A fuzzy logic model for differential diagnosis of lower urinary tract dysfunctions

Lower urinary tract dysfunctions (LUTD) restrict quality of life, resulting in decreased work productivity and emotional well‐being. However, most people are not diagnosed because they do not seek medical treatment. In addition, some facilities do not adequately train health professionals in the evaluation, diagnosis and treatment of these conditions. The study's objective was to develop a decision support system modelled on fuzzy logic that defines LUTD using the terminology of the International Continence Society. This methodological study aimed to develop a model that uses the maximum–minimum composition (max–min) of fuzzy relations that can perform differential diagnoses of LUTD. The model was tested in 100 cases (50 men and 50 women), and the data were obtained from medical records containing the clinical data and results of urodynamic studies. All medical records were reviewed by a specialist in urology. The model was capable of determining a diagnosis in full (62%) or partial (36%) agreement with the medical report. Agreement between the model and the medical report was excellent (kappa = 0·98, p ? 0·001, CI = 0·88–1) or substantial (kappa = 0·53, p ? 0·001, CI = 0·45–0·60), considering overestimative accordance (where accordance is assumed when at least one diagnosis is equal) and underestimative accordance (where accordance is assumed when all diagnoses are equal), respectively. The proposed model based on the max–min composition of fuzzy relationships is very simple and performed well. However, more tests are recommended before the model is used as a decision support system.     

Titanium elastic nailing in femoral diaphyseal fractures of children in 6-16 years of age

Background:

Management of femoral diaphyseal fractures in the age group of 6-16 years is controversial. There has been a resurgence worldwide for operative fixation.

Materials and Methods:

Twenty-two children (18 boys, 4 girls) aged 6-16 years with recent (> 3 days) femoral diaphyseal fractures (20 closed, 2 open) were stabilized with Titanium Elastic Nail (TEN). These fractures were in proximal third (n=3), middle third (n=15) and in the distal third (n=4) 17 patients underwent surgery within seven days of their injury. The results were evaluated using Flynn''s scoring criteria. Statistical analysis was done using Fischer''s exact test.

Results:

All 22 patients were available for evaluation after a mean of 26 months (14-36 months) of followup. Radiological union in all cases were achieved in a mean time of 8.7 weeks. Full weight bearing was possible in a mean time of 8.8 weeks. Mean duration of hospital stay was 9.8 days. The results were excellent in 13 patients (59.0%), successful in six (27.2%) and poor in three patients (13.6%). All patients had early return to school.

Conclusion:

Intramedullary fixation titanium elastic nailing is an effective treatment of diaphyseal fractures of the femur in properly selected patients of the 6-16 years age group.     

Adjuvant therapy for locally advanced renal cell cancer: A systematic review with meta-analysis

Background  

Many adjuvant trials have been undertaken in an attempt to reduce the risk of recurrence among patients who undergo surgical resection for locally advanced renal cancer. However, no clear benefit has been identified to date. This systematic review was conducted to examine the exact role of adjuvant therapy in renal cancer setting.     

Role of ATP and related purines in inhibitory neurotransmission to the pig urinary bladder neck

Background and purpose:

As adenosine 5′-triphosphate (ATP) is one of the inhibitory mediators of the bladder outflow region, this study investigates the possible release of ATP or related purines in response to electrical field stimulation (EFS) and the purinoceptor(s) involved in nerve-mediated relaxations of the pig urinary bladder neck.

Experimental approach:

Urothelium-denuded and intact phenylephrine-precontracted strips were mounted in organ baths containing physiological saline solution at 37°C and gassed with 95% O₂ and 5% CO₂ for isometric force recordings.

Key results:

EFS, in the presence of atropine, guanethidine and N^G-nitro-L-arginine, and exogenous purines, produced frequency- and concentration-dependent relaxations respectively. Adenosine 5′-diphosphate (ADP) and adenosine were more potent than ATP in producing relaxation, while uridine 5′-triphosphate, uridine 5′-diphosphate and α,β-methylene ATP were less effective. The non-selective P2 antagonist suramin, and the P2Y₁ and P1 receptor blockers 2′-deoxy-N6-methyladenosine 3′,5′-bisphosphate tetrasodium and 8-(p-sulphophenyl)theophylline, respectively, inhibited the responses to EFS and ATP. The P1 agonist''s potency was: 5′-N-ethylcarboxamidoadenosine (NECA)>4-2[[6-amino-9-(N-ethyl-b-D-ribofuranuronamidosyl)-9H-purin-2-yl]amino]ethyl]benzene propanoic acid hydrochloride>2-chloro-N⁶-cyclopentyladenosine>-2-chloro-6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-1-deoxy-N-methyl-b-D-ribofuranuronamide = adenosine. 4-(-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl) phenol, an A_2A antagonist, reduced the relaxations to EFS, adenosine and NECA. In urothelium-intact samples, relaxations to EFS and purines were smaller than in urothelium-denuded preparations. Neuronal voltage-gated Na⁺ channels blockade failed to modify ATP relaxations. At basal tension, EFS- and ATP-induced contractions were resistant to desensitization or blockade of P2X₁ and P2X₃ receptors.

Conclusions and implications:

ATP is involved in the non-adrenergic, non-cholinergic, non-nitrergic inhibitory neurotransmission in the pig bladder neck, producing relaxation largely through muscle A_2A receptors after breakdown to adenosine, and P2Y₁ receptors after breakdown to ADP. Antagonists of these receptors may be useful for urinary incontinence treatment produced by intrinsic sphincteric deficiency.     

One year open-label safety and efficacy trial with rotigotine transdermal patch in moderate to severe idiopathic restless legs syndrome

BackgroundLong-term efficacy and tolerability data are not yet available for patch formulations of dopamine agonists in restless legs syndrome.MethodsEfficacy and safety of rotigotine (0.5–4 mg/24 h), formulated as a once-daily transdermal system (patch), were investigated in an open extension (SP710) of a preceding 6-week placebo-controlled trial (SP709, 341 randomized patients) in patients with idiopathic restless legs syndrome. For efficacy assessment the international RLS severity scale (IRLS), the RLS-6 scales, the clinical global impressions (CGI) and the QoL-RLS questionnaire were administered. In addition, long-term tolerability and safety were assessed.ResultsOf 310 patients who finished the controlled trial, 295 (mean age 58 ± 10 years, 66% females) with a mean IRLS score of 27.8 ± 5.9 at baseline of SP709 were included. We report results after one year of this ongoing long-term trial. Two hundred twenty patients (retention rate = 74.6%) completed the 12-month follow-up period. The mean daily dose was 2.8 ± 1.2 mg/24 h with 4 mg/24 h (40.6%) being the most frequently applied dose; 14.8% were sufficiently treated with 0.5 or 1.0 mg/24 h. The IRLS total score improved by −17.4 ± 9.9 points between baseline and end of Year 1 (p < 0.001). The other measures of severity, sleep satisfaction and quality of life supported the efficacy of rotigotine (p < 0.001 for pre-post-comparisons of all efficacy variables). The tolerability was described as “good” or “very good” by 80.3% of all patients. The most common adverse events were application site reactions (40.0%), which led to withdrawal in 13.2%. Further relatively frequent adverse events were nausea (9.5%) and fatigue (6.4%). Two drug-related serious adverse events, nausea and syncope, required hospitalization. Symptoms of augmentation were not reported by the patients.ConclusionRotigotine provided a stable, clinically relevant improvement in all efficacy measures throughout one year of maintenance therapy. The transdermal patch was safe and generally well tolerated by the majority of patients. Comparable to any transdermal therapy, application site reactions were the main treatment complication.     

Efficacy of rotigotine for treatment of moderate-to-severe restless legs syndrome: a randomised, double-blind, placebo-controlled trial

BACKGROUND: Continuous administration of a dopamine agonist could be used to treat patients with restless legs syndrome. Our aim was to investigate the efficacy of transdermal rotigotine in the treatment of idiopathic restless legs syndrome. METHODS: In this randomised, double-blind, placebo-controlled trial, 458 patients with moderate-to-severe idiopathic restless legs syndrome (average baseline International Restless Legs Syndrome Study Group severity rating scale [IRLS] sum score of 28.1) were randomly assigned to receive transdermal rotigotine 1 mg over 24 h (n=115), 2 mg over 24 h (n=112), or 3 mg over 24 h (n=114), or to receive placebo (n=117). Study medication was delivered via patches, applied once a day for 6 months. Randomisation was done with a computer-generated randomisation list, stratified by centre. Primary efficacy outcomes were absolute change from baseline to end of maintenance in IRLS sum score and in the clinical global impressions (CGI) item 1 score, assessed by analysis of covariance in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00136045. FINDINGS: Efficacy analyses were done on 112 patients in the 1 mg group, 109 in the 2 mg group, 112 in the 3 mg group, and 114 in the placebo group. Mean change in IRLS sum score from baseline at the end of the maintenance phase was -13.7 (SE 0.9) in the 1 mg group, -16.2 (0.9) in the 2 mg group, -16.8 (0.9) in the 3 mg group, and -8.6 (0.9) in the placebo group (p<0.0001 for treatment difference vs placebo with each dose). Mean change in CGI item 1 score from baseline at the end of the maintenance phase was -2.09 (0.14) in the 1 mg group, -2.41 (0.14) in the 2 mg group, -2.55 (0.14) in the 3 mg group, and -1.34 (0.14) in the placebo group (p<0.0001 for treatment difference vs placebo with each dose). Skin reactions, mostly mild or moderate, were seen in 145 (43%) of 341 patients who received rotigotine and in two (2%) of 117 who received placebo. Ten patients had serious adverse event that were deemed to be related to rotigotine: elevation of liver enzymes (one patient), worsening of tinnitus (one patient), non-response to anticoagulation (one patient), electrocardiogram changes (one patient), and application-site reactions (six patients). No admissions to hospital were needed for the application-site reactions, and they all resolved within a short time of patch removal without any other therapeutic intervention. The rate of typical dopaminergic side-effects in patients who received rotigotine was low; no signs of augmentation were noted. INTERPRETATION: 24 h transdermal delivery of low-dose rotigotine could be used to relieve the night-time and daytime symptoms of restless legs syndrome. FUNDING: Schwarz Biosciences.     

The adaptation of enkephalin, tachykinin and monoamine neurons of the basal ganglia following neonatal dopaminergic denervation is dependent on the extent of dopamine depletion.

This study examined whether dopamine (DA) is necessary for the normal development of striatal enkephalin and striatonigral tachykinin peptide systems. The neurotoxin, 6-hydroxydopamine (6-OHDA) was used to induce DA deficiency on the third day of the postnatal period in Sprague-Dawley rat pups. The animals were sacrificed at 60 days of age. The levels of Met5-enkephalin (ME) and substance P (SP) were determined by radioimmunoassay and preproenkephalin (PPE) and preprotachykinin (PPT) mRNA abundance in the striatum were assessed by hybridization analysis. The concentrations of DA, 5-hydroxytryptamine (5-HT) and their acid metabolites were determined by high-pressure liquid chromatography with electrochemical detection. The lesioned animals were grouped on the basis of the degree of loss of DA, and changes in ME, SP and 5-HT systems were correlated with respect to the degree of DA loss. The nature and extent of the changes in these systems were dependent on the degree of DA depletion. A loss of more than 90% DA was necessary to result in increased levels of ME and its PPE mRNA and reduced levels of SP and its PPT mRNAs; however, increased levels of 5-HT could be observed at a lower degree of DA loss. The results indicate that the normal development of enkephalin and tachykinin and 5-HT systems of basal ganglia are dependent on the availability of DA and/or the integrity of the nigrostriatal dopaminergic neurons. The results are relevant to our further understanding of the neurobiology of DA deficiency disorders.     

Sister chromatid exchange and chromosome aberrations in mice after in vivo exposure of green S--a food colorant.

Sister chromatic exchanges (SCE) and chromosome aberrations (CA) in mice after in vivo exposure of Green S were carried out following single acute treatment. Except for the lowest dose (25 mg/kg body weight) a significant increase in the SCEs were observed in all the other doses (50, 100, and 200 mg/kg) tested. In CA study two higher doses (200 and 400 mg/kg) showed a significant increase in CA when compared with control. The minimum effective dose which induced SCE and CA was 50 and 200 mg/kg of body weight, respectively. The trend tests for the evidence of dose response effects were also significant for both SCE and CA. No significant differences were observed in cell replication kinetic (RI) analysis. A significant increase in the mitotic index (MI) was also observed in the highest dose (400 mg/kg) tested when compared with control. Thus the present study indicates that Green S can induce both SCE and CA in vivo in bone marrow cells of mice.     

合欢皮中新皂甙的结构鉴定

从合欢皮(Albizziae cortex)的95%乙醇提取物的正丁醇萃取部分中分离得到3个新的三萜皂甙,用化学方法及¹H-和¹³C-NMR,DEPT,COSY,TOCSY,HMQC-COSY,HMQC-TOCSY,HMBC,NOESY等波谱方法鉴定其结构为:I(1个三萜,9个糖,2个单萜),命名为合欢皂甙(julibroside)J₁;II(1个三萜,8个糖,2个单萜),命名为合欢皂甙J_{2;II(1个三萜,9个糖,2个单萜),命名为合欢皂甙J3。}