Safety and tolerability of transcranial magnetic and direct current stimulation in children: Prospective single center evidence from 3.5 million stimulations.

BACKGROUND: Non-invasive brain stimulation is being increasingly used to interrogate neurophysiology and modulate brain function. Despite the high scientific and therapeutic potential of non-invasive brain stimulation, experience in the developing brain has been limited. OBJECTIVE: To determine the safety and tolerability of non-invasive neurostimulation in children across diverse modalities of stimulation and pediatric populations. METHODS: A non-invasive brain stimulation program was established in 2008 at our pediatric, academic institution. Multi-disciplinary neurophysiological studies included single- and paired-pulse Transcranial Magnetic Stimulation (TMS) methods. Motor mapping employed robotic TMS. Interventional trials included repetitive TMS (rTMS) and transcranial direct current stimulation (tDCS). Standardized safety and tolerability measures were completed prospectively by all participants. RESULTS: Over 10 years, 384 children underwent brain stimulation (median 13 years, range 0.8-18.0). Populations included typical development (n = 118), perinatal stroke/cerebral palsy (n = 101), mild traumatic brain injury (n = 121) neuropsychiatric disorders (n = 37), and other (n = 7). No serious adverse events occurred. Drop-outs were rare (<1%). No seizures were reported despite >100 participants having brain injuries and/or epilepsy. Tolerability between single and paired-pulse TMS (542340 stimulations) and rTMS (3.0 million stimulations) was comparable and favourable. TMS-related headache was more common in perinatal stroke (40%) than healthy participants (13%) but was mild and self-limiting. Tolerability improved over time with side-effect frequency decreasing by >50%. Robotic TMS motor mapping was well-tolerated though neck pain was more common than with manual TMS (33% vs 3%). Across 612 tDCS sessions including 92 children, tolerability was favourable with mild itching/tingling reported in 37%. CONCLUSIONS: Standard non-invasive brain stimulation paradigms are safe and well-tolerated in children and should be considered minimal risk. Advancement of applications in the developing brain are warranted. A new and improved pediatric NIBS safety and tolerability form is included.

Robotic TMS mapping of motor cortex in the developing brain.

BACKGROUND: The human motor cortex can be mapped safely and painlessly with transcranial magnetic stimulation (TMS) to explore neurophysiology in health and disease. Human error likely contributes to heterogeneity of such TMS measures. Here, we aimed to use recently pioneered robotic TMS technology to develop an efficient, reproducible protocol to characterize cortical motor maps in a pediatric population. NEW METHOD: Magnetic resonance imaging was performed on 12 typically developing children and brain reconstructions were paired with the robotic TMS system. The system automatically aligned the TMS coil to target sites in 3 dimensions with near-perfect coil orientation and real-time head motion correction. Motor maps of 4 forelimb muscles were derived bilaterally by delivering single-pulse TMS at predefined, uniformly spaced trajectories across a 10 × 10 grid (7 mm spacing) customized to the participant's MRI. RESULTS: Procedures were well tolerated with no adverse events. Two male, eight-year-old participants had high resting motor thresholds that precluded mapping. The mean hotspot coordinate and centre of gravity coordinate were determined in each hemisphere for four forelimb muscles bilaterally. Average mapping time was 14.25 min per hemisphere. COMPARISON WITH EXISTING METHODS: Traditional manual TMS methods of motor mapping are time intensive, technically challenging, prone to human error, and arduous for use in pediatrics. This novel TMS robot approach facilitates improved efficiency, tolerability, and precision in derived, high-fidelity motor maps. CONCLUSIONS: Robotic TMS opens new avenues to explore motor map neurophysiology and its influence on developmental plasticity and therapeutic neuromodulation. Our findings provide evidence that TMS robotic motor mapping is feasible in young participants.

Comparison of prevalence, phenotype, and antimicrobial resistance of Salmonella serovars isolated from turkeys in Taiwan.

Salmonella spp. is a foodborne pathogen that causes zoonotic disease worldwide. The aim of this study was to investigate the prevalence of antimicrobial resistance of Salmonella isolated from turkey farms in Taiwan. During the past 2 yr, 243 strains of Salmonella were isolated from 2,040 samples (11.9%) from turkey farms, including 32.5% (52/160) from the intestines of 12-day-old turkey poults, 14.2% (119/840) from feces collected from the turkey growing periods, and 6.9% (72/1,040) from finishing periods. S. Albany (35.0%, 85/243), S. Schwarzengrund (23.0%, 56/243), and S. Hadar (19.3%, 47/243) were the most common serovars on turkey farms. For these strains, a high frequency of resistance was observed against florfenicol (97.5%), oxytetracycline (89.3%), doxycycline (78.6%), colistin (77.8%), ampicillin (75.7%), amoxicillin (75.3%), trimethoprim-sulfamethoxazole (73.7%), chloramphenicol (69.1%), and nalidixic acid (67.9%). floR (63.8%), tet (A) (60.5%), blaPSE (57.6%), blaTEM (42.0%), blaCTX-M (34.2%), cmlA (34.2%), and tet (D) (29.2%) were the most common resistance genes found in this study. The int1 gene was identified in 72.4% (176/243) of Salmonella isolates in which the conserved region 3' of class 1 integrons also was amplified, whereas none had the int2 gene. This study demonstrates that imported and fattening turkeys could be a reservoir for Salmonella isolates resistant to multiple antimicrobials. These results also reinforce the need to develop strategies and implement specific control procedures to reduce the development of antimicrobial resistance.

Association of urinary nerve growth factor levels with erectile function in young men with type 2 diabetes mellitus.

We investigated urine nerve growth factor (NGF) levels and erectile dysfunction in diabetic men <45 years of age. Urinary NGF levels were measured in 72 diabetic men and 20 control subjects without lower urinary tract symptoms or erectile dysfunction. Participants were evaluated using the International Prostate Symptom Score, quality of life index, Overactive Bladder Symptom Score (OABSS), the five-item version of the International Index of Erectile Function questionnaire (IIEF-5), the patient perception of bladder condition questionnaire, measurement of flow rate and post-void residual urine volume. The results showed that the diabetic men had significantly higher urinary normalized NGF/creatinine (Cr) levels compared to the healthy controls (0.48±1.2 vs 0.01±0.01, P=0.04). The increased urinary NGF/Cr levels correlated negatively with the IIEF-5 total score (P=0.03, coefficient=-0.26, -0.02 to -0.47). The 42 patients with urinary NGF/Cr levels <0.05 had higher IIEF-5 scores than the 30 patients with urinary NGF/Cr level ⩾0.05 (20.2±4.6 vs 16.9±6.7, P=0.03). We conclude that urinary NGF levels were associated with erectile dysfunction in the men with type 2 <45 years of age.

Photo-induced Doping in GaN Epilayers with Graphene Quantum Dots.

We demonstrate a new doping scheme where photo-induced carriers from graphene quantum dots (GQDs) can be injected into GaN and greatly enhance photoluminescence (PL) in GaN epilayers. An 8.3-fold enhancement of PL in GaN is observed after the doping. On the basis of time-resolved PL studies, the PL enhancement is attributed to the carrier transfer from GQDs to GaN. Such a carrier transfer process is caused by the work function difference between GQDs and GaN, which is verified by Kelvin probe measurements. We have also observed that photocurrent in GaN can be enhanced by 23-fold due to photo-induced doping with GQDs. The improved optical and transport properties from photo-induced doping are promising for applications in GaN-based optoelectronic devices.

Synergism between two amphenicol of antibiotics, florfenicol and thiamphenicol, against Staphylococcus aureus.

Synergistic effects between the same class of antibiotics are rarely reported. In the current study, two amphenicols, namely florfenicol and thiamphenicol, exhibited both in vitro and in vivo synergism against clinical isolates ofStaphylococcus aureusfrom chickens, cattle and pigs. Checkerboard assays on 21S. aureusisolates showed that in 80 per cent of methicillin-susceptibleS. aureus(MSSA) and 82 per cent of methicillin-resistantS. aureus(MRSA) isolates tested, the minimal inhibitory concentration (MIC) of florfenicol could be reduced by 75 per cent (1/4 MIC) or more (up to 1/16 MIC) when combined with 1/2 MIC of thiamphenicol to exhibit antimicrobial activity comparable to the respective drugs at original strength (1×MIC). A synergistic effect (fractional inhibitory concentration index ≤0.5 or ≥2-log10decrease in colony-forming unit/ml in time-kill study) was evident against 30 per cent of MSSA and 45 per cent of MRSA strains tested. A study in mice revealed that the florfenicol/thiamphenicol combination at reduced dosages provided sufficient protection againstS. aureuschallenge. The possible mechanism warrants further study but likely includes the facilitated uptake of thiamphenicol via florfenicol action, and this facilitation was not limited to amphenicol class. The present study may offer new strategy for combination therapy and provide potential alternatives for effective treatment againstS. aureusinfections.

Effect of detrusor botulinum toxin a injection on urothelial dysfunction in patients with chronic spinal cord injury: a clinical and immunohistochemistry study before and after treatment.

OBJECTIVE: The objective of this study is to investigate the changes of urothelial junction proteins, apoptosis and suburothelial inflammation after detrusor injection of botulinum toxin A (BoNT-A) in patients with spinal cord injury (SCI) and neurogenic detrusor overactivity (NDO). METHODS: A total of 26 patients with chronic suprasacral SCI and NDO were enroled. The urothelium was assessed by cystoscopic biopsy at baseline, 3 and 6 months after a single treatment of 300 U BoNT-A into the detrusor. Immunofluorescence staining of E-cadherin, zonula occludens-1 (ZO-1) and tryptase for mast cell activity were performed. Urothelial apoptosis was also evaluated. The differences in urothelial dysfunction were compared between baseline and 3 and 6 months after treatment. Bladder biopsies from patients undergoing anti-incontinence surgery served as controls. RESULTS: A single 300-U BoNT-A injection into the detrusor significantly decreased detrusor pressure and increased bladder compliance at 3 and 6 months after treatment. Significantly lower E-cadherin and ZO-1 expressions and increased mast cell and apoptotic cell counts were noted in SCI bladders compared with controls (all P<0.001). Significantly greater distributions of E-cadherin (P<0.001) and ZO-1 (P=0.05) expressions were noted 3 months after BoNT-A injection. However, these changes had declined by 6 months after treatment. Activated mast cells and urothelial apoptosis showed no significant differences between baseline and 3 or 6 months. CONCLUSION: Urothelial dysfunction and adhesive and junction protein concentrations in SCI patients' bladders recovered after BoNT-A treatment. However, this effect decreased with time. Thus, neurogenic inflammation after SCI was not adequately improved after a single BoNT-A injection.

Association of Attention deficit hyperactivity disorder and Kawasaki disease: a nationwide population-based cohort study.

AIMS: The association between Kawasaki disease (KD) and Attention deficit hyperactivity disorder (ADHD) has rarely been studied. In this study, we investigated the hypothesis that KD may increase the risk of ADHD using a nationwide Taiwanese population-based claims database. METHODS: Our study cohort consisted of patients who were diagnosed with KD between January 1997 and December 2005 (N = 651). For a comparison cohort, five age- and gender-matched control patients for every patient in the study cohort were selected using random sampling (N = 3255). The cumulative incidence of ADHD was 3.89/1000 (from 0.05 to 0.85) in this study. All subjects were tracked for 5 years from the date of cohort entry to identify whether or not they had developed ADHD. Cox proportional hazard regression analysis was performed to evaluate 5-year ADHD-free survival rates. RESULTS: Of all patients, 83 (2.1%) developed ADHD during the 5-year follow-up period, of whom 21 (3.2%) had KD and 62 (1.9%) were in the comparison cohort. The patients with KD seemed to be at an increased risk of developing ADHD (crude hazard ratio (HR): 1.71; 95% confidence interval (CI) = 1.04-2.80; p < 0.05). However, after adjusting for gender, age, asthma, allergic rhinitis, atopic dermatitis and meningitis, the adjusted hazard ratios (AHR) of the ADHD in patients with KD showed no association with the controls (AHR: 1.59; 95% CI = 0.96-2.62; p = 0.07). We also investigated whether or not KD was a gender-dependent risk factor for ADHD, and found that male patients with KD did not have an increased risk of ADHD (AHR: 1.62; 95% CI = 0.96-2.74; p = 0.07) compared with the female patients. CONCLUSIONS: The findings of this population-based study suggest that patients with KD may not have an increased risk of ADHD and whether or not there is an association between KD and ADHD remains uncertain.

Improved carrier injection in GaN-based VCSEL via AlGaN/GaN multiple quantum barrier electron blocking layer.

In this report, the improved lasing performance of the III-nitride based vertical-cavity surface-emitting laser (VCSEL) has been demonstrated by replacing the bulk AlGaN electron blocking layer (EBL) in the conventional VCSEL structure with an AlGaN/GaN multiple quantum barrier (MQB) EBL. The output power can be enhanced up to three times from 0.3 mW to 0.9 mW. In addition, the threshold current density of the fabricated device with the MQB-EBL was reduced from 12 kA/cm2 (9.5 mA) to 10.6 kA/cm2 (8.5 mA) compared with the use of the bulk AlGaN EBL. Theoretical calculation results suggest that the improved carrier injection efficiency can be mainly attributed to the partial release of the strain and the effect of quantum interference by using the MQB structure, hence increasing the effective barrier height of the conduction band.

Predictive factors of persistent infantile atopic dermatitis up to 6 years old in Taiwan: a prospective birth cohort study.

BACKGROUND: Atopic dermatitis affects 15-30% of children worldwide. Onset of disease usually occurs within the first year of life, over half of which regress by 6 years of age. The aim of this study was to investigate the risk factors related to the persistence of infantile atopic dermatitis. METHODS: In this birth cohort study, patients were enrolled prenatally and followed until 6 years of age; 246 patients had infantile atopic dermatitis at 6 months of age. Family history, maternal and paternal total and specific Immunoglobulin E (IgE) levels, and cord blood IgE were recorded. Clinical examination, questionnaire survey, and blood samples for total and specific IgE of the children were collected at each follow-up visit. RESULTS: Of the 246 patients with infantile atopic dermatitis at 6 months of age, 48 patients had persisted atopic dermatitis at 6 years of age (19.5%). Risk factors associated with persistent infantile atopic dermatitis included egg white sensitization (odds ratio: 3.801, P = 0.020), and atopic dermatitis involving two or more areas at 6 months old (odds ratio: 2.921, P = 0.018) after multivariate analysis with logistic regression. Patients with persistent infantile atopic dermatitis had a higher risk of asthma before 6 years old (39.6% vs 24.2%, P = 0.032). CONCLUSION: Egg white sensitization and the initial involvement of two or more areas at 6 months of age were associated with the persistent infantile atopic dermatitis. Patients with persistent infantile atopic dermatitis are more likely to develop asthma by 6 years of age.

Th17- and Treg-related cytokine and mRNA expression are associated with acute and resolving Kawasaki disease.

BACKGROUND: Kawasaki disease is a vasculitis most commonly afflicting children <5 years of age. Many autoimmune diseases are associated with up-regulation of T helper (Th) 17 cells, and down-regulation Treg cells. Few studies have examined the Th17/Treg expression in Kawasaki disease. METHODS: Blood samples were obtained from 186 children with Kawasaki disease at 24 h before IVIG therapy, followed by 3 days and 21 days after IVIG therapy. Thirty children with an acute febrile infectious disease and 30 healthy children were obtained as control. Plasma levels of Th17- and Treg-related cytokines including IL-6, IL-17A, IL-10, TGF-ß, and mRNA expression levels of RORγt and Foxp3 were tested. RESULTS: Patients with Kawasaki disease had higher levels of plasma IL-17A (25.35 ± 3.21 vs 7.78 ± 1.78 pg/ml, P < 0.001) and IL-6 (152.29 ± 21.94 vs 38.63 ± 12.40 pg/ml, P < 0.001) when compared to the febrile control group. IVIG resulted in a reduction in IL-6 and IL-17A at both 3 and 21 days after IVIG therapy. FoxP3 levels increased significantly 3 days after IVIG therapy (2.28 ± 0.34 vs 0.88 ± 0.14, P < 0.001). IVIG resistance was associated with higher levels of IL-10 and IL-17A. CONCLUSION: Kawasaki disease was associated with higher IL-17A and IL-6, a cytokine profile similar to other autoimmune diseases. IVIG therapy resulted in increased expression of Treg-related FoxP3. IVIG resistance was associated with higher levels of IL-10 and IL-17A. Our findings provide further evidence that Kawasaki disease is an autoimmune-like disease.

Clinical and genetic analysis of Taiwanese patients with hereditary spastic paraplegia type 5.

BACKGROUND AND PURPOSE: Spastic paraplegia type 5 (SPG5) is an autosomal recessive (AR) hereditary spastic paraplegia (HSP) associated with pure or complicated phenotypes. This study aimed to screen SPG5 in Taiwanese HSP patients. METHODS: Sequencing of the SPG5 gene, CYP7B1, was performed in a cohort of 25 ethnic Han Taiwanese patients with AR or sporadic HSP. Clinical information and magnetic resonance imaging (MRI) were analyzed in confirmed SPG5 patients. RESULTS: One (33%) AR kindred and four (18%) sporadic cases had CYP7B1 mutations. All of the SPG5 cases carried the mutation c.334 C>T (R112X). Haplotype analysis suggested a 'founder effect' in ethnic Hans for this mutation. The phenotype was either pure or complicated by cerebellar ataxia. For the primary HSP phenotype, there were profound dorsal column sensory deficits in all patients. Spine MRI showed thoraco-lumbar cord atrophy in some patients. CONCLUSIONS: Spastic paraplegia type 5 is a common cause of AR and sporadic HSPs that has a higher frequency in Taiwanese than in other ethnic groups. It is associated with a CYP7B1 founder mutation and its phenotype is characterized by pronounced dorsal column sensory loss, with cerebellar ataxia in some patients.

How to choose first-line treatment for men with predominant storage lower urinary tract symptoms: a prospective randomised comparative study.

AIMS: To compare the therapeutic effects and identify predictors of successful treatment of first-line antimuscarinic and α-blocker monotherapy for men with predominant storage lower urinary tract symptoms (LUTS). METHODS: This prospective randomised comparative study included men aged ≥ 40 years with a total IPSS ≥ 8, IPSS storage subscore (IPSS-S) ≥ voiding subscore (IPSS-V) and PVR ≤ 250 ml. Subjects were randomised to receive tolterodine 4 mg or doxazosin 4 mg daily for 12 weeks. The primary end-point included changes of total IPSS, IPSS subscore and global response assessment (GRA) after treatment. The secondary end-points included comparisons of baseline parameters between patients with a GRA ≥ 1 and GRA < 1. All adverse events were also recorded. RESULTS: This study was completed by 163 patients. The IPSS-T, IPSS-S and quality of life index decreased significantly in both groups. An improved outcome (GRA ≥ 1) at 4 weeks was reported in 51/74 patients (68.9%) receiving doxazosin and 69/89 patients (77.5%) receiving tolterodine. The rate of improved outcome in patients with a TPV < 40 ml was significantly higher in tolterodine group (73.3% vs. 57.6%, p = 0.040). Patients with tolterodine treatment failure (GRA < 1) had higher baseline IPSS-V and IPSS intermittency domain, whereas patients with doxazosin treatment failure had a higher baseline IPSS urgency domain. CONCLUSIONS: The rate of improved outcome was comparable between first-line tolterodine and doxazosin monotherapy for male storage LUTS. Antimuscarinic monotherapy was suggested for men with smaller prostate volume and higher urgency symptom scores, whereas α-blocker monotherapy was suggested for those with higher voiding symptom scores.

Antimicrobial susceptibility and genetic characterisation of oxytetracycline-resistant Edwardsiella tarda isolated from diseased eels.

Edwardsiellosis is one of the most important bacterial diseases in eels. Edwardsiella tarda (E. tarda) isolates (n=94) from diseased eels were screened against the eight most commonly used antimicrobial agents in aquaculture in Taiwan. These isolates were highly susceptible to ampicillin, amoxicillin, florfenicol, oxolinic acid and flumequine. In total, 20 of the 94 (21.3 per cent) isolates tested were resistant to oxytetracycline (OTC). Among the 20 tetracycline-resistant E. tarda isolates, tet(A) was the predominant resistance determinant and was detected in 100 per cent of the isolates, whereas 90 per cent of these isolates carried the tet(M) determinant. The efflux pump inhibitor omeprazole reduced the minimum inhibitory concentrations (MICs) of OTC for these isolates by twofold to eightfold, suggesting that an intact efflux pump, presumably encoded by tet(A), is required for high-level tetracycline resistance. Real-time PCR experiments showed that increased expression levels of tet(A) and tet(R) could contribute to OTC resistance. Southern blot hybridisation also confirmed that the 20 OTC-resistant E. tarda isolates all carried the TetA determinant on a plasmid that is approximately 50 or 70 kb in size, and restriction fragment length polymorphisms (RFLP) showed that the tet(A) gene was located on an 8-10 kb EcoRI fragment in all of these plasmids. The same plasmid type and RFLP patterns were detected across different farms in the same region, but differences in their pulsed-field gel electrophoresis (PFGE) patterns were observed. This suggests a possible role for horizontal spreading and local transmission of the plasmid in the OTC-resistant E. tarda population of eels from two different geographic origins.

How much improvement is needed for a real difference of lower urinary tract symptoms after long-term combination therapy for benign prostatic hyperplasia.

AIMS: Medical treatment is the first choice in the treatment of lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). This retrospective study investigated the changes of measured parameters after 4-year medical therapy based on the reported quality of life index (QoL-I) in the International Prostate Symptom Score (IPSS) questionnaire. MATERIALS AND METHODS: Patients with symptomatic BPH received 4-year treatment with doxazosin 4 mg and dutasteride 0.5 mg daily. All patients had a total prostate volume (TPV) of ≥ 30 ml and IPSS ≥ 8 at baseline. The measured parameters included IPSS, maximum flow rate (Qmax), postvoid residual volume (PVR), TPV and prostate specific antigen (PSA). The changes of parameters from baseline to 4th year were compared between patients with different QoL-I. RESULTS: Among 243 enrolled patients, 161(66.3%) completed the treatment, 82(33.7%) did not complete the 4-year treatment because of unsatisfactory results (51, 21%) or converted to surgery (31, 12.8%). At the 4th year, 147/161 (91.3%) patients reported a QoL-I of 0-2. All measured parameters show significant improvement. Among the patients with satisfactory QoL (QoL-I 0-2), IPSS ≤ 7 was noted in 113 (76.9%), Qmax ≥ 15 ml/s in 54 (36.79%), PVR < 50 ml in 83 (56.5%), TPV ≤ 39 ml in 63 (42.9%), and PSA ≤ 1.5 ng/ml in 66 (44.9%). Except for the IPSS, a significant change in each parameter from baseline to the 4th year was noted in less than 50% of the patients with satisfactory QoL. CONCLUSION: Based on the patients' reported QoL-I, a successful therapeutic result does not need the improvement of all measured parameters.

Maternal citrulline supplementation prevents prenatal dexamethasone-induced programmed hypertension.

Glucocorticoids are administered to premature infants to accelerate pulmonary maturation. In experimental model, prenatal dexamethasone (DEX) results in reduced nephron number and adulthood hypertension. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), can cause oxidative stress and is involved in the development of hypertension. L-citrulline can be converted to l-arginine (the substrate for NOS) in the body. Thus we intended to determine if maternal L-citrulline therapy can prevent prenatal DEX-induced programmed hypertension by restoration ADMA/nitric oxide (NO) balance, alterations of renin-angiotensin system (RAS) and sodium transporters, and epigenetic regulation by histone deacetylases (HDACs). Male offspring were assigned to four groups: control, pregnancy rats received intraperitoneal DEX (0.2 mg/kg body weight) daily on gestational days 15 and 16 (DEX), pregnancy rats received 0.25% L-citrulline in drinking water during the entire pregnancy and lactation period (CIT), and DEX + CIT. We found DEX group developed hypertension at 16 weeks of age, which was prevented by maternal L-citrulline therapy. Prenatal DEX exposure increased plasma ADMA concentrations and reduced renal NO production. However, L-citrulline reduced plasma ADMA level and increased renal level of NO in DEX + CIT group. Next, prenatal DEX-induced programmed hypertension is related to increased mRNA expression of angiotensin and angiotensin II type 1 receptor, and class I HDACs in the kidney. Prenatal DEX exposure increased renal protein abundance of Na(+)/Cl(-) cotransporter (NCC), which was prevented by L-citrulline therapy. The beneficial effects of L-citrulline therapy include restoration of ADMA/NO balance and alteration of NCC, to prevent the prenatal DEX-induced programmed hypertension.

Severity of lower urinary tract symptoms reflects different composition of bladder storage dysfunction and bladder outlet obstruction in men with symptomatic benign prostatic hyperplasia.

AIMS: Differentiation of different lower urinary tract dysfunctions (LUTD) is essential for selecting the optimal first-line medical treatment of lower urinary tract symptoms (LUTS). This study analysed the association of the severity of LUTS with LUTD and therapeutic results based on the International Prostate Symptom Score (IPSS) voiding to storage (V/S) ratio. MATERIALS AND METHODS: Lower urinary tract symptoms were evaluated in 849 men using the IPSS questionnaire and the IPSS-V/S ratio. The prostate measures, urinary flow measures, and C-reactive protein (CRP) were investigated at baseline and 1 month after treatment. Therapeutic results were assessed by changes in the quality of life index (QoL-I). The associations of the severity of LUTS with LUTD and therapeutic results were analysed. RESULTS: Mild (IPSS ≤ 7), moderate (8 ≤ IPSS ≤ 19) and severe LUTS (IPSS ≥ 20) were noted in 215, 461 and 173 men. IPSS-V/S ≤ 1 was noted in 81.4% of patients with mild LUTS, while IPSS-V/S > 1 was noted in 71.1% of patients with severe LUTS. After treatment with alpha-blockers in patients with IPSS-V/S > 1 and antimuscarinic agents in patients with IPSS-V/S ≤ 1 for 1 month, 84.0% and 88.8% of patients with mild LUTS had effective therapeutic results, respectively. In contrast, the therapeutic results were less effective in patients with moderate (64.9% and 63.8%, respectively) or severe LUTS (50% and 33.3%, respectively). CONCLUSION: Patients with benign prostatic hyperplasia (BPH) and mild LUTS have more bladder storage dysfunction, whereas patients with BPH and severe LUTS had higher grade of bladder outlet disorders in associated with storage symptoms. Treatment based on the IPSS-V/S ratio results in good therapeutic results in men with mild and moderate LUTS, but not in men with severe LUTS.

Adding Cyclooxygenase-2 inhibitor to alpha blocker for patients with benign prostate hyperplasia and elevated serum prostate specific antigen could not improve prostate biopsy detection rate but improve lower urinary tract symptoms.

AIMS: To investigate the impact of cyclooxygenase-2 (COX-2) inhibitor with α-adrenoceptor blocker (α-blocker) for men with benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) for detecting prostate cancer in men with elevated prostate specific antigen (PSA). MATERIALS AND METHODS: Male patients with clinical BPH, elevated serum PSA (> 4 ng/ml), and significant LUTS (International Prostate Symptom Score [IPSS] ≥ 8) were randomly assigned to receive doxazosin 4 mg daily plus celecoxib 200 mg daily (study group) or doxazosin 4 mg daily alone (control group) for 3 months. Patients were investigated for the changes in IPSS, maximum flow rate (Qmax), voided volume, postvoid residual (PVR) volume and serum PSA from baseline to 3 months after treatment. After the 3-month therapy, prostate biopsy was performed in the patients whose PSA were still higher than 4 ng/ml. RESULTS: A total of 82 patients completed the study. The improvement in IPSS-voiding was significantly greater in the study group than control group (p = 0.034). In the study group, patients with prostatic hyperplasia or inflammation on the prostate biopsy had a significantly better result than in patients with prostatic adenocarcinoma, typically in the changes of Qmax and voided volume (p = 0.012 and p = 0.005, respectively). The PSA level in the study group showed significant improvement after treatment (p < 0.01). However, prostate cancer detection rate failed to show any significant difference between the patients whose PSA levels decreased or not (6/21 = 29% vs. 5/24 = 20%, respectively, p = 0.447). CONCLUSIONS: Treatment with COX-2 inhibitor and α-blocker for 3 months could not improve prostatic cancer detection rate. But it could increase therapeutic effectiveness of LUTS in men with BPH and elevated PSA levels. The changes in Qmax and voided volume after combination treatment were significantly greater in patients with prostatic hyperplasia or inflammation than adenocarcinoma.

Intra-articular injection of the selective cyclooxygenase-2 inhibitor meloxicam (Mobic) reduces experimental osteoarthritis and nociception in rats.

OBJECTIVE: To study the effect of intra-articular injection of meloxicam (Mobic) on the development of osteoarthritis (OA) in rats and examine concomitant changes in nociceptive behavior and the expression of mitogen-activated protein kinases (MAPKs) in articular cartilage chondrocytes. METHODS: OA was induced in Wistar rats by right anterior cruciate ligament transection (ACLT); the left knee was not treated. The OA + meloxicam (1.0 mg) group was injected intra-articularly in the ACLT knee with 1.0 mg of meloxicam once a week for 5 consecutive weeks starting 5 weeks after ACLT. The OA + meloxicam (0.25 mg) group was treated similarly with 0.25 mg meloxicam. The sham group underwent arthrotomy only and received vehicle of 0.1 mL sterile 0.9% saline injections, whereas the naive rats in meloxicam-only groups were treated similarly with 1.0- and 0.25-mg meloxicam. Nociception was measured as secondary mechanical allodynia and hind paw weight-bearing distribution at before (pre-) and 5, 10, 15, and 20 weeks post-ACLT. Histopathology of the cartilage and synovia was examined 20 weeks after ACLT. Immunohistochemical analysis was performed to examine the effect of meloxicam on MAPKs (p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK)) expression in the articular cartilage chondrocytes. RESULTS: OA rats receiving intra-articular meloxicam treatment showed significantly less cartilage degeneration and synovitis than saline-treated controls. Nociception were improved in the OA + meloxicam groups compared with the OA group. Moreover, meloxicam attenuated p38 and JNK but enhanced ERK expression in OA-affected cartilage. CONCLUSIONS: Intra-articular injection of meloxicam (1) attenuates the development of OA, (2) concomitantly reduces nociception, and (3) modulates chondrocyte metabolism, possibly through inhibition of cellular p38 and JNK, but enhances ERK expression.

Therapeutic outcome and quality of life between urethral and detrusor botulinum toxin treatment for patients with spinal cord lesions and detrusor sphincter dyssynergia.

AIMS: Patients with spinal cord lesions and detrusor sphincter dyssynergia (DSD) may be treated with urethral sphincter botulinum toxin A (BoNT-A) injection for difficult urination or detrusor BoNT-A injection for incontinence. Although objective data showed improvement, patients might not be satisfied with the result especially in quality of life (QOL) issue. This study investigated the therapeutic results and QOL and patients' satisfaction to these two treatments. PATIENTS AND METHODS: Patients with spinal cord lesion and DSD were treated with urethral sphincter injection of 100 U of BoNT-A for main symptoms of difficult urination and detrusor injection of 200 U of BoNT-A for main symptom of incontinence. The urodynamic parameters, QOL scores using UDI-6 and IIIQ-7 and general satisfaction were compared between two groups. RESULTS: The overall satisfactory result was perceived in 60.6% and 77.3% in patients who received urethral and detrusor BoNT-A injection, respectively. Urodynamic parameters showed significant improvement in both groups. Urethral injection group had improvement in IIQ-7, but not in UDI-6 scores whereas detrusor injection group had improvement in all scores. The improvement of UDI-6 and IIQ-7 was significantly greater in detrusor than urethral injection group. Increase in incontinence grade was the major cause of dissatisfaction in urethral injection group, whereas increase in difficult urination and needing catheterisation were the main dissatisfaction causes in detrusor injection group. CONCLUSION: There was discrepancy between the objective urodynamic results and patient satisfaction in treatment of DSD by BoNT-A injection. Patients with DSD and treated with detrusor BoNT-A had greater QOL improvement than those treated with urethral injection.