Risk factors for gastrointestinal bleeding in critically ill patients. Canadian Critical Care Trials Group

BACKGROUND: The efficacy of prophylaxis against stress ulcers in preventing gastrointestinal bleeding in critically ill patients has led to its widespread use. The side effects and cost of prophylaxis, however, necessitate targeting preventive therapy to those patients most likely to benefit. METHODS: We conducted a prospective multicenter cohort study in which we evaluated potential risk factors for stress ulceration in patients admitted to intensive care units and documented the occurrence of clinically important gastrointestinal bleeding (defined as overt bleeding in association with hemodynamic compromise or the need for blood transfusion). RESULTS: Of 2252 patients, 33 (1.5 percent; 95 percent confidence interval, 1.0 to 2.1 percent) had clinically important bleeding. Two strong independent risk factors for bleeding were identified: respiratory failure (odds ratio, 15.6) and coagulopathy (odds ratio, 4.3). Of 847 patients who had one or both of these risk factors, 31 (3.7 percent; 95 percent confidence interval, 2.5 to 5.2 percent) had clinically important bleeding. Of 1405 patients without these risk factors, 2 (0.1 percent; 95 percent confidence interval, 0.02 to 0.5 percent) had clinically important bleeding. The mortality rate was 48.5 percent in the group with bleeding and 9.1 percent in the group without bleeding (P < 0.001). CONCLUSIONS: Few critically ill patients have clinically important gastrointestinal bleeding, and therefore prophylaxis against stress ulcers can be safely withheld from critically ill patients unless they have coagulopathy or require mechanical ventilation.     

Influence of test conditions on antifungal time-kill curve results: proposal for standardized methods

Bacterial infection is frequently diagnosed in cirrhotic patients with variceal hemorrhage. The aim of this study was to assess the incidence of failure to control bleeding in cirrhotic patients during the first 5 days after the episode of variceal bleeding in relation to the diagnosis of bacterial infection and use of antibiotics. One hundred seventy-seven consecutive admissions for gastrointestinal bleeding in 151 patients were evaluated prospectively. From them, 163 admissions for variceal bleeding in 137 patients were included in the main analysis. Bleeding was managed in a standardized protocol using octreotide or terlipressin with sclerotherapy or band ligation for active bleeding at endoscopy. The end points were defined as in Baveno guidelines related to transfusion requirement or fresh hematemesis after 6 hours from time zero. The standardized screening protocol for bacterial infection consisted of chest radiograph and blood, urine, and ascitic fluid cultures. Active bleeding was reported at endoscopy in 86 admissions (53%). Failure to control bleeding occurred in 76 patient admissions (47%). Empirical antibiotic treatment was used in 113 admissions (69%), whereas in 81% of them (91 admissions, 56%) 102 bacterial infections were documented. Multivariate analysis showed that proven bacterial infection (P < .0001) or antibiotic use (P < .003) as well as active bleeding at endoscopy (P < .001) and Child-Pugh score (P < .02) were independent prognostic factors of failure to control bleeding. The results remained unchanged when all patient admissions with gastrointestinal bleeding of any source were included in the multivariate analysis. Bacterial infection is associated with failure to control variceal bleeding and needs to be evaluated in the planning and analysis of clinical trials.     

Candida sepsis successfully treated by parenteral administration of 5-fluorocytosine

Candida sepsis has become one of the most common and dangerous forms of hospital acquired infection. The recommended drug for parenteral treatment of Candida sepsis is amphotericin B, however, its toxic effects preclude its usage in many patients, particularly in the presence of renal failure. A less toxic antifungal agent is 5-fluorocytosine. A patient with Candida albicans sepsis was treated successfully with 5-fluorocytosine by intravenous administration. The fungal infection developed during the course of acute renal failure, repeated surgical intervention, intravenous hyperalimentation, gastrointestinal bleeding and five months of antibiotic therapy. The clinical symptoms receded rapidly and cultures became sterile after one week of intravenous treatment. The predisposing factors, difficulties in prevention and diagnosis of fungal infection are discussed.     

Parenteral antibiotic prophylaxis of bacterial infections does not improve cost-efficacy of oral norfloxacin in cirrhotic patients with gastrointestinal bleeding

OBJECTIVE: Selective intestinal decontamination with norfloxacin is useful in the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding. However, bleeding cirrhotic patients with ascites, encephalopathy, or shock are at high risk to develop bacterial infections in spite of prophylactic norfloxacin. The aim of this study was to assess whether the addition of intravenous ceftriaxone could improve the efficacy of prophylaxis with norfloxacin in these patients. METHODS: Fifty-six cirrhotic patients with gastrointestinal hemorrhage and ascites, encephalopathy, or shock were randomized into two groups: Group 1 (n = 28) received oral norfloxacin 400 mg/12 h for 7 days, and group 2 (n = 28) received norfloxacin plus intravenous ceftriaxone 2 g daily during the first 3 days of admission. RESULTS: Ten patients were excluded because of community-acquired infection, surgery, or death within the first 24 h. The incidence of bacterial infections during hospitalization was 18.1% in group 1 and 12.5% in group 2 (p = NS). The incidence of severe infections (spontaneous bacterial peritonitis, bacteremia, or pneumonia) was also similar in both groups: 9% in group 1 versus 8.3% in group 2 (p = NS). There were no statistical differences between the two groups with respect to duration of hospitalization or mortality. The cost of antibiotic therapy (including prophylaxis and treatment of infections) was significantly higher in group 2. CONCLUSION: These results suggest that the addition of intravenous ceftriaxone during the first 3 days of hospitalization does not improve the cost-efficacy of oral norfloxacin in the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding and high risk of infection.     

Epstein-Barr virus associated natural killer cell leukemia: report of an autopsy case

A 20-year-old female was admitted because of high fever, hepatosplenomegaly, severe hepatic dysfunction and coagulopathy. Peripheral blood showed pancytopenia and granular lymphocytes bearing the natural killer cell phenotype (CD2+CD3-CD16+CD56+CD57-TCR alpha beta-TCR gamma delta-) constituted 97% of leucocytes. Southern blot analysis of DNA obtained from peripheral blood mononuclear cells showed germ-line configuration of TCR beta, gamma and delta chain genes. EBV-DNA was detected in a single episomal form by using EBV-terminal repeat probe. Bone marrow findings were consistent with hemophagocytic syndrome and administration of VP-16 was effective transiently. After ten months she died from massive gastrointestinal bleeding. An in situ hybridization study identified EBV-RNA (EBER-1) in atypical lymphocytes infiltrating bone marrow, spleen and lymph nodes. Sections of liver showed steatosis and infiltration of T cells (CD3+ and EBER-1-negative) in the portal areas and few atypical lymphocytes in sinusoids. The patients developed an EBV-associated clonal proliferation of natural killer (NK) cells, but the clinical features were suggestive of chronic active EBV infection or virus-associated hemophagocytic syndrome (VAHS) rather than leukemia. Bone marrow transplantation for NK cell leukemia is an issue to be discussed.     

Abdominal aneurysm

Ulcer bleeding in the upper gastrointestinal tract is one of severe complications in the patients with abdominal aortic aneurysm (AAA). Retrospective analysis of patients with AAA and prospective endoscopic study revealed ulcer lesions occurred more frequently in AAA patients than in controls. Decreased gastric mucosal blood flow (GMBF) and accompanied consumption coagulopathy (CC) mainly contribute to the development of postoperative ulcer bleeding. Recently, the number of AAA patients with ulcer bleeding has been decreased remarkably after we started the anti-ulcer therapy for AAA patients with low GMBF or/and the administration of heparin for the patients with CC.     

Protein C in the treatment of coagulopathy in meningococcal disease

OBJECTIVE: To evaluate the clinical and laboratory effects of the substitution of protein C (PC) as an adjunct to conventional therapy in the treatment of purpura fulminans associated with meningococcal sepsis. DESIGN: case series. SETTING: Medical and medical-surgical intensive care units of two university hospitals. PATIENTS: Three patients with purpura fulminans and multiple organ failure caused by Neisseria meningitidis. INTERVENTION: Intravenous administration of PC concentrate (100 IU/kg every 6 to 8 hrs). MEASUREMENTS AND MAIN RESULTS: The administration of PC resulted in normal or above normal levels of the plasma PC activity in all patients. The laboratory and clinical parameters reflecting the severity of coagulopathy improved during the treatment, as did peripheral ischemia and the clinical manifestations of multiple organ failure. No adverse events were noted. One patient died of cerebral edema. CONCLUSION: The administration of PC had a beneficial effect on coagulopathy and peripheral gangrene formation associated with meningococcal disease and showed no adverse effects.     

Severe gastrointestinal hemorrhage due to Mycobacterium avium complex in a patient receiving immunosuppressive therapy

Intense immunosuppressive therapy is used frequently for treatment of systemic vasculitides, collagenoses, rapidly progressive glomerulonephritis, and after organ transplantation. Numerous serious treatment-related side effects include localized or disseminated opportunistic infections, and require careful monitoring of immunosuppressed patients. Gastrointestinal infections with Mycobacterium avium complex (MAC) or other nontuberculous mycobacteria have been previously identified in HIV seropositive patients only. We now report the first case of an HIV seronegative patient who received immunosuppressive therapy for rapidly progressive glomerulonephritis. The patient presented with severe lower gastrointestinal bleeding and was diagnosed to have ulcerative colitis due to infection with MAC. The patient recovered promptly after administration of antimycobacterial therapy. MAC infection should be included in the differential diagnosis of gastrointestinal bleeding in all immunodeficient patients. The significance of repeated colonoscopy to obtain multiple biopsy specimens with histological examination for foam cells and specific staining for acid-fast organisms is emphasized.     

Depression and the risk of coronary heart disease in the Normative Aging Study

BACKGROUND: Epstein-Barr virus (EBV) infection is common after liver transplantation in children and is associated with the risk of posttransplant lymphoproliferative disorders (PTLD). METHODS: This retrospective study examined the frequency of gastrointestinal (GI) symptoms and the risk of PTLD in pediatric liver recipients who developed symptomatic EBV infection. We reviewed 172 children who received orthotopic liver transplants between March 1988 to December 1994. Twenty-two cases were retransplants. The mean age at transplantation was 3.7 years (range, 0.1-17 years). The immunosuppressive regimens consisted of induction therapy with Minnesota antilymphocyte globulin/antithymocyte globulin/OKT3 in most cases and maintenance therapy with prednisone and either cyclosporine or tacrolimus (FK506). RESULTS: After 1 year of minimum follow-up, 54 of 172 patients had symptomatic EBV infections (confirmed by serology, histology, or whole blood polymerase chain reaction. At the time of infection, 38.5% (21/54) had either diarrhea or GI bleeding or both. PTLD developed in 11 patients (6.4%). The incidence of PTLD was 42.9% (9/21) when GI bleeding or diarrhea was associated with EBV infections, compared with 6.1% (2/33) when EBV infection was not associated with GI symptoms. Seven of 10 (70%) patients with GI bleeding and 2 of 11 (18.2%) with diarrhea developed PTLD. Of seven patients examined by endoscopy for GI bleeding, two had biopsy-proven PTLD of the GI tract, whereas one of two patients examined by endoscopy for diarrhea had biopsy-proven PTLD. DISCUSSION: In summary, a high incidence of PTLD was found in patients who developed GI bleeding or diarrhea associated with EBV infection after pediatric liver transplantation. In these patients, endoscopy and biopsy may lead to early diagnosis of PTLD.     

Longterm outcome after injection sclerotherapy for oesophageal varices in children with extrahepatic portal hypertension

A consecutive series of 36 children with bleeding from oesophageal varices secondary to extrahepatic portal hypertension was successfully treated by endoscopic injection sclerotherapy and followed up over a mean period of 8.7 years after variceal obliteration. There were no deaths from portal hypertension or its treatment and morbidity related to oesophageal sclerotherapy was minimal. Endoscopic injection sclerotherapy alone proved safe and effective in controlling variceal bleeding from portal hypertension in over 80% of the children. Recurrent variceal bleeding developed in 10 (31%) patients but half of these were effectively treated by further sclerotherapy. Gastric variceal bleeding unresponsive to sclerotherapy necessitated successful portosystemic shunt surgery in four (13%) patients. Two children required splenectomy for painful splenomegaly. In most children injection sclerotherapy is the best treatment for the primary management of bleeding oesophageal varices, reserving portosystemic shunting or other surgical procedures for those with bleeding from gastrointestinal varices.     

Perioperative coagulopathy in patients undergoing primary cytoreduction

BACKGROUND: This study was performed to determine the frequency of a perioperative coagulopathy in patients undergoing primary cytoreduction for ovarian cancer or carcinoma of the peritoneum and to identify variables that might predict this phenomenon. METHODS: A retrospective review of 90 patients undergoing primary cytoreduction for ovarian cancer or carcinoma of the peritoneum was performed at Cedars Sinai Medical Center. Univariate analysis was performed to test the relationship between 15 variables and coagulopathy status. RESULTS: Six patients (6.7%) developed a perioperative coagulopathy that was unrelated to preoperative subcutaneous heparin or dilution. Coagulation disturbances developed intraoperatively before packed erythrocyte replacement equivalent to one blood volume. Four patients (4.4%) required a repeat laparotomy due to continued postoperative bleeding unresponsive to blood component replacement. Vascular pedicles were not the cause of bleeding in any patient. Univariate analysis demonstrated a significant association between perioperative coagulopathy and the following variables: ascites volume (P = 0.009), estimated blood loss (P = 0.002), preoperative serum albumin less than 3.5 g/dl (P < 0.0001), and metastasis greater than 10 cm (P = 0.033). CONCLUSIONS: Patients undergoing primary cytoreduction who have ascites, preoperative serum albumin less than 3.5 g/dl, or metastases greater than 10 cm may be at increased risk for development of a perioperative coagulopathy.     

One-week antibiotics versus maintenance acid suppression therapy for Helicobacter pylori-associated peptic ulcer bleeding

Bleeding peptic ulcer is the most important cause of upper gastrointestinal bleeding. Our aim was to compare the effect of anti-Helicobacter therapy with maintenance treatment of H2-receptor antagonist in the prevention of relapses of ulcer and bleeding. Patients with bleeding duodenal or gastric ulcers and H. pylori infection were randomized to receive either a one-week course of triple therapy with bismuth subcitrate, metronidazole, and tetracycline plus ranitidine or a six-week course of ranitidine 300 mg/day. After the ulcers healed, the antibiotic-treated patients were not given any medication, whereas the ranitidine-treated patients continued to receive a maintenance dose of 150 mg/day. One hundred twenty-six patients were randomized to receive anti-Helicobacter therapy and 124 patients to receive long-term ranitidine. H. pylori eradication was achieved in 98.2% in those who received triple therapy and 6.1% in those who received ranitidine (P < 0.0001). At the six-week follow-up, ulcer healing was documented in 88.2% in those who received triple therapy and 86.1% in those who received ranitidine (P = 0.639). Recurrent ulcer developed in nine of the ranitidine-treated patients and three of them presented with recurrent upper gastrointestinal bleeding. One patient in the antibiotic group developed recurrent ulcer without rebleeding (P = 0.01). It is concluded that eradication of H. pylori is sufficient for the prevention of recurrent bleeding ulcers.     

Risk factors for gastrointestinal bleeding

Gastrointestinal bleeding sometimes causes life-threatening state. It is important to understand the underlining risk factors for prevention and treatment of this condition. In 1997, 81 patients with massive gastrointestinal bleeding were admitted to the life-saving center in Kyoto First Red Cross Hospital. In these patients, 14 subjects (17%) had been receiving hemodialysis. Eight patients (10%) were taking anti-coagulant or antiplatelet drugs. Eight patients (10%) had hypertension and were given calcium antagonists. Seven subjects (9%) had liver cirrhosis and/or hepatocellular carcinoma. Because these patients often fall into life-threating state, we must pay special attention to the prevention and cure for gastrointestinal bleeding. For example, it may be necessary to change to heparin free hemodialysis for patients having active bleeding. In anticoagulated patients, it may be required that sufficient hemostatic therapy without risking thromboembolic sequelae. In addition to careful managements, we have better to consider the eradication therapy for all of these high risk groups with Helicobacter pylori infection.     

Diffuse gastrointestinal angiodysplasia associated with cryptogenic hepatic cirrhosis and coagulopathy simulating von Willebrand disease

Angiodysplasic lesions can be located anywhere in the gastrointestinal tract, but most of them are found in the cecum and right colon. Angiodysplasias are very infrequent in the stomach and small bowel. These lesions can be associated with several clinical conditions, such as certain coagulation disorders and liver diseases. We report the case of a diffuse gastrointestinal angiodysplasia in a female patient with idiopathic cirrhosis of the liver who developed a coagulopathy which mimicked von Willebrand disease. After repeated blood transfusions, which were not able to control the anemia of the patient, an antrectomy was performed because most lesions were located in the antrum. The procedure did not achieve a suitable control of the bleeding. Finally, a hormonal therapy combining estrogens and progestagens, was able to control, at least partially, the patient's chronic gastrointestinal bleeding.     

Future education: what do nurse executives need?

A small number of trauma patients with penetrating thoracic trauma will require formal pulmonary resections to repair severe injuries or control massive haemorrhage. Although previous reports on this subject have addressed the management of these injuries in battle conditions, civilian experience with this type of chest injury is limited. In a 3-year period, 259 patients underwent urgent thoracotomies for penetrating thoracic trauma. We retrospectively reviewed 43 patients who underwent lobectomies or pneumonectomies to control bleeding (93%) or bronchial injuries (7%). Handguns were the aetiologic agent in 41 patients (95%). The most common complication, pneumonia, was seen in 21 patients (87%). Fifteen patients (62%) developed respiratory failure. The complications of wound infection, post-operative haemorrhage and empyema were seen in equal frequency in four patients (16%). Two patients (8%) developed bronchopleural fistulas. Nine pneumonectomies and 34 lobectomies were performed with mortality rates of 66% and 38%, respectively (overall mortality, 44%). Ten (53%) deaths occurred in the operating room, late deaths (2-15 days) were secondary to sepsis and multiple organ dysfunction syndrome (MODS). Currently, the management of patients with devastating thoracic injuries to the thoracic cavity is divided into two stages. First, initial resuscitation with rapid surgery to control major bleeding, cardiac tamponade, tracheal disruptions and potentially lethal air embolism is indicated. Once the life-threatening conditions have been resolved, definitive surgical procedures are performed to repair injuries to any of the thoracic structures.     

An assessment of the safety of pediatric ibuprofen. A practitioner-based randomized clinical trial

OBJECTIVE: To test the hypothesis that ibuprofen increases the risk of hospitalization for gastrointestinal bleeding, renal failure, or anaphylaxis among febrile children. DESIGN: Randomized double-blind acetaminophen-controlled trial. SETTING: Outpatient pediatric and family medicine practices. PATIENTS: A total of 84,192 children. INTERVENTION: Patients were randomly assigned to receive 12 mg/kg of acetaminophen, 5 mg/kg of ibuprofen, or 10 mg/kg of ibuprofen. MAIN OUTCOME MEASURES: Hospitalizations for acute gastrointestinal bleeding, acute renal failure, and anaphylaxis. RESULTS: A total of 277 patients (0.3%) were unavailable for follow-up. Overall, 795 participants (1%) were hospitalized, primarily for infectious diseases; hospitalization rates did not differ according to treatment group. Four children had diagnoses of acute, nonmajor gastrointestinal bleeding (two in each ibuprofen dosage group); among ibuprofen-treated children, the observed risk of gastrointestinal bleeding, 7.2 per 100,000 (95% confidence interval, 2 to 18 per 100,000), was not significantly different from the risk among acetaminophen-treated children (P = .31). There were no hospitalizations for acute renal failure or anaphylaxis; the upper 95% confidence bound for the risk of either of these outcomes was 5.4 per 100,000 ibuprofen-treated children. Among a number of other possibly serious adverse drug events, low white blood cell count was marginally associated with ibuprofen treatment. Because this association was observed in the setting of multiple comparisons and white blood cell counts may have been low before treatment, causation is unclear. CONCLUSIONS: The risk of hospitalization for gastrointestinal bleeding, renal failure, or anaphylaxis was not increased following short-term use of ibuprofen in children. These data, however, provide no information on the risks of less severe outcomes or the risks of prolonged ibuprofen use.     

Reduced serum Gc-globulin concentrations in patients with fulminant hepatic failure: association with multiple organ failure

OBJECTIVE: To evaluate the association between admission serum concentrations of the actin-scavenger, Gc-globulin, and the subsequent development of multiple organ failure in patients with fulminant hepatic failure. DESIGN: Retrospective study. SETTING: A hepatologic intensive care unit. PATIENTS: Seventy-nine patients with hepatic encephalopathy grade 3 or 4. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Serum admission concentrations of both total and nonactin-complexed (free) Gc-globulin were determined. The development of cardiovascular failure, renal failure, pulmonary failure, intracranial hypertension, and infections were recorded in each patient. Both total and free Gc-globulin values were significantly lower in the patients, compared with normal controls. The Gc-globulin values were significantly reduced in patients who subsequently developed cardiovascular failure (p < .01), intracranial hypertension (p < .001), and infections (p < .001), compared with those patients who did not. No differences were found between patients with and without pulmonary or renal failure. Patients with total Gc-globulin values in the lowest quintile had on average 2.6 organ failures, whereas patients with Gc-globulin concentrations in the highest quintile had 0.9 organ failures. The corresponding figures for the lowest and highest quintiles of free Gc-globulin were 3.0 and 1.1 organ failures, respectively. Both total and free Gc-globulin were inversely correlated to the number of organ failures (p < .005 in both cases). Patients with multiple organ failure (> or = 2 organ failures) had significantly reduced Gc-globulin values compared with patients without multiple organ failure (p < .0001). CONCLUSIONS: In patients with fulminant hepatic failure, the lowest admission Gc-globulin concentrations were associated with the subsequent development of cardiovascular failure, intracranial hypertension, and infections. Lack of Gc-globulin correlated significantly with the development of multiple organ failure and may be pathogenetically involved in this condition.     

Randomised trial of eradication of Helicobacter pylori before non-steroidal anti-inflammatory drug therapy to prevent peptic ulcers

BACKGROUND: Helicobacter pylori infection is common in patients with peptic ulcers caused by the use of non-steroidal anti-inflammatory drugs (NSAIDs). But the pathogenic role of H pylori in this disease is controversial. We studied the efficacy of eradication of H pylori in the prevention of NSAID-induced peptic ulcers. METHODS: We recruited patients with musculoskeletal pain who required NSAID treatment. None of the patients had previous exposure to NSAID therapy. Patients who had H pylori infection but no pre-existing ulcers on endoscopy were randomly allocated naproxen alone (750 mg daily) for 8 weeks or a 1-week course of triple therapy (bismuth subcitrate 120 mg, tetracycline 500 mg, metronidazole 400 mg, each given orally four times daily) before administration of naproxen (750 mg daily). Endoscopy was repeated after 8 weeks of naproxen treatment or when naproxen treatment was stopped early because of bleeding or intractable dyspepsia. All endoscopic examinations were done by one endoscopist who was unaware of treatment assignment. The primary endpoint was the cumulative rate of gastric and duodenal ulcers. FINDINGS: 202 patients underwent endoscopic screening for enrolment in the trial, and 100 eligible patients were randomly assigned treatment. 92 patients completed the trial (47 in the naproxen group, 45 in the triple-therapy group). At 8 weeks, H pylori had been eradicated from no patients in the naproxen group and 40 (89%) in the triple-therapy group (p < 0.001). 12 (26%) naproxen-group patients developed ulcers: five had ulcer pain and one developed ulcer bleeding. Only three (7%) patients on triple therapy had ulcers, and two of these patients had failure of H pylori eradication (p = 0.01). Thus, 12 (26%) patients with persistent H pylori infection but only one (3%) with successful H pylori eradication developed ulcers with naproxen (p = 0.002). INTERPRETATION: Eradication of H pylori before NSAID therapy reduces the occurrence of NSAID-induced peptic ulcers.     

Systemic antibiotic prophylaxis after gastrointestinal hemorrhage in cirrhotic patients with a high risk of infection

In cirrhotic patients with gastrointestinal hemorrhage, bacterial infections are frequent and play a significant role in mortality. We have previously found that patients with a Child-Pugh's class C or a rebleeding are a subgroup of cirrhotic patients with a high risk of infection. The aims of the study were (1) to validate these indicators and (2) to assess the effectiveness of a systemic antibiotic treatment in preventing bacterial infections in bleeding cirrhotics with a high risk of infection. One hundred and nineteen bleeding cirrhotic patients were divided into 3 groups. Patients with a Child-Pugh's class A-B and no rebleeding (i.e., with a low risk of infection) constituted group 1 (n = 55). Patients with a high risk of infection were randomly allocated to serve as controls (group 2, n = 34) or to receive the ciprofloxacin and a combination of amoxicillin and clavulanic acid for 3 days after hemorrhage (group 3, n = 30). This antibiotic prophylaxis was administered first intravenously and then orally when the bleeding was controlled. The study period was defined as 10 days after hemorrhage. Incidence of bacterial infections was significantly higher in patients from group 2 than in patients from group 1 (52.9% vs. 18.2%; P < .001). Moreover, infections were more severe in group 2: a sepsis syndrome or a septic shock developed in 66.7% of infected patients from this group, but in only 20% of infected patients from group 1. Incidence of bacterial infections was much lower in patients from group 3 than in those from group 2 (13.3% vs. 52.9%; P < .001). Eight patients from group 2 (23.5%) and 4 patients from group 3 (13.3%) died during the first four weeks (P-not significant). Septic shock was the cause of death in 3 patients from group 2 and in only 1 patient from group 3. The cost of antibiotic therapy, including antibiotic prophylaxis in group 3, was $208 +/- $63 per patient in group 2 and $167 +/- $42 per patient in group 3 (P < .05). We conclude that (1) patients with a Child-Pugh's class C and/or a rebleeding are a subgroup of cirrhotic patients with a high risk of infection after gastrointestinal hemorrhage and that (2) in these patients, a prophylactic treatment with systemic antibiotics is very effective in preventing bacterial infections.     

The negative mucosal potential: separating central and peripheral effects of NSAIDs in man

Mixed connective tissue disease (MCTD) was first reported 25 years ago. This report provides an assessment of the course of juvenile (J) MCTD in 224 patients available in the literature until 1996, including our own 33 patients. Most patients improved and remissions were observed in 3-5% (up to 27%). Among the long-term problems, a loss in joint function was seen in up to 29% of the cases, renal involvement in up to 47%, restrictive lung disease in up to 54% and gastrointestinal manifestations consisting of oesophageal dysmotility in up to 29%. Cerebral involvement was rare but severe. Cardiovascular problems observed include cardiomyopathy, myopericarditis and pulmonary hypertension. Among other long-term problems were Raynaud's phenomenon and scleroderma-like skin changes in up to 86% of the patients. Seventeen of the 224 patients had died (7.6%) because of sepsis or infection (7), cerebral complications (3), heart failure (2), pulmonary hypertension (2), renal failure (2) or gastrointestinal bleeding (1). The mortality rate of JMCTD seems to be in the same range as that of juvenile systemic lupus erythematosus, dermatomyositis and scleroderma. When compared with the other connective tissue diseases, however, mainly minor long-term problems are seen in the surviving patients.