Elevated NADPH-oxidase activity in neutrophils from bile-duct-ligated rats: changes in the kinetic parameters and in the oxidase cytosolic factor p47.

Stimulated superoxide generation was 2-fold higher in neutrophils from 20 rats with common bile-duct ligation (CBDL) compared to that of 20 sham-operated control rats. In order to study the mechanism of the higher NADPH oxidase activity in CBDL rats, the kinetic parameters of NADPH oxidase were analyzed. The Vmax of the NADPH oxidase in CBDL rat neutrophils was significantly higher than that of control rat neutrophils (10.2 and 5.3 nmol/min, respectively). The membrane and cytosol fractions of the oxidase were studied in a cell-free system. Neutrophil cytosol from CBDL rats added to neutrophil membranes from either CBDL or control rats produced 22.4 +/- 1.6 and 21.0 +/- 1.4 nmol/10(6) cells per 10 min, respectively. When neutrophil cytosol from control rats was mixed with neutrophil membranes from control or CBDL rats the generation of superoxide was 10.6 +/- 1.4 and 10.0 +/- 1.5 nmol/10(6) cells per 10 min, respectively. These results suggest that the cytosol components of the oxidase regulate its activity. By immunoblot analysis it was shown that the amount of the cytosolic factor p47 in neutrophils of CBDL rats is higher than that present in an equal number of neutrophils from control rats.

Serious bacterial infections after endoscopic procedures.

Transient bacteremia during and after endoscopic procedures is a well- documented phenomenon, but complicated bacteremia such as endocarditis in patients at risk is considered to be extremely rare. The recommendations for prophylaxis before endoscopy in patients with valvular heart disease were recently released. We discuss 16 cases of complicated bacteremia that developed after endoscopy (eight cases previously published in the literature and eight cases we encountered). The endoscopic procedures were gastroscopy (five cases), sclerotherapy (six cases), sigmoidoscopy (three cases), and esophageal dilation (two cases). Fourteen patients had underlying disease: valvular heart disease (six patients), cirrhosis of the liver (five patients, one of whom also had a prosthetic knee), valvular heart disease and cirrhosis of the liver (two patients), and gastric carcinoma (one patient). The organisms involved were Streptococcus viridans (six cases), streptococcus group D (three cases), Streptococcus pneumoniae (two cases), Streptococcus microaerophilicus (two cases), Staphylococcus aureus (two cases), and Cardiobacterium hominis (one case). The patients presented with the following infections: endocarditis (12 patients), spontaneous bacterial peritonitis (two patients), septic arthritis (one patient), and brain abscess (one patient). The outcome was good in 15 patients; one patient died. Patients with valvular heart disease, cirrhosis of the liver, ascites, malignancies, or prosthetic joints who undergo endoscopic procedures should be considered for antibiotic prophylaxis.

Abnormalities in bilirubin and liver enzyme levels in adult patients with bacteremia. A prospective study.

Eighty-four patients with bacteremia were surveyed prospectively for biochemical markers of liver damage. Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and bilirubin levels were elevated in 44 (53%), 39 (47%), 45 (54%), and 5 (6%) of the patients on the first determination (2.0 +/- 0.1 days after onset of fever) and in 11 (13%), 17 (20%), 26 (31%), and 1 (1%) on the second determination (5.4 +/- 0.2 days after onset of fever), respectively. The elevation rarely exceeded three times the upper limit of normal. One patient had severe jaundice. An abnormality of at least one of these values was found in 55 patients (65%). There were no differences in site of infection, bacteria isolated, and outcome between patients with and without biochemical abnormalities. We conclude that in adult patients with bacteremia, elevation of liver enzymes and bilirubin is common, usually mild, of short duration, and of no prognostic significance.

Fulminant non--A-G viral hepatitis leading to liver transplantation.

BACKGROUND: All hepatotropic viruses are known to cause fulminant hepatic failure (FHF). However, in 30% to 40% of patients with FHF, the precise cause remains unknown. We aimed to better define this subgroup. METHODS: We evaluated the clinical course and outcome of 7 patients admitted during a 22-month period with fulminant viral hepatitis leading to liver transplantation; none had serologic or molecular evidence of hepatitis A, B, C, D, E, or G viral infection, thus the term non-A-G viral hepatitis. All known etiologies of FHF were excluded. RESULTS: All patients had prodromal symptoms suggestive of viral causes. Mean age was 30 years. The interval between onset of jaundice and appearance of encephalopathy was 23 days (range, 4-50 days). Five patients had grade III/IV encephalopathy. Serum alanine aminotransferase levels showed a single peak of activity. The duration between first symptoms and liver transplantation was 28 days (range, 12-71 days). Results of histological study of the explanted liver showed submassive (4 patients) or massive (3 patients) hepatocyte necrosis. In all patients, results of polymerase chain reaction analysis did not detect hepatitis B virus DNA, hepatitis C virus RNA, or hepatitis G virus RNA in the explanted liver. After transplantation, 2 patients showed (6 months later) increased liver enzyme levels of undetermined cause, and results of a liver biopsy showed mild lobular hepatitis; 1 patient had lymphoproliferative disorder (Epstein-Barr virus-originated); and 1 patient, aplastic anemia, which is known to be associated with seronegative viral hepatitis. The latter patient died, whereas the other 6 patients are alive (survival rate, 86%). CONCLUSIONS: Our patients with non-A-G viral hepatitis had a severe acute onset with progressive FHF requiring liver transplantation. There is some suggestion of recurrent viral disease after transplantation implicating other unknown viruses in the etiology.

Fibromyalgia in hepatitis C virus infection. Another infectious disease relationship.

BACKGROUND: Fibromyalgia syndrome (FS) is a common disorder of diffuse pain in the muscles or joints accompanied by tenderness at specific tender points and a constellation of related symptoms. The potential role of infections in the pathogenesis of FS has only recently been investigated. OBJECTIVES: To evaluate the prevalence of FS and to assess tenderness thresholds in patients infected with hepatitis C virus (HCV). METHODS: The study included 90 patients with HCV, 128 healthy, anti-HCV-negative controls, and 32 patients with non-HCV-related cirrhosis. Tenderness was measured by manual palpation (18 tender points) and with a dolorimeter. Fibromyalgia syndrome was diagnosed according to the 1990 American College of Rheumatology criteria. RESULTS: The diagnosis of FS was established in 14 patients (16%) with HCV, in 1 patient (3%) with non-HCV-related cirrhosis, and in none of the healthy controls (P < .001). Thirteen of the HCV-positive patients with FS were women. The patients with HCV had significantly (P < .01) more tender points (mean [+/- SD] 3.6 +/- 5.3) than the healthy controls (0.1 +/- 0.5) and the patients with non-HCV-related cirrhosis (1.2 +/- 2.7). Specifically, the patients with cirrhosis were most tender on both tenderness measures owing to the high proportion of women in this group. Patients with FS were significantly more tender than those without FS: their dolorimetry thresholds were 2.9 kg vs 6.0 kg (P < .001). CONCLUSIONS: A high prevalence of FS was observed in patients infected with HCV, especially women. Recognizing FS in patients with HCV will prevent misinterpretation of FS symptoms as part of the liver disease and will enable the physician to reassure the patient about these symptoms and to alleviate them.

Musculoskeletal manifestations and autoantibody profile in 90 hepatitis C virus infected Israeli patients.

OBJECTIVES: Recent interest has been expressed in rheumatic manifestations in hepatitis C virus (HCV)-infected populations. The aim of this study was to determine the prevalence and characteristics of the musculoskeletal manifestations and serological markers of autoimmunity in HCV-infected patients in Israel. METHODS: Ninety anti-HCV-positive patients were consecutively interviewed and examined. The prevalence of autoantibodies and their association with rheumatologic symptoms were also determined. RESULTS: Rheumatic manifestations were found in 28 subjects (31%), and included arthralgias (9%), arthritis (4%), cryoglobulinemia (11%), sicca symptoms (8%), cutaneous vasculitis (2%), polymyositis (1%), and antiphospholipid syndrome (1%). Rheumatic complications were not associated with liver disease severity, or subjects' gender. In addition, myalgia was reported by 22 patients (24%), and fibromyalgia was diagnosed in 14 (16%). Sixty-nine percent of the patients had at least one autoantibody detected in their serum, the most prevalent being rheumatoid factor (RF), 44%; antinuclear antibody (ANA), 38%; and IgM and IgG anticardiolipin antibodies (ac1), 28% and 22%, respectively. The frequency of autoantibodies was not associated with liver disease severity or rheumatic disorders. CONCLUSIONS: Musculoskeletal manifestations and autoimmune markers are common in HCV infection. An investigation of risk factors for HCV infection is pertinent in a patient presenting new rheumatic manifestations and should be included in the history of present illness. Future studies of these disorders may uncover the full spectrum of these associations and provide new insights into their operating mechanisms.

Fatal Clostridium sordellii ischio-rectal abscess with septicaemia complicating ultrasound-guided transrectal prostate biopsy.

Clostridium sordellii is a Gram-positive spore-forming anaerobic bacillus rarely encountered in human infection. A case of C. sordellii ischio-rectal abscess with rapidly fatal septicaemia is described which complicated ultrasound-guided transrectal biopsy of the prostate, despite ciprofloxacin prophylaxis. Neither C. sordellii ischio-rectal abscess nor ischio-rectal abscess complicating transrectal biopsy have been reported previously. Judging from our experience and the reviewed literature, the addition of prophylactic anti-anaerobe drugs should be strongly considered until an optimal prophylactic regimen will be defined by randomized controlled trials.

Salivary HCV-antibodies; a follow-up cohort study of liver disease patients.

We have recently shown in Liver Clinic patients that saliva instead of serum may be used for anti-HCV detection. As compared to blood withdrawing, saliva is easier to obtain, non invasive, especially for infants. In the present study, sequential determination of serum and salivary anti-HCV was performed in the same cohort for 36 months. Anti-HCV seropositive and seronegative patients were studied. Blood and saliva samples were obtained simultaneously. From the anti-HCV seronegative patients (n=33), 161 sequential serum and 161 matched saliva samples were obtained. All were anti-HCV negative. From the anti-HCV seropositive patients (n=35), 131 sequential serum and 131 matched saliva samples were obtained. All sequential serum samples were anti-HCV positive. Of the saliva samples 126 (96%) were anti-HCV positive and five (4%) were anti-HCV negative. These five samples were obtained from two patients with autoimmune hepatitis and HCV-RNA seronegative by PCR. The results suggest that saliva may serve as a substitute for serum for the detection of anti-HCV antibodies.

Beneficial effect of phlebotomy on hepatitis C virus-associated musculoskeletal manifestations.

Chronic hepatitis C virus (HCV) infection may lead to many extrahepatic manifestations which pose a serious therapeutic challenge. Recently, increasing evidence suggesting an association between iron overload and chronic HCV infection has emerged. However, the effect of iron reduction therapy on extrahepatic manifestations of HCV infection is unknown. We describe two patients with chronic HCV infection and severe rheumatic manifestations, namely: myalgia and seronegative nonerosive symmetrical polyarthritis. Interestingly, the response to anti-inflammatory and second line drugs was poor but unexpectedly recurrent phlebotomies was followed by marked improvement of the symptoms. This observation suggests that iron overload may have some role in the pathophysiology of HCV associated rheumatic complications. Further studies are needed to confirm our observation and to clarify the underlying mechanism.

Comparison of structural polypeptides, detected by immunoblotting technique, in the sera of spotted fever group rickettsia positive cases--symptomatic versus asymptomatic.

In an attempt to characterize the nature of symptomatic versus asymptomatic spotted fever group rickettsia (SFGR) infection, the immune response to R. conorii (boutonneuse fever) structural polypeptides was studied by Western-blot immunoassay. Sera from immunoperoxidase assay (IPA), SFGR seropositive (titre greater than or equal to 80) individuals, symptomatic and asymptomatic and from SFGR seronegative (IPA titre less than 80) individuals living in a kibbutz community in the desert region of Southern Israel were examined by immunoblot. This community suffered from a very high morbidity rate due to SFGR (21-fold higher than the national reported average). The entire community (n-326) has been followed-up since 1985, with serial serum samples being examined for specific IgG antibodies by IPA. The intensity of the immunoblot reaction correlated with specific IgG antibody titres as determined by IPA. This correlation was also observed between the decrease in the IgG titre and the strength of the antibody-antigen reaction by immunoblot over time for a given individual. IPA seropositive sera from asymptomatic as well as symptomatic spotted fever cases reacted to 8 individual polypeptides. In both cases antibodies to 22 kD, 24 kD, 26 kD, 28 kD, 30 kD, 32 kD, 34 kD, and 37 kD were found. In the IPA seronegative sera, antibodies to polypeptides in the range of 24 kD to 32 kD were not detected. The lack of detectable differences by immunoblotting between SFGR symptomatic vs, asymptomatic cases might be explained by other aspects of the immune response of each infected individual, and/or it is possible that virulent and non-virulent antigenically closely related SFGR strains infected symptomatic vs. asymptomatic individuals.

[Hydrothorax of hepatic origin. Description of a clinical case, pathophysiology]. / Hydrothorax d'origine hépatique. Description d'un cas clinique, pathophysiologie.

We admitted a 60 year old patient with severe right hydrothorax. He was known to suffer from decompensated non-alcoholic cirrhosis. His invaliding dyspnea was only temporarily improved by repeated thoracocentesis, due to the very rapid refilling of the thorax from the ascites; until the development of a "tension hydrothorax" with dangerous mediastinal deviation. By insertion a peritoneo-venous shunt described by LeVeen the clinical picture was improved, and the patient no longe required further pleural aspiration. Six per cent of cases of ascites complicating hepatic cirrhosis may be associated with hydrothorax of the same origin. The diaphragm is normally perforated by a multitude of tiny virtual holes, closed by the peritoneum and the thoracic pleura. The high intra-abdominal pressure in ascites tears these fragile membranes, and allows the peritoneal fluid to overflow into the pleural cavity. Usually treated by fluid restriction and diuretics, when this condition becomes intractable or when a tension hydrothorax appears, interfering with respiratory function a LeVeen peritoneo-venous shunt should be inserted.

[Embolic splenic infarction: a rare complication of atrial fibrillation].

Splenic infarction is a rare disorder. The typical clinical presentation is sudden pain in the left upper quadrant of the abdomen, and awareness to this possibility is the major clue for diagnosis. We describe a 49-year-old man with chronic atrial fibrillation and splenomegaly who was treated with anticoagulants. Because of hematuria, the regular dose of anticoagulant therapy was reduced. The hematuria stopped but he complained of sudden onset of pain in the left upper quadrant. Computerized tomography and isotope scan of the spleen confirmed the clinical suspicion of splenic infarction. Treatment with anticoagulants and analgesics was followed by clinical improvement.

[Heat stroke associated with massive hepatic necrosis].

Heat stroke in a 21-year-old soldier was complicated by acute renal failure with rhabdomyolysis, hypophosphatemia, hypocalcemia, sinus bradycardia and massive liver necrosis. Treatment included general supportive measures, forced alkaline diuresis and IV fresh frozen plasma and cryoprecipitate and was followed by complete recovery.

[Rational use of albumin].

The use of albumin has been a matter of debate since its introduction in the 1940's. Albumin is not only expensive but may also be harmful when administered inappropriately. Until recently our use of albumin was controlled by a number of authorized physicians who signed all albumin prescriptions. In August 1998, a multidisciplinary team reviewed the indications for albumin use and introduced simple guidelines for its supply and administration. As a result, the use of albumin has decreased by almost 70%. This indicates that rational use of albumin can be achieved by appropriate guidelines, without requiring administrative limitations. We believe that this conclusion holds true for other diagnostic and therapeutic procedures as well.