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Reduced platelet factor X-activating activity: a possible contribution to bleeding complications in polycythaemia vera and essential thrombocythaemia.

A recently described platelet coagulant activity, factor X-activating activity (FXAA), was studied in 33 patients with polycythaemia vera and in 5 with essential thrombocythaemia, in order to gain information about possible mechanisms responsible for the haemostatic disorders observed in myeloproliferative diseases. Other parameters of platelet function including bleeding time, spontaneous and ADP-, epinephrine- or collagen-induced platelet aggregation, serotonin content and malondialdehyde (MDA) production in response to thrombin, were investigated simultaneously. Compared to the range obtained from 27 control subjects (60-150%), FXAA was low in all 9 patients with bleeding complications (range: 5-39%), in 1 out of 7 patients with thrombotic manifestations (range: 38-200%) and in 9 out of 22 patients without symptoms (range: 38-500%). Only the bleeding group differed significantly from each of the others. Moreover, of all patients with reduced FXAA, those with bleeding could be clearly distinguished from those without such symptoms on the basis of the degree of the defect. Increased FXAA (above 150%) was found in 2 out of 7 thrombotic patients and in 2 out of 22 asymptomatics. MDA production was significantly lower in the haemorrhagic group and enhanced in the thrombotic one as compared to control subjects or asymptomatic patients. However, a large area of overlap was observed between the four groups. None of the other platelet function parameters studied (bleeding time, platelet aggregation, platelet serotonin content) correlated with the clinical type of haemostatic complication. Our results suggest a significant association between reduced FXAA and bleeding tendency. These findings may be of relevance in understanding the pathogenesis of abnormal bleeding in patients with polycythaemia vera and essential thrombocythaemia.

Adolescent↗

Antenatal bleeding and fetal heart rate.

Objective of the paper was to determine the fetal heart rate (FHR) changes that occur in preterm fetuses whose mothers have suffered antepartum bleeding, versus uncomplicated controls. Over a 12-year span, 91 patients with significant antenatal bleeding (bleeding requiring inhospital observation) were examined and compared to 75 controls with uncomplicated normal pregnancies. None of the women were in labor and all were evaluated at 25-37 weeks' gestation. Excluded were: patients with any other complication (i.e., premature rupture of membranes, intrauterine growth retardation, diabetes, hypertension, collagen vascular disease, postuterine surgery, substance abuse and twins). Analysis of the FHR tracings included baseline heart rate, long-term FHR variability, and number and amplitude of FHR accelerations in 20-min segments. There was no difference in baseline heart rate in the preterm fetuses of pregnancies complicated by antepartum bleeding versus controls. However, the parameters associated with FHR reactivity (number of accelerations in 20 min, and amplitude of accelerations) were higher to a statistically significant degree in fetuses of pregnancies complicated by antenatal bleeding than in controls. Fetuses of mothers suffering antenatal bleeding exhibited significant higher rates of reactive FHR patterns at earlier gestational ages than did controls. In conclusion, there is a significant increase in FHR reactivity in pregnancies in which significant antenatal bleeding occurs, suggesting a probable acceleration in fetal central nervous system maturation in these fetuses.

Case-Control Studies↗

Correlation between serum-ascites albumin concentration gradient with gastrointestinal bleeding in patients of portal hypertension.

Non-availability of endoscopic screening to detect portal hypertensive patients at a high risk of index gastrointestinal (GI) haemorrhage led us to examine the relationship between serum-ascitic albumin concentration gradient (SAAG) measurements and the occurrence of GI haemorrhage in patients with portal hypertension and ascites. Fifty-six consecutive patients of portal hypertension with ascites attending the GI surgery outpatients clinic were divided into two groups on the basis of history: (a) those who had no history of GI bleeding; and (b) those who had an episode of GI bleeding within the past 21 days. Child-Pugh score was calculated for all patients. All the patients were assessed by ultrasonography and SAAG was estimated. Groups (a) and (b) were compared and sensitivity, specificity, positive and negative predictive value of using SAAG as a possible screening test for GI bleeding were calculated. SAAG values correlated significantly with bleeding and splenomegaly. For prediction of bleeding, SAAG had a sensitivity of 100% and specificity of 33.33%, positive predictive value of SAAG for GI bleeding was 71.4% and the negative predictive value was 100%. Estimation of SAAG is possible even in a small, modestly equipped laboratory, and could provide a new means for the identification of high-risk patients for GI bleeding and define patients more accurately for future clinical studies. The results of the present study are encouraging for clinicians working in developing countries and may help in optimizing prophylactic therapy and where available, improving the cost effectiveness of screening endoscopy.

Adolescent↗

Endoscopic injection therapy for bleeding peptic ulcer using absolute alcohol.

The injection of sclerosants and adrenaline in a bleeding peptic ulcer is known to arrest bleeding in the majority of patients. However, there are very few studies from India on this subject. Injection therapy was carried out using absolute alcohol in 21 patients with bleeding gastric ulcer and 55 with bleeding duodenal ulcer. Injection therapy successfully controlled bleeding in all 76 patients. Bleeding recurred in two patients who were successfully managed with a second injection of absolute alcohol. Post-injection blood transfusion was required in 16 (76%) patients with gastric ulcer compared with only 12 (22%) of those with a duodenal ulcer. The difference was statistically significant (P < 0.001). No complication of injection therapy was noted. It is concluded that injection therapy using absolute alcohol is a safe and effective therapy for managing patients with bleeding peptic ulcer.

Adolescent↗

Bleeding associated with eptifibatide targeting higher risk patients with acute coronary syndromes: incidence and multivariate risk factors.

The objective of this study was to determine the safety of the glycoprotein IIb/IIIa receptor inhibitor eptifibatide in patients at high risk for adverse clinical outcomes and to determine risk factors for eptifibatide-associated bleeding. Consecutive patients (n = 175) who presented with an acute coronary syndrome and who were at high risk for adverse clinical outcomes were prospectively observed for eptifibatide-associated bleeding, which was classified according to Thrombolysis in Myocardial Infarction (TIMI) and Global Use of Strategies to Open Occluded arteries (GUSTO) criteria. High risk was defined as unstable angina or non-Q-wave myocardial infarction with at least one of the following: left ventricular ejection fraction < 40%, diabetes mellitus, ST segment depression or transient ST segment elevation, serum [troponin I] > 2.5 ng/mL, and recurrent angina symptoms after initiation of conventional antianginal therapy. Bleeding incidences in the patients in this study were compared with those in the 4722 eptifibatide-treated patients in the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial. Compared to PURSUIT patients, the population in this study was similar in age but had a higher proportion of females, African Americans, hypertension, diabetes, prior myocardial infarction, heart failure, and revascularization. Bleeding incidences in this study's patients were similar to or lower than those in the PURSUIT population: TIMI major 1.1% versus 10.8%, TAMI minor 12.6% versus 13.1%, GUSTO severe 1.7% versus 1.5%, GUSTO moderate 3.9% versus 11.3%, and GUSTO mild 19.7% versus 26.1%. Renal dysfunction was an independent risk factor for TIMI (odds ratio = 9.1 ([95% CI= 1.6-52.5]) and GUSTO (odds ratio = 6.1 [95% CI = 1.2-30.0]) bleeding. In conclusion, despite being at higher risk for adverse outcomes, patients administered eptifibatide according to this study's institutional guidelines had comparable or lower bleeding rates than in the PURSUIT trial. Renal dysfunction is an independent risk factor for eptifibatide-induced bleeding.

Acute Disease↗

The use of recombinant activated factor VII for refractory bleeding post complex cardiothoracic surgery.

We reviewed the outcome following use of recombinant activated factor VII (rVIIa) in patients with major bleeding post cardiothoracic surgery in our unit between January 2002 and July 2004. The unit consists of 16 cardiothoracic intensive care beds in a public metropolitan teaching hospital which serves as a referral centre for heart and lung transplant surgery. Patients with refractory bleeding following cardiothoracic surgical procedures who were treated with rVIIa were identified. A total of 12 episodes of rVIIa use were recorded in ten patients, including three episodes with ventricular assist devices, and 5 heart and/or lung transplants. The median dose used was 85 microg/kg. Chest tube drainage decreased in all patients following administration of rVlIIa; median chest tube drainage decreased from 445 ml/h to 171 ml/h (P = 0.03). Despite cessation of bleeding, mortality was high when rVIIa was used after more than 24 hours. In six episodes, despite early rVIIa use (within six hours), continued bleeding necessitated return to theatre, where a surgical source of bleeding was found. In this small retrospective study, rVIIa significantly reduced bleeding that was refractory to standard blood product transfusion. In this series of patients, those that did not respond to rVIIa early in the postoperative phase were found to have a surgical source of bleeding.

Adult↗

Safety of citrate based hemofiltration in critically ill patients at high risk for bleeding: a comparison with nadroparin.

PURPOSE: To study the incidence and severity of bleeding in high risk critically ill patients during high volume, citrate based continuous veno-venous hemofiltration (CVVH). DESIGN: A prospective 1-year observational cohort study comparing citrate based CVVH with nadroparin based CVVH. PROCEDURES: Critically ill patients with multiple organ dysfunction and in need of CVVH were observed for bleeding complications during their CVVH sessions. Pre-defined criteria determined that patients were treated with citrate based CVVH in case of active bleeding or increased risk for bleeding. Otherwise nadroparin was used as anticoagulant. Statistical and outcome methods: The incidence of bleeding complications, the number of transfused blood cell concentrates and the filter-run-time were recorded. Analyses were made by non-parametric tests. MAIN FINDINGS: Fifty-five patients received 272 CVVH sessions. In the citrate group 14.8% experienced a bleeding complication compared to 25% in the nadroparin group (p=0.04). The number of transfused red blood cell concentrates was not different between groups. The nadroparin group had a longer filter run time (median 31.5 hours versus 22.5 hours, p=0.0001). CONCLUSIONS: In high risk critically ill patients citrate based anticoagulation for CVVH is safe in terms of bleeding complications and transfusion requirements.

Anticoagulants↗

Plasma tissue factor pathway inhibitor levels as a marker for postoperative bleeding after enoxaparin use in deep vein thrombosis prophylaxis in orthopedics and general surgery.

Low-molecular-weight heparins (LMWH) are widely used as antithrombotic prophylactic pharmaceutical agents in orthopedic and general surgery. Their antithrombotic characteristics are expressed by plasma mediators such as anti-Xa, anti-IIa, and increased release of tissue factor pathway inhibitor (TFPI) from vascular endothelium. The purpose of this clinical research is to study the relation between plasma levels of these mediators and postoperative bleeding. Forty-one consecutive patients undergoing hip or knee arthroplasty (n = 36) and colectomy (n = 5) received the standard enoxaparin (a LMWH) dose preoperatively (general surgery) or immediately postoperatively (orthopedic surgery). Major bleeding was defined as a postoperative drop of > or = 5 g/dL) of hemoglobin. The authors observed that there was a linear relationship between an increase in free/total TFPI ratio levels and postoperative bleeding. When that ratio increased by > 60%, the hemoglobin dropped to > 5 g/dL (n = 17). This relationship between free/total TFPI ratio increase and postoperative bleeding was statistically significant (P < 0.001). Those who did not bleed (hemoglobin drop was less than 5 g/dL) (n = 24) had a ratio increase (if any) of less than 50%. However, the authors did not observe any statistical relationship between anti-Xa, anti-IIa, or prothrombin time and postoperative bleeding in patients receiving LMWH for deep vein thrombosis prophylaxis in orthopedic and general surgery patients. The authors recommend a pre- and postoperative ratio level measurement whenever major bleeding is anticipated, as adjustments of LMWH dose or frequency might be necessary.

Biomarkers↗

Plasma tissue factor pathway inhibitor levels as a marker for postoperative bleeding after enoxaparin use in deep vein thrombosis prophylaxis in orthopedics and general surgery.

Low-molecular-weight heparins (LMWH) are widely used as antithrombotic prophylactic pharmaceutical agents in orthopedic and general surgery. Their antithrombotic characteristics are expressed by plasma mediators such as anti-Xa. anti-IIa, and increased release of tissue factor pathway inhibitor (TFPI) from vascular endothelium. The purpose of this clinical research is to study the relation between plasma levels of these mediators and postoperative bleeding. Forty-one consecutive patients undergoing hip or knee arthroplasty (n = 36) and colectomy (n = 5) received the standard enoxaparin (a LMWH) dose preoperatively (general surgery) or immediately postoperatively (orthopedic surgery). Major bleeding was defined as a postoperative drop of > or = 5 g/dL) of hemoglobin. The authors observed that there was a linear relationship between an increase in free/total TFPI ratio levels and postoperative bleeding. When that ratio increased by >60%, the hemoglobin dropped to >5 g/dL (n = 13). This relationship between free/total TFPI ratio increase and postoperative bleeding was statistically significant (P < 0.001). Those who did not bleed (hemoglobin drop was less than 5 g/dL) (n = 28) had a ratio increase (if any) of less than 50%. However, the authors did not observe any statistical relationship between anti-Xa, anti-IIa, or prothrombin time and postoperative bleeding in patients receiving LMWH for deep vein thrombosis prophylaxis in orthopedic and general surgery patients. The authors recommend a pre- and postoperative ratio level measurement whenever major bleeding is anticipated, as adjustments of LMWH dose or frequency might be necessary.

Anticoagulants↗

An observational study examining the impact of capecitabine on warfarin antithrombotic activity and bleeding complications.

OBJECTIVE: The objectives of this study are to quantify the frequency of concomitant use of capecitabine and warfarin, and to quantify the rate of bleeding events and elevated international normalized ratio (INR) among concomitant users of warfarin and capecitabine. RESEARCH DESIGN AND METHODS: We conducted a retrospective population-based study within the Henry Ford Health System (Detroit, MI) and the Kaiser Permanente Medical Care Program of Northern California (Oakland, CA). The study population included patients prescribed concomitant capecitabine and warfarin from 1 April 1997 through 31 July 2002. Data from the medical records of concurrent users were extracted through 31 August 2002. MAIN OUTCOME MEASURES: Concomitant use of capecitabine and warfarin, bleeding events, and INR laboratory results, collected from computerized databases and medical record review. RESULTS: Overall, 11% of capecitabine users also received warfarin (99 / 883). Among 17 patients who received warfarin for venous access device prophylaxis, one bleeding event occurred during concomitant capecitabine/warfarin use (rate = 35.7 bleeding events per 100 person-years, 95% confidence interval [CI] 0.9-198.9), and no events occurred during use of warfarin alone (95% CI 0.0-136.2) (p = 0.50). Among patients prescribed warfarin for indications other than port prophylaxis, no bleeding events occurred during concomitant use of capecitabine and warfarin (95% CI 0.0-34.6), and one event occurred during warfarin use alone (rate = 9.2 bleeding events per 100 person-years, 95% CI 0.2-51.3) (p = 0.54). We found one INR elevation > 3.0 among concomitant capecitabine/warfarin users receiving warfarin for port prophylaxis (rate = 35.7 per 100 person-years) and no INR elevations > 3.0 during use of warfarin alone (p = 0.46). Among patients using warfarin for indications other than port prophylaxis, the rates of INR > 3.0 were 309.7 per 100 person-years (95% CI 213.2-434.9) during concomitant capecitabine/warfarin use and 193.5 events per 100 person-years (95% CI 119.8-295.8) during use of warfarin alone (p = 0.09). CONCLUSIONS: The results of our study show a low prevalence of capecitabine and warfarin concomitant use. We did not find large differences in the rates of bleeding events and elevated INR in patients receiving concomitant capecitabine and warfarin when compared with use of warfarin alone. While these results do not imply a lack of biologic interaction, our findings indicate that patients appear to be appropriately managed in clinical practice.

Aged↗

Can somatostatin control acute bleeding from oesophageal varices in Schistosoma mansoni patients?[ISRCTN63456799].

BACKGROUND: Management of patients with bleeding oesophageal varices comprises of mainly diagnostic endoscopy, sclerotherapy and band ligation. One of the major problems to do any of the above is the active bleeding which makes any intervention difficult. The neuropeptide hormone somatostatin administered exogenously has caused a reduction in portal hypertension and variceal bleeding in patients suffering from liver cirrhosis. We believe that the symptomatic use of somatostatin for variceal bleeding in Schistosoma mansoni infected subjects can reduce bleeding, thereby alleviating the pathology caused by schistosomiasis. METHODS/DESIGN: We herein present a study protocol for establishing this neuropeptide as a potential therapeutic agent in schistosomiasis. Adolescent subjects, age range varying from 12-17 years will be selected, based on several inclusion criteria, most important being infection with Schistosoma mansoni with bleeding from oesophageal varices in the last 24 hours. One group of schistosomiasis patients will be treated with somatostatin and praziquantel, the other with propanolol and praziquantel. Survival graphs will be set up to correlate somatostatin administration with survival time. A two part questionnaire will be set up to control treatment outcomes. The pre-treatment part of the clinical questionnaire will identify inclusion criteria questions, the post-treatment part of the questionnaire will identify treatment outcomes. DISCUSSION: We expect that the administration of somatostatin as a bolus followed by a 24 hour long infusion, will stop bleeding immediately, delay rebleeding as compared to the control study group and delay mortality in the somatostatin treated subjects.

Adolescent↗

Incidence, cost, and outcomes of bleeding and chemotherapy dose modification among solid tumor patients with chemotherapy-induced thrombocytopenia.

PURPOSE: To describe the incidence and outcomes of bleeding and chemotherapy dose modifications associated with chemotherapy-induced thrombocytopenia (platelets < 50,000/microL). PATIENTS AND METHODS: Six hundred nine patients with solid tumors or lymphoma were followed-up during 1,262 chemotherapy cycles complicated by thrombocytopenia for development of bleeding, delay or dose reduction of the subsequent cycle, survival, and resource utilization. The association between survival and bleeding or dose modification was examined using the Cox proportional hazards model. Predisposing factors were identified by logistic regression. RESULTS: Bleeding occurred during 9% of cycles among patients with previous bleeding episodes (P <.0001), baseline platelets less than 75,000/microL (P <.0001), bone marrow metastases (P =.001), poor performance status (P =.03), and cisplatin, carboplatin, carmustine or lomustine administration (P =.0002). Major bleeding episodes resulted in shorter survival and higher resource utilization (P <.0001). Chemotherapy delays occurred during 6% of cycles among patients with more than five previous cycles (P =.003), radiotherapy (P =.03), and disseminated disease (P =.04). They experienced similar clinical outcomes but used significantly more resources. Dose reductions occurred during 15% of cycles but were not associated with poor clinical outcomes or excess resource utilization. Significantly shorter survival and higher resource utilization were observed among the 20% of patients who failed to achieve an adequate response to platelet transfusion. CONCLUSION: The incidence of bleeding is low among solid tumor patients overall but exceeds 20% in some subgroups. These subgroups are easily identifiable using routinely available clinical information. A clinical prediction rule is being developed. Poor response to platelet transfusion is a clinically and financially significant downstream effect of thrombocytopenia and warrants further investigation.

Antineoplastic Agents↗

Angiogenic effects of norplant contraception on endometrial histology and uterine bleeding.

Norplant, a sc contraceptive device, releases levonorgestrel in a sustained fashion. Its effectiveness is offset by irregular bleeding patterns. Because vascular endothelial growth factor (VEGF) is stimulated by synthetic progestogens in vitro and in vivo, we postulated that correlations between this angiogenic factor and uterine bleeding patterns might exist. Twenty-eight women who were exposed to Norplant and 13 control women were prospectively followed for 6-8 months. Bleeding diaries were collected, hysteroscopies were performed, endometrial biopsies were obtained for standardized histological evaluation, and VEGF histochemical immunostaining (H)-scores were assigned. Cluster determination-34 (CD34) staining was also performed to quantify the number of endometrial blood vessels per high-power field. Irregular uterine bleeding was common among women using Norplant devices. Endometrial VEGF H-scores were greater in women using Norplant than in control women. New findings of this study show that vessel density did not correlate with epithelial VEGF H-scores but was highly associated with the intensity of stromal and perivascular VEGF. VEGF expression in the latter regions correlated significantly with hysteroscopic abnormalities and irregular bleeding. The expression of this angiogenic protein, particularly in the stromal and perivascular compartments, correlated with microvascular density, hysteroscopically documented hypervascularity, and uterine bleeding profiles. Irregular bleeding with Norplant use appears to reflect paracrine-mediated effects on vascular function by angiogenic factors, such as VEGF.

Adult↗

Temporal and spatial association of matrix metalloproteinases with focal endometrial breakdown and bleeding upon progestin-only contraception.

The pathogenesis of irregular endometrial bleeding, the main reason for stopping contraception with progestins only, is unknown. Based on the recent reappraisal of the mechanisms of menstrual bleeding, we hypothesized that matrix metalloproteinases initiate this disorder. Volunteers upon Norplant treatment provided endometrial biopsies at the start of a bleeding episode and during nonbleeding intervals. Focal stromal breakdown, collagen fiber lysis, and collagenase-1 messenger ribonucleic acid were evidenced in most bleeding endometria, but never in the nonbleeding ones. In the breaking down areas, immunolabeling for gelatinase A was strongly increased, and that of progesterone and estrogen receptors was decreased. Explants from bleeding endometria produced high collagenase and gelatinase activities, whereas release from nonbleeding endometria was negligible. Bleeding endometria released more latent and active forms of collagenase-1 and active gelatinases A and B, but less tissue inhibitor of metalloproteinases-1, than nonbleeding endometria. Collagenase-1 release closely correlated with that of interleukin-1alpha. In contrast, N:-acetyl-beta-hexosaminidase and tissue inhibitor of metalloproteinases-2 were similarly released in both groups. Thus, endometrial bleeding occurs together with focal stromal breakdown, collagen lysis, expression and activation of several matrix metalloproteinases, and decreased production of tissue inhibitor of metalloproteinases-1. These results may lead to new pharmacological treatment of this common medical problem.

Adult↗

Early treatment of ruptured aneurysms with Guglielmi detachable coils: effect on subsequent bleeding.

The major causes of mortality and morbidity in patients surviving the rupture of a saccular aneurysm are subsequent bleeding and vasospasm. The purpose of this study was to evaluate the influence of early treatment of ruptured aneurysms with Guglielmi detachable coils on the incidence of subsequent bleeding. Thirteen patients were treated within 72 hours of initial aneurysm rupture with Guglielmi detachable coils. Excluding three patients who died 2, 4, and 12 weeks after initial hemorrhage, all others have been followed up for intervals between 6 and 36 months (mean, 16 mo). None of these have had either clinical or radiographic evidence of subsequent bleeding. Assuming that there is a 30% incidence of subsequent bleeding in conservatively (nonsurgically) treated patients, the 0% subsequent bleed rate observed in this subgroup was significant at a P value of 0.01. Only one procedure-related complication occurred in this series, and 9 of 13 (69%) aneurysms were 100% occluded at the time of initial treatment. All aneurysms were at least 90% occluded at the end of initial treatment. In addition to reducing the risk of subsequent bleeding, early treatment facilitated the institution of an aggressive approach for management of both vasospasm and increased intracranial pressure. Patient outcome, as measured by the Glasgow Outcome Scale, was good in 9 of 13 (69%), poor in 1 of 13 (8%), and death in 3 of 13 (23%) patients. The results of this study suggest that early Guglielmi detachable coil treatment of ruptured aneurysms may be effective in reducing the incidence of subsequent bleeding and can be performed with a low incidence of complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Effects of lansoprazole on indomethacin-induced gastric bleeding and mucosal lesions in rats].

The effects of lansoprazole given intravenously on indomethacin-induced gastric bleeding and mucosal lesions were investigated in rats in comparison with those of omeprazole, famotidine and ranitidine. Lansoprazole inhibited gastric bleeding induced by indomethacin with an ID50 value of 0.29 mg/kg. Omeprazole and famotidine significantly inhibited gastric bleeding, but ranitidine provided negligible inhibition. A correlation was found between the inhibitory action of lansoprazole on gastric bleeding, and acid secretion, and its inhibitory action on gastric bleeding was almost completely abolished by adding 50 mM-HCl to the gastric perfusate, suggesting that lansoprazole's inhibitory action on gastric bleeding was mainly due to its antisecretory action. Lansoprazole inhibited the development of gastric lesions induced by indomethacin with an ID50 value of 0.10 mg/kg, whereas histamine H2-receptor antagonists did not display a potent inhibitory effect. ID50 values for omeprazole, famotidine and ranitidine were 0.69, 2.58 and 24.6 mg/kg, respectively. These results indicate that lansoprazole has a potent inhibitory action on indomethacin-induced gastric bleeding and mucosal lesions and that it is useful in the treatment of acute gastric mucosal lesions.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Gastric bleeding and increased gastric vascular permeability induced by platelet activating factor (PAF): effect of drugs that affect arachidonate metabolism.

The injurious effect of platelet activating factor (PAF) on gastric mucosa was studied by measuring bleeding in the acid perfused stomach of anesthetized rats. The effect of PAF on gastric mucosal vascular permeability (GMVP) was assessed by dye-leakage in the saline perfused stomach of anesthetized rats. Intravenous infusion of PAF (100 ng/kg/min for 20 min) apparently caused gastric bleeding under the gastric luminal perfusion with 150 mM HCl solution,, with the peak response at 50-70 min; biopsy indicated the presence of mucosal lesions. GMVP was markedly increased with the peak response at 20-40 min. Pretreatment with CV-3988 (1 or 10 mg/kg, i.v.), a PAF antagonist, dose-dependently blocked the PAF-induced gastric bleeding and increase in GMVP. Pretreatment with hydrocortisone acetate (20 or 40 mg/kg, s.c.) reduced PAF-induced gastric bleeding and increase in GMVP, in contrast to the aggravation by caffeic acid (1 or 5 mg/kg, s.c.). Indomethacin (1 or 5 mg/kg, s.c.) prevented PAF-induced gastric bleeding, and it depressed the increase in GMVP in the case of the lower dose. Prostaglandin E2 (50 or 500 micrograms/kg, s.c.) significantly reduced PAF-induced gastric bleeding, but had little effect on PAF-induced increase in GMVP. 1-Benzylimidazole (10 or 50 mg/kg, s.c.) also inhibited PAF-induced gastric bleeding and depressed the increase in GMVP at the higher dose. These results suggest that increased GMVP plays a significant role in producing the gastric damage by PAF. Changes in the mucosal level of cyclooxygenase products, especially thromboxanes, by drugs modifying the arachidonate metabolism would be closely associated with their prevention or aggravation of gastric damage induced by PAF.

Animals↗

[The blood urea nitrogen/creatinine ratio in localizing the bleeding site in pediatric patients with gastrointestinal hemorrhage].

The reliability of the blood urea nitrogen/creatinine (B/C) ratio in localizing the bleeding site in pediatric patients with gastrointestinal hemorrhages was evaluated retrospectively. Supplementary experiments on rats and rabbits were also conducted. The study population included 69 children ranging in age from 6 days to 16 years (mean age, 7y8m) with successful radiographic, endoscopic, and surgical identification of the bleeding site. Patients with renal disease, liver disease and coagulopathy were excluded. The upper gastrointestinal bleeding site was segregated from the lower one defined by the ligament of Treitz. For the 38 upper gastrointestinal bleeders, B/C values ranged from 7.8-69.0 (mean 28.8 +/- 15.4 SD). For the 31 lower gastrointestinal bleeders the values ranged from 4.3-28.5 (mean 18.9 +/- 6.9 SD). A significant difference between the two groups was noted after (p less than 0.01) analysis. No patients with lower gastrointestinal bleeding had values higher than 30. In the group of 17 bleeders with a value higher than 30, 8 patients were examined again from 2-5 days after they had been identified as having bleeding to prove that the bleeding had stopped. At the time of identification of no-bleeding, B/C values were calculated at under 30 in every patient. There was no significant correlation between Hb (g/dl) and B/C. With respect to our experiments on animals, the B/C ratio was evaluated in rats with gastric or small intestinal ulcers. Though B/C was 34.4 +/- 4.4 under normal conditions, it increased significantly to 114.0 +/- 8.8 in rats with gastrointestinal ulcers, while in those with small intestinal ulcers B/C did not increase significantly (40.3 +/- 12.3). Twenty ml of blood from ear veins of rabbits was infused into a) stomach b) small intestine (no-hemolysis blood) c) small intestine (hemolysis blood). For a) and c), B/C increased in a similar pattern. For b) the increase was small. Infusing 5 ml, 10 ml, and 15 ml of the whole blood into the stomach indicated that the volume of blood did not influence the change of B/C values, while the infusion of 3 ml of serum caused only a small increase. According to these studies the increase in the B/C ratio after upper gastrointestinal hemorrhage has been postulated to result from the procedure in which the hemorrhage blood is fragmented or hemolyzed by HCl and digestive enzymes in the gastric juices; and consequently the BUN in red blood cells as well as in serum is rapidly absorbed from the upper small intestine. Volume of blood has little influence upon B/C.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗