Expression of 15-lipoxygenase-1 in human colorectal cancer.

Recently, we reported the induction of reticulocyte type 15-lipoxygenase (15-Lox-1) in a human colorectal carcinoma cell line that had been stimulated by butyrate to undergo apoptosis and cell differentiation (H. Kamitani et al., J. Biol. Chem., 273: 21569-21577, 1998). To determine if 15-Lox-1 is expressed in human colorectal cancer tissue, 21 matched pairs of colorectal tumor and adjacent normal tissue were examined by immunoblot analysis using specific antibodies for human 15-Lox-1, prostaglandin H synthase (also called cyclooxygenase, Cox)-1 and Cox-2. Eighteen of the 21 were found to have 15-Lox-1 in both tumor tissue and matched adjacent normal tissue, with the 15-Lox-1 expression being significantly higher in most of the tumor tissue. The expression of Cox-2 was also elevated in most tumors, whereas Cox-1 was frequently expressed at lower levels in the tumor tissue than in the paired normal tissue. Reverse-phase high-performance liquid chromatography analysis of arachidonate metabolites, formed on incubation of arachidonic acid with a crude enzyme preparation from the colon samples, revealed the formation of 15-hydroxy-5Z,8Z,11Z,13E-eicosatetraenoic acid with a much lower level of 12-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (15-hydroxy-5Z,8Z,11Z,13E-eicosatetraenoic acid:12-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid, 6.5:1) which also indicate the presence of 15-Lox-1. Furthermore, reverse transcription-PCR with primers specific for human 15-Lox-1 or 15-Lox-2 cDNA indicated that 15-Lox-1 mRNA was present in the colorectal tumors. The sequence of the PCR product was identical to the human 15-Lox-1. Immunohistochemical studies showed 15-Lox-1 localization in the glandular epithelium of human colorectal tumor tissue. These results suggest that 15-Lox-1 is highly expressed in human colorectal cancer epithelial cells and that its expression may have a role in colorectal carcinogenesis.

Comparison of the computed tomography values of the bone fragment gap after sagittal split ramus osteotomy in mandibular prognathism with and without asymmetry.

The purpose of this study was to compare computed tomography (CT) Hounsfield unit values of bone fragment gaps after sagittal split ramus osteotomy (SSRO) in patients with and without asymmetry, and to evaluate differences between the deviated and non-deviated sides in asymmetric patients. Thirty-two patients who underwent a bilateral SSRO were included in this retrospective study. Patients were divided into symmetric and asymmetric groups by cephalometric analysis. CT values of the bone fragment gap were measured at 1 week and at 1 year after surgery. There were significant differences between CT values obtained at 1 week and at 1 year after surgery for all measurement points. However, there were no significant differences in CT values between symmetric and asymmetric patients at either 1 week or 1 year after surgery. Among asymmetric patients, there were no significant differences between the deviated and non-deviated sides at 1 week or 1 year after surgery. This study showed ossification of the bone fragments and adaptation to change the mandible form in patients with and without asymmetry following SSRO.

Changes in the computed tomography (pixel) value of mandibular ramus bone and fixation screws after sagittal split ramus osteotomy.

The purpose of this retrospective study was to evaluate the changes in computed tomography (CT) values of ramus bone and screws after sagittal split ramus osteotomy (SSRO) setback surgery. The subjects were 64 patients (128 sides) who underwent bilateral SSRO setback surgery. They were divided into six groups according to the fixation plate type used and the use or not of self-setting α-tricalcium phosphate (Biopex): group 1: titanium plate and screws; group 2: titanium plate and screws with Biopex; group 3: poly-l-lactic acid (PLLA) plate and screws; group 4: PLLA plate and screws with Biopex; group 5: uncalcined and unsintered hydroxyapatite particles and poly-l-lactic acid (uHA/PLLA) plate and screws; group 6: PLLA/uHA plate and screws with Biopex. CT values (pixel values) of the lateral cortex, medial cortex, osteotomy site, and screws were measured preoperatively, immediately after surgery, and 1 year postoperatively using horizontal CT images at the mandibular foramen taken parallel to the Frankfort horizontal plane. There were significant differences in the time-course change of pixel values for the lateral cortex (P<0.0001) and the osteotomy site (P<0.0001) among the six groups. This study suggests that the fixation plate type and use of bone alternative material may affect bone quality during the process of bone healing after SSRO.

Changes in occlusal function after orthognathic surgery in mandibular prognathism with and without asymmetry.

This study aimed to evaluate the postoperative changes in masticatory function in patients with jaw deformities with or without asymmetry treated by orthognathic surgery. Thirty female patients who underwent a Le Fort I osteotomy with sagittal split ramus osteotomy (SSRO) were enrolled. The patients were divided into symmetry and asymmetry groups. The bite force, occlusal contact area, and bite force balance were measured before and at 1, 3, and 6 months and 1 year after surgery; these measurements were compared statistically within and between the two groups. In the symmetry group, there was a significant difference in the preoperative bite force and the 1 month postoperative bite force (P=0.0033). In the asymmetry group, the bite force before surgery was significantly different from that at 1 month (P=0.0375) and at 1 year (P=0.0353) after surgery. Significant differences in the bite force were also observed between the following time points: 1 month and 1 year (P=0.0003), 3 months and 1 year (P=0.0034), and 1 month and 6 months (P=0.0486). The occlusal contact area, bite force, and occlusal balance tended to change after Le Fort I osteotomy with SSRO, with a significantly improved bite force in patients with asymmetry before surgery.

Cyclic adenosine 3',5'-monophosphate modulation of mullerian duct regression.

(Bu)2cAMP inhibits the action of testicular Mullerian inhibiting substance (MIS) in vitro, but it is unknown whether the intracellular nucleotide diminishes production of MIS by the testis or interferes with its action at the Mullerian duct. When added to the 14 1/2-day old rat embryo Mullerian duct in organ culture, (Bu)2cAMP (0.1 or 1.0 mM) inhibited regression caused by biologically active exogenous MIS fractions, as well as that produced by the fetal testis (1.0 mM). Dibutyryl cyclic guanosine 3',5'-monophosphate was ineffective against exogenous MIS fractions or the fetal testis. The phosphodiesterase inhibitor, methyl-isobutyl-xanthine, had the same inhibitory effect on the MIS-fraction (0.1 or 1.0 mM), as well as against MIS secreted from the fetal testis (1.0 mM). Theophylline at 1.0 mM inhibited the action of the MIS fraction. The presence of (Bu)2cAMP in the medium was required for at least the first 24 h of the 72-h incubation to significantly inhibit MIS action. These results indicate that intracellular cAMP inhibits the action of MIS at the Mullerian duct itself by a potentially reversible change in the cells. We speculate that cAMP may act by altering the state of differentiation in the cells, perhaps by mediating phosphorylation of intracellular (and extracellular) proteins.

Arachidonate 12-lipoxygenase in porcine anterior pituitary cells: its localization and possible function in gonadotrophs.

Arachidonate 12-lipoxygenase, which oxygenates positions 12 and 13 of arachidonic and linoleic acids, is present in porcine anterior pituitary cells. Colocalization of the 12-lipoxygenase with various pituitary hormones was examined by immunohistochemical double-staining using antibodies against 12-lipoxygenase and various anterior pituitary hormones. Under light microscopy, approximately 7% of the cells producing luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were positive for 12-lipoxygenase, whereas the enzyme was detected in less than 2% of the cells producing thyrotrophin, prolactin, growth hormone (GH), and adrenocorticotrophin. In an attempt to examine the participation of 12-lipoxygenase metabolites in pituitary hormone release, we incubated the primary culture of porcine anterior pituitary cells with 12-hydroperoxy-arachidonic acid or 13-hydroperoxy-linoleic acid. Significant stimulation of LH and FSH release by these hydroperoxides was observed at 10 microM in a time-dependent manner. At doses around 10 microM these compounds produced responses of similar magnitude to 1 nM gonadotrophin-releasing hormone (GnRH), but higher concentrations (30 microM) of the compounds were required for GH release. In contrast, 12-hydroxy-arachidonic and 13-hydroxy-linoleic acids were almost ineffective. Furthermore, the gonadotrophin release by 1 nM GnRH was inhibited by nordihydroguaiaretic acid (a lipoxygenase inhibitor) with an IC50 of about 5 microM. Thus, the hydroperoxy (but not hydroxy) products of 12-lipoxygenase may be involved in the release of pituitary hormones especially LH and FSH.

Serum osteoprotegerin/osteoclastogenesis-inhibitory factor during pregnancy and lactation and the relationship with calcium-regulating hormones and bone turnover markers.

Pregnancy and lactation induce dynamic changes in maternal bone and calcium metabolism. A novel cytokine termed osteoprotegerin (OPG)/osteoclastogenesis-inhibitory factor (OCIF) was recently isolated; this cytokine inhibits osteoclast maturation. To define the effects of pregnancy and lactation on circulating OPG/OCIF in mothers, we studied the changes in the levels of OPG/ OCIF as well as those of calcium-regulating hormones and biochemical markers of bone turnover in the maternal circulation during pregnancy (at 8-11 weeks, at 22-30 weeks, at 35-36 weeks and immediately before delivery) and lactation (at 4 days and at 1 month postpartum). Serum intact parathyroid hormone levels did not change and were almost within the normal range in this period. In contrast, serum 1,25-dihydroxyvitamin D levels increased with gestational age and were above the normal range during pregnancy. After delivery, they fell rapidly and significantly (P<0.01) to the normal range. The levels of serum bone-specific alkaline phosphatase, one of the markers of bone formation, increased with gestational age. After delivery, these levels were further increased at 1 month postpartum. The levels at 1 month postpartum were significantly higher than those at 8-11 and 22-30 weeks of pregnancy (P<0.01 and P<0.05 respectively). The levels of serum C-terminal telopeptides of type I collagen, one of the markers of bone resorption, did not change during pregnancy. After delivery, they rapidly and significantly (P<0.01) rose at 4 days postpartum, and had then fallen by 1 month postpartum. Circulating OPG/OCIF levels gradually increased with gestational age and significantly (P<0.01) increased immediately before delivery to 1.40+/-0.53 ng/ml (means+/-S.D.) compared with those in the non-pregnant, non-lactating controls (0.58+/-0.11 ng/ml). After delivery, they fell rapidly to 0.87+/-0.27 ng/ml at 4 days postpartum and had fallen further by 1 month postpartum. These results suggest that the fall in OPG/OCIF levels may be partially connected with the marked acceleration of bone resorption after delivery.

Various scoring systems evaluating histologic features of chronic hepatitis C treated with interferon.

Various scoring systems for chronic hepatitis have been proposed; however, there is no standard scoring system for studies of interferon (IFN) therapy in patients with chronic hepatitis C. The aims of this study were to determine the most useful system reflecting histologic changes in biopsy specimens from complete responders and predicting the efficacy of IFN therapy. Patients with chronic hepatitis C were administered IFN-alpha for 6 months. Forty-six patients were included in this study and categorized as complete responders (n = 15), partial responders (n = 24), and nonresponders (n = 7) according to viral and biochemical responses to the therapy. Biopsy specimens obtained from each patient before and after treatment were evaluated under 3 different systems: Histological Activity Index (HAI), modified HAI, and Scheuer classification. Complete responders showed considerable improvement in both grade and stage on the modified HAI and Scheuer classifications. On the HAI, a considerable improvement was observed in grade but not in stage. No significant change was observed in partial responders or nonresponders on any system. Prediction of complete response was not possible under any system, but the pretreatment score reflecting piecemeal necrosis on any 1 of the 3 classifications and the fibrosis score on Scheuer classification were predictors of nonresponse. The modified HAI system and Scheuer classification were amply useful in evaluating histologic changes in complete responders. Scores higher than 4 of the categories reflecting piecemeal necrosis on any system and fibrosis scores of 3 or 4 on Scheuer classification predicted nonresponse to IFN therapy.

Acetylcholinesterase and manometry in the diagnosis of the constipated child.

We studied 309 constipated infants and children who underwent rectal manometry (n = 261) and/or punch rectal biopsy, in which acetylcholinesterase histochemistry (n = 124) was compared with routine histologic examination (n = 93) for diagnostic accuracy. A 99% diagnostic accuracy was achieved with acetylcholinesterase histochemistry compared with 61% accuracy with routine hematoxylin-eosin staining on punch rectal biopsy. We recommend screening cooperative, quiet patients with rectal manometry. Most patients with abnormal manometric studies or those on whom manometry cannot be performed should have superficial punch biopsy (except those ill infants who require urgent operative intervention). This plan of management provides the least invasive but the most accurate evaluation of the constipated child. Deep rectal biopsy can be avoided except in the very rare child with hypoganglionosis or "skip-area" aganglionosis, which can be detected by manometry.

Hyperventilation and cold-pressor stress echocardiography for noninvasive diagnosis of coronary artery spasm.

We report the usefulness of 2-dimensional echocardiography during the cold-pressor test immediately after hyperventilation for noninvasive diagnosis of coronary vasospasm in 43 patients with suspected vasospastic angina. The stress test consisted of hyperventilation for 6 minutes, followed by cold water pressor stress for 2 minutes under continuous electrocardiographic and echocardiographic monitoring. Coronary angiography with an intracoronary injection of acetylcholine was performed within 2 weeks after the stress test. Coronary spasm was observed in 33 patients by angiography. Multivessel spasm was diagnosed in 26 patients by stress echocardiography and in 23 patients by angiography. The stress-induced wall motion abnormalities occurred earlier than the ST-segment changes and chest pain. The wall motion abnormalities shown on the echocardiogram correlated well with the vascular territories of the coronary artery that had the spasm. The sensitivity, specificity, and diagnostic accuracy of hyperventilation and cold-pressor stress echocardiography for detecting vasospastic angina against coronary angiography with an intracoronary injection of acetylcholine were 91%, 90%, and 91%, respectively. However, the sensitivity, specificity, and diagnostic accuracy of hyperventilation and cold-pressor stress electrocardiography for detecting vasospastic angina were 48%, 100%, and 60%, respectively. No major side effects were observed during or after the stress test. Echocardiographic monitoring during the stress test detected spasm unaccompanied by either ST- segment changes or chest pain and revealed the location of multivessel coronary spasm. Hyperventilation and cold-pressor stress echocardiography is thus a noninvasive and useful tool for the diagnosis of vasospastic angina.

Treatment of high-risk solid tumors of childhood with myeloablative chemotherapy and autologous stem cell transplantation.

Sixteen consecutive stem cell transplantations (SCT) were performed after myeloablative chemotherapy in patients with high-risk solid tumors of childhood. Seven patients received autologous bone marrow transplantation (ABMT), seven received peripheral blood stem cell transplantation (PBSCT) and two received ABMT + PBSCT. The progression-free survival was similar in three types of transplants (57% ABMT, 43% PBSCT vs. 50% ABMT + PBSCT). The rate of relapse in site of distant organs was also similar (57% ABMT, 57% PBSCT vs. 50% ABMT + PBSCT). There was no statistically significant difference in the hematopoietic recovery time between each group. PBSCT group had a significantly fewer days of food intolerance and a lower morbidity than ABMT group. The disease-free survival was 71% for neuroblastoma, 50% for small round cell tumors and 25% for rhabdomyosarcoma. Post-SCT therapy for possible reinfused tumor cells should be mandatory to decrease the frequency of relapse.

Estrogen inhibition of Mullerian inhibiting substance in the chick embryo.

Diethylstilbestrol (DES) feminizes the embryonic chick testes and causes retention of the Mullerian duct, an observation made by Etienne Wolff in 1939. The present study was designed to determine if the feminized testis could produce Mullerian Inhibiting Substance (MIS). DES in various doses was injected into the air sac or yolk of 5-day chick embryos, with removal of the gonads at 13-16 days of incubation. That the DES-treated testis was feminized was documented by the development of a left "ovarian" cortex, yet this gonad continued to produce MIS as estimated by a graded organ-culture assay. The male chick Mullerian ducts, exposed to both endogenous MIS and exogenous estrogen (DES), however, were preserved, indicating that the Mullerian duct retention seen in DES-treated embryos was not caused by suppression of MIS secretion. These data support the hypothesis that MIS and estrogens interact at the target-organ (i.e., Mullerian duct), resulting in Mullerian duct retention. The implications of this hypothesis for mammalian sexual development especially in regard to the effect of DES-treatment on male fetuses, and the possible role of MIS and estrogens in testicular descent are considered.

The ontogeny of Mullerian inhibiting substance in the gonads of the chicken.

Mullerian inhibiting substance (MIS) was studied in the testis, ovary, and ovotestis of the domestic fowl, from early embryonic development to adulthood by a graded organ-culture method using the urogenital ridge of a 14.5 day fetal rat. The chick testis had high levels of MIS from 8 days of embryonic development (4-5+) until sexual maturity, when activity declined (2+) but persisted throughout adulthood. The right gonad (ovotestis) of the hen showed moderate levels of MIS activity from 8 to 12 days of embryonic life (1-3+) before its normal involution by the time of hatching (21 days). The left gonad (ovary) of the hen also produced MIS at levels similar to that seen in the testis. Activity was high during embryonic development (4+) and after hatching, and persisted in the adult hen at diminished levels (2+). MIS production by the female gonads explains regression of the right Mullerian duct, but the mechanisms that allow preservation of the left duct remain unexplained. Evidence suggests that ovarian estrogens may interact with MIS at the receptor level to protect the left Mullerian duct. MIS persists in the sexually mature gonads of both the hen and cockeral, long after the Mullerian duct has regressed, suggesting a wider role for this substance in reproductive physiology.

Long-term results of surgical treatment in infants with total colonic aganglionosis.

The authors describe the long-term results of the surgical treatment of total colonic aganglionosis (TCA) in nine boys who have been treated since 1975. The principal operative procedure was endorectal pull-through of the ganglionic ileum, with the aganglionic colon as an onlay patch. The procedure was employed in five infants, using the right or left colon. Ileorectostomy with an onlay patch was used in two patients; ileoanostomy without the patch was used in two. The distal end of the pulled-through ileum was, on average, 39 cm from the ileocecal junction. The average follow-up period was 11.0 years. Diarrhea and distension were temporary after the pull-through, and all patients ultimately tolerated normal feeding. Considering the variation in operative techniques, we were unable to demonstrate any advantage of one procedure over another. Z scores for height and weight at the last follow-up examination correlated with the weight gain before the definitive surgery and inversely correlated with the length of resected distal ileum at the time of operation.

Recto-vagino-vestibuloplasty using a vagino-colonic flap with double colonic implantation for rectocloacal fistula.

This technique was devised to obtain a good cosmetic appearance of the perineum and a functional neovagina, without any need for a dilator, by using a vaginocolonic flap marsupialized to the perineum and by creating a vestibule with noncornifying squamous epithelium. The technique was used to treat a 2 year old girl who had a single small orifice in the upper part of a featureless perineum, with a high-confluence rectocloacal fistula between a short urethra and double vagina, which was separated by a septum. A long inverted U-shaped flap at the posterior wall of the vagina was reversed to become the anterior wall of the distal vagina. The urogenital sinus (UGS) was preserved to serve as the urethra. The colon distal to the colostomy was divided into two loops; a segment of the distal loop was opened and trimmed to form a flap, and served as the posterior wall of the distal vagina. The proximal segment was pulled down to become the rectum. To construct the vestibule, a vertical midline incision was made from the fused labia minora to the perineum, cutting back the UGS. The anterior wall of the vagina, which was pulled through just behind the UGS, was divided vertically and sutured around the opened UGS and the suitably prepared labia minora. The posterior wall, which consisted of the colonic flap, was sutured to the incised perineal skin, creating a posterior commissure. At present, 2 1/2 years after the repair, the patient is dry between completely continent urinations and has little vaginal discharge.(ABSTRACT TRUNCATED AT 250 WORDS)

Hirschsprung's disease: catecholamine content, alpha-adrenoceptors, and the effect of electrical stimulation in aganglionic colon.

In order to assess abnormalities in the adrenergic mechanism in the intestine of Hirschsprung's disease, catecholamine concentrations, alpha-adrenoceptors, and the effect of electrical field stimulation were examined in aganglionic segments of colon or rectum. The aganglionic segment had a higher concentration of norepinephrine, assayed with high performance liquid chromatography with an electrochemical detector, whereas concentrations of epinephrine or dopamine were similar in normal and pathological segments. In four patients with extensive aganglionosis, the norepinephrine concentration in aganglionic colon segments decreased progressively in descending, transverse, and ascending colon. The tissue content of alpha-adrenoceptors and their affinity assayed from the specific binding of [3H]dihydro-alpha-ergocryptine appeared similar in normal and aganglionic segments of the rectosigmoidal colon. Electrical field stimulation of normal rectosigmoidal colon segments caused relaxation at low frequencies and contraction at a very high frequency. Relaxation was not abolished by blocking concentrations of propranolol or phentolamine. In aganglionic segments, the predominant response to electrical field stimulation was contraction, which was inhibited by either atropine or tetrodotoxin. These results indicate that an alpha-adrenergic system and cholinergic innervation apparently exist in aganglionic colon segments and that dysfunction of the colon appears to result from lack of a nonadrenergic inhibitory system.

More than 10 years' follow-up to total colonic aganglionosis--severe iron deficiency anemia and growth retardation.

Seven cases of total colonic aganglionosis were reviewed with a follow-up period of 10 to 26 years, focusing on the relationship between the length of aganglionic ileum and postoperative metabolic disorders. Pulled-through ileum ranged from 0 to 65 cm from the ileocecal valve, and suprapelvic side-to-side anastomosis was performed between the pulled-through ileum and 17 to 40 cm of aganglionic colon (left side and transverse colon, four; right side colon, one; no colonic patch, two). Hemoglobin level in three out of four patients with ileal involvement of more than 25 cm was below 11 g/dL (10.9, 7.7, 6.6 g/dL, respectively). Serum iron level was less than 30 micrograms/dL (27, 21, 20, 18 micrograms/dL, respectively) in four out of five patients with ileal involvement of more than 10 cm. Serum vitamin B12 level was below 100 (100, 46 pg/dL, respectively) in two patients whose pulled-through ileum was 45 cm and 65 cm, respectively from the ileocecal valve. One patient needs periodical parenteral iron therapy and one was treated as megaloblastic anemia. In the patients with ileal involvement of more than 25 cm, both weight and height for age are very low at less than the fifth percentile, except for one patient whose side patch was at the right colon. One patient still needs parenteral nutritional support. Severe iron deficiency anemia, low level of B12, and growth retardation are apparent in the patients with total colonic aganglionosis with ileal involvement. Colonic side-to-side anastomosis does not substitute for the loss of terminal ileum.

A quantitative study of acetylcholine in Hirschsprung's disease.

This is the first report on acetylcholine (Ach) quanititaion of the aganglionic colon by a chemical assay. Ach content in the colon of Hirschsprung's disease was measured by pyrolysis gas chromatography, which was found to be a simple, accurate, and reliable method. Microwave irradiation on the surgical resected specimens was performed before extraction procedure to abolish acetylcholinesterase (Ach-E) and cholineacetyltransferase (CAT) activity in the tissue. Ach content in the ganglionic colon was 8.51 +/- 3.15 nmole/g (n 5 in contrast to 23.79 +/- 14.17 nmole/g (n = 19) in the aganglionic segment of Hirschsprung's disease. The meaning of elevated Ach level in the aganglionic segment was discussed from the pathophysiologic standpoint.

Outcomes of ileocolic conduit for biliary drainage in infants with biliary atresia; comparison with Roux-en-Y type reconstruction.

This study was undertaken to define the role of an ileocolic conduit that was devised as anti-reflux procedure in comparative study with Roux-en-Y type reconstruction in infants with biliary atresia treated at a single institution. The ileocolic conduit (IC) consisted of 30 cm of distal ileum anastomosed to the portahepatis and a 10-cm segment of ascending colon vented through the abdominal wall, which was later anastomosed to the second portion of the duodenum. In the Roux-en-Y type reconstruction (RY), 40 to 60 cm of jejunum was used for the hepatic limb. Twenty-three infants in group IC and 16 infants in group RY were entered in this study. Mean ages at definitive surgery were 65.3 +/- 23.1 days for group IC and 65.0 +/- 19.5 days for group RY. The two groups were compared for the postoperative outcomes in terms of bile excretion, incidence of cholangitis, esophageal varices, survival rate, and the effects on physical development. The follow-up ranged from 4 to 15 years. Bile excretion was obtained in all infants in both groups. Twenty infants (87.0%) in group IC and 10 infants (62.5%) in group RY became anicteric. Cholangitis occurred in 60.9% of group IC, compared with 83.3% for group RY, in which 6 infants required revision to complete diversion of Roux-en-Y limb (Suruga II). There was the same occurrence rate of esophageal varices for both groups. However, the varices tended to develop later in group IC (53.0 +/- 18.4 months) than in group RY (12.7 +/- 6.0 months) (P < .02).(ABSTRACT TRUNCATED AT 250 WORDS)

Calculation of biliary atresia prognostic index using a multivariate linear model.

The purpose of this study was to determine the relative value of liver function markers in predicting the magnitude of morbidity and to develop a quantitative estimate of the prognostic risk using a multivariate regression model in patients who have been operated on for biliary atresia. The study sample consisted of 37 patients who had undergone a Kasai portoenterostomy; the jaundice disappeared in 32 and persisted in five. A computer-based stepwise regression procedure produced the linear predictive models by the equation: biliary atresia prognostic index (BAPI) = 9.2 Cu:Zn + 1.0 ZTT + 3.2 TB - 0.05 ChE + 9.9 for infants under 1 year of age, and BAPI = 10.3 Cu:Zn + 0.8 ZTT + 0.03 GGTP - 0.12 ChE + 25.6 for children over 1 year of age. In validation of these models, the indexes fluctuated from -17 to 122, and the degree of morbidity increased linearly with the increase in BAPI. Postoperatively the patients were classified into four categories according to the dynamics of their postoperative course: A (BAPI < 25), successful cases that should not require liver transplantation (40.5%); B (25 < or = BAPI < or = 50), improved cases that have extended survival with their native liver (29.7%); C (50 < BAPI < or = 75), cases that improved in terms of disappearance of jaundice but ultimately will require liver transplantation (8.1%); and D (BAPI > 75), cases that require early referral for transplantation (21.6%). (The percentages indicate the distribution rate of patients at the time of final follow-up evaluation.) These models allow quantification of the risk of morbidity from progressive liver cirrhosis in the individual patient, permitting the clinician to consider whether such patients should be considered for liver transplantation.