Quality of life and defecative function 10 years or longer after posterior sagittal anorectoplasty and laparoscopic-assisted anorectal pull-through for anorectal malformation.

PURPOSE: In our center, patients with anorectal malformation, including males with recto-vesical (RV)/recto-bladder neck (RBN)/recto-prostatic urethral (RU) fistulas, and females with recto-vaginal (RV) fistulas have been treated by posterior sagittal anorectoplasty (PSARP) before 2000, and by laparoscopic-assisted anorectal pull-through (LAARP) thereafter. We would like to compare the quality of life (QOL) and long-term defecative function between these two groups of patients 10 years after reconstructive surgery. METHODS: Patients who underwent LAARP between 2001 and 2005 were compared with historical controls treated with PSARP between 1996 and 2000. Degrees of continence were graded by the Krickenbeck classification and Kelly's score. QOL was assessed by Hirschsprung's disease/Anorectal Malformation Quality of Life (HAQL) questionnaire. Results were compared using Chi-square test and t test. RESULTS: There were 14 LAARP and 7 PSARP patients. All attained voluntary bowel movements. Moderate to severe soiling (Krickenbeck Grade 2 and 3) was found in 3/14 LAARP (21.4%) and 1/7 PSARP (14.3%) patients, p = 1.00. Constipation requiring use of laxatives was present in 3/14 LAARP (28.6%) and 1/7 PSARP (14.3%) patients, p = 0.62. Mean Kelly's scores were 3.79 ± 0.98 (LAARP) and 4.71 ± 1.25 (PSARP), p = 0.12. No patient required Malone antegrade continence enema (MACE). The QOL scores based on the HAQL questionnaire were comparable between the two groups in all areas except social functioning, in which the LAARP patients attained a significantly lower mean score (26.4 vs 71.7, p = 0.0001). CONCLUSION: The 10-year outcome between LAARP and PSARP patients in terms of QOL and defecative function is comparable. Impairment in social functioning in these patients is reflected by the self-reported lower level of functioning.

K-complexes, spindles, and ERPs as impulse responses: unification via neural field theory.

To interrelate K-complexes, spindles, evoked response potentials (ERPs), and spontaneous electroencephalography (EEG) using neural field theory (NFT), physiology-based NFT of the corticothalamic system is used to model cortical excitatory and inhibitory populations and thalamic relay and reticular nuclei. The impulse response function of the model is used to predict the responses to impulses, which are compared with transient waveforms in sleep studies. Fits to empirical data then allow underlying brain physiology to be inferred and compared with other waves. Spontaneous K-complexes, spindles, and other transient waveforms can be reproduced using NFT by treating them as evoked responses to impulsive stimuli with brain parameters appropriate to spontaneous EEG in sleep stage 2. Using this approach, spontaneous K-complexes and sleep spindles can be analyzed using the same single theory as previously been used to account for waking ERPs and other EEG phenomena. As a result, NFT can explain a wide variety of transient waveforms that have only been phenomenologically classified to date. This enables noninvasive fitting to be used to infer underlying physiological parameters. This physiology-based model reproduces the time series of different transient EEG waveforms; it has previously reproduced experimental EEG spectra, and waking ERPs, and many other observations, thereby unifying transient sleep waveforms with these phenomena.

Increased sexual desire with exogenous testosterone administration in men with obstructive sleep apnea: a randomized placebo-controlled study.

Testosterone (T) deficiency, sexual dysfunction, obesity and obstructive sleep apnea (OSA) are common and often coexist. T prescriptions have increased worldwide during the last decade, including to those with undiagnosed or untreated OSA. The effect of T administration on sexual function, neurocognitive performance and quality of life in these men is poorly defined. The aim of this study was to examine the impact of T administration on sexual function, quality of life and neurocognitive performance in obese men with OSA. We also secondarily examined whether baseline T might modify the effects of T treatment by dichotomizing on baseline T levels pre-specified at 8, 11 and 13 nmol/L. This was a randomized placebo-controlled study in which 67 obese men with OSA (mean age 49 ± 1.3 years) were randomized to receive intramuscular injections of either 1000 mg T undecanoate or placebo at baseline, week 6 and week 12. All participants were concurrently enrolled in a weight loss program. General and sleep-related quality of life, neurocognitive performance and subjective sexual function were assessed before and 6, 12 and 18 weeks after therapy. T compared to placebo increased sexual desire (p = 0.004) in all men, irrespective of baseline T levels. There were no differences in erectile function, frequency of sexual attempts, orgasmic ability, general or sleep-related quality of life or neurocognitive function (all p = NS). In those with baseline T levels below 8 nmol/L, T increased vitality (p = 0.004), and reduced reports of feeling down (p = 0.002) and nervousness (p = 0.03). Our findings show that 18 weeks of T therapy increased sexual desire in obese men with OSA independently of baseline T levels whereas improvements in quality of life were evident only in those with T levels below 8 nmol/L. These small improvements would need to be balanced against potentially more serious adverse effects of T therapy on breathing.

The value of the 24-h delayed abdominal radiograph of barium enema in the diagnosis of Hirschsprung's disease.

AIM OF STUDY: The objective of this study is to determine the diagnostic value of the 24-h delayed film for Hirschsprung's disease (HD). Other features of the barium enema were also examined, in particular the correlation between the radiological transition zone (TZ) and the final pathology. METHODS: All patients with suspected HD from 2003 to 2013 who had undergone barium enema and rectal biopsy were reviewed retrospectively to study the correlation between radiological features of barium enema with the final diagnosis as well as severity. RESULTS: A total of 182 patients were admitted for suspected HD during the study period, of which 82 had both investigations done. 68 patients had radiological features suggestive of the disease and ultimately, 12 patients had the disease confirmed with rectal biopsy. Among those without radiological features of HD, 2 patients were found to have the disease. Thus, the sensitivity of the 24-h delayed film was 85.7 % and the specificity was 17.6 %. The positive predictive value (PPV) of this test was 20.6 % and the negative predictive value (NPV) was 85.7 %. Regarding the level of TZ, it was not detected in the barium enema in 7 (50 %) out of the 14 patients. For those with the presence of TZ, 6 (85.7 %) of them correlated well with the intra-operative findings and 4 (57.1 %) of them correlated well with the final histology. CONCLUSION: The 24-h delayed film of barium enema has a high NPV and is useful to rule out HD. However, rectal biopsy is still suggested for disease confirmation given its low PPV. Lastly, once present, the level of radiological TZ is also a useful predictor for the actual disease involvement.

Clinical experience in managing pediatric patients with ultra-short bowel syndrome using omega-3 fatty acid.

Total parenteral nutrition (TPN) remains an important component of the management of short bowl syndrome in pediatric patients. However, prolonged TPN is known to be associated with cholestasis. Recently, the use of omega-3-fatty acid (Omegaven) has been proposed to improve TPN cholestasis. We present the early outcome after administration of Omegaven in four patients with ultra-short bowel syndrome. Based on our experience, it appears that omega-3 fatty acid can reverse and prevent the advent of TPN-related cholestasis, thereby significantly improving the process of intestinal adaptation. We suggest that clinicians consider this treatment option before proceeding to invasive surgery to reverse cholestasis. Prospective randomized trials are necessary to define a standard protocol and elucidate other potential benefits of this novel agent.

Evaluation of pyrrolidin-2-imines and 1,3-thiazolidin-2-imines as inhibitors of nitric oxide synthase.

Syntheses and evaluation of pyrrolidin-2-imines and 1,3-thiazolidin-2-imines as inhibitors of nitric oxide synthase (NOS) are discussed. An extensive SAR was established for pyrrolidin-2-imines class of compounds. The amidines came out as the most potent inhibitors in addition to displaying selectivity.

Differential effect of tetrandrine on aortic relaxation and chronotropic activity in rat isolated aorta and atria.

Tetrandrine is known as a calcium blocker which can induce bradycardia as well as hypotension. It was however reported that the heart rate was unchanged during tetrandrine-induced hypotension. The possibility of different tissue sensitivity to various concentrations of tetrandrine was therefore investigated using the rat isolated aorta and atria. It was found that tetrandrine (1 x 10(-5) M) was sufficient to suppress more than 90% of the aortic contraction induced by norepinephrine (1 x 10(-8) M) or KCl (50 mM). However, only 10% of the initial heart rate was suppressed by 1 x 10(-5) M tetrandrine. It was therefore concluded that the aorta and atria might have different sensitivity to tetrandrine.

Mechanism of the aortic relaxation induced by low concentrations of berberine.

The mechanism of the aortic relaxation induced by a low concentration of berberine was investigated in rat isolated aorta. It was found that the aortic relaxation induced by berberine below 1 x 10(-6) M was solely endothelium dependent. Denuded aorta and methylene blue pretreated aorta did not demonstrate aortic relaxation with such berberine concentrations. Higher concentrations (above 1 x 10(-6) M berberine), however, induced aortic relaxation irrespective of the presence of intact endothelium or methylene blue pretreatment. Since methylene blue is known as a direct inhibitor of nitric oxide synthase beside being a nonspecific guanylyl cyclase inhibitor, the present data suggest that the mechanism of the aortic relaxation induced by a low berberine concentration is solely dependent on the presence of endothelium.

Lack of anticholinergic activity by baicalin in the isolated trachea of guinea pig.

The anticholinergic effect of baicalin on the trachea from asthmatic guinea pig had been described elsewhere. Using 1 x 10(-5) M bethanechol to induce contraction in the isolated trachea from non-asthmatic guinea pig, baicalin below 1 x 10(-4) M was unable to attenuate the bethanechol-induced tracheal contraction; however, 1 x 10(-4) M baicalin was demonstrated to increase the tracheal contraction in the presence of bethanechol. Baicalin (1 x 10(-4) M) was also able to induce tracheal contraction in the absence of bethanechol, and this baicalin-induced tracheal contraction was shown to be atropine-sensitive. These data suggested that the baicalin effect on the isolated trachea from non-asthmatic guinea pig was not anticholinergic in nature.

Endothelium-dependent higenamine-induced aortic relaxation in isolated rat aorta.

The pharmacological action of higenamine in isolated rat aorta was investigated. Although the beta-adrenoceptor antagonist propranolol (1 x 10(-5) M) completely blocked the beta-adrenoceptor agonist higenamine in inducing a positive chronotropic activity in isolated mouse atria, the higenamine-induced aortic relaxation was not completely antagonized by this concentration of propranolol. The present data also demonstrate that the higenamine-induced aortic relaxation was attenuated in the absence of endothelium. These findings suggest that the beta-adrenoceptor specificity to higenamine in aorta is different from that of beta-1 in atria; moreover, the beta-adrenoceptors sensitive to higenamine are mainly located in the endothelial layer.

Lack of calcium-antagonizing activity of dehydroevodiamine on the chronotropic and inotropic activities of mouse isolated atria.

Dehydroevodiamine (DeHE) was reported to induce bradycardia and to have calcium-antagonizing activity besides other actions. The purpose of the present study was to investigate if DeHE could act as a calcium antagonist on the chronotropic and inotropic activities of mouse isolated atria. The data showed that DeHE induced bradycardia but did not decrease the contraction amplitude of the right atrium. Moreover, DeHE did not attenuate the contraction amplitude of the electrically driven left atrium and, in the presence of 1 x 10(-4) M DeHE, the contraction amplitude of left atrium was increased when the calcium concentration in Krebs solution was further increased. Since calcium antagonists are known to inhibit chronotropic and inotropic activities, it seems unlikely that DeHE acts as a calcium antagonist on the chronotropic and inotropic activities of mouse isolated atria.

Ribozyme-mediated in vitro cleavage of transcripts arising from the major transforming genes of human papillomavirus type 16.

Human papillomaviruses (HPV) have been strongly implicated as important cofactors in the development of several human malignancies, particularly anogenital carcinomas. Products arising from the E6 and E7 open reading frames (ORFs) from HPV-16, a type commonly associated with human cervical carcinoma, are essential for viral transformation. Unfortunately, a highly effective treatment for this infection is not available. To develop a novel treatment for this disease, ribozymes were designed to cleave all transcripts encoding HPV-16 E6 and E7 ORFs in proximity to their translational start sites ("AUG"). Cleavage sites for Rz110 and Rz558 occur immediately 3' to nucleotides 110 and 558 of the viral genomic DNA, respectively. Oligonucleotides corresponding to these ribozymes were synthesized and inserted into a eucaryotic viral vector derived from the nonpathogenic parvovirus, adeno-associated virus. Ribozyme transcription from this vector, termed CWRT7:SVN, is under control of both the highly active Rous sarcoma virus long terminal repeat and bacteriophage T7 promoters. T7 transcripts of the E6 and E7 ribozymes efficiently cleaved their cognate targets in vitro under a variety of conditions, including physiological temperature. These results may provide the basis for the development of a ribozyme-based, gene therapeutic treatment for HPV-associated diseases.

Yin-yang 1 activates the c-myc promoter.

Previous studies on the murine c-myc promoter demonstrated that a ubiquitously present protein, common factor 1 (CF1), bound at two sites located -260 and -390 bp from the P1 transcription start site. CF1 has been purified to near homogeneity and shown to be identical to the zinc finger protein Yin-yang 1 (YY1) as judged by similarity of molecular weight and other biochemical properties, immunological cross-reactivity, and the ability of recombinant YY1 to bind to CF1 sites. In cotransfection experiments, YY1 is a strong activator of transcription from c-myc promoter-based reporters. Furthermore, in murine erythroleukemia cells, overexpressed YY1 causes increased levels of c-myc mRNA initiated from both major transcription initiation sites of the endogenous c-myc gene.

Preoperative and intraoperative localisation of gastrointestinal bleeding of obscure origin.

In the past six years, 37 patients with gastrointestinal bleeding of obscure origin had their bleeding sites localised preoperatively or intraoperatively. Preoperative investigations followed a regime consisting of endoscopy, barium meal and follow through, small bowel enema, 99mTc pertechnetate scan, 99mTc-labelled red blood cell scan and selective coeliac and mesenteric angiography. Bleeding lesions were localised preoperatively in 36 patients. In one patient, diagnostic laparotomy had to be carried out immediately before any investigation because the bleeding was severe. At operation, angiosarcoma of ileum was found. Unless preoperative investigations showed the lesions to be in anatomically fixed organs like the duodenum or colon, the lesions had still to be found at operation. Palpation and transillumination detected the lesion intraoperatively in 21 patients while only some lesions were found in three patients with multiple lesions. Sigmoidoscopy through enterotomies was required in one patient. Intraoperative enteroscopy was done for small lesions not found grossly at operation in nine patients, to detect additional lesions in three patients or to rule out suspicious lesion shown on preoperative tests in one patient. In another patient with diffuse lymphoma of small bowel with bleeding from only a small segment of jejunum, injection of methylene blue intraoperatively through a previously placed angiographic catheter stained the bleeding segment of jejunum blue. This segment was identified easily and resected. These preoperative and intraoperative localisation procedures were simple and effective and we recommend them to be used more freely.

Intra-operative fibreoptic enteroscopy for bleeding lesions in the small intestine.

Twenty-five patients with gastrointestinal bleeding proved to have lesions in the small intestine. Intra-operative fibreoptic enteroscopy was performed on seven patients, in six patients through the anus and in one patient through an enterotomy and the anus. The indications for fibreoptic enteroscopy were inability to find the lesions in the 3 patients, multiple small lesions in 3 patients and to rule out suspicious pathology in the jejunum shown on a small bowel enema in a patient with ileal ulcers. In all instances, the fibreoptic enteroscopy was useful in localizing lesions, in detecting additional lesions and in ruling out the suspicious lesions. It can be performed easily and is safe. No complication developed from its use in this series.