Long-term efficacy of biofeedback therapy in patients with dyssynergic defecation: results of a median 44 months follow-up.

BACKGROUND: The beneficial effect of biofeedback therapy (BFT) over a period of more than 2 years has not been studied in a large group of patients. The aim of this study was to evaluate the long-term efficacy of BFT for dyssynergic defecation (DD). METHODS: We evaluated the results for 347 consecutive constipated patients with DD who underwent BFT for a median of five sessions between 2004 and 2009. Initial responses were assessed immediately after the completion of BFT. A responder was defined as a subject with at least a three-point improvement from before to after BFT on an 11-point global bowel satisfaction (GBS) scale, or a two-point improvement if the baseline GBS was more than six points. The probability of remaining a responder was estimated by non-parametric maximum likelihood estimation. KEY RESULTS: The initial response rate to BFT was 72.3% (n = 251), Parkinson's disease and higher baseline GBS scores were associated with initial non-response. The long-term efficacy of BFT was analyzed in 103 patients who were followed up for more than 6 months; the initial effects of BFT were maintained in 85 of the patients (82.5%) during a median of 44 months of follow-up (IQR = 12-68). The probability of remaining a responder was 60% at 2 years, and 58% at 5 years. CONCLUSIONS & INFERENCES: The efficacy of BFT is maintained for more than 2 years after BFT in a considerable proportion of constipated patients with DD. BFT is effective and durable treatment for managing DD.

Diagnostic sensitivity of culture and drug resistance patterns in Korean patients with intestinal tuberculosis.

SETTING: It is challenging to differentiate between intestinal tuberculosis (ITB) and Crohn's disease in areas where TB is still prevalent. The use of diagnostic tools and verifying the drug resistance patterns of ITB can be helpful for its correct diagnosis. OBJECTIVE: To determine the diagnostic sensitivity of a culture assay using colonoscopic biopsy specimens and the drug resistance patterns of Mycobacterium tuberculosis isolated from ITB. DESIGN: Data from 400 patients diagnosed with ITB were retrospectively analysed. RESULTS: Of the 400 patients, 170 (42.5%) were males; the median age at diagnosis was 40 years. The sensitivity of culture was 44.1% (145/329). Resistance to at least one anti-tuberculosis drug was identified in 13 (17.6%) and multidrug-resistant TB (MDR-TB) was diagnosed in two (2.7%) of the 74 patients for whom drug susceptibility testing was performed. Including M. tuberculosis isolated from respiratory specimens, the proportion of MDR-TB was 4.4% (5/113); previous anti-tuberculosis treatment was an independent risk factor for MDR-TB (26.7% vs. 1.0%, P < 0.01). CONCLUSION: Culture of colonoscopic biopsy specimens shows substantial diagnostic sensitivity; the frequency of MDR-TB is higher in previously treated cases than in new cases.

POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1) inhibits endothelial cell senescence through a p53 dependent pathway.

Vascular cell senescence, induced by the DNA damage response or inflammatory stress, contributes to age-associated vascular disease. Using complementary DNA microarray technology, we found that the level of POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1) is downregulated during endothelial cell (EC) senescence. PATZ1 may have an important role as a transcriptional repressor in chromatin remodeling and transcription regulation; however, the role of PATZ1 in EC senescence and vascular aging remains unidentified. Knockdown of PATZ1 in young cells accelerated premature EC senescence, which was confirmed by growth arrest, increased p53 protein level and senescence-associated ß-galactosidase (SA-ß-gal) activity, and repression of EC tube formation. In contrast, overexpression of PATZ1 in senescent cells reversed senescent phenotypes. Cellular senescence induced by PATZ1 knockdown in young cells was rescued by knockdown of p53, but not by knockdown of p16(INK4a). PATZ1 knockdown increased ROS levels, and pretreatment with N-acetylcysteine abolished EC senescence induced by PATZ1 knockdown. Notably, PATZ1 immunoreactivity was lower in ECs of atherosclerotic tissues than those of normal arteries in LDLR(-/-) mice, and immunoreactivity also decreased in ECs of old human arteries. These results suggest that PATZ1 may have an important role in the regulation of EC senescence through an ROS-mediated p53-dependent pathway and contribute to vascular diseases associated with aging.

Study to compare the efficacy and safety of fluconazole cream with flutrimazole cream in the treatment of superficial mycosis: a multicentre, randomised, double-blind, phase III trial.

Fluconazole, which is a drug of the azole family, is safely used in systemic treatment of oral and intravenous injection, but it is difficult to use fluconazole as a topical application because of its large molecular weight and strong hydrophilic property. This study is a multicentre, double-blind, randomised, non-inferiority study to compare the antifungal effect and safety of fluconazole cream 0.5% and 1% with flutrimazole cream 1% in superficial mycosis. A total of 162 subjects selected to participate in this study were equally divided into three groups and assigned to be given fluconazole cream 0.5%, fluconazole cream 1%, and flutrimazole cream 1% in the ratio of 1 : 1. The primary index of drug efficacy was determined by complete mycological cure in which no fungus was detected on KOH smear test 4 weeks after application of fluconazole. The secondary index of efficacy was defined as complete mycological cure 4 weeks after the application of fluconazole, improvement of clinical symptoms and overall effectiveness assessed by the research staff. According to this study, on comparing the efficacy of cure of superficial dermatomycosis after 4 weeks of application, both fluconazole 0.5% and fluconazole 1% cream were found to be equally effective and non-inferior to flutrimazole 1% cream. Given the effectiveness and safety of the drug, both fluconazole 0.5% and 1% cream might be said to be optimal concentration in the treatment of superficial dermatomycosis.

CD30-positive T-cell-rich pseudolymphoma induced by gold acupuncture.

Cases of pseudolymphoma induced by intradermal gold injection or gold piercing have previously been described. Most of these cases showed the histopathological finding of B-lymphocyte predominant lymphocytoma cutis. We describe a patient with gold acupuncture-induced T-cell-rich pseudolymphoma. Some T cells showed positive staining with CD30. The lesions responded to an intralesional injection of triamcinolone acetonide.

Effect of Korea red ginseng on the blood pressure in conscious hypertensive rats.

The change of blood pressure and heart rate after intravenous injection of Korea red ginseng (KRG) were studied in the conscious normotensive and one-kidney, one-clip Goldblatt hypertensive (1K, 1C-GBH) rats. Crude saponin (CS) of KRG (50, 100 mg/kg i.v.) induced a hypotensive effect and bradycardia in a dose-dependent manner in the anesthetized rats. On the other hand, CS of KRG (100 mg/kg) induced a hypotensive effect and reflex tachycardia in the conscious rats. Saponin-free fraction (SFF) of KRG did not affect them in the anesthetized normotensive rats (P>.05). The maximal hypotensive effect by CS of KRG in the conscious 1K, 1C-GBH hypertensive rats and L-nitroarginine methyl ester (L-NAME, 40 mg/kg)-treated conscious hypertensive rats was not different from that of conscious normotensive rats (Delta 31.6+/-6.3, Delta 27.5+/-5.8 vs. Delta 26.7+/-4.3 mmHg, P>.05). However, pretreatment of L-NAME significantly inhibited the reflex tachycardia by CS of KRG (70.8+/-7.0 vs. 30.6+/-15.0 bpm, P<.05). Hemolysate-sensitive nitric oxide (NO) current by the CS of KRG was greater than that of the SFF of KRG (651.9+/-128.2 pA for CS and 164.9+/-92.5 pA for SFF, P<.001). These findings suggest that KRG has a hypotensive effect and its effect may be due to saponin fraction of KRG in the conscious rats. The releasing effect of NO of KRG, like NO donor, may be partly contributed to the hypotensive effect of KRG.

KGF prevents hyperoxia-induced reduction of active ion transport in alveolar epithelial cells.

We evaluated the effects of acute hyperoxic exposure on alveolar epithelial cell (AEC) active ion transport and on expression of Na+ pump (Na+-K+-ATPase) and rat epithelial Na+ channel subunits. Rat AEC were cultivated in minimal defined serum-free medium (MDSF) on polycarbonate filters. Beginning on day 5, confluent monolayers were exposed to either 95% air-5% CO2 (normoxia) or 95% O2-5% CO2 (hyperoxia) for 48 h. Transepithelial resistance (Rt) and short-circuit current (Isc) were determined before and after exposure. Na+ channel alpha-, beta-, and gamma-subunit and Na+-K+-ATPase alpha1- and beta1-subunit mRNA levels were quantified by Northern analysis. Na+ pump alpha1- and beta1-subunit protein abundance was quantified by Western blotting. After hyperoxic exposure, Isc across AEC monolayers decreased by approximately 60% at 48 h relative to monolayers maintained under normoxic conditions. Na+ channel beta-subunit mRNA expression was reduced by hyperoxia, whereas alpha- and gamma-subunit mRNA expression was unchanged. Na+ pump alpha1-subunit mRNA was unchanged, whereas beta1-subunit mRNA was decreased approximately 80% by hyperoxia in parallel with a reduction in beta1-subunit protein. Because keratinocyte growth factor (KGF) has recently been shown to upregulate AEC active ion transport and expression of Na+-K+-ATPase under normoxic conditions, we assessed the ability of KGF to prevent hyperoxia-induced changes in active ion transport by supplementing medium with KGF (10 ng/ml) from day 2. The presence of KGF prevented the effects of hyperoxia on ion transport (as measured by Isc) relative to normoxic controls. Levels of beta1 mRNA and protein were relatively preserved in monolayers maintained in MDSF and KGF compared with those cultivated in MDSF alone. These results indicate that AEC net active ion transport is decreased after 48 h of hyperoxia, likely as a result of a decrease in the number of functional Na+ pumps per cell. KGF largely prevents this decrease in active ion transport, at least in part, by preserving Na+ pump expression.

More characters or more taxa for a robust phylogeny--case study from the coffee family (Rubiaceae).

Using different data sets mainly from the plant family Rubiaceae, but in parts also from the Apocynaceae, Asteraceae, Lardizabalaceae, Saxifragaceae, and Solanaceae, we have investigated the effect of number of characters, number of taxa, and kind of data on bootstrap values within phylogenetic trees. The percentage of supported nodes within a tree is positively correlated with the number of characters, and negatively correlated with the number of taxa. The morphological analyses are based on few characters and weakly supported trees are expected. The percentage of supported nodes is also dependent on the kind of data analyzed. In analyses of Rubiaceae based on the same number of characters, RFLP data give trees with higher percentage of supported nodes than rbcL and morphological data. We also discuss the support values for particular nodes at the familial and subfamilial levels. Two new data sets of ndhF and rbcL sequences of Rubiaceae are analyzed and together with earlier studies of the family we can conclude that the monophyly of the Rubiaceae is supported and within the family there are three well supported, but not easily characterized, large subfamilies, Rubioideae, Cinchonoideae s.s. and Ixoroideae s.l. There are also a few genera (Luculia and Coptosapelta) unclassified to subfamily.

Chronic effects of topical application of capsaicin to the sciatic nerve on responses of primate spinothalamic neurons.

The responses of 144 spinothalamic tract (STT) cells were recorded in 15 anesthetized macaque monkeys (Macaca fascicularis). Three to 4 weeks prior to the acute experiment, the sciatic nerve was surgically exposed on one or both sides so that capsaicin or vehicle could be applied. Responses of STT cells recorded in 3 experimental groups were compared: untreated (21 cells), vehicle-treated (40 cells), and capsaicin-treated (83 cells). The background activity of cells in the vehicle- and capsaicin-treated groups was the same as in the untreated group (that is, cells on the side contralateral to surgery). Responses to innocuous (BRUSH) and noxious (PINCH) mechanical stimuli were unchanged by vehicle or by capsaicin treatment. However, responses to other noxious (PRESSURE and SQUEEZE) mechanical stimuli were significantly increased in the vehicle-treated group. Compared with a large reference population, all experimental groups showed a significant increase in overall responsiveness to mechanical stimuli (as determined by cluster analysis), greatest in the vehicle-treated group. Responses to noxious heat stimuli were significantly reduced in the capsaicin-treated group for 45 degrees C and 47 degrees C stimuli. Volleys in A fibers, probably A delta fibers, evoked prolonged responses in many STT cells of all treatment groups. Electron microscopic counts of axons in the sciatic nerves of animals treated with capsaicin showed a reduced number of C fibers but no appreciable loss of myelinated axons. This loss of unmyelinated sensory fibers was presumably responsible for the reduction in the responses of the STT cells to noxious heat stimuli. Increased responses to some noxious mechanical stimuli and to A fiber volleys may have been the consequence of several factors, including surgical manipulation, a chemical action of vehicle and a contralateral action of capsaicin treatment.