‐horseradish peroxidase injections, we examined the laminar patterns of projections to and between the three major subdivisions of the motion‐processing lateral suprasylvian (LS) complex [areas posteromedial lateral suprasylvian area (PMLS), anteromedial lateral suprasylvian (AMLS), posterolateral lateral suprasylvian area (PLLS)] of cat extrastriate cortex and of an adjoining form‐processing area, 21a. We counted ∼ 145,000 labelled projection cells in 20 cortical areas in 11 cats, and applied various analyses to the data, expressed as the percent supragranular layer (%SG) origin of each connection. We report two main results. (i) A wide range of %SG values was obtained, both from each individual cat and across the 163 projections examined. Nonetheless, both hierarchical and non‐parametric cluster analyses of the pooled connection origins suggested the presence of three distinct laminar projection classes, constrained by graded %SG values of 0–33%, 39–69% and 76–97%. These conformed, respectively, to feedback, lateral and feedforward laminar patterns seen qualitatively in our material. (ii) Hierarchical connectivity analyses suggested that PMLS, AMLS and PLLS are ordered in a hierarchical sequence. Macaque motion areas V5/MT, MST and FST are arranged in a similar sequence, and areas at equivalent levels of the two motion hierarchies have some analogous functional specializations. Our findings provide the first objective support for the three laminar projection classes that underpin existing theoretical models of hierarchical cortical organization, and they suggest that the implementation of higher‐order motion processing evolved along similar lines in the cat and monkey visual cortex.
Effect of combined treatment with methylprednisolone and soluble Nogo‐66 receptor after rat spinal cord injury
Authors: Ji Benxiu , Li Mingwei , Budel Stephane , Pepinsky R. Blake , Walus Lee , Engber Thomas M. , Strittmatter Stephen M. , Relton Jane K.
Published: August 2005

Methylprednisolone (MP) is a synthetic glucocorticoid used for the treatment of spinal cord injury (SCI). Soluble Nogo‐66 receptor (NgR) ectodomain is a novel experimental therapy for SCI that promotes axonal regeneration by blocking the growth inhibitory effects of myelin constituents in the adult central nervous system. To evaluate the potential complementarity of these mechanistically distinct pharmacological reagents we compared their effects alone and in combination after thoracic (T7) dorsal hemisection in the rat. Treatment with an ecto‐domain of the rat NgR (27–310) fused to a rat IgG [NgR(310)ecto‐Fc] (50 µm intrathecal, 0.25 µL/h for 28 days) or MP alone (30 mg/kg i.v., 0, 4 and 8 h postinjury) improved the rate and extent of functional recovery measured using Basso, Beattie, Bresnahan (BBB) scoring and footprint analysis. The effect of MP treatment on BBB score was apparent the day after SCI whereas the effect of NgR(310)ecto‐Fc was not apparent until 2 weeks after SCI. NgR(310)ecto‐Fc or MP treatment resulted in increased axonal sprouting and/or regeneration, quantified by counting biotin dextran amine‐labeled corticospinal tract axons, and increased the number of axons contacting motor neurons in the ventral horn gray matter caudal to the lesion. Combined treatment with NgR(310)ecto‐Fc and MP had a more pronounced effect on recovery of function and axonal growth compared with either treatment alone. The data demonstrate that NgR(310)ecto‐Fc and MP act in a temporally and mechanistically distinct manner and suggest that they may have complementary effects.
The anterior ectosylvian visual area of the ferret: a homologue for an enigmatic visual cortical area of the cat?
Authors: Manger Paul R. , Engler Gerhard , Moll Christian K. E. , Engel Andreas K.
Published: August 2005

The present paper describes the results of electrophysiological mapping experiments focused on the anterior limb of the ectosylvian gyrus of the ferret (Mustela putorius). The aim was to determine if the ferret possessed a homologous cortical area to the anterior ectosylvian visual area (AEV) of the domestic cat, but not clearly delineated in any other mammal studied to date. We were able to gather data on the visuotopic organization of a region that we consider to be a homologue of cat AEV. The visual map in this area showed a distinct visuotopic organization and covered a large extent of the visual field. Within the ferret AEV there were clusters of bimodal recording sites (somato‐visual and audio‐visual) that were located adjacent to surrounding unimodal cortical areas (such as the second somatosensory area and primary and secondary auditory areas). The ferret AEV, like that of the cat, was topographically isolated from other visual cortical areas by intervening auditory and somatosensory areas. Taken together these features suggest that the region described here as AEV in the ferret is indeed a direct homologue of the previously described cat AEV.
Activation of cerebellar parallel fibers monitored in transgenic mice expressing a fluorescent Ca2+ indicator protein
Authors: Díez‐García Javier , Matsushita Shinichi , Mutoh Hiroki , Nakai Junichi , Ohkura Masamichi , Yokoyama Jennifer , Dimitrov Dimitar , Knöpfel Thomas
Published: August 2005

Genetically encoded fluorescent Ca2+ indicator proteins (FCIPs) are promising tools to study Ca2+ signaling in large assemblies of nerve cells. Currently, there are few examples of stable transgenic mouse lines that functionally express such sensors in well‐defined neuronal cell populations. Here we report the generation and characterization of transgenic mice expressing an FCIP under the 5′ regulatory sequences of the Kv3.1 potassium channel promoter. In the cerebellar cortex, expression was restricted to granule cells. We first demonstrated reliable measurements of Ca2+ transients from beams of parallel fibers and compared the FCIP signals with intrinsic autofluorescence signals. We demonstrate that, in a transgenic line that exhibits a high expression level of the FCIP, autofluorescence signals are negligible and stimulation‐induced fluorescence transients represent FCIP signals. Using frontal cerebellar slices we imaged antidromic activation of granule cells following electrical stimulation of parallel fibers and orthodromic activation of beams of parallel fibers following electrical stimulation of granule cells. We found that paired pulse‐induced presynaptic Ca2+ transients of parallel fibers are not affected by blockade of N‐methyl‐d‐aspartate receptors.
Neurturin has multiple neurotrophic effects on adult rat sacral parasympathetic ganglion neurons
Authors: Wanigasekara Yewlan , Keast Janet R.
Published: August 2005

Neurturin (NTN) is an important neurotrophic factor for parasympathetic neurons; however, no studies to date have investigated the signalling mechanisms downstream of GFRα2 and Ret activation underlying this neurotrophic support. This is particularly important for pelvic parasympathetic neurons, which are prone to injury during surgical procedures such as prostatectomy, and where there are no current therapies for axonal regeneration. To address this issue we have cultured dissociated adult rat pelvic ganglion neurons and also examined the structural changes in pelvic ganglion neurons after axotomy. Axotomised penile neurons deprived of target‐derived support had smaller somata than intact neurons. Studies of cultured adult pelvic ganglion neurons also demonstrated that NTN stimulated soma growth. Further experiments showed that NTN reduced the up‐regulation of tyrosine hydroxylase expression in cultured pelvic parasympathetic neurons. NTN stimulated the extension of neurites in cultured parasympathetic, but not sympathetic, pelvic ganglion neurons. Inhibition of phosphatidylinositol 3‐kinase prevented initiation of neurite outgrowth, whereas inhibition of the mitogen‐activated protein kinase and the Src family kinase pathways disrupted NTN‐stimulated microtubule assembly. Surprisingly, NTN did not activate the transcription factor cAMP‐response element binding protein (CREB), which is typically involved in neurotrophic signalling in sympathetic neurons. This is the first study to identify signalling pathways activated by NTN in adult parasympathetic neurons. Our results may lead to a better understanding of regenerative mechanisms in parasympathetic neurons, especially for those innervating urogenital organs. Our results also indicate that neurotrophic signalling in parasympathetic neurons is different from that in other types of peripheral neurons.
A perspective on protein profiling of blood
Authors: Katz Jonathan E. , Mallick Parag , Agus David B.
Published: August 2005

Protein profiling of blood is going to lead to huge changes in the development of biomarkers and perhaps also in producing targets for the medical treatment of cancer. Experts in this field from Los Angeles have written an outstanding mini‐review about this topic.

Renal cancer has been an area of interest to all of those involved in urological oncology, particularly from the point of view of adjuvant medical treatment either to prevent metastatic disease or to treat it. Authors from Los Angeles have produced a review of great interest on this subject.

There are three other reviews on important issues. Authors from Paris have written about microsatellite instability and TCC of the upper urinary tract, and authors from Bristol have written a mini‐review about the options available when considering orthotopic bladder reconstruction. Finally, authors from Dublin have written about a significant problem in renal transplantation, delayed graft function.
Long‐term side‐effects of intermittent androgen suppression therapy in prostate cancer: results of a phase II study
Authors: Malone Shawn , Perry Gad , Segal Roanne , Dahrouge Simone , Crook Juanita
Published: August 2005

OBJECTIVE

To assess the feasibility and tolerability of intermittent androgen suppression therapy (IAS) in prostate cancer.

PATIENTS AND METHODS

Patients with recurrent or metastic prostate cancer received cyclical periods of treatment with leuprolide acetate and nilutamide for 8 months, and rest periods. Cycles were repeated at progression until the treatment failed to achieve normal prostate‐specific antigen (PSA) levels. Patients were followed with PSA level, testosterone level, haemoglobin level, weight and bone mineral density evaluations. The median time to treatment failure, recovery from anaemia, or normalization of testosterone level was estimated by the Kaplan‐Meier method.

RESULTS

In all, 95 patients received 245 cycles; the median duration of rest periods was 8 months and median time to treatment failure 47 months. Testosterone recovery during rest periods was documented in 117 (61%) of cycles. Anaemia was mild and reported in 33%, 44% and 67% of cycles 1, 2 and 3, respectively. Sexual function recovered during the rest periods in 47% of cycles. There was no significant overall change in body mass index at the end of the treatment period. Osteoporosis was documented in at least one site evaluated in 41 patients (37%).

CONCLUSIONS

IAS has the potential to reduce side‐effects, including recovery of haemoglobin level, return of sexual function and absence of weight gain at the end of the study period.
A lower dose of thalidomide is better than a high dose in metastatic renal cell carcinoma
Authors: Srinivas Sandy , Guardino Alice E.
Published: August 2005

OBJECTIVE

To conduct a dose‐finding trial using a single low dose and dose escalation of a higher dose of thalidomide in patients with metastatic renal cell carcinoma (RCC), and to evaluate the antineoplastic effectiveness of thalidomide as an anti‐angiogenic agent on RCC.

PATIENTS AND METHODS

The 14 patients enrolled in the study had progressive measurable metastatic RCC and consented to participate. Patients were randomized to either a fixed low dose of 200 mg of thalidomide or to a high dose of 800 mg that was increased to a maximum dose of 1200 mg daily. Patients were evaluated for response after 8 weeks of therapy.

RESULTS

Stable disease was achieved in six patients and was seen in both the low‐dose and high‐dose thalidomide groups. The median overall survival was 9 months. The low‐dose thalidomide regimen was better tolerated and patients survived longer than those on the high‐dose regimen (16 vs 6 months, P = 0.04)

CONCLUSION

The use of low‐dose thalidomide in patients with metastatic RCC was well tolerated and they survived for longer than those on the high‐dose regimen.
Epstein‐Barr virus infection in sarcomatoid renal cell carcinoma tissues
Authors: Kim Kwang Hee , Han Eun Mee , Lee Eung Seok , Park Hong Seok , Kim Insun , Kim Young‐Sik
Published: August 2005

OBJECTIVE

To determine whether Epstein‐Barr virus (EBV) infection is related to renal cell carcinoma (RCC) tissues.

MATERIALS AND METHODS

We investigated EBV infection and its genotypes in 73 cases of different types of RCC and 18 of non‐neoplastic kidney. EBV infection and its genotypes were determined by EBV‐encoded RNAs in situ hybridization (EBER‐ISH) and polymerase chain reactions for EBV‐encoded nuclear antigen 1 (EBNA‐1) and EBNA‐3C. The immunophenotype and EBV status of the EBV‐infected cells were examined by double‐labelling of EBER‐ISH and/or immunohistochemistry for lymphoid cell markers, EBV proteins, and CD21.

RESULTS

EBER‐ISH signals were detected in five of 73 RCC tissues (6.8%), but in none of 18 non‐neoplastic kidneys. Interestingly, EBER‐ISH was positive only in five of the 10 sarcomatoid RCCs, and of these, four also showed amplification of EBNA‐1. EBV was located exclusively in the tumour‐infiltrating B lymphocytes of sarcomatoid RCCs. The genotype of EBV was determined as type 1. A few EBV‐infected B cells expressed BZLF1 (an EBV immediate‐early gene product) while none expressed EBNA‐2 or latent membrane protein 1. This indicates that the B cells are of EBV latency type I, often replicating EBV. EBV infection did not affect the survival rates of patients with sarcomatoid RCC (P = 0.635, Kaplan–Meier analysis, log‐rank test).

CONCLUSION

EBV is present only in tumour‐infiltrating B lymphocytes of sarcomatoid RCCs. The present study suggests that sarcomatoid RCC modulates a function of EBV‐specific T cells controlling EBV replication, or stimulates differentiation of memory B cells into plasma cells.
A case‐control study of risk factors in men with chronic pelvic pain syndrome
Authors: Pontari Michel A. , McNaughton‐Collins Mary , O'Leary Michael P. , Calhoun Elizabeth A. , Jang Thomas , Kusek John W. , Landis J. Richard , Knauss Jill , Litwin Mark S. ,   The CPCRN Study Group
Published: August 2005

In the section on the lower urinary tract this month there are several papers of general interest. First, authors from the USA present a case‐control study of risk factors in men with chronic pelvic pain syndrome. There are also papers presenting important data on alfuzosin, dutasteride, and tamsulosin versus naftopidil, respectively. In addition, the use of thermo‐expandable prostate stents is further explored by authors from the UK and Denmark. Finally, authors from Austria describe the use of a new minimally invasive device in the treatment of incontinence after prostatectomy.

OBJECTIVE

To compare the demographic, behavioural, clinical and medical history characteristics of men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and asymptomatic controls, to identify characteristics that might be associated with this syndrome.

PATIENTS AND METHODS

Self‐administered epidemiological questionnaires were completed by 463 men with CP/CPPS and 121 asymptomatic age‐matched controls. We compared the prevalence of possible risk factors between men with CP/CPPS and controls, using generalized Mantel‐Haenszel tests, and developed multivariate predictive models using logistic regression methods, adjusting for clustering by clinical centre within both methods.

RESULTS

Compared to controls, men with CP/CPPS reported a significantly greater lifetime prevalence of nonspecific urethritis (12% vs 4%, P = 0.008), cardiovascular disease (11% vs 2%, P = 0.004), neurological disease (41% vs 14%, P < 0.001), psychiatric conditions (29% vs 11%, P < 0.001), and haematopoietic, lymphatic or infectious disease (41% vs 20%, P < 0.001).

CONCLUSION

A wide range of self‐reported medical conditions was associated with CP/CPPS. Further studies are necessary to determine whether they play a role in the pathogenesis of CP/CPPS.
The economic impact of using alfuzosin 10 mg once daily in the management of acute urinary retention in the UK: a 6‐month analysis
Authors: Annemans Lieven , Cleemput Irina , Lamotte Mark , McNeill Alan , Hargreave Timothy
Published: August 2005

OBJECTIVE

To calculate the economic consequences of using alfuzosin 10 mg once daily for managing acute urinary retention (AUR) related to benign prostatic hyperplasia (BPH).

METHODS

We examined whether alfuzosin use during hospitalization for AUR and for 6 months after a successful trial without catheter (TWOC) is cost effective compared to placebo and immediate prostatectomy, from the perspective of patients managed in the National Health Service (NHS) in the UK. A decision‐analysis model was developed to estimate the costs of various treatment options within the first 6 months after a first episode of AUR. Clinical data were obtained from a large randomized clinical trial comparing alfuzosin 10 mg with placebo, and from published reports. Cost data were obtained from both NHS and resource‐use data gathered during the clinical trial. A Monte Carlo analysis, allowing variability in all uncertain variables of the model, was used to calculate the uncertainty surrounding the results.

RESULTS

Treating patients with alfuzosin during initial hospitalization for AUR and in the first 6 months after a successful TWOC generates a cost‐saving of £349 relative to placebo. Savings related to immediate prostatectomy were £892; both savings were significant (P < 0.05). Alfuzosin treatment was associated with a lower rate of prostatectomy after discharge from hospital after a successful TWOC.

CONCLUSION

Treatment with alfuzosin 10 mg once daily before and after a successful TWOC has both clinical and economic benefits. It decreases the need for emergency surgery for BPH and reduces treatment costs in the first 6 months.
Pelvic floor exercises for erectile dysfunction
Authors: Dorey Grace , Speakman Mark J. , Feneley Roger C.L. , Swinkels Annette , Dunn Christopher D.R.
Published: August 2005

Associate Editor

Michael G. Wyllie

Editorial Board

Ian Eardley, UK

Jean Fourcroy, USA

Sidney Glina, Brazil

Julia Heiman, USA

Chris McMahon, Australia

Bob Millar, UK

Alvaro Morales, Canada

Michael Perelman, USA

Marcel Waldinger, Netherlands

OBJECTIVE

To examine the role of pelvic floor exercises as a way of restoring erectile function in men with erectile dysfunction.

PATIENTS AND METHODS

In all, 55 men aged > 20 years who had experienced erectile dysfunction for ≥ 6 months were recruited for a randomized controlled study with a cross‐over arm. The men were treated with either pelvic floor muscle exercises (taught by a physiotherapist) with biofeedback and lifestyle changes (intervention group) or they were advised on lifestyle changes only (control group). Control patients who did not respond after 3 months were treated with the intervention. All men were given home exercises for a further 3 months. Outcomes were measured using the International Index of Erectile Function (IIEF), anal pressure measurements and independent (blinded) assessments.

RESULTS

After 3 months, the erectile function of men in the intervention group was significantly better than in the control group (P < 0.001). Control patients who were given the intervention also significantly improved 3 months later (P < 0.001). After 6 months, blind assessment showed that 40% of men had regained normal erectile function, 35.5% improved but 24.5% failed to improve.

CONCLUSION

This study suggests that pelvic floor exercises should be considered as a first‐line approach for men seeking long‐term resolution of their erectile dysfunction.
Partial nephrectomy with perfusion cooling for imperative indications: a 24‐year experience
Authors: Steffens Joachim , Humke Ulrich , Ziegler Manfred , Siemer Stefan
Published: August 2005

OBJECTIVE

To report our 24‐year experience with open nephron‐sparing surgery for renal tumours, using cold ischaemia achieved by renal artery perfusion, as partial nephrectomy for imperative indications is a surgical challenge.

PATIENTS AND METHODS

From 1980 to 2004, open partial nephrectomy was performed in 717 patients; of these, 65 (9.1%) with a solitary kidney, synchronous bilateral tumours or renal failure in the opposite kidney (imperative indication) had surgery under cold ischaemia, achieved by continuous perfusion of Ringer's lactate at 4 °C through the renal artery, which was clamped and cannulated. The tumour was resected in a bloodless field, with biopsies taken from the tumour bed. Focusing on patients with an imperative indication and cold perfusion, we report our perfusion technique, and the ischaemia time, complication rate and cancer‐specific survival rate of these patients.

RESULTS

The mean (sd, range) operative duration was 132 (103, 91–252) min and ischaemia time 49 (37, 31–71) min. The most common complications were postoperative haemorrhage in 19%, urinary fistula in 8% and acute renal failure in 6% of patients. There were no specific complications related to the perfusion technique (renal artery stenosis, renal artery or vein thrombosis). The mean (sd, range) long‐term follow‐up of 95 (71, 4.3–231) months showed increased but constant creatinine values (95 µmol/L before, 182 µmol/L after surgery; P < 0.05) with no need for long‐term dialysis. The tumour‐specific survival rate was 94%, 76% and 76% after 1, 5 and 10 years, respectively.

CONCLUSIONS

Partial nephrectomy under cold ischaemia remains reserved for selected patients with renal tumours with an imperative indication. The technique provides excellent intraoperative visibility in an absolutely bloodless field, allows surgery with no pressure of time, and makes ex vivo workbench surgery with autotransplantation unnecessary. Perfusion cooling allows good tumour‐specific long‐term results, with stable residual kidney function sufficient to prevent dialysis.