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Biomedical subjects

M Nio

Publications and source records attributed to M Nio.

At least 37 records · Page 2Linked to original sources

Multi-institutional randomized clinical study on the comparative effects of intracavital chemotherapy alone versus immunotherapy alone versus immunochemotherapy for malignant effusion.

The current prospective randomized study was designed to compare the effects of intracavitary (i.c.) chemotherapy vs immunotherapy vs immunochemotherapy for malignant effusion. Between 1992 and 1995, a total of 42 patients with malignant effusion were registered, and 41 patients were eligible for statistical analysis. The primary diseases of the eligible patients included 27 gastric, four colorectal, four pancreatic, three lung, two liver and one oesophageal cancers. The patients with malignant effusion were randomly assigned into one of three i.c. therapeutic regimens: chemotherapy alone with weekly injection of anticancer agents (ACAs: cisplatin, mitomycin-C, adriamycin, etc.) (Group A, n = 13); immunotherapy alone with weekly injection of streptococcal preparation OK-432 (Group B, n = 14); or immunochemotherapy with ACAs and OK-432 (Group C, n = 14). The response of the effusion, patient survival and the kinetics of cytokines in the effusion were compared. There were no differences in the patients' backgrounds. The side-effects of the regimens included pain, anorexia, fever, leucopenia and anaemia and there were no differences in their incidence among the three groups. One patient died after cisplatin (CDDP) administration in Group A. Cytologic examination revealed that tumour cells in the effusion disappeared in 23% of Group A cases, 36% of Group B cases and 36% of Group C cases. The malignant effusion did not disappear in any of the Group A cases; however, the effusion disappeared in 29% of Group B cases and 43% of Group C cases (P = 0.03, Group A vs Group C). Furthermore, the 50% survival period was 1.6 months for Group A, 2.4 months for Group B and 3.5 months for Group C. The 6-month survival rate was 7% for Group A, 6% for Group B and 34% for Group C, and the 1-year survival rate was 0%, 0% and 17% respectively (P = 0.048, Group A vs Group C by the log-rank test). The analysis of the cytokine kinetics revealed a prominent increase in the level of interleukin-6 in the effusion in Group C. These results suggest that i.c. immunochemotherapy with OK-432 and ACAs may be more beneficial than i.c. chemotherapy alone or immunotherapy alone.

Adjuvants, Immunologic↗

Apoptosis and cell proliferation in biliary atresia.

Biliary atresia (BA), which is thought to result from progressive destruction of the bile ducts by a necroinflammatory process, is the most common cause of obstructive jaundice in infancy. Abnormalities in the cell turnover of remodelling ductal plates are considered one of the important aetiological factors in this disorder, but little work has been done on this topic. Programmed cell death or apoptosis was therefore examined by TdT-mediated dUTP biotin nick end labelling (TUNEL) and cell proliferation by Ki67 immunostaining in 34 cases of BA. The results were compared with normal control liver (five cases) and congenital dilatation of the bile ducts (CDB, five cases) in order to study the cell turnover or tissue dynamics of BA. The TUNEL labelling index (LI) in bile ducts (48.9 +/- 13.2 per cent) was significantly higher than that of the control normal liver (3.6 +/- 2.8 per cent) and of CDB (2.5 +/- 5.1 per cent). The Ki67 LI in the bile ducts of BA (15.0 +/- 5.57 per cent) was also significantly higher than that of CDB (8.6 +/- 5.4 per cent). No significant differences of the TUNEL and Ki67 LIs in hepatocytes were, however, observed between BA, CDB, and normal liver. The TUNEL LI was significantly higher than the Ki67 LI in the bile ducts of BA. BA is therefore associated with increased and disorganized cell turnover of the bile ducts, which is related to malformation of the ductal plate or abnormal bile duct development.

Apoptosis↗

Hepatic and serum bile acid compositions in patients with biliary atresia: a microanalysis using gas chromatography-mass spectrometry with negative ion chemical ionization detection.

Hepatic and serum bile acids in five patients with biliary atresia were preoperatively determined by microanalysis using gas chromatography-mass spectrometry with negative ion chemical ionization detection. The hepatic content of total bile acids was markedly elevated (3079+/-711 nmol/g protein), most of which were primary bile acids. Accumulation of unconjugated bile acids (2.93% to 4.62% of the total) was observed in the liver tissue of these patients, although only trace amounts were detected in their sera. The ratio of glycine-conjugated to taurine-conjugated bile acids was 0.44+/-0.18 in liver tissue and 0.79+/-0.52 in serum and these values were significantly lower than those of controls. This study has shown that the composition of bile acids in serum does not reflect that in liver tissue faithfully. The accumulation of these hydrophobic bile acids may contribute to initiating or exacerbating liver injury in infants with cholestatic liver diseases.

Bile Acids and Salts↗

Length of transplanted small bowel required for adequate weight gain in rats.

Progress has been made toward developing a clinically successful small-bowel transplant procedure, but there has been little research concerning the functional aspects of the transplanted small bowel. Using a rat model, our study examined the length of transplanted small bowel required to provide adequate weight gain. The rats were divided into six groups; groups 1 and 2 were considered controls. Group 1 (n = 6) underwent a gastrostomy. Group 2 (n = 3) underwent a jejunoile-ectomy followed by re-establishment of intestinal continuity and anastomosis of the native proximal small bowel to an abdominal stoma and the distal portion to the ascending colon. Groups 3 (n = 5), 4 (n = 4), 5 (n = 5), and 6 (n = 4) underwent small-bowel transplantation, receiving 100%, 50%, 25%, and 15% transplants, respectively. The donor small-bowel anastomoses were the same as the native small-bowel anastomoses in group 2. All of the rats began to produce stool within 4 days of becoming dependent upon the transplanted small bowel. By the end of postoperative week 4, there was no significant difference between the percentages of preoperative body weight in groups 1-4 (range 125.7%-130.0%). Although the weight gain in group 5 was significantly less than that in groups 1-4 (P < 0.05), it was adequate (111.8%); group 6 animals lost weight (94.7%). It is concluded that a 50% or more small-bowel transplant with or without an ileocecal valve provides ample weight gain; minimally adequate weight gain is achieved by a 25% transplant without an ileocecal valve; and the graft begins to function soon after transplantation.

Animals↗

Clinical significance of 99mTc-DTPA galactosyl human serum albumin scintigram in follow-up after Kasai operation.

The scintigram using 99mTechnetium-DTPA galactosyl human serum albumin (99mTc-GSA) which binds to asialoglycoprotein receptors on hepatocytes is a good index of hepatocyte function in various liver diseases in adult patients. In 43 patients (4 months to 30 years old) who had undergone Kasai procedure, we performed 53 series of 99mTc-GSA scintigrams and checked the laboratory data of blood draw and the clinical status. The indices for blood clearance and liver accumulation were evaluated on the basis of the dynamic data after 99mTc-GSA injection. HH15 as an index of the blood clearance, and LHL15 as an index of the accumulation of the hepatocytes were calculated and the HH15/LHL15 ratio (H/L15) was examined. 99mTc-GSA scintigram correlated with liver function and clinical status. Our results revealed that 1) The deterioration of the liver functions and clinical status correlates proportionally with H/L15, 2) The results of 99m Technetium-GSA scintigram correlate with several liver function tests, especially direct bilirubin, albumin and choline esterase, 3) This scintigram is an useful index of clinical status and hepatic function as well as the change of the hepatic parenchymal reserve in BA patients, especially for the evaluation of liver transplantation.

Adolescent↗

Assessment of nutritional status of postoperative patients with biliary atresia.

Some patients of biliary atresia (BA) suffer from chronic hepatic dysfunction and/or persistent jaundice. The adverse effects of chronic liver disease on nutrition and growth should be considered on BA patients. We studied 45 BA patients ranging in age from 0.5 to 38 years and divided them into 2 groups. Group A contains the patients whose total bilirubin > or = 2 mg/100 ml, and Group B contains the patients whose total bilirubin < 2 mg/100 ml. We measured height, weight, triceps skin fold (TSF), midarm circumference (MAC) and midarm muscle area (MAMA). Visceral protein kinetics was evaluated on the basis of serum albumin and prealbumin levels. Caloric and protein intake was calculated by collecting intake data for 3 days. The results of this study were; 1) The mean TSF in Group A (47th percentile) was not significantly different from that in Group B (53th percentile). 2) The mean MAMA was significantly lower (p < 0.01) in Group A (16.4th percentile) than in Group B (36.7th percentile) 3) The prealbumin level was significantly lower (p < 0.001) in Group A (mean 9.9 mg/100 ml) than in Group B (mean 18.8 mg/100 ml). The authors conclude that the evaluation of MAMA and prealbumin were very useful to characterize the low metabolic status of protein in the damaged liver. And repeated nutritional assessment was necessary to evaluate liver function and provide adequate nutrition in BA patients.

Adolescent↗

The outcome of surgery for biliary atresia and the current status of long-term survivors.

Between 1953 and 1995, 300 patients with biliary atresia underwent surgery at Tohoku University Hospital. The 10-year survival of patients who were operated on in or before 1965 was 9%. But the survival rate went up to 61% in patients operated on between 1976 and 1985. Eighty-five patients including 2 who developed liver failure after Kasai operation and underwent liver transplantation have survived more than 10 years. Eleven of them (13%) have recurrent or persistent jaundice. Of the 30 patients who have survived more than 20 years (10 males and 20 females, age range; 20 to 41 years), 20 underwent hepatic portoenterostomy, 8 underwent hepaticoenterostomy and the remaining 2 underwent hepatic portocholecystostomy. None of these patients has undergone liver transplantation. Twenty-two patients have led near-normal lives. The remaining 8 patients have experienced some troubles due to cholangitis, portal hypertension, intrahepatic gallstones and so on. Two of them are considered as candidates for liver transplantation. While the majority of long-term survivors of biliary atresia have good quality of life, close long-term follow-up is essential even in patients with biliary atresia aged 20 years or more.

Adolescent↗

Abnormal distribution of nerve fibers in the liver of biliary atresia.

We investigated changes in the pattern of hepatic innervation in liver specimens from 15 infants with biliary atresia and 4 age-matched controls by immunohistochemical methods. In the control, nerve fibers identified by immunoreactivity for neural cell adhesion molecule (NCAM) and S100 protein were present around the branches of hepatic arteries, portal veins and bile ducts in the portal areas and the hepatic lobules. In biliary atresia, NCAM and S100 positive nerve fibers were increased in the vicinity of the hepatic arteries and the portal veins in the enlarged portal areas, while no nerve fibers were observed around bile ducts and periportal ductules which became NCAM positive. No innervation in the lobules was seen in any cases regardless of the histological alteration. These findings may suggest that the abnormal innervation in the liver with biliary atresia does not occur as a result of structural changes in liver architecture caused by portal fibrosis and inflammation, but is associated with immaturity or malformation of hepatic innervation in the patients.

Bile Ducts↗

Japanese Biliary Atresia Registry, 1989 to 1994.

The Japanese Biliary Atresia Society founded in 1980 for the aim of investigations of all aspects of biliary atresia (BA), started a nationwide registry of BA patients in 1989. A total of 626 cases were registered from 1989 to 1994. The male to female ratio was 0.58. Corrective surgery was performed in 603 patients. Regarding the type of obstruction, 63 cases were Type I, atresia of the common bile duct, 9 were Type II, atresia of the hepatic ducts, and 543 were Type III, atresia of the porta hepatis. As initial corrective procedures, original Roux-en Y, Suruga II and Roux-en Y with intestinal valve were mainly employed. Jaundice cleared in 346 patients (57%) and decreased in 131, while it persisted in 120. The 5-year-follow-up showed that 34 patients, 49% of the patients who were followed up, were alive without jaundice, while 28 (41%) are dead. Thirty five, 33% of the patients who were entered to the Registry, were lost to follow-up.

Biliary Atresia↗

Water transport in native and transplanted porcine jejunum.

Adequate absorptive function of transplanted small intestine is essential for success of this procedure. This study compared water transport under basal and meal stimulated conditions in the transplanted swine jejunum to native jejunum. Six female adolescent Yorkshire swine were randomized to undergo construction of either a 25-cm native proximal jejunal Thiry-Vella Fistula (TVF), n=3, or a 25-cm proximal jejunal allograft TVF, n=3. Immunosuppression in the transplanted animals was accomplished with intravenous methylprednisolone, azathioprine, and cyclosporin. Jejunal absorption studies, each 4 hr long, were performed utilizing 14C-polyethylene glycol to calculate net water flux. Each animal underwent at least three fasting and three postprandial studies. New water flux was negative, i.e., secretory, in both the native and transplanted proximal swine jejunum. In the basal state, integrated hourly water transport was more secretory in the native bowel vs the transplanted bowel during the 2nd, 3rd, and 4th experimental hr (-4.6 +/- .8 vs -2.1 +/- .7 cc, P = 0.034; -4.4 +/- .7 vs -1.8 +/- .6 cc, P = 0.012; and -4.7 vs 1.3 +/- .5 cc, P < 0.005), respectively. In native jejunum, integrated hourly water transport was less secretory 2 and 3 hr postprandially compared to basal (-1.9 +/- .5 vs -4.4 +/- .7 cc, P = 0.016; and -2.0 +/- .5 vs -4.7 +/- .7 cc, P = 0.021), respectively. This postprandial proabsorptive response did not occur in the transplanted jejunum. Native and transplanted jejunal water flux in the postprandial state did not differ significantly. We conclude that there is higher secretion in native vs transplanted jejunum during fasting. The postprandial proabsorptive response of the proximal porcine jejunum is abolished by transplantation.

Animals↗

Current status of 21 patients who have survived more than 20 years since undergoing surgery for biliary atresia.

Between 1952 and 1993, 289 patients with biliary atresia underwent surgery at the authors' institution. Twenty-two of them survived more than 20 years; one has since died of hepatic failure (at age 28 years). Of the 21 current survivors (age range, 20 to 39 years), 13 underwent hepatic portoenterostomy; the others had hepaticoenterostomy. None of these patients has undergone liver transplantation. Sixteen patients have led near-normal lives. This includes three married women, one of whom has given birth to a healthy baby boy. Of the six patients who had portal hypertension, three underwent both splenectomy and proximal splenorenal shunting in or before 1985. None of these patients has required additional treatment for portal hypertension. The quality of life of one patient has been severely affected by an unrelated condition (Turner's syndrome). A 22-year-old man was diagnosed as having intrahepatic stones 3 years ago. In another 22-year-old man, hepatic dysfunction developed after frequent episodes of cholangitis. He is now being considered for liver transplantation. The majority of the long-term survivors have good quality of life. However, a few continue to suffer from complications including recurrent cholangitis. Close long-term postoperative follow-up is required for patients with biliary atresia.

Adult↗

[Long-term outcome of surgery for biliary atresia].

Between 1953 and 1995, 300 patients with biliary atresia underwent surgery at Tohoku University Hospital. Among them, 31 patients survived more than 20 years, while one of these patients died of hepatic failure at the age of 28 years. Of the 30 surviving patients (10 males and 20 females, age range; 20 to 41 years), 20 underwent hepatic portoenterostomy, 8 underwent hepaticoenterostomy and the remaining 2 underwent hepatic portocholecystostomy. None of these patients has undergone liver transplantation. Twenty-two patients have led near normal lives. This includes three married women, one of whom gave birth to 2 healthy babies. The remaining 8 patients have had experienced some troubles due to cholangitis, portal hypertension and intrahepatic gallstones. Two of them who have progressive liver dysfunction are being considered as candidates for liver transplantation. The quality of life of one patient has been severely affected by an unrelated (Turner's syndrome). While the majority of long-term survivors of biliary atresia have good quality of life, close long-term postoperative follow-up is required.

Adult↗

The effect of hepatic portal dissection on the portal vein structure in biliary atresia.

Superior mesenteric portograms were performed on 30 patients with biliary atresia (BA) at the time of initial portoenterostomy in 20, and at the stoma closure operation in 10. A withered-branch-shaped irregularity of the intrahepatic portal vein (PV) and collateral vessels were seen in 2 of 11 patients with portal pressures (PP) of 200 to 300 mmH2O; in 1 of 2 patients with PPs of over 300 mmH2O at the initial operation; and in 3 jaundice-free patients with PPs of 285, 320, and 305 mmH2O, respectively, at the stoma closure operation. Collaterals were the only abnormalities seen in two additional jaundice-free patients with PPs of 370 and 183 mmH2O, respectively. No anatomic changes in the extrahepatic PV at the porta hepatis were found on the portograms of either group of patients. Thus, we conclude that portal dissection itself does not affect the PV structure anatomically, a finding which has important implications in determining whether or not portoenterostomy adversely affects potential liver transplantation.

Biliary Atresia↗

A prospective randomized trial of delayed versus immediate repair of congenital diaphragmatic hernia.

From March 1990 to January 1993, a randomized prospective study was performed to determine the optimal timing of surgery for infants with high-risk congenital diaphragmatic hernia (CDH). Thirty-two CDH patients who presented with respiratory distress within 12 hours after birth were randomly divided into two groups: Group A had early repair (within 6 hours), and group B had delayed repair (at 96+ hours). Extracorporeal membrane oxygenation (ECMO) was initiated in both groups as necessary. Fourteen patients were assigned to group A, and 18 were assigned to group B. Two patients initially assigned to group A had acute deterioration, and their operations had to be postponed. Data were collected, but these patients were eliminated from the study. The two groups were comparable based on gestational age, birth weight, Bohn's criteria, and oxygenation and ventilatory index. Nine of 12 group A patients (75%) survived, and 13 of 18 group B patients (72%) survived (P > .05, not significant). The ECMO requirements for the two groups were not significantly different (8 of 12 (67%) v 16 of 18 (89%); P > .05). Surgical intervention for bleeding complications related to ECMO was required in three of eight (38%) with immediate repair and seven of 16 (44%) with delayed repair (P > .05). There was no difference in survival nor incidence of ECMO between the two groups. This is the first prospective study of timing of hernia repair that supports the conclusions of earlier reports of retrospective studies.

Extracorporeal Membrane Oxygenation↗

Remodeling of the alveolar structure in the paraquat lung of humans: a morphometric study.

To correlate the progression of fibrosing lung lesions with an impediment of respiratory function, autopsy lungs from 15 patients who died after ingesting paraquat were submitted to histopathologic and morphometric analysis. The basic lung lesion proved to be a remodeling of alveolar structure caused by deposition of matrix on the septal surface, with proliferating mesenchymal cells. Morphometry, using a geometric model, and stereology showed that the mean thickness D of septa, including the matrix, enlarged after an exponential function of days after ingestion, reaching the alveolar breadth of 200 microns on day 22 and showing the alveoli totally obliterated. The exponential nature of this finding suggested that the paraquat lung is a self-accelerating and therefore a malignant lesion, in contrast to the slowly progressing fibrosis that follows usual interstitial pneumonia. In a whole-lung distribution analysis performed in three cases, D was shown to become increasingly heterogenous over time, with ordinary alveolar tissue remaining in at least part of the lung even in the most advanced case. Thus, heterogenous distribution of the disease was considered to be a sine qua non for a lung disease to run a chronic course.

Adult↗

Management of splenic abscess in immunocompromised children.

Splenic abscess is an infrequent complication in the immunocompromised patient. Six patients underwent splenectomy for presumed splenic abscess from 1987 to 1991. Chemotherapy altered the immune system of four patients; the human immunodeficiency virus (HIV) rendered the other two vulnerable to infection. Five presented with fever but none had leukocytosis; only one exhibited palpable splenomegaly; three had abdominal pain. Cultures documented systemic infection in all but one, an HIV-positive individual. Respiratory embarrassment was the indication for surgery in one patient. In five cases the decision for surgical intervention was made after computed tomography (CT) indicated the presence of multiple splenic lesions and systemic antibiotics failed to resolve the fevers. CT additionally showed hepatic and/or renal microabscesses in four patients. Signs and symptoms experienced preoperatively resolved with splenectomy in all six patients. No additional surgery was required for the patients with extrasplenic abscesses. Surgical pathology determined that three spleens had fungal and two had mycobacterial abscesses. The other was shown to be a spindle cell sarcoma; no abscess was present. This patient had preoperative blood cultures positive for mycobacteria, and the same organism was recovered from retroperitoneal nodes sampled at the time of splenectomy for the sarcoma. Follow-up indicates that no patients experienced surgical complications or sequelae related to their splenic pathology. Splenectomy is necessary and effective in treating splenic abscesses in immunocompromised patients and is appropriate for diagnosis as well as therapy.

Abscess↗