Cholelithiasis prevalence and risk factors in individuals with severe or profound intellectual and motor disabilities.

BACKGROUND: The prevalence and risk factors of cholelithiasis in individuals with severe or profound intellectual and motor disabilities (SPIMD) are poorly characterised. Thus, we aimed to investigate the prevalence and risk determinants of cholelithiasis in a cohort with SPIMD under medical care in a residential facility. METHODS: We categorised 84 patients in a residential hospital for persons with SPIMD into groups: those with (Group CL) and without (Group N) cholelithiasis. Gallstones were detected via computed tomography, ultrasonography or both. We evaluated gastrostomy status, nutritional and respiratory support, constipation, and bladder and kidney stones. Data were significantly analysed using univariate and multivariate logistic regression analyses. RESULTS: The prevalence rate of cholelithiasis in our SPIMD cohort was 27%. There were no significant differences in sex, age, weight, height, or Gross Motor Function Classification System between the two groups. However, more patients received enteral nutrition (39.13% vs. 6.56%; P = 0.000751) and were on ventilator support (56.52% vs. 19.67%; P = 0.00249) in Group CL than in Group N. Enteral nutrition [odds ratio (OR) 10.4, 95% confidence interval (CI) 1.98-54.7] and ventilator support (OR 20.0, 95% CI 1.99-201.0) were identified as independent risk factors for the prevalence of cholelithiasis in patients with SPIMD. CONCLUSIONS: Patients with SPIMD demonstrated an increased prevalence of cholelithiasis, with a notable association between nutritional tonic use and respiratory support. Therefore, to emphasise the need for proactive screening, it is crucial to devise diagnostic and therapeutic strategies specific to patients with SPIMD. Further investigation is essential to validate our findings and explore causative factors.

Mice with cleavage-resistant N-cadherin exhibit synapse anomaly in the hippocampus and outperformance in spatial learning tasks.

N-cadherin is a homophilic cell adhesion molecule that stabilizes excitatory synapses, by connecting pre- and post-synaptic termini. Upon NMDA receptor (NMDAR) activation by glutamate, membrane-proximal domains of N-cadherin are cleaved serially by a-disintegrin-and-metalloprotease 10 (ADAM10) and then presenilin 1(PS1, catalytic subunit of the γ-secretase complex). To assess the physiological significance of the initial N-cadherin cleavage, we engineer the mouse genome to create a knock-in allele with tandem missense mutations in the mouse N-cadherin/Cadherin-2 gene (Cdh2 R714G, I715D, or GD) that confers resistance on proteolysis by ADAM10 (GD mice). GD mice showed a better performance in the radial maze test, with significantly less revisiting errors after intervals of 30 and 300 s than WT, and a tendency for enhanced freezing in fear conditioning. Interestingly, GD mice reveal higher complexity in the tufts of thorny excrescence in the CA3 region of the hippocampus. Fine morphometry with serial section transmission electron microscopy (ssTEM) and three-dimensional (3D) reconstruction reveals significantly higher synaptic density, significantly smaller PSD area, and normal dendritic spine volume in GD mice. This knock-in mouse has provided in vivo evidence that ADAM10-mediated cleavage is a critical step in N-cadherin shedding and degradation and involved in the structure and function of glutamatergic synapses, which affect the memory function.

Randomized clinical trial of extensive intraoperative peritoneal lavage versus standard treatment for resectable advanced gastric cancer (CCOG 1102 trial).

BACKGROUND: A survival benefit of extensive intraoperative peritoneal lavage (EIPL) has been reported in patients with gastric cancer with positive peritoneal cytology. The hypothesis of this study was that EIPL may reduce peritoneal recurrence in patients with advanced gastric cancer who undergo surgery with curative intent. METHODS: This was an open-label, multi-institutional, randomized, phase 3 trial to assess the effects of EIPL versus standard treatment after curative gastrectomy for resectable gastric cancer of T3 status or above. The primary endpoint was disease-free survival (DFS); secondary endpoints were overall survival, peritoneal recurrence-free survival and incidence of adverse events. RESULTS: Between July 2011 and January 2014, 314 patients were enrolled from 15 institutions and 295 patients were analysed (145 and 150 in the EIPL and no-EIPL groups respectively). The 3-year DFS rate was 63·9 (95 per cent c.i. 55·5 to 71·2) per cent in the EIPL group and 59·7 (51·3 to 67·1) per cent in the control group (hazard ratio (HR) 0·81, 95 per cent c.i. 0·57 to 1·16; P = 0·249). The 3-year overall survival rate was 75·0 (67·1 to 81·3) per cent in the EIPL group and 73·7 (65·9 to 80·1) per cent in the control group (HR 0·91, 0·60 to 1·37; P = 0·634). Peritoneal recurrence-free survival was not significantly different between the two groups (HR 0·92, 0·62 to 1·36; P = 0·676). No intraoperative complications related to EIPL were observed. CONCLUSION: EIPL did not improve survival or peritoneal recurrence in patients who underwent gastrectomy for advanced gastric cancer. Registration number: 000005907 (http://www.umin.ac.jp/ctr/index.htm).

ANTECEDENTES: Se ha descrito que un lavado peritoneal extenso intraoperatorio (extensive intraoperative peritoneal lavage, EIPL) proporciona un beneficio en la supervivencia en pacientes con cáncer gástrico con citología peritoneal positiva. La hipótesis de este estudio era que el EIPL podría disminuir la recidiva peritoneal en pacientes con cáncer gástrico avanzado sometidos a cirugía con intención curativa. MÉTODOS: Ensayo clínico fase 3, abierto, multicéntrico y aleatorizado para evaluar los efectos de un lavado peritoneal extenso intraoperatorio (EIPL) frente a tratamiento estándar tras gastrectomía curativa por cáncer gástrico ≥T3 resecable. La variable de resultado primaria fue la supervivencia libre de enfermedad (disease-free survival, DFS), y las variables de resultado secundarias fueron la supervivencia global (overall survival, OS), la supervivencia libre de recidiva peritoneal y la incidencia de efectos adversos. RESULTADOS: Entre julio de 2011 y enero de 2014, se reclutaron 314 pacientes de 15 instituciones y se analizaron los datos de 295 pacientes (145 en el grupo con EIPL y 150 en el grupo sin EIPL). La DFS a los 3 años fue 63,9% (i.c. del 95% 55,5-71,2) en el grupo con EIPL y 59,7% (i.c. del 95% 51,3-67,1) en el grupo control (cociente de riesgos instantáneos, hazard ratio, HR 0,81 (i.c. del 95% 0,57-1,16), P = 0,249). La OS a los 3 años fue 75,0% (i.c. del 95% 67,1-81,3) en el grupo con EIPL y 73,7% (i.c. del 95% 65,9-80,1) en el grupo control (HR 0,91 i.c. del 95% 0,60-1,37), P = 0,634). No se observaron diferencias estadísticamente significativas entre los dos grupos en la supervivencia libre de recidiva peritoneal (P = 0,676, HR 0,92 (i.c. del 95% 0,62-1,36). No se observaron complicaciones intraoperatorias relacionadas con EIPL. CONCLUSIÓN: El EIPL no mejoró la supervivencia o la recidiva peritoneal en pacientes sometidos a gastrectomía por cáncer gástrico avanzado.

Randomized clinical trial of duct-to-mucosa pancreaticogastrostomy versus handsewn closure after distal pancreatectomy.

BACKGROUND: Postoperative pancreatic fistula (POPF) remains a major cause of morbidity after distal pancreatectomy. The aim of this study was to investigate whether duct-to-mucosa pancreaticogastrostomy of the pancreatic stump decreased clinical POPF formation compared with handsewn closure after distal pancreatectomy. METHODS: This multicentre RCT was performed between April 2012 and June 2014. Patients undergoing distal pancreatectomy were assigned randomly to either duct-to-mucosa pancreaticogastrostomy or handsewn closure. The primary endpoint was the incidence of clinical POPF. Secondary endpoints were rates of other complications and length of hospital stay. RESULTS: Some 80 patients were randomized, and 73 patients were evaluated in an intention-to-treat analysis: 36 in the pancreaticogastrostomy group and 37 in the handsewn closure group. The duration of operation was significantly longer in the pancreaticogastrostomy group than in the handsewn closure group (mean 268 versus 197 min respectively; P < 0·001). The incidence of clinical POPF did not differ between groups (7 of 36 versus 7 of 37; odds ratio (OR) 1·03, 95 per cent c.i. 0·32 to 3·10; P = 1·000). The rate of intra-abdominal fluid collection was significantly lower in the pancreaticogastrostomy group (6 of 36 versus 21 of 37; OR 0·15, 0·05 to 0·45; P < 0·001). There were no statistically significant differences in the rates of other complications or length of hospital stay. CONCLUSION: Duct-to-mucosa pancreaticogastrostomy did not reduce the incidence of clinical POPF compared with handsewn closure of the pancreatic stump after distal pancreatectomy. Registration number UMIN000007426 (http://www.umin.ac.jp).

Concurrent analysis of human equilibrative nucleoside transporter 1 and ribonucleotide reductase subunit 1 expression increases predictive value for prognosis in cholangiocarcinoma patients treated with adjuvant gemcitabine-based chemotherapy.

BACKGROUND: The aim of this study was to investigate the predictive and prognostic values of intratumoural human equilibrative nucleoside transporter 1 (hENT1) and ribonucleotide reductase subunit 1 (RRM1) expression in advanced cholangiocarcinoma patients treated with adjuvant gemcitabine-based chemotherapy (AGC). METHODS: Intratumoural hENT1 and RRM1 expression levels were investigated immunohistochemically in 127 patients with advanced cholangiocarcinoma who underwent surgical resection (68 with AGC and 59 without AGC). The impacts of hENT1 and RRM1 expression on survival were evaluated. RESULTS: High intratumoural hENT1 and RRM1 expression levels were observed in 86 (68%) and 67 (53%) patients, respectively. In a multivariate analysis of 68 patients who received AGC, high hENT1 (P=0.044) and low RRM1 expression (P=0.009) were independently associated with prolonged disease-free survival (DFS), whereas low RRM1 expression (P=0.024) was independently associated with prolonged overall survival (OS). Moreover, concurrent high hENT1 and low RRM1 expression was a powerful independent predictor of prolonged DFS (P<0.001) and OS (P=0.001) when the combined classification of hENT1 and RRM1 was introduced. CONCLUSIONS: Concurrent analysis of hENT1 and RRM1 expression may increase the predictive value of these biomarkers for survival of advanced cholangiocarcinoma patients treated with AGC.

Physical impairment and walking function required for community ambulation in patients with cervical incomplete spinal cord injury.

STUDY DESIGN: Cross-sectional study. OBJECTIVE: To identify the physical impairments and walking function required for community ambulation in patients with cervical incomplete spinal cord injury (ISCI). SETTING: Chubu Rosai Hospital, Nagoya, Japan. METHODS: Forty patients with cervical ISCI (mean age: 49.9 years, American Spinal Injury Association Impairment Scale D) were included. The primary outcome measure was community ambulation based on Spinal Cord Independence Measure outdoor scores for a distance of >480 m. We measured the upper- and lower-extremity motor scores (UEMS and LEMS), sensory and spasticity. The walking tests included 10 m of walking at a comfortable- and maximum-walking speed (CWS and MWS; m s(-1)), 6 min walking test (6 MWT; m) and the walking index for spinal cord injury II (WISCI II). Multivariate logistic regression models were used to assess the physical impairments associated with community ambulation. Receiver operating characteristic curves were analyzed to determine the cutoff points for physical impairment and walking function. RESULT: The LEMS (beta coefficient (ß)=0.71) and UEMS (ß=0.41) were independently associated with community ambulation in patients with cervical ISCI. The cutoff points of the LEMS, UEMS, CWS, MWS, 6MWT and WISCI II were 41.5, 36.5, 1.00 m s(-1), 1.32 m s(-1), 472.5 m and 17.5, respectively, which suggests moderate to high accuracy. CONCLUSION: The LEMS and UEMS were the most important factors affecting community ambulation in patients with cervical ISCI. The cutoff points of the walking function tests were highly accurate; therefore, these points can serve as targets for walking training in the future.

Sympathetic afferent stimulation inhibits central vagal activation induced by intravenous medetomidine in rats.

AIM: To examine whether sympathetic afferent stimulation (SAS) inhibits central vagal activation induced by α2 -adrenergic stimulation. METHODS: In anaesthetized Wistar-Kyoto rats, a cardiac microdialysis technique was applied to the left ventricle, and the effect of α2 -adrenergic stimulation by medetomidine on myocardial interstitial acetylcholine (ACh) levels was examined in the absence (n = 6) or the presence (n = 6) of SAS delivered from the left stellate ganglion. The effect of electrical vagal efferent stimulation on myocardial interstitial ACh release was also examined in the absence or the presence of SAS (n = 6). RESULTS: Intravenous medetomidine (0.1 mg kg(-1) ) significantly increased myocardial interstitial ACh levels in the absence of SAS (from 1.95 ± 0.79 to 3.36 ± 1.61 nM, P < 0.05), but not in the presence of SAS (from 1.67 ± 0.67 to 2.01 ± 0.78 nM). In contrast, electrical vagal nerve stimulation increased myocardial interstitial ACh level to the same degree regardless of SAS (from 1.66 ± 0.16 to 3.93 ± 0.72 nM without SAS vs. 4.05 ± 0.89 nM with SAS). CONCLUSION: Sympathetic afferent stimulation inhibited medetomidine-induced ACh release, but not electrical stimulation-induced ACh release, suggesting that SAS inhibited medetomidine-induced vagal activation via central mechanisms. While central vagal activation by α2 -adrenergic agonists could be an alternative to electrical vagal activation, blocking sympathetic afferent input may be important to increase the efficacy of α2 -adrenergic agonists in enhancing vagal nerve activity.

High-frequency dominant depression of peripheral vagal control of heart rate in rats with chronic heart failure.

AIM: To examine whether dynamic characteristics of the peripheral vagal control of heart rate (HR) are altered in chronic heart failure (CHF). METHODS: The right vagal nerve was electrically stimulated according to a binary white noise signal, and the transfer function from vagal nerve stimulation (VNS) to HR was estimated in the frequency range from 0.01 to 1 Hz in five control rats and five CHF rats under anaesthetized conditions. The rate of VNS was changed among 10, 20 and 40 Hz. RESULTS: A multiple linear regression analysis indicated that the increase in the VNS rate augmented the ratio of the high-frequency (HF) gain to the steady-state gain in the control group but not in the CHF group. As a result, the dynamic gain of the transfer function in the frequencies near 1 Hz decreased more in the CHF group than in the control group. CONCLUSION: Changes in the dynamic characteristics of the peripheral vagal control of HR may contribute to the manifestation of decreased HF components of HR variability observed in CHF.

Maternal and preterm fetal sheep responses to dexmedetomidine.

BACKGROUND: The α(2) adrenergic receptor agonist dexmedetomidine has some unique pharmacologic properties that could benefit pregnant patients (and their fetuses) when they require sedation, analgesia, and/or anesthesia during pregnancy. The purpose of the present study was to delineate maternal and fetal responses to an intravenous infusion of dexmedetomidine. METHODS: This study was conducted on surgically-recovered preterm sheep instrumented for physiologic recording and blood sampling. Maternal and fetal cardiovascular and blood gas parameters and fetal cerebral oxygenation levels were recorded before, during, and after 3h of dexmedetomidine infusion to the ewe at a rate of 1 µg/kg/h. RESULTS: Drug infusion produced overt sedation but no apparent respiratory depression as evidenced by stable maternal arterial blood gases; fetal blood gases were also stable. The one blood parameter to change was serum glucose, By the end of the 3-h infusion, glucose increased from 49±10 to 104±33mg/dL in the ewe and from 22±3 to 48±16mg/dL in the fetus; it declined post-drug exposure but remained elevated compared to the starting levels (maternal, 63±12mg/dL, P=0.0497; and fetal, 24±4mg/dL, P=0.012). With respect to cardiovascular status, dexmedetomidine produced a decrease in maternal blood pressure and heart rate with fluctuations in uterine blood flow but had no discernable effect on fetal heart rate or mean arterial pressure. Likewise, maternal drug infusion had no effect on fetal cerebral oxygenation, as measured by in utero near-infrared spectroscopy. CONCLUSIONS: Using a clinically-relevant dosing regimen, intravenous infusion of dexmedetomidine produced significant maternal sedation without altering fetal physiologic status. Results from this initial acute assessment support the conduct of further studies to determine if dexmedetomidine has clinical utility for sedation and pain control during pregnancy.

Influence of ion source configuration and its operation parameters on the target sputtering and implantation process.

In the work, investigation of the features and operation regimes of sputter enhanced ion-plasma source are presented. The source is based on the target sputtering with the dense plasma formed in the crossed electric and magnetic fields. It allows operation with noble or reactive gases at low pressure discharge regimes, and, the resulting ion beam is the mixture of ions from the working gas and sputtering target. Any conductive material, such as metals, alloys, or compounds, can be used as the sputtering target. Effectiveness of target sputtering process with the plasma was investigated dependently on the gun geometry, plasma parameters, and the target bias voltage. With the applied accelerating voltage from 0 to 20 kV, the source can be operated in regimes of thin film deposition, ion-beam mixing, and ion implantation. Multi-component ion beam implantation was applied to α-Fe, which leads to the surface hardness increasing from 2 GPa in the initial condition up to 3.5 GPa in case of combined N(2)-C implantation. Projected range of the implanted elements is up to 20 nm with the implantation energy 20 keV that was obtained with XPS depth profiling.

Central vagal activation by alpha(2) -adrenergic stimulation is impaired in spontaneously hypertensive rats.

AIM: To elucidate the abnormality of vagal control in spontaneously hypertensive rats (SHR) by measuring left ventricular myocardial interstitial acetylcholine (ACh) release in response to α(2) -adrenergic stimulation as an index of in vivo vagal nerve activity. METHODS: A cardiac microdialysis technique was applied to the rat left ventricle in vivo, and the effect of α(2) -adrenergic stimulation by medetomidine or electrical vagal nerve stimulation on myocardial interstitial ACh levels was examined in normotensive Wistar-Kyoto rats (WKY) and SHR under anaesthetized conditions. RESULTS: Intravenous medetomidine (0.1 mg kg(-1) ) significantly increased the ACh levels in WKY (from 2.4 ± 0.6 to 4.2 ± 1.3 nmol L(-1) , P < 0.05, n = 7) but not in SHR (from 2.5 ± 0.7 to 2.7 ± 0.7 nmol L(-1) , n = 7). In contrast, electrical vagal nerve stimulation increased the ACh levels in both WKY (from 1.0 ± 0.4 to 2.9 ± 0.9 nmol L(-1) , P < 0.001, n = 6) and SHR (from 0.9 ± 0.2 to 2.2 ± 0.4 nmol L(-1) , P < 0.001, n = 6). Intravenous administration of medetomidine (0.1 mg kg(-1) ) did not affect the vagal nerve stimulation-induced ACh release in either WKY or SHR. CONCLUSION: Medetomidine-induced central vagal activation was impaired in SHR, whereas peripheral vagal control of ACh release was preserved. In addition to abnormal sympathetic control, vagal control by the central nervous system may be impaired in SHR.

Effect of glycogen synthase kinase 3 ß-mediated presenilin 1 phosphorylation on amyloid ß production is negatively regulated by insulin receptor cleavage.

Presenilin 1 (PS1), a causative molecule of familial Alzheimer's disease (AD), is known to be an unprimed substrate of glycogen synthase kinase 3 ß (GSK3ß) [Twomey and McCarthy (2006) FEBS Lett 580:4015-4020] and is phosphorylated at serine 353, 357 residues in its cytoplasmic loop region [Kirschenbaum et al. (2001) J Biol Chem 276:7366-7375]. In this report, we investigated the effect of PS1 phosphorylation on AD pathophysiology and obtained two important results--PS1 phosphorylation increased amyloid ß (Aß) 42/40 ratio, and PS1 phosphorylation was enhanced in the human AD brains. Interestingly, we demonstrated that PS1 phosphorylation promoted insulin receptor (IR) cleavage and the IR intracellular domain (IR ICD) generated by γ-secretase led to a marked transactivation of Akt (PKB), which down-regulated GSK3ß activity. Thus, the cleavage of IR by γ-secretase can inhibit PS1 phosphorylation in the long run. Taken together, our findings indicate that PS1 phosphorylation at serine 353, 357 residues can play a pivotal role in the pathology of AD and that the dysregulation of this mechanism may be causally associated with its pathology.

Amyloid beta inhibits ectodomain shedding of N-cadherin via down-regulation of cell-surface NMDA receptor.

Dysfunction in the synapse is recognized as an early and the primary pathological process in Alzheimer's disease (AD). N-cadherin, an essential adhesion molecule for excitatory synaptic contact, forms a complex with presenilin 1 (PS1) and beta-catenin in the synaptic membrane. N-cadherin is sequentially cleaved by ADAM10 and PS1/gamma-secretase, producing a cytoplasmic fragment, N-cadherin C-terminal fragment (Ncad/CTF2) after NMDA receptor stimulation [Marambaud P, Wen PH, Dutt A, Shioi J, Takashima A, Siman R, Robakis NK (2003) A CBP binding transcriptional repressor produced by the PS1/epsilon-cleavage of N-cadherin is inhibited by PS1 FAD mutations. Cell 114:635-645; Reiss K, Maretzky T, Ludwig A, Tousseyn T, de Strooper B, Hartmann D, Saftig P (2005) ADAM10 cleavage of N-cadherin and regulation of cell-cell adhesion and beta-catenin nuclear signalling. EMBO J 24:1762]. Ncad/CTF2 translocates to the nucleus together with beta-catenin to enhance beta-catenin nuclear signaling [Uemura K, Kihara T, Kuzuya A, Okawa K, Nishimoto T, Bito H, Ninomiya H, Sugimoto H, Kinoshita A, Shimohama S (2006a) Activity-dependent regulation of beta-catenin via epsilon-cleavage of N-cadherin. Biochem Biophys Res Commun 345:951-958]. To examine whether an impairment of N-cadherin metabolism is involved in AD pathogenesis, we investigated the effect of amyloid beta peptide (Abeta) treatment on sequential N-cadherin cleavage. Here, we demonstrate that both synthetic and cell-derived Abeta species inhibit ectodomain shedding of mouse N-cadherin. Inhibition of N-cadherin cleavage by Abeta treatment was suggested to be mediated by the enhanced endocytosis of NMDA receptor, resulting in reduced turnover of N-cadherin. Since both N-cadherin and beta-catenin are essential for synaptic plasticity, impairment of N-cadherin cleavage caused by Abeta may underlie the synapse toxicity involved in AD pathogenesis.

Inclusion of an S-nitrosylating agent in the insufflating gas does not alter gastric activity in rats following pneumoperitoneum.

BACKGROUND: We have previously shown that mixing the S-nitrosylating agent ethyl nitrite with carbon dioxide can attenuate pneumoperitoneum-induced decreases in splanchnic blood flow, but it was unclear if this agent would alter gastric function. This question was answered using rats by assessing gastric emptying and gastrointestinal transit times following gavage with radioactive chromium. METHODS: There were five experimental groups: absolute control, anesthesia control, and carbon dioxide alone or with 100 or 300 parts per million ethyl nitrite. The period of insufflation was 1 h, and all animals were euthanized 6.5 h after chromium administration. RESULTS: The mean amount of radioactivity remaining in the stomach ranged between 16% and 27% of the total administered; these differences were not statistically significant (p > 0.05). Modest differences in chromium distribution were identified in the gastrointestinal tract, but for all treatments, the peak amount of radioactivity was located in the distal portion. Location of the peak, expressed as a percentage of total tract length, varied between 70% and 85% (p = 0.366). CONCLUSIONS: This study found no adverse effect of ethyl nitrite on postoperative gastric emptying or gastrointestinal transit time following pneumoperitoneum. The findings support continued assessment of the clinical utility of ethyl nitrite in the setting of laparoscopic surgery.

Sudden death of a patient with primary hypereosinophilia, colon tumours, and pulmonary emboli.

A 33 year old man was admitted to hospital six days after the onset of abdominal pain. There was hypereosinophilia, but the cause could not be identified (primary hypereosinophilia). The hypereosinophilia, high C reactive protein concentration, and gastrointestinal symptoms were alleviated by corticosteroid treatment. Unexpectedly, after this apparent recovery, he was found dead on the 27th day after admission. Necropsy disclosed two solid tumours primarily composed of eosinophils in the ascending and transverse colon. The cause of the sudden death was pulmonary artery emboli, derived from a thrombus in the left iliac vein.

Magnitude of abdominal incision affects the duration of postoperative ileus in rats.

BACKGROUND: The pathogenesis of reduced postoperative ileus (POI) in laparoscopic gastrointestinal (GI) surgery still remains controversial. The aim of this study was to investigate the effect of surgical incision on postoperative ileus. METHODS: The effects of length, depth, and site of the incision on GI transit were compared using the geometric center of 51Cr in rats. The inhibitory mechanism of abdominal incision on GI transit also was studied. RESULTS: The findings showed that 5 cm of abdominal skin and the 5-cm back muscle incision had no significant effect on GI transit. However, the 5-cm abdominal muscle-fascia incision and a 5-cm laparotomy significantly delayed GI transit. Gastrointestinal transit after a 5-cm laparotomy was significantly delayed, as compared with that of a 1-cm laparotomy regardless whether intestinal manipulation was performed or not. Guanethidine and yohimbine, but not propranolol, significantly improved the impaired GI transit after a 5-cm laparotomy. CONCLUSIONS: The results suggest that the longer and deeper abdominal incision more profoundly inhibits GI transit. The inhibitory effect of abdominal incision is mediated via the activation of the somatosympathetic reflex and alpha-2 adrenoceptors.

A comprehensive physiological model of circulation enables automatic piloting of hemodynamics in patients with acute heart failure.

A comprehensive physiological model of the whole circulation is mandatory to quantitatively diagnose pathophysiology and to guide an appropriate treatment. Such a model would enable automatic piloting of hemodynamics in patients with acute heart failure. By extending Guyton's model, so as to deal with heart failure predominantly affecting left heart and to quantify left atrial pressure, we constructed such a model consisting of a venous return (VR) surface and a cardiac output (CO) curve. VR surface, the integrated property of systemic and pulmonary vascular beds, relates VR and left and right atrial pressures (P(LA), P(RA)) linearly as VR = V/W - G(R)P(RA) - G(L)P(LA), given total blood volume (V). CO curve, the pumping ability of hearts, relates CO and either P(LA) or P(RA) approximately by logarithmic functions, respectively, as CO = S(L) [ln (P(LA)- B(L)) + C(L)] = S(R) [ln (P(RA) - B(R)) + C(R)]. The slopes (S(R) and S(L)) of CO curve mainly describes the pump performance. W, G(R), G(L), B(R), B(L), C(R) and C(L) are parameters. We validate the model with animal experiments. Parameters W, G's, B's and C's were relatively constant in 19 dogs. In other 8 dogs, with or without acute left heart failure, we determined V and S's from a single set of CO, P(RA), P(LA) and standard parameter values. We then predicted hemodynamics (CO, P(RA), P(LA)) for altered V from -8 to +8 ml/kg. We identified standard values of parameters as W (0.13 min), G(R) (19.6 ml/min/kg/mmHg), G(L) (3.5 ml/min/kg/mmHg). B(L) (2.1 mmHg), C(L) (1.9), B(R) (2.0 mmHg) and C(R) (0.80). Using these, we could accurately predict CO (y = 0.93x + 6.5, r2 = 0.96, Figure 2), P(RA) (y = 0.87x + 0.4, r2 = 0.91) and P(LA) (y = 0.90x + 0.48, r2 = 0.93). Our comprehensive physiological model of circulation is useful in accurately predicting hemodynamics from the measurement of a single set of CO, P(RA) and (P(LA) following blood volume changes. Therefore, this model enables continuous monitoring of blood volume and pump performance for automatic hemodynamic piloting.

Perfusion-weighted MRI of spinal dural arteriovenous fistula.

A 72-year-old woman was admitted with rapidly progressive paraplegia and sphincter disturbance. T2-weighted images of the thoracic spine showed intramedullary high signal with flow voids suggesting dilated medullary veins. Conventional spinal angiography demonstrated a dural arteriovenous fistula draining into perimedullary veins. Perfusion-weighted MRI demonstrated a prolonged mean transit time and increased blood volume in the high-signal area. The loss of normal perfusion gradient and venous hypertension and were thought to produce these differences. The time-to-peak was almost identical in the high-signal and isointense areas, although the bolus of contrast medium arrived earlier in the former. Arteriovenous shunting was thought to cause faster inflow. These changes may have resulted in increased blood volume in the spinal cord. The high signal has been attributed to oedema due to venous congestion, but there has been no histological confirmation. Perfusion MRI in this case supports this hypothesis.

Physicians's reports on the impact of living wills at the end of life in Japan.

CONTEXT: A growing number of Japanese people have completed advance directives, especially living wills, even though there is no legislation recognising such documents and little empirical research on their impact on clinical care at the end of life in Japan. OBJECTIVES: To investigate physicians' attitudes about living wills and their experiences with patients who had completed a living will and later died. DESIGN: Self administered survey and qualitative study using open question and content analysis. SETTING: Japan. PARTICIPANTS: Physicians known to have cared for a patient who had presented a living will prior to death. MEASUREMENTS: The physician's response to receiving a living will, communication about the living will, the impact of the living will on clinical care, demographics, and their opinion on advance directives, especially living wills. MAIN RESULTS: Fifty five per cent of respondents approved of advance directives in general, and 34% had more opportunities to communicate with a patient and his/her family after receiving the living will. Sixty nine per cent of the physicians who received a living will did not, however, change their course of therapy as a consequence of receiving the living wills. Based on the analysis, we identified three areas of concern in the comments on living wills: (1) concerns relative to patients, physicians, and families; (2) social context, and (3) clinical and administrative concerns. The physicians raised various topics for discussion; they tended to describe the issues from a clinical perspective. CONCLUSIONS: Our identified areas of concern should prove helpful in better understanding the clinical and ethical implications of living wills in Japan.