Cellulose acetate beads induce release of interleukin-1 receptor antagonist, but not tumour necrosis factor-alpha or interleukin-1beta in human peripheral blood.

OBJECTIVE: Dramatic improvements in clinical symptoms of rheumatoid arthritis and ulcerative colitis were observed after patients received granulocyte and monocyte adsorptive apheresis with a column containing cellulose acetate (CA) beads as adsorptive carriers. This study was to investigate the effect of CA beads on the generation of anti-inflammatory and pro-inflammatory cytokines in human blood. MATERIALS AND METHODS: We incubated human whole blood with CA beads at 37 degrees C for up to 2 h and measured tumour necrosis factor-alpha (TNF-alpha) interleukin-1beta (IL-1beta) and IL-1 receptor antagonist (IL-1ra) produced by leucocytes. IL-1ra was also measured at the inflow and outflow of a column containing CA beads as leucocyte adsorptive carriers for the treatment of patients with ulcerative colitis. RESULTS: CA beads induced significant release of IL-1ra from leucocytes, but not TNF-alpha or IL-1beta. In contrast, all three cytokines were released when leucocytes were stimulated with lipopolysaccharide. IL-1ra was also markedly elevated in the outflow of the leucocyte apheresis column. CONCLUSIONS: These results indicate that CA beads selectively induce IL-1ra release from leucocytes which should contribute to the anti-inflammatory effect of granulocyte and monocyte adsorptive apheresis with CA beads as apheresis carriers.

Laparoscopic adhesiolysis for recurrent small bowel obstruction: long-term follow-up.

BACKGROUND: Recurrent small bowel obstruction caused by postoperative adhesions has traditionally been treated by conventional laparotomy, but laparoscopic management of acute small bowel obstruction has been reported. The aim of this study was to assess the long-term efficacy and clinical outcome of laparoscopic adhesiolysis for recurrent small bowel obstruction. METHODS: After conservative treatment, elective laparoscopic treatment was attempted in 17 patients hospitalized for recurrent small bowel obstruction after abdominal or pelvic surgery. RESULTS: Postoperative adhesions were identified laparoscopically in all patients. Laparoscopic treatment was possible in 14 patients (82.4%). Conversion to laparotomy was required for 3 patients (17.6%) because of intestinal perforation (n = 1) or a convoluted mass of adherent bowel (n = 2). Long-term follow-up was possible in 16 patients. Two recurrences of small bowel obstructions were noted over a mean follow-up period of 61.7 months. CONCLUSIONS: Laparoscopic adhesiolysis is a safe and effective treatment for recurrent small bowel obstruction. Conversion to laparotomy should be considered in patients with dense adhesions.

Development of duodenal cancer in a patient with familial adenomatous polyposis.

A Japanese woman with familial adenomatous polyposis in whom a duodenal ampullary adenoma underwent malignant change during a 10-year follow-up period is reported. After restorative proctocolectomy in 1989, and extensive small bowel resection for desmoid disease in 1991, regular surveillance duodenoscopies, including three to nine biopsies (mean, 4.8) were performed annually or biannually. Until 1995, the endoscopic findings of duodenal polyposis (including an ampullary polyp) did not progress and the histopathology did not worsen. In 1996, there was an increase in the number and size of the duodenal polyps, and the ampulla of Vater looked enlarged. Open surgery was discussed but not proceeded with because of the risk for short bowel syndrome. In January 1998, she was admitted with a diagnosis of acute pancreatitis. Duodenoscopy and radiological examination revealed that an advanced ampullary cancer had developed, and histopathology revealed a well-differentiated adenocarcinoma. Multiple hepatic metastases and ascites led to her death, in June, 1998. This in-vivo demonstration of the adenoma-carcinoma sequence highlights current limitations in the surveillance and treatment of duodenal lesions.

Preoperative chemotherapy for advanced esophageal cancer and relation with histological effect.

The results of surgical treatment for advanced esophageal cancer remain extremely poor. Irradiation and chemotherapy are not superior to surgery. Perioperative morbidity and the influence on long-term survival of a combination of surgery and preoperative chemotherapy were investigated in patients with advanced esophageal cancer. Forty-nine patients with advanced esophageal squamous cell carcinoma were subjected to preoperative chemotherapy of cisplatin-5-fluorouracil. Fifty-seven patients were chosen as a historical control group who had not undergone chemotherapy before surgery but had the same histological stages as the chemotherapy group. The response to chemotherapy was assessed by histological studies of surgical specimens. The survival rates noted no significant difference between preoperative chemotherapy plus surgery and a resection alone. However, subclassification according to the grading of chemotherapeutic effectiveness showed that, compared with control, preoperative chemotherapy was beneficial to high responders (P = 0.01), ineffective in low responders (P = 0.61), and detrimental to nonresponders (P = 0.03). Postoperative morbidity was significantly higher in the chemotherapy group than in the control group (P = 0.02). These findings suggest that preoperative chemotherapy is necessary only for high responders and we therefore need to reliably identify non-, low, and high responders before chemotherapy to improve the survival and quality of life of patients with advanced esophageal cancer.

The beneficial effects of recombinant human insulin-like growth factor-I (IGF-I) on wound healing in severely wounded senescent mice.

The effects of recombinant insulin-like growth factor I (rIGF-I) on wound healing were tested using senescent and young BDF-1 mice, aged 108 weeks and 10 weeks, respectively. After inflicting a full thickness dermal burn encompassing 15% of the body surface, a skin incision, 2 cm in length, was made in the back. A silicone tube containing a piece of polyvinyl sponge was then implanted into a subcutaneous pocket in the flank to collect body fluid. An osmotic pump was buried in the abdominal subcutaneous tissue for the continuous infusion of rIGF-I, the control being treated with the solvent of IGF-I, physiological saline, only. The administration of IGF-I produced favorable effects on wound healing in the senescent mice, shown by enhanced tensile strength and an elevated concentration in the hydroxyproline of the polyvinyl sponge content. The IGF-I-treated severely wounded senescent mice healed better than their counterparts and their skeletal muscles contained more glutamine. Furthermore, they showed more enhanced cutaneous hypersensitivity towards dinitrofluorobenzene than the controls, suggesting an enhanced grade of cellular immunity. There were no conspicuous differences between the two groups of young mice. These data may suggest the beneficial effects of rIGF-I on wound healing, especially in geriatric surgery.

Reconstruction of the thoracic esophagus, with extended jejunum used as a substitute, with the aid of microvascular anastomosis.

BACKGROUND: After radical ablation of tumors, colon or jejunum is pulled up for reconstruction of the thoracic esophagus when stomach is unusable. However, esophagocolonic or esophagojejunal anastomotic leak is relatively frequent because of the potential for vascular insufficiency of conduit extended upward. METHODS: To overcome this disadvantage, 14 consecutive patients with esophageal or gastric carcinomas whose stomachs were unusable were subjected to thoracoesophageal reconstruction through upward extension of the jejunum with microvascular anastomosis. Jejunal vessels were used as graft vessels, and internal thoracic vessels were used as recipient vessels. If needed, arcade vessels were severed to ease extension. RESULTS: All extended jejunums survived, and there were no operative deaths. Two of four initial series of patients, whose arcade vessels were not severed despite undue tension at the anastomotic site, had esophagojejunal anastomotic leaks that healed spontaneously. CONCLUSIONS: Some clinical functional problems still exist, but we believe this a safe and useful method for reconstruction of the esophagus where stomach cannot be used.

Isolation of tumor associated antigens from Lewis lung carcinoma by affinity chromatography on peanut agglutinin-agarose.

Receptors for peanut agglutinin (PNA) were isolated from Lewis lung carcinoma cells (3LL) by detergent solubilization and affinity chromatography on PNA-agarose. The isolated receptors showed heterogeneous yet distinct molecular species when they were analyzed by SDS gel electrophoresis. In vivo inoculation of the isolated receptors could induce potent cytotoxic effector cells against 3LL cells, which were detected by Winn's tumor neutralization assay. The PNA receptors were also effective in preventing the settlement of the intravenously injected 3LL tumors in the lung. These findings suggest that PNA receptors can be used for immunological therapy of certain cancers.

Steroid 16 alpha-hydroxylase from human fetal liver; inhibition by steroids.

The 16 alpha-hydroxylase system in fetal liver which used dehydroepiandrosterone (DHA) or pregnenolone as substrate, was apparently inhibited by various endogenous and synthetic steriods: DHA, pregnenolone, their sulfates, androstenediol, androstenetriol, estrone, estradiol-17 beta, ethynylestradiol and chlormadinone-acetate. The inhibition constants (Ki) towards DHA were as follows; pregnenolone 22 muM, DHA-sulfate 13 muM, pregnenolone-sulfate 21 muM, androstenediol 16 muM, androstenetriol 53 muM estrone 32 muM, estradiol-17 beta 74 muM, ethynylestradiol 22 muM and chlormadinone-acetate 27 muM. The Ki values towards pregnenolone were DHA 6.3 muM, DHA-sulfate 8.3 muM, pregnenolone-sulfate 3.9 muM, androstenediol 8.7 muM, androstenetriol 14.7 muM, estradiol-17 beta 15.4 muM and ethynylestradiol 16.0 muM, respectively. The reaction products, 16 alpha OH-DHA and 16 alpha OH-pregnenolone, showed little inhibitory effect upon the 16 alpha-hydroxylase.

Inhibition of fetal adrenal 21-hydroxylase by naturally occurring steroids.

Inhibitory effects of naturally occurring steroids on 21-hydroxylase activity were determined by measuring the initial conversion rate of 17-hydroxyprogesterone (17alpha-hydroxy-4-pregnene-3, 20-dione) to 11-deoxycortisol (17alpha, 21-dihydroxy-4-pregnene-3, 20-dione) in incubation experiments with the microsomal fraction (10,000--105,000 X g percipitate) of the human fetal adrenal gland. The apparent Michaelis constant (Km) for conversion of 17-hydroxyprogesterone was 13.3 X 10(-6)M. Human fetal adrenal 21-hydroxylase was inhibited by some of the steroids produced in the feto-placental unit. The following steroids acted as competitive inhibitors of the reaction; progesterone (Ki = 20.0 X 10(-6)M), 11-deoxycortisol (Ki = 87.5 X 10(-6)M) and estradiol-17beta (Ki = 87.5 X 10(-6)M). The most potent inhibitor among the estrogens was estradiol-17beta.

A radioimmunoassay of serum 16alpha-hydroxypregnenolone with specific antiserum.

A radioimmunoassay for plasma 16alpha-hydroxypregnenolone has been developed using anti-16alpha-hydroxypregnenolone antiserum produced in rabbits immunized with 16 alpha-hydroxypregnenolone-3-succinate-bovine serum albumin. Radioimmunoassay data were processed and analysed for its validity using a four parameter logistic curve fitting routine with use of the IBM call system. The assay system was satisfactory for a routine use. The 16alpha-hydroxypregnenolone concentrations in the umbilical cord blood at term ranged from 223 to 324 ng/ml. Gas liquid chromatographic analysis revealed a similar result, and also the presence of this steroid in the adrenal gland of the human fetus at midtrimester was confirmed. It is speculated that this steroid is secreted from fetal adrenals.

Biosynthetic pathways for corticoids and androgen formation in human fetal adrenal tissue in vitro.

Eleven incubations of minced human fetal adrenal tissue from two fetuses at midtrimester of pregnancy terminated for socio-economic reasons, were performed for different periods of time with labelled pregnenolone, progesterone, 17alpha-hydroxyprogesterone and deoxycorticosterone (DOC). The order of magnitudes of enzyme activity when progesterone was used as a substrate and incubated with midterm fetal adrenals was 17alpha-hydroxylase, 21-hydroxylase and 16alpha-hydroxylase. The activity of 3beta-hydroxysteroid dehydrogenase and delta5-4 isomerase was almost negligible as compared to other enzymic activities as mentioned above. Similar biosynthetic pathways for adrenal corticoids formation were observed in human fetal adrenals as reported in human adults and animals; once progesterone was converted into DOC, further 17alpha-hydroxylation did not take place.