Katsuhisa Tanjoh

Early hemoperfusion with an immobilized polymyxin B fiber column eliminates humoral mediators and improves pulmonary oxygenation

IntroductionThe objective of this study was to clarify the efficacy and mechanism of action of direct hemoperfusion with an immobilized polymyxin B fiber column (DHP-PMX) in patients with acute lung injury or acute respiratory distress syndrome caused by sepsis.MethodThirty-six patients with sepsis were included. In each patient a thermodilution catheter was inserted, and the oxygen delivery index and oxygen consumption index were measured. DHP-PMX was performed in patients with a normal oxygen delivery index and oxygen consumption index (> 500 ml/minute per m2 and >120 ml/minute per m2, respectively). The Acute Physiology and Chronic Health Evaluation II score was used as an index of the severity of sepsis, and survival was assessed after 1 month. The humoral mediators measured were the chemokine IL-8, plasminogen activator inhibitor-1, and neutrophil elastase (NE). These mediators were measured before DHP-PMX treatment, and at 24, 48, and 78 hours after the start of treatment. The arterial oxygen tension (PaO2)/fractional inspired oxygen (FiO2) ratio was measured before DHP-PMX treatment and at 24, 48, 72, 92, and 120 hours after the start of treatment.ResultsAll patients remained alive after 1 month. Before DHP-PMX treatment, the Acute Physiology and Chronic Health Evaluation II score was 24 ± 2.0, the IL-8 level was 54 ± 15.8 pg/ml, plasminogen activator inhibitor-1 was 133 ± 28.1 ng/ml, and NE was 418 ± 72.1 μg/l. These three humoral mediators began to decrease from 24 hours after DHP-PMX treatment, and the decline became significant from 48 hours onward. The PaO2/FiO2 ratio was 244 ± 26.3 before DHP-PMX treatment but improved significantly from 96 hours onward. There were significant negative correlations between the PaO2/FiO2 ratio and blood levels of NE and IL-8.ConclusionThe mechanism of action of DHP-PMX is still not fully understood, but we report the following findings. The mean blood levels of plasminogen activator inhibitor-1, NE, and IL-8 were significantly decreased from 48 hours after DHP-PMX treatment. The mean PaO2/FiO2 ratio was significantly improved from 96 hours after DHP-PMX treatment. Improvement in the PaO2/FiO2 ratio appeared to be related to the decreases in blood NE and IL-8 levels.

Reduced effectiveness of vasopressin in repeated doses for patients undergoing prolonged cardiopulmonary resuscitation

INTRODUCTION The efficacy of repeated administration of vasopressin alone during prolonged cardiopulmonary resuscitation (CPR) remains unconfirmed. This study was conducted to estimate the effectiveness of the repeated administration of vasopressin vs. epinephrine for cardiopulmonary arrest (CPA) patients receiving prolonged CPR. METHODS We conducted a prospective randomized controlled study on patients who experienced out-of-hospital CPA. The patients were randomly assigned to receive a maximum of four injections of either 40IU of vasopressin (vasopressin group) or 1mg of epinephrine (epinephrine group) immediately after emergency room (ER) admission. Patients who received vasopressors before ER admission or suffered non-cardiogenic CPA were excluded after randomization. RESULTS In total, 336 patients were enrolled (vasopressin group, n=137; epinephrine group, n=118). No differences were found between these groups (vasopressin group vs. epinephrine group) in the rates of return of spontaneous circulation (ROSC) (28.7% vs. 26.6%), 24-h survival (16.9% vs. 20.3%), or survival to hospital discharge (5.6% vs. 3.8%). In a subgroup analysis by the Fishers exact test, the rate of ROSC was higher in the vasopressin group than in the epinephrine group, among the patients whose arrests were witnessed (48.1% vs. 27.8%, p=0.010) or who received bystander CPR (68.0% vs. 38.5%, p=0.033). When the independent predictors of ROSC were calculated in the subgroup analysis, however, vasopressin administration (Odds ratio: 0.87-0.28) did not affect the outcome. CONCLUSIONS This is the first report of a possible vasopressin-alone resuscitation without additional epinephrine. However, repeated injections of either vasopressin or epinephrine during prolonged advanced cardiac life support resulted in comparable survival.

Pathophysiological studies on the relationship between postgastrectomy syndrome and gastric emptying function at 5 years after pylorus-preserving distal gastrectomy for early gastric cancer.

Pylorus-preserving distal gastrectomy (PPG) has frequently been performed on patients with early gastric cancer in Japan to prevent the postgastrectomy syndrome seen after conventional distal gastrectomy (CDG). The long-term postoperative quality of life (QOL) and gastric emptying function in patients after PPG has not been assessed in detail. To clarify the usefulness of PPG for treating early gastric cancer we investigated the relation between postgastrectomy syndrome and gastric emptying function 5 years after PPG and then compared the results with those 5 years after CDG. Altogether, 32 patients who underwent curative gastrectomy at our clinic for early gastric cancer (submucosal cancer without lymph node metastasis) were studied. Ten subjects who underwent PPG with D2 lymphadenectomy without preserving the hepatic and pyloric branches of the vagal nerve [group A: eight men, two women; age 33–70 years (mean 60.7 years)] were interviewed and asked about appetite, weight loss, epigastric fullness, reflux esophagitis, and early dumping syndrome. They were compared with patients after CDG [group B: 36–72 years (mean 63.6 years)]. Esophagogastric endoscopy, abdominal ultrasonography, and gastric emptying function were also studied. The gastric emptying time of a semisolid diet was measured with a radioisotope method using 99mTc-labeled rice gruel; the gastric emptying time of a liquid diet was measured with the acetaminophen method using orange juice. The control subjects (group C) consisted of 18 healthy volunteers (10 men, 8 women) without gastrointestinal symptoms aged 38 to 68 years (mean 60.8 years). The following results were obtained: PPG (group A) alleviated postoperative gastrointestinal symptoms such as appetite loss, reflux esophagitis, early dumping syndrome, lost body weight, endoscopic reflux esophagitis, endoscopic gastritis in the remnant stomach, and postogastrectomy cholecystolithiasis better than did CDG (group B). The only weak point with the PPG procedure was that it produced a feeling of epigastric fullness. The pattern of the gastric emptying curve for the semisolid diet was almost the same among groups A, B, and C, although delayed gastric emptying was clearly more frequent in group A than in group B or C (p < 0.05). Gastric emptying with the liquid diet in group B was significantly faster than that in groups A and C (p < 0.01). Gastric emptying in groups A and C was similar. These results showed that PPG improved the postoperative QOL, but the delayed emptying of semisolid diet after PPG led to a feeling of epigastric fullness after meals due to retention of contents in the residual stomach. Epigastric fullness after meals continued in many patients after PPG. Thus the only disadvantage of the PPG procedure is the sensation of epigastric fullness and gastric stasis due to delayed gastric emptying of a semisolid diet.

Physiologic effects of cisapride on gastric emptying after pylorus-preserving gastrectomy for early gastric cancer.

Abstract. Pylorus-preserving gastrectomy (PPG) has been considered reasonable reduction surgery. However, even patients in whom more than 1 year passed after surgery frequently have a feeling of gastric fullness after meals and long-term retention of foods in the residual stomach. To treat this syndrome, cisapride has been administered. We studied the emptying time of a semisolid diet (radioisotope method using 99m Tc-tin colloid-labeled rice gruel) and the emptying time of a fluid diet (acetaminophen method with orange juice) before and after oral administration of cisapride (15 mg/day for 1 month) in 14 patients (10 men, 4 women; 32–70 years old, average 60.6 years) who underwent PPG (Billroth I procedure, D 2 lymph node dissection, curability A) for treatment of early gastric cancer. Ten healthy volunteers without gastrointestinal symptoms and digestive diseases (7 men, 3 women; 28–61 years old, average 49.8 years) were enrolled as controls. The results showed obviously delayed emptying time of the semisolid diet before administration of cisapride in patients with PPG compared with that of the control group, whereas the emptying curves for the fluid diet showed an almost normal pattern. One month after the start of cisapride administration the emptying time of the semisolid diet was improved, and the emptying curves were close to the patterns in the control group. Emptying of the fluid diet was slightly accelerated compared with that before administration of cisapride, and the emptying curves showed almost the same pattern as in the control group. A postgastrectomy symptom, “gastric fullness,” after PPG was alleviated by cisapride. These results showed that cisapride improved delayed emptying of a semisolid diet after PPG and prevented the feeling of gastric fullness after meals due to retention in the residual stomach.

Studies on gastrointestinal hormone and jejunal interdigestive migrating motor complex in patients with or without early dumping syndrome after total gastrectomy with Roux-en-Y reconstruction for early gastric cancer.

BACKGROUND There has been no report concerning fasting Roux limb motilities and gut hormone in patients with early dumping syndrome (EDS) after total gastrectomy with Roux-en-Y reconstruction. The present study investigated interdigestive migrating motor complex, phase III (IMMC-pIII) in the Roux limb, changes in the plasma gut hormone levels, and the relationships among those parameters and EDS. METHODS Forty-eight patients (35 men, 13 women; aged 33 to 69 years, mean, 59.8) 1.5 to 2.0 years (mean 1 year, 8 months) after total gastrectomy with Roux-en-Y reconstruction for early gastric cancer were allocated to two groups based on the presence or absence of EDS. The occurrence of IMMC-pIII was compared and changes in the plasma levels of both motilin (MT) and somatostatin (SOM) were monitored. RESULTS None of the patients with EDS (n = 8) were recognized as having IMMC-pIII. In the IMMC-pIII positive group, MT and SOM increased sequentially from phase I through IMMC-pIII. In the IMMC-pIII negative group, MT and SOM were significantly lower than in the IMMC-pIII positive group during phases I, II, and IMMC-pIII (P <0.05, P <0.01, P <0.01, respectively). CONCLUSIONS There is an absence of IMMC-pIII in patients with EDS, and both MT and SOM might be necessary for IMMC-pIII generation.

Role of Nitric Oxide in the Colon of Patients with Ulcerative Colitis

Abstract. The cause of impaired motility, such as diarrhea and toxic megacolon, in patients with ulcerative colitis (UC) is unknown. Nitric oxide (NO) has been shown to be a neurotransmitter in the nonadrenergic noncholinergic (NANC) inhibitory nerves in the human gut. To assess the physiologic significance of NO in the colon of patients with UC, we investigated enteric nerve responses on lesional and normal bowel segments derived from patients with ulcerative colitis (n= 6) and patients who underwent colon resection for colonic cancers (n= 10). A mechanographic technique was used to evaluate in vitro muscle responses to electrical field stimulation (EFS) of adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers, includingNG-nitro-l-arginine (l-NNA) and l-arginine. The results showed that (1) NANC inhibitory nerves were found to act on both normal colon and UC colon; (2) the colon with UC was more strongly innervated by NANC inhibitory nerves than the normal colon; (3) l-NNA concentration-dependently inhibited the relaxation in response to EFS in the colon of both normal and UC colon; and (4) this inhibitory effect in the colon of both normal and UC patients was reversed by l-arginine; (5) NO acts more strongly in the UC colon than the normal colon. These findings suggest that NANC inhibitory nerves play an important role in the impaired motility observed in patients with UC and that NO plays an important role as a neurotransmitter in NANC inhibitory nerves of human colon.

Hemoperfusion with an immobilized polymyxin B column reduces the blood level of neutrophil elastase.

Background: We investigated whether direct hemoperfusion with an immobilized polymyxin B column (DHP with PMX) could reduce the blood level of neutrophil elastase. Methods: 20 sepsis patients were enrolled in the study. DHP with PMX was performed twice within a 24-hour period. Neutrophil elastase was measured 7 times. Results: Neutrophil elastase was 468 ± 75.1 µg/l, while it was 1,531 ± 201.7 µg/l immediately after the first session, declined to 351 ± 73.9 µg/l before the second session of DHP with PMX, and increased again to 599.3 ± 112.7 µg/l immediately after the second session, 328 ± 73.7 µg/l at 24 h, 264 ± 39.3 µg/l at 48 h, and 230 ± 36.1 µg/l at 72 h after DHP with PMX. The levels from 48 h onwards were significantly lower compared with that before treatment. Conclusion: DHP with PMX has an overall effect that reduces circulating neutrophil elastase levels.

A role of nitric oxide in Hirschsprung's disease

Nitric oxide (NO) has recently been shown to be a neurotransmitter in the nonadrenergic noncholinergic (NANC) inhibitory nerves in the gastrointestinal tract. To clarify the significance of NO in Hirschsprungs disease (HD), enteric nerve responses in colonic tissue obtained from HD patients were investigated. Colonic tissue specimens were obtained from four patients with HD and from 11 patients without constipation who were used as controls. A mechanograph was used to evaluate in vitro colonic responses to electrical field stimulation (EFS) of the adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers, and NG-nitro-L-arginine (L-NNA) and L-arginine with the following results: (1) NANC inhibitory nerves were found to act on normal human colon, but had no effect on aganglionic colon; (2) L-NNA concentration dependently inhibited the relaxation in response to EFS in the normal colon, but had no effect on aganglionic colon; and (3) this inhibitory effect was reversed by L-arginine in the normal colon, but had no effect on the aganglionic colon. Nitric oxide mediates the relaxation reaction of NANC inhibitory nerves in the human colon, but the effect of NO was absent in aganglionic colon. The loss of action by NO may be implicated in the impaired motility observed in aganglionic colon.

ROLE OF NON-ADRENERGIC NON-CHOLINERGIC INHIBITORY NERVES IN THE COLON OF PATIENTS WITH ULCERATIVE COLITIS

Abstract: The cause of impaired colonic motility in patients with ulcerative colitis (UC) is unknown. The non-adrenergic non-cholinergic (NANC) inhibitory nervous system is one of the most important factors in the enteric nervous system of human gut. To assess the physiological significance of NANC inhibitory nerves in the colon of patients with UC, we investigated the enteric nerve responses of colonic tissues from patients with this disease. Colonic tissues were obtained from the lesional sigmoid colons of six patients with UC. Normal sigmoid colonic tissues obtained from ten patients with colonic cancer were used as controls. A mechanographic technique was used to evaluate in-vitro muscle responses to the electrical field stimulation (EFS) of adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers. NANC inhibitory nerves were found to act on both normal colon and the lesional colon of patients with UC, but colon with UC was more strongly innervated by NANC inhibitory nerves than was the normal colon. These findings suggest that NANC inhibitory nerves play an important role in the impaired motility observed in the colon of patients with UC.

Characterization of multicomponent crystal formed between indomethacin and lidocaine

Purpose: Crystalline complex was formed between indomethacin (IDM) and lidocaine (LDC) at molar ratio 2:1 from ethanol solution. The purpose of this study was elucidation of an interactive manner between IDM and LDC in ethanol solution and mechanism of the complex formation through solid state as well as liquid state. Methods: The chemical and physical nature of the complex was clearly elucidated by the alliance of powder X-ray diffractometry, differential scanning calorimetry, and infrared spectroscopy. The complex was also formed via solid-state reaction by cogrinding and heating treatment without any solvent. Results: The complexation process was estimated to be as follows: (i) mixing and contact of two components, (ii) disorder of crystalline LDC by grinding or fusion, and then (iii) crystal growth by heating. In addition, 1H-NMR coupled with microchanneled cell for synthesis monitoring revealed that a primary interactive force between IDM and LDC molecule was coulomb energy.