Development and validation of a transanal endoscopic rectal purse string simulator.

BACKGROUND: Rectal purse string placement for transanal mesorectal excision is challenging, and practice is difficult. The objective of this study is to build an endoscopic rectal purse string simulator and provide evidence for the validity of its use. METHODS: A low-cost transanal endoscopic rectal purse string simulator was created and used to measure the performance of participants. Participants included general surgery residents, fellows, and staff surgeons from several Canadian university-affiliated institutions across Canada. The performance of the rectal purse string placement was measured by the time to completion of the task as well scoring with a modified objective structured assessment of technical skills (OSATS) score and a modified advanced laparoscopic suturing (ALS) score. RESULTS: Thirty-nine participants were recruited into the study. Participants were split into three groups, based on prior experience with laparoscopic suturing, for the analysis of suturing a rectal purse string on the simulator based on three performance measures. There was a significant difference found in all three measures of performance in the three groups (time to completion p = 0.014, mean blinded OSATS score p = 0.007, mean blinded ALS score p = 0.020). Participants with previous laparoscopic suturing had significantly faster times to completion and higher skills scores when compared to residents (time: 5.1 ± 1.4 min vs 9.0 ± 4.8 min, p = 0.005; OSATS: 19.7 ± 2.8 vs 13.0 ± 5.8, p = 0.00398, ALS: 27.4 ± 4.0 vs 18.9 ± 8.5, p = 0.0151). CONCLUSIONS: A transanal endoscopic purse string simulator was constructed and preliminary testing has shown variable performance based on prior laparoscopic suturing experience.

Vaginal cuff dehiscence after total laparoscopic hysterectomy: examination on 677 cases.

INTRODUCTION: Total laparoscopic hysterectomy has been reported as having a higher incidence of vaginal cuff dehiscence compared with the abdominal and/or vaginal hysterectomy. The cause of vaginal cuff dehiscence after total laparoscopic hysterectomy is not specified, but possible causes may be the use of thermal energy for vaginal incision, reduced suturing width due to magnification, low quality of laparoscopic suturing skills and early resumption of regular activities after surgery. METHODS: We performed 677 cases of total laparoscopic hysterectomy for benign diseases, such as fibroids or adenomyosis, from January 2007 to December 2008 in our institute. We experienced four cases (0.6%) of vaginal cuff dehiscence. We checked the operative parameters for these cases, such as whether the retroperitoneum was sutured or not and intrapelvic adhesion, as well as examined operative duration, blood loss, weight of removed organs, and body mass index. RESULTS: Sexual intercourse was the triggering event for three cases (96 days, 103 days and 47 days after total laparoscopic hysterectomy) and the other case occurred during defecation (18 days and no sexual intercourse after total laparoscopic hysterectomy). There were no significant differences in vaginal cuff dehiscence with or without retroperitoneum suture and intrapelvic adhesion. CONCLUSION: After these four cases of vaginal cuff dehiscence, we recognized the need to review these cases carefully in order to discover the cause and how to prevent this from occurring in other patients. We do not have the answers to prevent this complication at present, but reducing the power-source and attempting different suturing techniques may be important steps.

Experimental evidence of phase coherence of magnetohydrodynamic turbulence in the solar wind: GEOTAIL satellite data.

Magnetohydrodynamic (MHD) turbulence is commonly observed in the solar wind. Nonlinear interactions among MHD waves are likely to produce finite correlation of the wave phases. For discussions of various transport processes of energetic particles, it is fundamentally important to determine whether the wave phases are randomly distributed (as assumed in the quasi-linear theory) or have a finite coherence. Using a method based on the surrogate data technique, we analysed the GEOTAIL magnetic field data to evaluate the phase coherence in MHD turbulence in the Earth's foreshock region. The results demonstrate the existence of finite phase correlation, indicating that nonlinear wave-wave interactions are in progress.

Utilisation of the time constant calculated from heart rate recovery after exercise for evaluation of autonomic activity in horses.

REASONS FOR PERFORMING STUDY: Heart rate (HR) recovery immediately after exercise is controlled by autonomic functions and the time constant (T) calculated from HR recovery is thought to be an index of parasympathetic activity in man. OBJECTIVES: To investigate whether it is possible to evaluate autonomic function using the time constant in horses. METHODS: Five Thoroughbred horses were subjected to a standard exercise test. Following pre-medication with saline, atropine and/or propranolol, the horses ran for 2.5 min at a speed of 8 m/sec at a 10% incline and T was calculated from HR after the exercise. Secondly, 7 Thoroughbred horses were then trained for 11 weeks and T and maximal oxygen uptake (VO2max) measured at intervals of 1 or 2 weeks. In 6 horses, T with atropine pre-medication was also measured before and after the whole training period. Furthermore, the HR variability at rest was evaluated by power spectral analysis at intervals of 3 or 4 weeks. RESULTS: Time constant was increased by atropine and/or propranolol pre-medication, decreased with the progress of training and inversely correlated with VO2max during training (r = 0.43, P<0.005). Parasympathetic blockade significantly decreased T only after and not before, the training; however, T was lower in post training than in pretraining, irrespective of parasympathetic blockade. On the other hand, parasympathetic activity at rest was attenuated and sympathetic activity became predominant following the training. CONCLUSION: Heart rate recovery is affected by sympathetic withdrawal and parasympathetic reactivation in horses and suggests that physical training hastened HR recovery by improving the parasympathetic function after exercise with aerobic capacity. However, the effects of other factors need to be considered because the training effect appeared on T even under parasympathetic blockade. The parasympathetic activity at rest is in contrast to that after exercise, suggesting that T does not reflect parasympathetic activity at rest. POTENTIAL RELEVANCE: If demonstrated how HR recovery is controlled after exercise, its analysis will be important in the evaluation of physical fitness in horses.

Immunomodulatory effects of selective leucocytapheresis as a new adjunct to interferon-alpha2b plus ribavirin combination therapy: a prospective study in patients with high plasma HCV viraemia.

Efficacy of interferon-alpha2b (IFN) + ribavirin (IFN/RBV) combination in patients with high plasma hepatitis C virus (HCV) is very poor. Dysregulated CD4+ /CD8+ T cells is involved in both impaired cell-mediated immunity and resistance to IFN. Adsorptive granulocytes and monocytes apheresis (GMA) can remove infected leucocytes which are extrahepatic HCV reservoirs and also has been associated with intriguing immunomodulation and increases in CD4+ T cells. Our aim was to see if GMA enhances the efficacy of IFN/RBV. Twenty-four patients, 13 IFN resistant and 11 IFN naive were enrolled. Seventeen were genotype 1b and 7 were 2a or 2b. Mean plasma HCV-RNA was 612.9 (100-850) kIU/mL and alanine aminotransferase, 108 (41-373) U/L. GMA was performed with Adacolumn at one session/day for five consecutive days and IFN/RBV was started within 24 h after the last GMA session. Daily 6 million units of IFN, six times/week for 2 weeks and then three times/week for 22 weeks were given with RBV (600-800 mg/day/patient). Patients were followed for 6 months. GMA was associated with a significant increase in lymphocyte counts, complement activation fragment C3a and falls in tissue necrosis factor-alpha, and IL-8 produced by peripheral blood leucocytes. At week 24, 20 of 24 patients (83%) were HCV negative and by end of follow-up (week 49), the remission was sustained in 14 of 24 patients (58%) including 100% of patients with 2a or 2b. In conclusion, enhanced efficacy of IFN/RBV following GMA might be attributed to a more efficient immune function and a renewed IFN signaling towards HCV.

Effect of purine-free low-malt liquor (happo-shu) on the plasma concentrations and urinary excretion of purine bases and uridine--comparison between purine-free and regular happo-shu.

To determine whether purine-free and regular low-malt liquor beverages (happo-shu) increase the plasma concentration and urinary excretion of purine bases (hypoxanthine, xanthine, uric acid) and uridine, 6 healthy males were given regular (10 ml/kg of body weight) and purine-free happo-shu (10 ml/kg of body weight). Plasma concentration-time curves were plotted, and the areas under the curves for uric acid and total purine bases (the sum of hypoxanthine, xanthine, and uric acid) were greater in the regular than in the purine-free happo-shu ingestion experiment (both p < 0.05). In addition, the total urinary excretion of xanthine, total purine bases, and uridine was greater in the regular than in the purine-free happo-shu ingestion experiment (p < 0.05 in all cases), although the total urinary excretion of hypoxanthine and uric acid was no different between the regular and the purine-free happo-shu ingestion experiments. These results suggest that uridine contained in regular happo-shu might contribute to an increase in the urinary excretion of uridine along with ethanol, and that the purines contained in regular happo-shu may contribute to the increase in plasma concentration of uric acid due to purine degradation.

Parametric instabilities of circularly polarized Alfvén waves in a relativistic electron-positron plasma.

Dispersion relation and nonlinear evolution of the parametric instabilities of circularly polarized Alfvén waves in a relativistic electron-positron plasma are investigated by theoretical and numerical approaches. In the nonrelativistic limit, when 2omega(2)(p)>omega20, the characteristics of the instabilities are similar to those in an electron-ion plasma, except that the modulational instability takes place only if v(2)(s)

Effects of novelty stress on neuroendocrine activities and running performance in thoroughbred horses.

This study investigated the effects of novelty stress on neuroendocrine activities and running performance in Thoroughbred horses. First, to examine the neuroendocrine responses to novelty stress, we exposed horses to two types of novel environmental stimuli (audiovisual or novel field stimuli). After the stimuli, plasma concentrations of vasopressin, catecholamines and adrenocorticotropin (ACTH), as well as heart rates, were significantly increased in each experiment. Second, we investigated neuroendocrine activities during incremental exercise. Plasma concentrations of vasopressin, catecholamines, ACTH and blood lactate increased as the exercise load increased. Finally, we investigated the effects of novelty stimuli on neuroendocrine activities and running performance during supra-maximal exercise (110% VHRmax). When the novelty stimuli were presented to horses, the increases in plasma vasopressin and catecholamines due to exercise load were significantly smaller than those in the control experiments. Blood lactate during supra-maximal exercise was also significantly lower and total run time until exhaustion was prolonged in the novel environmental stimuli compared to the control. These results suggest that novelty stimuli facilitate vasopressin release from the posterior pituitary in addition to activating the sympatho-adrenomedullary and the hypothalamic-pituitary-adrenocortical axes in thoroughbred horses, and increase exercise capacity, resulting in improvement of running performance during supra-maximal exercise.

Biomechanical implications of uphill training on the aetiology of tendinitis.

It has been reported that a small decrease in the strain in the superficial digital flexor tendon (SDFT) occurs if the toe is raised during walking. Although walking on a slope appears similar to raising the toe, it is unclear whether uphill exercise decreases the strain in the SDFT. Because the force or strain on tendons is one of the important factors leading to tendon stress injury, we hypothesised that reducing the force in the SDFT during exercise may prevent tendinitis. The purpose of this study was to determine the effects of treadmill inclination on the force in the SDFT in the walking horse. 'Arthroscopically implantable force probes' (AIFP) were implanted into the SDFT of the forelimb of 4 horses. The AIFP output was recorded during walking on a treadmill inclined at 0%, 3%, 8% and then 0% again. When the inclination increased from 0 to 8%, the first peak of force in the SDFT decreased significantly, the second increased significantly, but the maximal force and the area under the force-time curve did not change. In conclusion, uphill walking on an inclined treadmill did not decrease the maximal force in the SDFT or the area under the force-time curve, however, the patterns of force were altered. Future research should focus on the force distributions of tendons and ligaments at faster gaits, because the effects of a change in hoof angle and slope may be greater at faster gaits.

Effect of norepinephrine on the urinary excretion of purine bases and oxypurinol.

To examine whether norepinephrine affects the plasma concentrations and urinary excretion of purine bases and oxypurinol, we orally administered allopurinol (300 mg) to 5 healthy subjects and 9 hours later intravenously administered norepinephrine (12 to 20 microg/kg body weight), which causes a more than 10 mm Hg increase in diastolic pressure for 2 hours. Norepinephrine decreased the urinary excretion of uric acid by 33% (P <.01), oxypurinol by 32% (P <.01), and xanthine by 51% (P <.01), as well as the fractional clearance of uric acid by 32% (P <.01), oxypurinol by 24% (P <.05), and xanthine by 21% (P <.05) when measured 1 to 2 hours after administration. These results indicate that norepinephrine decreases the urinary excretion of uric acid, oxypurinol, and xanthine, probably via hemodynamic change. It is also suggested that the hypouricemic effect of allopurinol may be more potent than that expected in gout patients with enhanced sympathetic tone, such as in salt-sensitive hypertension.

Spontaneous regression of hepatic adenoma in a patient with glycogen storage disease type I after hemodialysis: ultrasonographic and CT findings.

A 23-year-old woman was admitted to our hospital with recurrent gouty arthritis. Laboratory findings showed hypoglycemia, lactic acidosis, hyperlipidemia, and hyperuricemia, with normal values of serum alfa-fetoprotein (AFP) and protein induced by vitamin K absence (PIVKA-II). A diagnosis of glycogen storage disease type I (GSD-type I) was made on the basis of the laboratory data, liver biopsy findings, and partially deficient thrombocyte glucose-6-phosphatase (G-6-Pase) activity. Ultrasonography and computed tomography revealed multiple focal hepatic masses. Biopsied specimens of the lesion demonstrated a hepatic adenoma, which changed in appearance in the relatively short period between echography and computed tomography. This interesting phenomenon may highlight the importance for careful follow-up of hepatic adenomas, because of the potential of rupture, hemorrhage, or malignant transformation. During follow-up, the present patient received hemodialysis due to renal failure, and the adenoma regressed spontaneously after 8 years. Included are diagnostic images, demonstrating the association of hepatic adenoma and GSD-type I.

An atypical case of primary renal tubular hypokalaemic metabolic alkalosis with chronic tophaceous gout.

A 55-year-old woman was referred to our ward for further evaluation of marked hyperuricaemia and suspected tophi. On physical examination, huge subcutaneous nodules were observed on the knee joints as well as a small nodule on the lateral side of the left sole. Blood chemistry showed marked hyperuricaemia (0.85 mmol/l), hypokalaemia (2.7 mmol/l) and a mild degree of renal insufficiency. Arterial blood gas analysis showed signs of metabolic alkalosis. Daily urinary uric acid excretion on a purine non-restricted diet was 8.9 mmol/day. Uric acid clearance and fractional uric acid clearance were 0.8 ml/min and 2.6%, respectively. Plasma renin activity was 21.8 ng/ml/h, and plasma angiotensin II and aldosterone concentrations were 61 and 121 pg/ml, respectively. However, pressor response to an intravenous administration of angiotensin II was normal. The urinary calcium to creatinine molar ratio was 0.069, and serum magnesium concentration was normal to supranormal. A biopsy of the subcutaneous nodule showed a typical appearance of tophus. Based on these findings, the patient was diagnosed with an atypical case of renal tubular hypokalaemic metabolic alkalosis, with marked hyperuricaemia and tophi as the initial manifestations. So far, only four cases of Bartter's syndrome with gout and/or hyperuricaemia have been described in Japan. This rare case is presented and its mechanism of hyperuricaemia discussed.

Effect of fenofibrate on plasma concentration and urinary excretion of purine bases and oxypurinol.

OBJECTIVE: To investigate whether fenofibrate increases the clearance of purine bases (hypoxanthine, xanthine, uric acid) and oxypurinol. METHODS: We administered fenofibrate (150 mg) 3 times a day for 3 days, and then allopurinol (300 mg) 4 h after the last administration of fenofibrate, to 5 healthy subjects. Ten hours later, a clearance study was done. RESULTS: Following 3 day administration of fenofibrate, fractional clearance of xanthine, uric acid, and oxypurinol increased by 41% (p < 0.05), 101% (p < 0.01), and 51% (p < 0.01), respectively, compared to baseline values, while the respective plasma concentrations decreased by 46% (p < 0.05), 46% (p < 0.05), and 19% (p < 0.05). CONCLUSION: Our results suggest that fenofibrate, fenofibric acid, or fenofibrate derivatives can increase fractional clearance of xanthine, uric acid, and oxypurinol by acting on their common renal pathways. It is suggested that the hypouricemic effect of combination therapy using allopurinol and fenofibrate may be less than additive.

Comparison of the effects in vitro of tea tree oil and plaunotol on methicillin-susceptible and methicillin-resistant strains of Staphylococcus aureus.

The effects in vitro of tea tree oil (TTO) and plaunotol were examined by monitoring the growth of a standard strain of Staphylococcus aureus FDA 209P and of fourteen methicillin-susceptible strains of S. aureus (MSSA), together with twenty methicillin-resistant strains (MRSA). The minimum inhibitory concentrations (MIC) and the doses for 50% inhibition of growth (ID50) were determined by the micro-broth dilution (MD) method, and the broth dilution with shaking (BDS) method, respectively. The MIC of plaunotol for 50 and 90% of the MSSA and MRSA were assessed by the MD method, as 16 microg/ml and > or = 1,024 microg/ml, respectively. No antibacterial effects of TTO on MSSA and MRSA were detected by the MD method. The growth-inhibitory effects of TTO on S. aureus by the BDS method were examined, and it appeared that TTO was effective over a lower range of concentrations than previously reported. It seems that TTO is very effective in vitro against MSSA and MRSA at high concentrations but less effective below 40 microg/ml of TTO.

Widespread cellular distribution of aldehyde oxidase in human tissues found by immunohistochemistry staining.

Aldehyde oxidase (EC 1.2.3.1) is a xenobiotic metabolizing enzyme that catalyzes a variety of organic aldehydes and N-heterocyclic compounds. However, its precise pathophysiological function in humans, other than its xenobiotic metabolism, remains unknown. In order to gain a better understanding of the role of this enzyme, it is important to know its exact localization in human tissues. In this study, we investigated the distribution of aldehyde oxidase at the cellular level in a variety of human tissues by immunohistochemistry. The enzyme was found to be widespread in respiratory, digestive, urogenital, and endocrine tissues, though we also observed a cell-specific localization in the various tissues studied. In the respiratory system, it was particularly abundant in epithelial cells from the trachea and bronchium, as well as alveolar cells. In the digestive system, aldehyde oxidase was observed in surface epithelia of the small and large intestines, in addition to hepatic cells. Furthermore, the proximal, distal, and collecting tubules of the kidney were immunostained with various intensities, while glomerulus tissues were not. In epididymus and prostate tissues, staining was observed in the ductuli epididymidis and glandular epithelia. Moreover, the adrenal gland, cortex, and notably the zona reticularis, showed strong immunostaining. This prevalent tissue distribution of aldehyde oxidase in humans suggests some additional pathophysiological functions besides xenobiotic metabolism. Accordingly, some possible roles are discussed.

Idiopathic hemochromatosis with the mutation of Ala176Val heterozygous for HFE gene.

Most patients with hereditary hemochromatosis are homozygous for C282Y in the HFE gene in populations of Celtic origin, but the genetic cause of this disease is unknown in Japan because of its rarity. A 48-year-old Japanese patient was recently diagnosed with idiopathic hemochromatosis. Analysis of the entire coding region of the patient's HFE by RT-PCR showed a heterozygous nucleotide substitution at nucleotide 527 from C to T, which resulted in A176V amino acid substitution. Another mutation at nucleotide 942 from T to C was observed, but this was a nonsense mutation. C282Y and another mutation, H63D, were not found in the patient. The mutation may have a possible role on the cause of hemochromatosis in this Japanese case.

Decreased activities of lipoprotein lipase and hepatic triglyceride lipase in patients with gout.

Postheparin plasma lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) activities were measured in 30 male primary gout patients as well as in control subjects. The activities of these lipolytic enzymes were significantly decreased in the patients as compared with the controls (gout v control; LPL, 5.4 +/- 0.4 v 7.9 +/- 0.9 U; HTGL, 14.6 +/- 2.0 v 17.9 +/- 3.4 U) when matched with serum triglyceride concentration. Further, LPL activity was negatively correlated with serum- and very-low-density lipoprotein (VLDL)-triglyceride in gout patients, while that of HTGL was negatively correlated with low-density lipoprotein (LDL)-triglyceride in both gout patients and control subjects. These results suggest that decreased activities of LPL and HTGL may contribute, in part, to the increased concentrations of serum-, VLDL-, and LDL-triglyceride seen in gout patients, leading to a higher risk for coronary atherosclerotic diseases in gout.

Spot urine uric acid to creatinine ratio used in the estimation of uric acid excretion in primary gout.

OBJECTIVE: Uric acid overexcretion in patients with gout is frequently assessed by the measurement of 24 hour urinary uric acid excretion, which is cumbersome with ambulatory patients, and requires accurate timing and complete collection of the specimen. We assessed whether uric acid to creatinine ratio (Uua/Ucr) in spot urine is useful for the estimation of uric acid overexcretion in patients with gout. METHODS: One hundred thirty male patients with gout and 33 non-gout male control subjects were studied. Early morning urine and/or a portion of 24 h collected urine (24 h urine) were used as spot urine samples. Uric acid overexcreters were defined as those with a 24 h urinary uric acid excretion > or = 1000 mg/day, while uric acid underexcreters were defined as those with uric acid clearance < 6 ml/min. RESULTS: There was a significant relationship between 24 h urinary uric acid excretion and early morning urine Uua/Ucr in patients with gout, while no such relationship was observed in controls. No significant difference in Uua/Ucr was observed between patients with gout and controls, or in Uua/Ucr between gout uric acid overexcreters and underexcreters in early morning urine. A significant difference in this value was observed between the 2 groups in the 24 h urine specimens. Although the diagnostic accuracy of gout uric acid overexcretion was 87.2% using early morning urine and 89.6% using 24 h urine, the sensitivity of gout uric acid overexcretion was only 25.0% when using early morning urine and 25.0% when using 24 h urine, when the cutoff value of Uua/Ucr was 0.63 and 0.64, respectively. CONCLUSION: Uua/Ucr using spot urine, especially early morning urine, is not an accurate indicator of uric acid overexcretion in patients with gout.

Fas ligand-induced caspase-1-dependent accumulation of interleukin-18 in mice with acute graft-versus-host disease.

Acute graft-versus-host disease (aGVHD), the fatal side effects of bone marrow transplantation, was shown to be accompanied by elevation of serum levels of interleukin 18 (IL-18). In this study, the mechanism underlying the accumulation of IL-18 in aGVHD in mice was investigated. Lethally irradiated recipients having transplantation with H-2 disparate donor splenocytes demonstrated aGVHD and contained markedly elevated serum levels of IL-18. In contrast, recipients having transplantation with gld/gld spleen cells, which lack functional Fas ligand (FasL), contained only normal ranges of IL-18, indicating FasL-mediated IL-18 release in aGVHD. The wild-type hosts engrafted with caspase-1-deficient cells revealed marked increases of IL-18 similar to those engrafted with wild-type cells, whereas caspase-1-deficient recipients engrafted with wild-type cells showed only a slight elevation of serum IL-18, indicating that IL-18 elevation is derived from host cells in a caspase-1-dependent manner. These results suggest FasL-mediated caspase-1-dependent IL-18 secretion in aGVHD in mice.

Identification of a new point mutation in the human xanthine dehydrogenase gene responsible for a case of classical type I xanthinuria.

A 60-year-old Japanese man was diagnosed as having hypouricemia at an annual health check-up. The routine laboratory data was not remarkable except that the patient's hypouricemia and plasma levels of xanthine and hypoxanthine were much higher than those of normal subjects. Furthermore, the patient's daily urinary excretion of xanthine and hypoxanthine was markedly increased compared with reference values. The xanthine dehyrogenase activity of the duodenal mucosa was below the limits of detection. Nevertheless, allopurinol was metabolized to oxypurinol in vivo. Based on these findings, a subtype of classical xanthinuria (type I) was diagnosed. The xanthine dehyrogenase protein was detected by Western blotting analysis. Sequencing of the cDNA of the xanthine dehyrogenase obtained from the duodenal mucosa revealed that a point mutation of C to T had occurred in nucleotide 445. This changed codon 149 from CGC (Arg) to TGC (Cys), a finding that has not been previously reported in patients with classical xanthinuria type I.