Increase in urinary sodium excretion in spinal cord injury patients in the emergency department.

OBJECTIVE: Spinal cord injury (SCI) is a pathological condition known to produce hyponatremia. The aim of this study was to elucidate the dynamics of urinary sodium excretion in patients with spinal cord injury. METHODS: SCI patients undergoing intensive care management were enrolled in this study. These patients were divided into two groups: those with Frankel Grade A spinal cord injury manifesting complete, severe motor disorders (FA group) and those with incomplete spinal cord injury (non-FA group). The occurrence of episode of hyponatremia (serum sodium <135 mmol/L), hypotension, and bradycardia during the first 14 hospital days was counted and fractional excretion of sodium (FENa) was calculated on the 1st, 7th, and 14th hospital days. RESULTS: Thirty-four patients (FA group, n = 9; non-FA group, n = 25) were included. Eight patients (88.9 %) in the FA group and three patients (12 %) in the non-FA group experienced at least one episode of hyponatremia during the first 14 hospital days. In the FA group, the FENa was significantly increased on the 7th and 14th hospital days compared to the 1st hospital day. FENa on the 14th hospital day was a significant independent predictor of hyponatremic episodes. Hypotension and bradycardia as the symptoms of sympathetic blockade differed significantly as independent predictors of increased FENa on the 14th hospital day. CONCLUSION: Urinary sodium excretion calculated by FENa increased in patients with severe spinal cord injury. Sympathetic blockade due to SCI may increase urine sodium excretion and lead to hyponatremia.

[Delayed augmentation effect of cytokine production after hyperthermia stimuli].

Heatstroke is considered an important condition that may contribute to endothelial cell damage. The aim of this study was to assess temporal profiles of the cytokine (IL-6 and IL-8) and mRNA production when endothelial cells undergo higher temperature stimuli. In the first group, human umbilical vascular endothelial cells (HUVECs)were cultured at 4 different temperatures (37, 38, 39 or 40 degrees C) for 1, 3 and 5 h. In the second group, HUVECs were cultured at 37 degrees C for 4 h or 23 h, after stimulation by heating for one hour at the same culture temperatures used in the first group (37 degrees C to 40 degrees C). After culturing, IL-6 and IL-8 mRNA and protein levels were measured. It has been found the cytokine mRNA levels being significantly higher (p < 0.001) in all cells incubated at higher temperatures than those in the control (cultivation at 37 degrees C). At the same time, the productionof IL-6 and 8 at a higher temperature (39, 40 degrees C) was significantly lower (p < 0.001) than at 37 degrees C (control), and the decrease was temperature dependent. However, IL-6 and IL-8 levels were significantly greater in the cells at 23 h after transient hyperthermic (40 degrees C, 1 h) stimulation than in control ones (p < 0.001).After a transient hyperthermia, the production of the cytokines in HUVECs is initially inhibited and then augmented. The results indicated that tissue injury might continue to develop after a hyperthermic event. There might be a potent risk for underestimation of cytokine induced tissue injury in the acute phase of a heatstroke.

Organ dysfunction assessment score for severe head injury patients during brain hypothermia.

The purpose of this study was to evaluate the utility of a novel organ dysfunction assessment score developed for patients with severe traumatic brain injury during therapeutic brain hypothermia. The Brain Hypothermia Organ Dysfunction Assessment (BHODA) score is calculated through the combined assessment of 6 indices: central nervous system (CNS) function, respiratory function, cardiovascular function, hepatosplanchnic circulation, coagulation, and metabolism. The CNS, hepatosplanchnic circulation, and metabolic indices were based on measurements of cerebral perfusion pressure, gastric tonometry, and blood glucose, respectively. Thirty-nine patients with severe closed head injuries (scores of 3 to 8 on the Glasgow Coma Scale) were enrolled. Seven patients (18%) died during hospitalization. Outcome was favorable in 20 patients and unfavorable in 19. The BHODA score proved useful in describing sequences of complications during therapeutic brain hypothermia. A total maximum BHODA score of more than 13 points corresponded to a mortality of 70%. In a multivariate model, the total maximum BHODA score was independently associated with neurological outcome (odds ratio for unfavorable neurological outcome, 2.590: 95% confidence interval, 1.260, 5.327). In conclusion, the BHODA score can help assess multiple organ dysfunction/failure during therapeutic hypothermia and may be useful for predicting outcome.

Rewarming following accidental hypothermia in patients with acute subdural hematoma: case report.

A 57-year-old man was admitted to the Emergency and Critical Care Department with accidental hypothermia (31.5 degrees C) after resuscitation from cardiopulmonary arrest (CPA). Brain CT revealed an acute subdural hematoma. Active core rewarming to 33 degrees C was performed using an intravenous infusion of warm crystalloid. The patient underwent craniotomy soon after admission, with bladder temperature maintained at 33 to 34 degrees C throughout the surgery. Therapeutic hypothermia (34 degrees C) was continued for 2 days, followed by gradual rewarming. After rehabilitation, the patient was able to continue daily life with assistance. Traumatic brain injury (TBI) following CPA is associated with extremely unfavorable outcomes. Very few patients with acute subdural hematomas presenting with accidental hypothermia and CPA have been reported to recover. No suitable strategies have been clearly established for the rewarming performed following accidental hypothermia in patients with TBI. Our experience with this patient suggests that therapeutic hypothermia might improve the outcome in some patients with severe brain injury. It also appears that the method used for rewarming might play an important role in the therapy for TBI with accidental hypothermia.

Importance of cerebral perfusion pressure management using cerebrospinal drainage in severe traumatic brain injury.

OBJECTIVE: To evaluate hemodynamics in patients with severe traumatic brain injury (TBI) after cerebral perfusion pressure (CPP) management using cerebrospinal fluid (CSF) drainage. METHODS: Twenty-six patients with TBI (Glasgow Coma Score = 8 or less) were investigated. Mean arterial blood pressure, CPP, cardiac index (CI), systemic vascular resistance index (SVRI), and central venous pressure were measured. The patients were divided into 2 groups after craniotomy: the intraparenchymal ICP (IP-ICP) monitoring group (n = 14) and ventricular ICP (V-ICP) monitoring group (n = 12). Patient hemodynamics were investigated on the second hospital day to identify differences. Measurements indicated a target CPP above 70 mmHg and a central venous pressure of 8 10 mmHg in both groups. Mannitol administration (IP-ICP group) or CSF drainage (V-ICP group) was performed whenever the CPP remained below 70 mmHg. RESULTS: High SVRI and low CI (p < 0.05) were observed in the IP-ICP group. The V-ICP group exhibited a reduction in the total fluid infusion volume of crystalloid (p < 0.01) and a reduction in the frequency of hypotensive episodes after the mannitol infusion. CONCLUSIONS: CPP management using CSF drainage decreases the total infusion volume of crystalloid and may reduce the risk of aggravated brain edema after excess fluid resuscitation.

Clinical characteristics of postoperative contralateral intracranial hematoma after traumatic brain injury.

OBJECTIVES: To investigate the clinical characteristics of contralateral intracranial hematoma (ICH) after traumatic brain injury. METHODS: The subjects included 149 patients with traumatic ICH treated by hematoma evacuation. The patients were retrospectively divided into a bilateral ICH (B-ICH) group and unilateral ICH (U-ICH) group after craniotomy using brain CT scans for comparison of the following parameters: complicated expanded brain bulk from the cranial window, hypotension during craniotomy, and outcome. RESULTS: Post-craniotomy brain CT scans revealed U-ICH in 106 patients and B-ICH in 43 patients. Average Glasgow Coma Scale on arrival did not differ between the groups, but a higher proportion of patients in the B-ICH group deteriorated after admission (p = 0.02). The B-ICH patients also exhibited a significantly higher rate of expanded brain bulk from the cranial window (p < 0.05). No significant difference was observed between the groups with hypotension during craniotomy. The B-ICH group exhibited a lower rate of favorable outcome (p < 0.05) and higher mortality (p < 0.05). CONCLUSION: The B-ICH patients had a worse outcome than the U-ICH patients. Contralateral ICH was difficult to forecast based on pre- and intraoperative clinical conditions. Subdural hematoma or contusional ICH was frequently observed as a contralateral ICH.

Changes in coagulative and fibrinolytic activities in patients with intracranial hemorrhage.

OBJECTIVE: To investigate whether any changes occur in the coagulative/fibrinolytic cascade in patients with subarachnoid hemorrhage (SAH) or hypertensive intracerebral hemorrhage (HICH). DESIGN AND METHODS: Subjects included 143 patients with intracranial hemorrhage (SAH, n = 50; HICH, n = 82; ROSC-SAH [return of spontaneous circulation after cardiopulmonary arrest due to SAH], n = 11). Coagulative and fibrinolytic factors were measured in blood samples taken on admission. RESULTS: The prothrombin fragment 1+2 level was significantly higher (p < 0.005) in SAH patients than in HICH patients. The fibrinolytic factors (plasmin alpha 2-plasmin inhibitor complex, D-dimer, or fibrinogen degradation products) in SAH and ROSC-SAH were both significantly higher than those in HICH, but the significance of difference was stronger in the case of ROSC-SAH (p < 0.05). DISCUSSION: Both coagulative and fibrinolytic activities were altered after the onset of SAH. These results demonstrate that the coagulative/fibrinolytic cascade might be activated via different mechanisms in different types of stroke. It remains unclear, however, whether a significant alteration of the fibrinolytic cascade in patients with ROSC-SAH might be a nonspecific phenomenon attributable to the reperfusion after collapse.

Brain oxygen metabolism may relate to the temperature gradient between the jugular vein and pulmonary artery after cardiopulmonary resuscitation.

OBJECTIVE: A gradient between the jugular vein temperature and core body temperature has been reported in animal and clinical studies; however, the pathophysiological meaning of this phenomenon remains unclear. This study was conducted to identify the temperature gradient between the jugular vein and pulmonary artery in comatose patients after cardiopulmonary resuscitation. MATERIALS AND METHODS: The temperatures of the jugular vein and pulmonary artery were measured in 19 patients at 6 and 24 hours after cardiopulmonary resuscitation. Jugular venous blood saturation (SjO2; %) was also measured concomitantly. The patients were divided into 2 groups: high SjO2 (SjO2 > 75%: H-group; n = 10) and normal SjO2 (SjO2 < or = 75%: N-group; n = 9). The temperature gradient was calculated by subtracting the temperature of the pulmonary artery from that of the jugular vein (jugular - pulmonary = dT degrees C). Statistical significance was defined as p < 0.05. RESULTS: dT was significantly lower in the H-group than in the N-group at 6 hours (0.120 +/- 0.011: mean +/- SD vs. 0.389 +/- 0.036: p = 0.0012) and 24 hours (0.090 +/- 0.005 vs. 0.256 +/- 0.030: p = 0.0136) after cardiopulmonary resuscitation. CONCLUSION: The temperature gradient between the jugular vein and pulmonary artery was significantly lower in patients with high SjO2 after cardiopulmonary resuscitation. This temperature gradient may be reflected in brain oxygen metabolism.

Acceleration of chemokine production from endothelial cells in response to lipopolysaccharide in hyperglycemic condition.

UNLABELLED: Chronic hyperglycemia is an established risk factor for endothelial damage. It remains unclear, however, whether brief hyperglycemic episodes after acute stress alter the function of vascular endothelial cells in response to endotoxin. We hypothesize that brief hyperglycemic episodes enhance the production of interleukin-8 (IL-8) after lipopolysaccharide (LPS) stimulation. METHODS: Human umbilical vein endothelial cells (HUVECs; 1 x 10(5) cells/mL, cells from subcultures 2-5, n = 6) were cultivated in various concentrations of glucose (200, 300, 400, and 500 mg/dL) with or without LPS stimulation (1 microg/mL) for 24 hours. After culture, IL-8 levels in the supernatant were measured using ELISA. RESULTS: HUVECs cultured at glucose concentrations of 300 and 400 mg/dL produced more (p < 0.01) IL-8 than control cells (200 mg/dL). HUVECs cultured at glucose concentrations of 300 and 400 mg/dL also produced more (p < 0.01) IL-8 than those cultured in the absence of LPS. CONCLUSIONS: Hyperglycemic conditions enhance IL-8 production by vascular endothelial cells, and this response is augmented by LPS. Infections may foster neutrophil accumulation at injury sites. These results suggest that it is important to manage even short-term increases in blood glucose after acute stress.

Physiological studies on vasoactive intestinal peptide in rat small bowel isografts.

BACKGROUND: Vasoactive intestinal peptide (VIP) is released by stimulation of nonadrenergic noncholinergic (NANC) inhibitory nerves. In order to evaluate the function of VIP in jejunal isografts, we examined the enteric nerve responses in isografted rat jejunum compared with normal jejunum. METHODS: Orthotopic entire small bowel transplantation (SBT) with portocaval drainage was performed from Lewis rats to Lewis rats. Grafted tissue specimens were obtained 130 days after SBT (n = 8). As controls, normal segments of the jejunum were obtained from nontransplanted Lewis rats (n = 20). A mechanograph was used to evaluate in vitro jejunal responses to electrical field stimulation (EFS) of the adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers and VIP. RESULTS: The isografted jejunum was more strongly innervated by excitatory nerves, especially NANC excitatory nerves, than the normal jejunum (P <.05). VIP mediated relaxation reactions of NANC inhibitory nerves in the normal but to a lesser extent in the isografted jejunum (P <.05). CONCLUSIONS: The increased NANC excitatory nerves and the decreased effects of VIP in mediating NANC inhibitory nerves may largely relate to the peristaltic abnormalities seen in the isografted LEW rat jejunum.

Midazolam for continuous sedation in Japanese critical care patients: phase II study.

This prospective study was undertaken to evaluate the efficacy and safety of midazolam as a sedative agent in 14 critically ill patients without coma admitted to the intensive care unit at Nihon University Itabashi Hospital, Japan. Adequate sedation (sedation score [SS] 4-6) was induced with 0.058- 0.372 mg/ kg midazolam and maintained with a dose range of 0.03-0.4 mg/kg per h. Most burn or trauma patients required higher midazolam doses than patients with cardiovascular disease. The most frequent adverse events observed were hypotension, heart-rate fluctuation and electrocardiogram abnormalities. Pharmacokinetic analysis of the population suggested that lower drug clearance rates correlated with presence of complications. Plasma concentrations (EC50) of SS 5, estimated by logistic regression analysis, varied among patients (mean 194 ng/ml). Midazolam infusion achieved successful sedation in this critical care setting, but the optimum dose differed by patient and was influenced by the presence of complications.

A novel operative technique on proximal gastrectomy reconstructed by interposition of a jejunal J pouch with preservation of the vagal nerve and lower esophageal sphincter.

BACKGROUND/AIMS: This article describes the surgical techniques and postoperative status for proximal gastrectomy reconstructed by interposition of a jejunal J pouch with preservation of the vagal nerve and lower esophageal sphincter. METHODOLOGY: We have performed a new technique for reducing postgastrectomy sequelae such as reflux esophagitis, early dumping syndrome, and microgastria in early gastric cancer located in the proximal third of the stomach. The technique consists of proximal gastrectomy with preservation of the hepatic, pyloric, celiac branch of the vagal nerve, and abdominal esophagus (lower esophageal sphincter), and reconstruction by interposition of a jejunal J pouch. To reserve pyloric function, pyloroplasty can be omitted by preservation of the pyloric branch from the vagal nerve. To restore loss of reservoir function, the reconstruction is performed with an interposed jejunal J pouch. Sacrifice of the mesenteric arcades is kept to a minimum to preserve the autonomic nerve and blood flow in the mesentery. RESULTS: All of the patients who underwent this operation were able to eat an adequate amount of food at 6 months after surgery and they were satisfied with their postoperative status. And that, we have not experienced postgastrectomy disorders such the dumping syndrome and reflux esophagitis. CONCLUSIONS: Therefore, this method is useful for preventing the postoperative disorders in patients with early gastric cancer located in the proximal third of the stomach.

The role of nitric oxide (NO) in the human internal anal sphincter.

PURPOSE: Nitric oxide (NO) has recently been shown to be a neurotransmitter in nonadrenergic noncholinergic (NANC) inhibitory nerves in the human gut. To clarify the physiological significance of NO in the human internal anal sphincter (IAS), we investigated enteric nervous responses in normal IAS muscle strips above the dentate line, obtained from patients with rectal cancer. METHODS: Normal IAS muscle strips above the dentate line, obtained from ten patients who underwent rectal amputation for low rectal cancers were used. The subjects consisted of eight men and two women, aged from 46-72 years (mean age, 54.2 years). A mechanographic technique was used to evaluate in-vitro IAS muscle responses to electrical field stimulation (EFS) of adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers, N(G)-nitro-L-arginine (L-NNA) and L-arginine. RESULTS: Excitatory nerves were mainly involved in the regulation of enteric nerve responses to EFS in the baseline condition of the study, and NANC inhibitory nerves acted on the normal IAS. L-NNA concentration-dependently inhibited the relaxation in response to EFS in the human IAS, and this inhibitory effect in the IAS was reversed by L-arginine. CONCLUSIONS: These findings suggest that NANC inhibitory nerves play important roles in regulating relaxation of the human IAS, and that NO plays an important role as a neurotransmitter in NANC inhibitory nerves of the human IAS.

Operative technique on nearly total gastrectomy reconstructed by interposition of a jejunal J pouch with preservation of vagal nerve, lower esophageal sphincter, and pyloric sphincter for early gastric cancer.

Nearly total gastrectomy preserving the vagal nerve, the lower esophageal sphincter (LES), and the pyloric sphincter was developed as a function-preserving surgical technique to improve postgastrectomy disorders. In this paper, application criteria and technique are outlined, and postoperative quality of life was clinically investigated. Ten subjects who underwent this surgical operation (group A: 7 male and 3 female subjects at age 48 to 68 years with a mean age of 58.3 years) were interviewed to inquire about reflux esophagitis, dumping syndrome, and microgastria. Group A was compared with 20 cases of conventional total gastrectomy with D2 lymphadenectomy, excision of the lower esophageal sphincter (LES), total vagotomy, and single jejunal interposition (group B: 16 male and 4 female subjects at age 48 to 72 years with a mean age of 63.9 years). Included were cases with early cancer (M or SM1 of N0) localizing at the middle third and lower stomach, which was not applicable to endoscopic excision of gastric mucosa or partial gastric excision in M cancer, 2 cm or farther from the margin of the cancer to the esophagogastric mucosa cephalad junction and 3.5 cm or farther from the margin of the cancer to the pyloric caudad sphincter; in SM1 cancer, 4 cm or farther from the oral-side margin of the cancer to esophagogastric mucosa junction and 5.5 cm or farther from the anal-side margin of the cancer to the pyloric sphincter. In excision with lymph nodes, hepatic and celiac branches bifurcating from anterior and posterior trunks of the vagal nerve were preserved. To preserve LES, the esophagus was severed at the His angle at right angle to the longitudinal axis of the esophagus. The antrum was severed at 1.5 cm from the pyloric sphincter, preserving the arteria supraduodenalis. An alternative gaster was created as a 15-cm jejunal pouch with a 5-cm jejunal conduit for orthodromic peristaltic movement, using an automatic suture instrument to complete side-to-side anastomosis of folded jejunum with 1- to 1.5-cm long upper end of the pouch not anastomosed. The abdominal esophagus was mechanically anastomosed with a jejunal J pouch, and anastomosis of the pyloric antrum with a jejunal conduit was manually completed by stratum anastomosis. In group A, food ingestion per time could be taken the same as that of a healthy person, with no reflux esophagitis and dumping syndrome being noticed. Reflux esophagitis developed more significantly in group B than in group A (p < 0.05). In food ingestion per time, group B was significantly delayed compared with group A (p < 0.05). The present results suggested that the surgical technique proposed is a function-preserving gastric surgery appropriate to prevent postgastrectomy disorder of subjects.

Relationship between gastroduodenal interdigestive migrating motor complex and quality of life in patients with distal subtotal gastrectomy for early gastric cancer.

A total of 40 patients (28 males, 12 females; mean age, 56.6 years; range, 41-72 years), 1-1.5 years (mean, 1.4 years) after subtotal gastrectomy for early gastric cancer (Billroth I, D2 lymph node dissection, curability A) were divided into 2 groups according to the occurrence of interdigestive migrating motor complex (IMMC), phase III from the duodenum, and their postoperative quality of life was compared. Results were as follows: (i) patients in the IMMC, phase III positive group (28 patients) had evidently more appetite and ate more food, with less decrease in body weight compared with the IMMC, phase III negative group (12 patients); and (ii) patients in the IMMC, phase III positive group had clearly less symptoms, such as early dumping symptoms (systemic symptoms), symptoms of reflux esophagitis (e.g. heartburn, feeling of regurgitation, difficult swallowing), nausea, abdominal pain, diarrhea, abdominal distention, and borborygmus, compared with the negative group. These results showed more satisfactory quality of life in the IMMC, phase III positive group compared with the negative group.

Relation between gastroduodenal interdigestive migrating motor complex and postoperative gastrointestinal symptoms before and after cisapride therapy following distal gastrectomy for early gastric cancer.

A total of 30 patients (18 men, 12 women; 43-79 years, mean 58.9 years) 1.0 to 1.5 years (mean 1.25 years) after distal gastrectomy for early gastric cancer (Billorth I, D2 lymph node dissection, curability A) were divided into two groups based on the occurrence of interdigestive migrating motor complex (IMMC) phase III (pIII) from the duodenum and their postoperative gastrointestinal symptoms. They were compared before and after cisapride therapy (at an oral dose of 7.5 mg/day for 3 months). Results were as follows. Before cisapride therapy: (1) Patients in the IMMC-pIII-positive group (n = 20) had more appetite and ate more food with less decrease in body weight than those in the IMMC-pIII-negative group (n = 10); (2) patients in the IMMC-pIII-positive group clearly had fewer symptoms, such as early dumping (systemic) symptoms, symptoms of reflux esophagitis (e.g., heartburn, feeling of regurgitation, difficult swallowing), nausea, abdominal pain, diarrhea, abdominal distension, and borborygmus, than the IMMC-pIII-negative group. After cisapride therapy: eight patients (80%) in the IMMC-pIII-negative group became IMMC-pIII-positive, and their appetite and food consumption were obviously improved; body weight increased in six patients (60%), with alleviation of other abdominal symptoms and disappearance of the early dumping syndrome. These results showed a more satisfactory condition in regard to gastrointestinal symptoms in the IMMC-pIII-positive group than in the IMMC-pIII-negative group. It is concluded that cisapride therapy results in the occurrence of IMMC-pIII and subsequently alleviates various abdominal symptoms, contributing to the improved postoperative gastrointestinal condition of patients after gastrectomy.

Antisense oligodeoxynucleotides to human inducible nitric oxide synthase selectively inhibit induced nitric oxide production by human vascular endothelial cells: an experimental study.

OBJECTIVE: To find out whether the antisense oligodeoxynucleotide designed against the complementary DNA to human inducible NO synthase (iNOS) would block the translation from iNOS mRNA to NO in human vascular endothelial cells. DESIGN: Prospective controlled study. SETTING: Research laboratory, Japan. MATERIAL: Cultured human vascular endothelial cells. INTERVENTIONS: Human vascular endothelial cells were cultured for 24 hours, and divided into two groups, one of which was exposed to antisense oligodeoxynucleotides and the other to sense oligodeoxynucleotides at 100, 200, 400 and 800 micromol/L, respectively, for 18 hours. They were then exposed to interferon-gamma (1000 units/ml) and recombinant human tumour necrosis factor alpha (500 units/ml) to stimulate NO production. Each experiment was repeated ten times. RESULTS: Clear bands expressing cDNA of iNOS mRNA were identified in agarose gels in all cultured cells in both groups. The mean nitrite concentration in the supernatants of cultured cells in the group with the addition of antisense oligodeoxynucleotides was significantly lower than that in the group with sense oligonucleotides added at 200, 400, and 800 micromol/L. CONCLUSION: These findings indicate that the antisense oligodeoxynucleotides inhibited the NO production dependently, by preventing only their translation but not the processing, before their transcription from DNA into iNOS mRNA.

Role of nitric oxide in the left-sided colon of patients with diverticular disease.

BACKGROUND/AIMS: Non-adrenergic non-cholinergic inhibitory nerves are the most important nerves in the enteric nervous system of the human gut. Recently, it has been established that nitric oxide is released by stimulation of non-adrenergic non-cholinergic inhibitory nerves. Therefore, in order to evaluate the function of nitric oxide in the left-sided colon of patients with diverticular disease, we examined the enteric nerve responses in colonic tissues from patients with this disease, and also used the left-sided normal colon as a control. METHODOLOGY: Colonic tissue specimens (the diverticular bearing segments) were obtained from 9 patients with diverticular disease of the left-sided colon, and normal segments of the left-sided colon were obtained from 16 patients with ascending colon cancer. A mechanograph was used to evaluate in vitro colonic responses to electrical field stimulation of adrenergic and cholinergic nerve before and after treatments with various autonomic nerve blockers, NG-nitro-L-arginine, and L-arginine. RESULTS: 1) The diverticular colon was more strongly innervated by cholinergic nerves than the normal colon (P < 0.01); 2) Non-adrenergic non-cholinergic inhibitory nerves were found to act on the normal colon and to a lesser extent in the diverticular colon (P < 0.05). 3) Nitric oxide mediates the relaxation reaction of non-adrenergic non-cholinergic inhibitory nerves in the normal colon and to a lesser extent in the diverticular colon. CONCLUSIONS: These findings suggest that the intrinsic intestinal innervation contains excitatory and inhibitory nerves and that the former, especially cholinergic nerves, are dominant in the left-sided colon with diverticula. In addition, diminution of action of non-adrenergic non-cholinergic inhibitory nerves by substances such as nitric oxide may be largely related to the high intraluminal pressure by colonic segmentation observed in the left-sided colon with diverticula.

Peptidergic nerves in the colon of patients with ulcerative colitis.

BACKGROUND/AIMS: The cause of impaired motility, such as diarrhea and toxic megacolon, in patients with ulcerative colitis is unknown. Neuropeptides have recently been shown to be a neurotransmitter in the non-adrenergic non-cholinergic inhibitory and excitatory nerves in the human gut. To clarify the physiological significance of vasoactive intestinal polypeptide, substance P and neurotensin in the colon of patients with ulcerative colitis, we investigated the enteric nerve responses on lesional and normal bowel segments derived from patients with ulcerative colitis and patients who underwent colon resection for colonic cancers. METHODOLOGY: Twenty-four specimens were obtained from the lesional colon of 6 patients with ulcerative colitis (4 male, 2 female; ages 14-51 years, mean: 40.3 years). The patients with ulcerative colitis had chronic disease (4 with moderate disease, 2 with severe disease). Seventy-two specimens were obtained from the normal colon of 10 patients with colonic cancer (8 men and 2 women; ages 40-56 years, mean: 51.2 years). A mechanographic technique was used to evaluate in vitro muscle responses to these peptides of adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers. RESULTS: (1) Peptidergic nerves such as vasoactive intestinal polypeptide, substance P, and neurotensin nerves were found to act on both normal colon and ulcerative colitis colon; (2) the colon with ulcerative colitis was more strongly innervated by vasoactive intestinal polypeptide nerves than the normal colon; (3) Substance P and neurotensin nerves act more weakly in the UC colon that the normal colon. CONCLUSIONS: These findings suggest that peptidergic nerves play an important role in the impaired motility observed in patients with UC.

Physiological studies on nitric oxide in the right sided colon of patients with diverticular disease.

BACKGROUND/AIMS: Previously, we reported that non-adrenergic non-cholinergic (NANC) inhibitory nerves are decreased in the left-sided colon of patients with diverticular disease, contributing to their intraluminal high pressure by segmentation (1). It is established that nitric oxide (NO) is released by stimulation of NANC inhibitory nerves. Among Oriental people, including the Japanese, right-sided diverticular disease has predominated more frequently than among Western people. In order to evaluate the function of NO in the right-sided colon of patients with diverticular disease, we examined the enteric nerve responses in colonic materials from patients with this disease, using the right-sided normal colon as a control. METHODOLOGY: Colonic tissue specimens were obtained from 8 patients with diverticular disease of the right-sided colon, and normal segments of the right-sided colon were obtained from 11 patients with localized diseases. A mechanograph was used to evaluate in vitro colonic responses to electrical field stimulation (EFS) of adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers, N(G)-nitro-L-arginine (L-NNA), and L-arginine. RESULTS: 1) Cholinergic nerves were more dominant in the diverticular colon than in the normal colon (p<0.01). 2) NANC inhibitory nerves were found to act on the normal colon and to a lesser extent in the diverticular colon (p<0.05). 3) NO mediates the relaxation reaction of NANC inhibitory nerves in the normal colon and to a lesser extent in the diverticular colon. CONCLUSIONS: The intrinsic intestinal innervation contains excitatory and inhibitory nerves and the former, especially cholinergic nerves, are dominant in the right-sided colon with diverticula. In addition, reduction of the action of NANC inhibitory nerves by substances such as NO may be largely related to the tight intraluminal pressure by colonic segmentation observed in the right-sided colon with diverticula.