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Biomedical subjects

F Y Lee

Publications and source records attributed to F Y Lee.

At least 19 recordsLinked to original sources
PubMed1995

Correlation of cytogenetic results with immunophenotype, genotype, clinical features, and ras mutation in acute myeloid leukemia. A study of 235 Chinese patients in Taiwan.

Of 235 consecutive patients with de novo acute myeloid leukemia (AML), clonal chromosomal abnormalities were detected in 151 (64%) of them. Twenty-four of the 71 patients with M2 AML had t(8;21), 35 of the 36 M3 patients had t(15;17), and 11 of the 45 M4 leukemia disclosed inv(16). Six of the eight patients with 11q23 abnormality had M4 or M5 subtype of leukemia. The incidence of t(15;17) and t(8;21) was higher in our patients than in patients from most Western countries. Immunophenotyping was performed on 197 patients. Patients with t(15;17) were associated with negativity to HLA-DR, CD11b, and CD34. Patients with t(8;21) expressed CD13 and CD33 less frequently than other patients, but all showed CD15 positivity. Coexpression of lymphoid-associated antigens on the leukemic blasts was detected in 52 patients (26%), including all 7 patients with t(9;22), 3 of the 8 patients with t/del(11)(q23), 2 of the 25 patients with t(15;17), and 2 of the 22 patients with t(8;21). Seven (35%) of the 20 patients coexpressing lymphoid markers showed immunoglobulin heavy chain or T-cell receptor beta-chain gene rearrangements, while only 2 (4%) of the 53 patients without lymphoid antigen expression did so. Patients with inv(16), t(8;21), and t(15;17) had a better prognosis than other patients. Of all surface antigens tested, only CD15, CD11b, and HLA-DR were of prognostic value: CD15 with a higher complete remission (CR) rate and CD11b or HLA-DR with a shorter CR duration. N-ras mutations were detected in 7 (18%) of the 40 patients in the study, including two of the three patients with inv(16). This study demonstrated differences in clinical features, immunophenotypes, and genotypes among different cytogenetic subgroups.

Adolescent↗
PubMed1995

Mechanism of anti-proliferation caused by YC-1, an indazole derivative, in cultured rat A10 vascular smooth-muscle cells.

An indazole derivative, YC-1, was identified in this study to be capable of reversibly and effectively inhibiting proliferation of rat A10 vascular smooth-muscle cells (VSMCs) in vitro. YC-1 (1-100 microM) dose-dependently inhibited [3H]thymidine incorporation into DNA in rat A10 VSMCs that were synchronized by serum depletion and then restimulated by addition of 10% foetal calf serum (FCS), whereas FCS-induced [3H]thymidine incorporation into rat synchronized endothelial cells was unaffected by this agent. The dose of YC-1 required to cause inhibition of FCS-induced proliferation was similar to that necessary for the formation of cellular cyclic GMP (cGMP). Guanylate cyclase activity in soluble fractions of VSMCs was activated by YC-1 (1-100 microM), whereas cGMP-specific phosphodiesterase activity was unaffected by this compound. The anti-proliferative effect of YC-1 was mimicked by 8-bromo-cGMP, a membrane-permeable cGMP analogue, and was antagonized by KT 5823 (0.2 microM), a selective inhibitor of protein kinase G. The anti-proliferative effect of YC-1 was also antagonized by Methylene Blue (50 microM), a guanylate cyclase inhibitor, and was potentiated by 3-isobutyl-1-methylxanthine (500 microM), a phosphodiesterase inhibitor. These results verified that YC-1 is a direct soluble guanylate cyclase activator in A10 VSMCs, and the anti-proliferative effect of YC-1 is mediated by cGMP. YC-1 still inhibited FCS-induced DNA synthesis even when added 10-18 h after restimulation of the serum-deprived A10 VSMCs with 10% FCS. Flow cytometry in synchronized populations revealed an acute blockage of FCS-inducible cell-cycle progression at a point in the G1/S-phase in YC-1 (100 microM)-treated cells. The inhibition of proliferation by YC-1 was demonstrated to be independent of cell damage, as documented by several criteria of cell viability. In conclusion, YC-1 reversibly and effectively inhibited the proliferation of VSMCs, suggesting that it has potential as a therapeutic agent in the prevention of vascular diseases.

Animals↗
PubMed1995

Bacterial translocation to mesenteric lymph nodes is increased in cirrhotic rats with ascites.

BACKGROUND/AIMS: Cirrhotic patients are predisposed to develop spontaneous bacteremias and/or peritonitis, mainly caused by enteric bacteria. The aim of this study was to investigate if bacterial translocation, which is the passage of bacteria from the intestinal lumen to regional lymph nodes and/or the systemic circulation, is increased in a rat model of cirrhosis. METHODS: Rats were studied after 12-16 weeks of CCl4 inhalation, when samples of mesenteric lymph nodes, blood, liver, and spleen for standard bacteriologic cultures and a fragment of colon and liver for histology were obtained. Immunostaining of the cecum was performed using a polyclonal anti-Escherichia coli antibody. RESULTS: A significantly greater proportion of rats with cirrhosis and ascites (5 of 9; 56%) had positive mesenteric lymph node cultures compared with cirrhotics without ascites (0 of 9) and normal controls (0 of 12) (P < 0.01). In one cirrhotic rat, E. coli was isolated from both mesenteric lymph nodes and ascites. Rats with cirrhosis and ascites had significantly greater cecal submucosal edema and inflammation than rats with no ascites and controls. Immunoreactivity with E. coli was present in the cecal wall in 3 of 5 animals with E. coli translocation to mesenteric lymph nodes. CONCLUSIONS: In cirrhotic rats, bacterial translocation is increased after the development of ascites and may be a major factor in the development of spontaneous infections in cirrhosis.

Animals↗
PubMed1995

Acute leukemic transformation of myelodysplastic syndrome--immunophenotypic, genotypic, and cytogenetic studies.

The clinical and biological characteristics of myelodysplastic syndrome (MDS) in acute leukemic transformation were studied in 23 patients. All had myeloid transformation according to FAB criteria, but coexpression of lymphoid-associated antigens was detected in five of the 20 patients who underwent an immunophenotypic study. Rearrangement of the immunoglobulin heavy chain gene was also observed in one of the five patients who coexpressed lymphoid markers and that of the T-cell receptor beta chain gene in another one. None had pure lymphoid transformation. Clonal chromosomal abnormalities were noted in 12 (63%) of the 19 patients who underwent cytogenetic study, most commonly - 7 (six patients or 32%). In the 18 patients who underwent serial analyses both at MDS diagnosis and at acute transformation, seven (39%) underwent karyotypic evolution. The most common new or additional aberrations were +8 and +21. N-ras gene mutation was detected in two of the nine patients at acute leukemic transformation. The median interval from diagnosis of MDS to onset of acute transformation was 10 months (1-36 months). Patients with a normal karyotype at diagnosis had a significantly longer chronic phase duration than those with chromosomal abnormalities (median of 20 months vs. 5 months). However, all had a short survival time after diagnosis of acute leukemia, whether chromosomal anomalies were present or not.

Adolescent↗
PubMed1995

Endotoxemia in patients with chronic liver diseases: relationship to severity of liver diseases, presence of esophageal varices, and hyperdynamic circulation.

Plasma endotoxin levels were investigated using a quantitative Limulus assay in patients with chronic liver diseases and correlated with the severity of liver diseases, the presence of esophageal varices, and hemodynamic parameters. The plasma endotoxin levels were significantly higher in chronic hepatitis patients with acute exacerbation (10.1 +/- 1.3 pg/ml, n = 13, p < 0.05) and patients with cirrhosis (7.0 +/- 0.7 pg/ml, n = 126, p < 0.05) than in healthy subjects (2.9 +/- 0.2 pg/ml, n = 45). Chronic hepatitis patients (n = 30) had plasma endotoxin levels which were similar to those in healthy subjects (4.6 +/- 0.5 vs. 2.9 +/- 0.2 pg/ml, p > 0.05) but lower than those in chronic hepatitis patients with acute exacerbation (4.6 +/- 0.5 vs. 10.1 +/- 1.3 pg/ml, p < 0.05). Endotoxemia (plasma endotoxin level > 5.7 pg/ml) was found in 27%, 85% and 41% of patients with chronic hepatitis, chronic hepatitis with acute exacerbation, and cirrhosis, respectively. In patients with cirrhosis, the plasma endotoxin levels progressively increased in relation to the severity of liver dysfunction (Pugh's class A/B/C = 4.9 +/- 0.5/7.9 +/- 1.4/10.2 +/- 2.0 pg/ml, p < 0.05). In contrast, plasma endotoxin levels were comparable between patients with cirrhosis with and without esophageal varices (p > 0.05). Chronic hepatitis patients with acute exacerbation (no collaterization) had much higher plasma endotoxin levels than those in patients with cirrhosis and large varices (p < 0.05), whereas compensated patients with cirrhosis and large esophageal varices had plasma endotoxin levels similar to those seen in chronic hepatitis patients (no collaterization) (p > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Circulation↗
PubMed1995

Changes in portal hypertensive gastropathy after endoscopic variceal sclerotherapy or ligation: an endoscopic observation.

To determine the effect of endoscopic variceal sclerotherapy or ligation on portal hypertensive gastropathy, 90 cirrhotic patients with esophageal variceal bleeding were randomized to receive sclerotherapy (n = 44) or ligation (n = 46). Follow-up endoscopic observations of the gastric mucosa were recorded at 3-month intervals after variceal eradication. Clinical characteristics in both groups were similar. Probability for a change in the severity of portal hypertensive gastropathy was not related to method of eradication. Most cases of portal hypertensive gastropathy that changed in severity returned to baseline status with time, but the return was faster after ligation than after sclerotherapy. According to the results of multivariate analyses, sclerosant volume was the only factor associated with a significant difference between the group with static gastropathy (n = 15) and that with dynamic change in gastropathy (n = 23) after sclerotherapy. No relevant factors were found in the patients receiving ligation. We conclude that changes in the severity of portal hypertensive gastropathy after endoscopic variceal sclerotherapy or ligation are reversible. Most cases of gastropathy return to baseline status sooner or later.

Esophageal and Gastric Varices↗
PubMed1995

Pituitary down-regulation prior to in-vitro fertilization and embryo transfer: a comparison between a single dose of Zoladex depot and multiple daily doses of Suprefact.

In order to further evaluate the endocrinological, embryological and clinical efficacy of a single injection of the gonadotrophin-releasing hormone (GnRH) analogue Zoladex (goserelin), 142 women underwent pituitary down-regulation prior to in-vitro fertilization and embryo transfer: 71 with a single injection of Zoladex depot (group I) and 71 matched controls with multiple daily injections of Suprefact (buserelin; group II). Ovarian stimulation was performed with human menopausal gonadotrophin (HMG) and ovulation induction with human chorionic gonadotrophin (HCG). HMG and hydroxyprogesterone caproate depot were given for luteal phase support. The mean (+/- SD) age (34.01 +/- 4.42 versus 34.81 +/- 4.00 years), mean total dosage of HMG (61.25 +/- 26.87 versus 56.17 +/- 25.18 ampoules), mean daily dosage of HMG (4.74 versus 4.94 ampoules), duration of HMG stimulation (12.91 +/- 3.68 versus 11.31 +/- 3.46 days) and oestradiol concentration on the day of HCG (10,082 +/- 8007 versus 9440 +/- 7840 pmol/l) were similar in both groups but the mean total number of injections (GnRH and HMG) (13.55 +/- 3.35 versus 55.37 +/- 31.92) was significantly lower in group I. Furthermore, the proportion of women down-regulated by 2 weeks and pregnancy rate per embryo transfer were significantly higher in the Zoladex group, while miscarriage rates were similar. We conclude that a single dose of Zoladex is quicker, more convenient and should be investigated as an equally effective alternative to multiple doses of Suprefact for pituitary down-regulation prior to assisted conception. Further studies are required to test the teratogenicity and effectiveness of Zoladex.

Adult↗
PubMed1995

Comparison of endoscopic variceal injection sclerotherapy and ligation for the treatment of esophageal variceal hemorrhage: a prospective randomized trial.

To determine the efficacy of endoscopic variceal sclerotherapy (EVS) and ligation (EVL) in the management of esophageal variceal bleeding, 134 cirrhotic patients were randomized to receive either treatment. The clinical and endoscopic characteristics were similar in both groups. Active bleeding was controlled with ligation (20 of 20) as efficiently as with sclerotherapy (14 of 16). Elective sclerotherapy consumed less time than ligation (7.9 +/- 1.8 minutes vs. 11.5 +/- 2.7 minutes, P < .001), but there was no difference between emergent sclerotherapy (14.5 +/- 5.8 minutes) and ligation (14.9 +/- 4.1 minutes). Ligation reduced one grade of variceal size more quickly than sclerotherapy (1.1 +/- 0.4 vs. 2.0 +/- 1.7 session, P < .001). The rebleeding rate was lower with ligation (13 of 67 vs. 28 of 67, P < .01). Esophageal ulcer was the most common source of rebleeding. Recurrence of varices appears more probable with ligation (P = .079). The complication rate was higher with sclerotherapy (15 of 67 vs. 3 of 67, P < .01), with esophageal stricture being the most common cause. Survival rate was the same in both groups even after stratifying patients into good and poor hepatic reserve groups. Hepatic failure was the major cause of death, followed by exsanguination. In summary, EVL was superior to EVS regarding rebleeding and complications but not in other aspects such as time consumption in elective treatment and recurrence of varices. Substantial results for long-term follow-up are required before conclusion of the treatment of choice.

Esophageal and Gastric Varices↗
PubMed1994

YC-1, a novel activator of platelet guanylate cyclase.

YC-1 [3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole] inhibited the aggregation of and ATP release from washed rabbit platelets induced by arachidonic acid (AA), collagen, U46619, platelet-activating factor (PAF), and thrombin in a concentration-dependent manner. YC-1 also disaggregated the clumped platelets caused by these inducers. The thromboxane B2 formation caused by collagen, PAF, and thrombin was inhibited by concentrations of YC-1 that did not affect formation of thromboxane B2 and prostaglandin D2 caused by AA. YC-1 suppressed the increase of intracellular Ca2+ concentration and generation of inositol 1,4,5-trisphosphate caused by these five aggregation inducers. Both the cAMP and cGMP contents of platelets were increased by YC-1 in a concentration- and time-dependent manner. Like sodium nitroprusside, YC-1 potentiated formation of cAMP caused by prostaglandin E1 but not that by 3-isobutyl-1-methylxanthine. Adenylate cyclase and cAMP phosphodiesterase activities were not altered by YC-1. Activity of cGMP phosphodiesterase was unaffected by YC-1. Activities of guanylate cyclase in platelet homogenate and cytosolic fraction were activated by YC-1, whereas particulate guanylate cyclase activity was unaffected. The antiplatelet effect of sodium nitroprusside but not that of YC-1 was blocked by hemoglobin and potentiated by superoxide dismutase. After intraperitoneal administration for 30 minutes, YC-1 prolonged the tail bleeding time of conscious mice. These data indicate that YC-1 is a direct soluble guanylate cyclase activator in rabbit platelets. It may also possess antithrombotic potential in vivo.

1-Methyl-3-isobutylxanthine↗
PubMed1994

Insulin-like growth factor I regulation of Swarm rat chondrosarcoma chondrocytes in culture.

Insulin-like growth factor I (IGF-I) is anabolic for chondrocytes and is thought to be important in regulating such normal cartilaginous tissues as the epiphyseal growth plate. In the present studies, we have investigated the role of IGF-I in the regulation of neoplastic cartilage. Chondrocytes cultured from a transplantable rat chondrosarcoma were analyzed for responsiveness to IGF-I with respect to DNA and glycosaminoglycan synthesis as determined by labeling with radioactive thymidine and sulfate, respectively. Stimulation of [3H]thymidine and [35S]sulfate incorporation by IGF-I was two to four times that in serum-free controls, with half-maximal stimulation at 1 x 10(-9) M. The efficacy of IGF-I was approximately one-half of that of serum in stimulating [3H]thymidine incorporation and was comparable to that of serum for [35S]sulfate incorporation. When Swarm rat chondrosarcoma chondrocytes were cultured in the presence of IGF-I and exposed to graded concentrations of anti-IGF-I antibody, [3H]thymidine incorporation and [35S]sulfate incorporation were attenuated in a dose-dependent fashion to 29 and 25% of antibody-free controls, respectively. Nonspecific antibody not raised against IGF-I was not inhibitory. These observations suggest that the majority of IGF-I action on these cells is susceptible to immunoinhibition. To estimate the contribution of IGF-I to the regulation of these cells by serum, Swarm rat chondrosarcoma chondrocytes were cultured with graded concentrations of either calf serum or fetal calf serum in the presence of anti-IGF-I antibody, nonspecific antibody, or no other additives. Specific antibody attenuated the effect of calf serum on both [3H]thymidine and [35S]sulfate incorporation with overall inhibition of 52% (P < 0.01) and 48% (P < 0.001), respectively. Nonspecific antibody super-imposed small, variably stimulatory or inhibitory effects on those of calf serum. When chondrosarcoma chondrocytes were incubated with fetal calf serum, anti-IGF-I antibody exerted a minimal inhibitory effect, reducing both [3H]thymidine and [35S]sulfate incorporation by less than 25%. The immunoinhibition of both pre- and postnatal serum could be overcome in a dose-dependent fashion by increasing serum concentrations. These results suggest that the factors influencing Swarm rat chondrosarcoma chondrocytes may be developmentally regulated and that the contribution of IGF-I to the action of serum increases between fetal and post-natal life. These data support the hypothesis that chondrosarcoma is a somatomedin-responsive neoplasm and suggest that this tumor may be susceptible to interventions directed toward mechanisms that block insulin-like growth factor action.

Animals↗
PubMed1994

Effects of octreotide on postprandial systemic and hepatic hemodynamics in patients with postnecrotic cirrhosis.

The effects of octreotide on postprandial hemodynamic responses were evaluated in 20 patients with postnecrotic cirrhosis. They were randomly assigned to receive either a 100-micrograms bolus with a 100-micrograms/h infusion of octreotide or a placebo. Placebo administration did not affect any of the hemodynamic values. However, after a liquid meal of 500 kcal, postprandial increases in the hepatic venous pressure gradient and hepatic blood flow were observed in patients receiving placebo, while the systemic hemodynamic values remained unchanged. In contrast, in patients receiving octreotide, the hepatic blood flow was significantly decreased 30 min after administration, while the hepatic venous pressure gradient and the systemic hemodynamic values were not affected. After ingestion of a meal, the mean values of the hepatic blood flows were not significantly different from basal values. Moreover, the wedged hepatic venous pressure, the hepatic venous pressure gradient and the systemic hemodynamic values were not affected by meal ingestion. However, during octreotide infusion, hepatic blood flow 30 min after the meal had a tendency to increase compared to before the meal. In conclusion, octreotide inhibited the postprandial increase in portal pressure in patients with postnecrotic cirrhosis. In addition, octreotide decreased hepatic blood flow in the fasting state. When given before a meal, the increase in blood flow induced by the meal restored the hepatic blood flow to basal levels.

Adult↗
PubMed1994

A double-blind randomized controlled trial of colchicine in patients with hepatitis B virus-related postnecrotic cirrhosis.

The preliminary results of a prospective double-blind controlled trial of colchicine in 100 patients with hepatitis B virus-related cirrhosis are reported. The patients, 94 males and 6 females, aged 32-80, were assigned to receive either 1 mg of colchicine or an identical placebo orally on a daily basis. The duration of the follow up ranged from 15 to 51 months (median 26 months). Seventy percent had histological proof of cirrhosis. On entry, 80 patients were in Child-Pugh class A, 19 were in class B, and one was in class C. Compared to the placebo group, there was no improvement in the colchicine group after a 24-month follow up in any of the biochemistry data, for example, serum albumin, alkaline phosphatase, alanine and aspartate aminotransferase, bilirubin, and prothrombin time. The difference in the cumulative survival rates at 51 months did not reach statistical significance (p = 0.8) in either group. There was no histological improvement in 30 patients who were willing to undergo repeated liver biopsies. No trend toward improvement of the hepatic pressure gradient was observed in these patients. The serum levels of aminopropeptide of type III procollagen increased significantly in patients in both groups after 24 months of therapy (1.07 +/- 0.06 vs. 1.36 +/- 0.06 U/ml in the colchicine group, 0.93 +/- 0.09 vs. 1.25 +/- 0.07 U/ml in the placebo group; p < 0.05). In addition, neither the clinical deterioration of cirrhosis nor death was prevented in patients receiving colchicine therapy. This report indicates that colchicine has no effect in the treatment of HBV-related postnecrotic cirrhosis.

Adult↗
PubMed1994

Endoscopic injection for the treatment of bleeding ulcers: local tamponade or drug effect?

Fifty-two patients with Forrest Ia or Ib bleeding ulcers were randomized to receive endoscopic injection therapy with either 1:10,000 epinephrine in water (Group I) or distilled water (Group II). Twenty-five out of 27 patients in group I, versus 22 out of 25 patients in group II, achieved initial hemostasis after endoscopic injection therapy (p > 0.05). Five patients who did not respond to local injection had bleeding controlled by heater probe thermocoagulation or surgical intervention. Three patients in each group developed rebleeding after initial hemostasis. Four of these patients had bleeding controlled by surgical intervention, while the other two died of underlying diseases. No change in systemic blood pressure, but a significant drop in the pulse rate were noted in both groups after injection therapy. Patients with shock at admission or ulcer size greater than 2 cm had a significantly higher rebleeding rate after initial hemostasis than patients with normal blood pressure and ulcers under 2 cm (p < 0.05). No serious complications were observed after injection therapy, and no significant difference in the amounts of solution required for successful hemostasis was noted between the two groups. We conclude that a local tamponade with distilled water is as effective and safe as diluted epinephrine solution for endoscopic injection therapy.

Double-Blind Method↗
PubMed1994

Study on the vascular reactivity and alpha 1-adrenoceptors of portal hypertensive rats.

1. Vascular hyporesponsiveness in portal hypertension has been demonstrated to various vasoconstrictors including noradrenaline (NA). The present study aimed to determine whether the attenuated vascular responsiveness to NA is due to a change in the affinity or the number of alpha 1-adrenoceptors. 2. Partial portal vein ligation (PVL) was performed in Sprague-Dawley rats to produce portal hypertension. Vascular responsiveness to NA was assayed in portal vein, mesenteric artery or tail artery. The affinity and number of alpha 1-adrenoceptors were determined by specific binding of [125I]-HEAT (2-beta-4-hydroxy-3-iodophenyethyl-aminomethyltetralone). 3. In the presence of yohimbine (10(-7) M, an alpha 2-adrenoceptor antagonist), propranolol (10(-6) M, a beta-adrenoceptor antagonist), and two catecholamine uptake inhibitors, desipramine (10(-7) M) and normetanephrine (10(-6) M), the maximum responses to NA were decreased in all three blood vessels of PVL rats: 45% decrease in portal vein, 25% in mesenteric artery and 18% in tail artery. 4. The EC50 values of NA and the pA2 values of prazosin, an alpha 1-adrenoceptor antagonist, in all three blood vessels were not significantly different between sham-operated and PVL rats. 5. The KD and Bmax values for specific binding of [125I]-HEAT or the Ki values for NA in the crude membrane preparations of either mesenteric artery or tail artery were also not significantly different between the two groups. 6. It is concluded that the vascular hyporesponsiveness to NA in the mesenteric artery or tail artery of PVL rats is not due to changes in the affinity or number of alpha 1-adrenoceptors.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1994

Clinical courses and predictors for rebleeding in patients with peptic ulcers and non-bleeding visible vessels: a prospective study.

Detailed characterisation of non-bleeding visible vessels in terms of colour, size evolution, and time of rebleeding is important in determining the natural history of these lesions. The colour and size of non-bleeding visible vessels were observed endoscopically every day for three days and then every other day until rebleeding or flattening of visible vessels occurred in 140 patients. Rebleeding happened in 61 (44%) patients. Of them, 59 (97%) rebled within 72 hours. Flattening of visible vessels happened in 79 (56%) patients and 77 of 79 (98%) had flattening of visible vessels within 72 hours. Rebleeding rate increased with increasing length of exposed vessels (r = 0.96, p < 0.001). Coffee ground fluid or blood retention in the stomach and ulcer size > or = 2.0 cm were independent predictors for rebleeding using multivariate analysis. It is suggested that patients with non-bleeding visible vessels and independent predictors for rebleeding may need early aggressive treatment.

Adult↗
PubMed1994

Nitric oxide modulates hepatic vascular tone in normal rat liver.

This study investigated whether nitric oxide (NO) plays a role in the intrahepatic portal circulation in normal rat livers perfused in situ. N omega-nitro-L-arginine (NNA), a specific NO biosynthesis inhibitor, significantly increased baseline portal pressure compared with controls (P < 0.05). Concentration-effect curves to norepinephrine (NE) were performed. Perfusate flow was maintained as constant, and perfusion pressure was continuously measured. NNA markedly enhanced the responsiveness to NE. This effect was abolished by the addition of L-arginine, a specific NO substrate. Presence of indomethacin did not alter the response to NE. The response to NE in the presence of indomethacin and NNA was significantly more than the response to NE in the presence of NNA alone. In vivo, intraportal infusion of NNA significantly enhanced the portal pressure compared with vehicle. This study demonstrates that NO contributes to the basal vascular tone and attenuates the response to NE in intrahepatic portal vascular bed of normal rats. These results support a functional role of NO in the regulation of the intrahepatic portal circulation in normal rats. This study also suggests a synergistic, albeit limited, role of prostacyclin in the intrahepatic circulation.

Animals↗
PubMed1994

Characteristics of patients with bleeding peptic ulcer requiring emergency endoscopy and aggressive treatment.

OBJECTIVES: Patients with an ulcer and active bleeding or a nonbleeding, visible vessel are high-risk for further bleeding and should receive aggressive therapy. In this study, we tried to identify clinical parameters that predict these high-risk groups. METHODS: Over a 7-month period, 16 clinical parameters were analyzed prospectively in 316 patients with bleeding peptic ulcer. A multivariate analysis was used to find the independent predictors for the high-risk patients. RESULTS: A total of 114 patients (36%) was found to have a spurting hemorrhage (eight patients), oozing hemorrhage (27 patients), or a nonbleeding visible vessel (79 patients). Using an univariate analysis, a statistically significant predictor was the appearance of coffee ground fluid or blood from the nasogastric tube. This predictor also emerged as an independent factor (odds ratio, 0.4333; 95% confidence interval, 0.263-0.714). CONCLUSIONS: Patients with bleeding peptic ulcer who have coffee ground fluid or blood from the nasogastric tube should receive an emergency endoscopy and aggressive treatment.

Emergencies↗