Serum cytochrome c level as a prognostic indicator in patients with systemic inflammatory response syndrome

BACKGROUND: Apoptosis may play an important role in the development of systemic inflammatory response syndrome (SIRS) and progression to multiple organ dysfunction syndrome (MODS). To quantify the extent of apoptosis in these morbidities, we developed a sandwich ELISA system to measure serum cytochrome c (cyt-c) levels and we investigated the prognostic significance of cyt-c concentration in SIRS/MODS patients. METHODS: Cyt-c concentrations in patients with SIRS (n=53) with or at risk for MODS were measured and compared with those of control subjects (n=14). RESULTS: Cyt-c concentrations in SIRS/MODS patients increased (0.24-210 ng/ml), whereas those in control subjects were under detection limits (0.1 ng/ml). Cyt-c concentrations in non-survivors increased significantly compared with those in survivors both on the day of admission and on the fifth hospital day. A significant positive correlation was found between cyt-c concentration and two representative organ dysfunction scores, APACHE II and multi-organ failure (MOF) score. Cyt-c concentrations increased earlier than MOF score during the exacerbation phase and rapidly decreased during the convalescence phase in a survivor, but the level continued to be high in a non-survivor. CONCLUSIONS: Determination of serum cyt-c concentrations may be useful to assess the severity of organ dysfunction and to predict the prognosis of SIRS/MODS patients.     

Common and subtypic determinants of hepatitis B surface antigen particles: susceptibility to reduction and/or alkylation evaluated with monoclonal antibodies.

The specificity of five monoclonal antibodies, three raised against hepatitis B surface antigen (HBsAg) particles and two against envelope polypeptides, was tested for on a panel of 366 sera containing HBsAg of various subtypes (131 adw, 146 adr, 39 ayw and 50 ayr). Three monoclonals bound to HBsAg irrespective of subtypes, and therefore, were directed to the common antigenic determinants of HBsAg. Of these, two raised against particles (No. 824 and No. 7922) did not bind with reduced HBsAg particles. The other raised against peptides (No. 5124) bound to reduced HBsAg particles. It did not, however, bind to reduced and alkylated HBsAg particles, thereby indicating that it was directed to an epitope involving cysteine residues not contributing to the conformation. The remaining two monoclonals were directed to subtypic determinants not identical to any of d, y, w and r determinants. The subtypic determinant detectable by one of them (No. 4403), raised against HBsAg polypeptides, markedly increased after reduction of HBsAg particles with or without alkylation. In contrast, the subtypic determinant, detectable by the other monoclonal (No. 2155) raised against particles, substantially decreased after reduction. Non-identity of common or subtypic determinants detectable by the five monoclonals were established by blocking tests in which labeled antibody was competed by non-labeled antibody, of a homologous or heterologous specificity, for the binding with HBsAg. These monoclonals would be useful in studies for immunochemical configuration of HBsAg particles and epidemiology of novel subtypic determinants.     

State of hepatitis B virus DNA in peripheral blood mononuclear cells from persistently infected individuals: correlation with e antigen and viral DNA in the serum as well as with the activity of liver disease

Peripheral blood mononuclear cells (PBMC) were harvested from 76 asymptomatic carriers of hepatitis B virus (HBV) and 100 patients with type B chronic liver disease. DNA was extracted from cells and tested for the binding with radiolabeled HBV DNA probe by Southern blot hybridization technique. Among 34 asymptomatic carriers who had hepatitis B e antigen (HBeAg) and HBV DNA in the serum, HBV DNA was detected in 29 (85%) PBMC. In remarkable contrast, of the remaining 42 carriers seronegative for HBeAg, only 1 (2%) had HBV DNA in the serum, and none exhibited HBV DNA in PBMC. Among 32 patients seropositive for HBeAg, HBV DNA was detected in 28 (88%) sera, and in 24 (75%) PBMC. Of 68 patients seronegative for HBeAg, HBV DNA was found in 10 (15%) sera, and in 7 (10%) PBMC. Among 62 cases with HBV DNA in PBMC, only 1 had it integrated into the host's DNA. The remaining 61 had free HBV DNA in PBMC. Only 8 of them possessed replicative intermediate forms of HBV DNA, with molecular sizes less than 2.0 kilobases as observed in liver infected with HBV, and they all were patients with chronic active hepatitis. HBV DNA was not detectable in PBMC from 172 controls comprising 44 healthy individuals and 128 patients with non-A, non-B hepatitis. Based on these results, the state of HBV DNA in PBMC reflects the phase of HBV infection with HBeAg in the serum, and a high activity of hepatitis accompanied by active HBV replication.     

Laparoscopic features of primary biliary cirrhosis in AMA-positive and AMA-negative patients

BACKGROUND AND STUDY AIMS: Antimitochondrial antibody (AMA)-negative primary biliary cirrhosis (PBC) has been difficult to diagnose. Laparoscopic features of AMA-negative PBC were evaluated in comparison with those of AMA-positive PBC and autoimmune hepatitis. PATIENTS AND METHODS: 71 patients who fulfilled the diagnostic criteria for PBC were enrolled in the study; 48 were AMA-positive and 23 were AMA-negative. As a disease control, 46 autoimmune hepatitis patients were included. Both the frequency and specificity of each laparoscopic finding were evaluated. A laparoscopic scoring system was introduced, which used, common and uncommon laparoscopic findings, and was evaluated for the diagnosis of AMA-negative PBC. RESULTS: The characteristic laparoscopic findings for AMA-positive PBC were yellowish-white marking (92 %), dark-brown discoloration (73 %), gentle undulation (67 %), reddish patch (38 %), and yellowish-white nodules (32 %). On the other hand, laparoscopic findings such as trench-like depression, reddish markings, and wide and small depressions were uncommon in PBC compared with autoimmune hepatitis. The frequencies of characteristic and uncommon laparoscopic findings did not differ statistically between AMA-positive and AMA-negative PBC, but were different between AMA-positive or AMA-negative PBC and autoimmune hepatitis. Scores based on common and uncommon laparoscopic findings were 5.5 +/- 1.5 (mean +/- SD) in AMA-positive PBC, 5.6 +/- 2.0 in AMA-negative PBC, and - 0.30 +/- 0.5 in autoimmune hepatitis. CONCLUSION: The laparoscopic findings in AMA-negative PBC did not differ from those of AMA-positive PBC. A laparoscopic scoring system may be helpful in the diagnosis of AMA-negative PBC.     

Use of early-phase dynamic spiral computed tomography for the primary screening of multiple trauma

The effectiveness of early-phase dynamic spiral computed tomography (CT) of the whole body for screening multiple trauma was compared with that of conventional incremental CT. Thirty-six patients with suspected blunt hemorrhagic injuries were prospectively assigned to undergo either standard uniphasic incremental CT or spiral CT enhanced during the early arterial phase. In comparison with incremental CT, the wider scan coverage in spiral CT resulted in the detection of more injuries. Spiral CT showed an excellent enhancement of both the arteries and parenchyma with a reduced volume of contrast material, however, more contrast artifacts were observed. All extravasations detected in spiral CT were from the arteries and required subsequent interventions including transcatheter embolization. Primary screening with early-phase dynamic spiral CT for hemorrhagic multiple trauma was found to be useful for determining the applications of subsequent angiographic intervention as well as evaluating lesions caused by injury.