Antigen specificity of antihistone antibodies in systemic sclerosis

OBJECTIVES: The aim of the study was to determine the prevalence and clinical significance of antibodies to individual histone components in systemic sclerosis (SSc). METHODS: Serum samples from patients with limited cutaneous SSc (lSSc; n = 42) and diffuse cutaneous SSc (dSSc; n = 28) were examined for IgG and/or IgM antibodies to individual histone components and complexes by enzyme linked immunosorbent assay (ELISA). RESULTS: The level of IgG antibody to total histones was significantly higher in lSSc and dSSc than in normal controls. The level of IgM antibody to total histones was significantly higher in lSSc, but not in dSSc, than in normal controls. IgG antibody to total histones tended to be increased in dSSc when compared with that in lSSc. On the other hand, IgM antibody to total histones tended to be increased in lSSc when compared with that in dSSc. Although SSc showed various antihistone specificities, H2B, H2A-H2B, (H2A-H2B)-dsDNA were main antigens recognised by IgG antibodies in both lSSc and dSSc. Although IgM antibodies to H2B and H2A-H2B were also detected in both lSSc and dSSc, serum samples from lSSc patients exhibited highest IgM reactivity with H1. CONCLUSION: SSc may be included among conditions in which heterogeneous antihistone antibodies are produced. IgM antibodies to the most accessible histone H1 may be related to mild clinical features (lSSc) and IgG antibodies to the inner core molecules of native histone such as H2B or complexes including H2B may be associated with severe clinical features (dSSc) in Ssc.     

Chlamydia trachomatis antibody detection and diagnosis of reactive arthritis

OBJECTIVE: To investigate whether determining the presence of serum or synovial fluid (SF) IgG and IgA of anti-Chlamydia antibodies with two recent commercially available enzyme-linked immunosorbent assays (ELISA) using synthetic peptides or recombinant antigen could be helpful to detect possible Chlamydia trachomatis (CT)-involved disease in rheumatological patients without evidence of urogenital CT infection. METHODS: The prevalence of such antibodies was determined in samples from patients with well-defined disease, i.e. CT sexually acquired arthritis and from patients with other inflammatory arthropathies unrelated to CT. RESULTS: When considering IgG and/or IgA anti-MOMP or anti-LPS antibodies, a sensitivity of 100% was obtained for serum and SF samples, but with a low specificity. A sensitivity and a specificity equal or close to 80% were observed for the SF IgG anti-MOMP antibodies. CONCLUSION: Clinically, the most appropriate determination was the SF IgG anti-MOMP antibodies. This commercially available ELISA test could be useful for the diagnosis of probable CT reactive arthritis.     

Elevated methemoglobin in patients with sepsis

BACKGROUND: It has been reported that large amounts of nitric oxide (NO) are released in patients with sepsis. NO is converted to methemoglobin and nitrate. This study was designed to determine whether blood methemoglobin levels were increased in patients with sepsis or septic shock. METHODS: Forty-five critically ill patients including 8 with sepsis but without shock, 6 with septic shock and 31 non-septic patients were enrolled in the study. For septic and septic shock patients, blood methemoglobin concentrations were measured during sepsis or septic shock and at the time of recovery or just before the onset of sepsis. For the remaining non-septic patients, methemoglobin concentrations were measured at ICU admission and discharge. RESULTS: Blood methemoglobin levels in the presence of sepsis or septic shock were significantly (P < 0.05) higher than those in non-septic patients and those at recovery or just before the onset of sepsis in both septic and septic shock patients. CONCLUSIONS: Blood methemoglobin concentration may be useful as a marker of the onset of sepsis or septic shock.     

Serological follow-up of patients with paracoccidioidomycosis treated with itraconazole using Dot-blot, ELISA and western-blot

Twenty-seven mycologically proven cases of paracoccidioidomycosis (PCM) were treated with itraconazole (100-200 mg/day in month 1 and 100 mg/day until month 6-8) and evaluated clinically and serologically, up to 3.5 years post-therapy, using Dot-blot and ELISA for measuring the titers of IgG, IgA and IgM anti-P.brasiliensis antibodies and Western-blot for determining IgG, IgA and IgM antibodies against the antigen components of the fungus. Before treatment, 81.5% (Dot-blot) and 84% (ELISA) of the patients presented elevated IgG anti-P.brasiliensis antibody titers which dropped slightly with treatment. On the other hand, the percentages of pre-treatment high-titered sera for IgA and IgM anti-P.brasiliensis were lower (51.9% and 51.8%: Dot-blot; 16.5 and 36%: ELISA, respectively) but the titers tended to become negative more frequently with treatment. Prior to treatment, the percentages of positivity for IgG, IgA and IgM anti-P.brasiliensis antibodies in Western-blot were 96%, 20.8% and 41.6%, respectively. Antigens with molecular weights varying from 16-78 kDa, from 21-76 kDa and from 27-78 kDa were reactive for IgG, IgA and IgM antibodies, respectively. The most frequently reactive antigenic components had molecular weights of 27, 33 and 43 kDa for IgG, and 70 for IgA and IgM antibodies. During the period of study, the patients responded well to treatment. The present data confirm the diversity and complexity of the humoral response in PCM, and the importance of utilizing different serological tests to detect IgG, IgA and IgM anti-P. brasiliensis antibodies.     

Foreign residency: specialist candidate in the United States

OBJECTIVE: Endotoxin as the inciting agent of cytokines and other mediators, whose high level expression correlates with the septic shock and MOF, has been the one of leading causes of death in ICU. METHODS: For treating sepsis and MOF caused by endotoxin, the anti-lipid A of LPS antibody was used, 19 burned patients whose TBSA varied from 50% to 100% were divided into anti-LPS treatment group and nontreated group. RESULTS: The levels of serum endotoxin, IL-6, IL-8, TNF and soluble IL-2R were lower obviously in patients of anti-LPS group than those of nontreated group (P < 0.05). CONCLUSION: Clinical study surggests that anti-lipid A of LPS antibody can act as an therapeutic agent against gram-negative bacterin infection in burned patients.     

Different anticoagulant and immunological properties of anti-prothrombin antibodies in patients with antiphospholipid antibodies

Lupus anticoagulant (LA) antibodies are acquired inhibitors of coagulation belonging-together with anticardiolipid (aCL) antibodies-to the family of antiphospholipid antibodies. Since LA antibodies affect coagulation reactions via recognition of the complex of lipid-bound prothrombin, they may be better named anti-prothrombin antibodies. We studied their immunological properties in the plasma of 59 patients with antiphospholipid antibodies by means of specific ELISA systems that allowed the characterization of the interaction of these antibodies with human prothrombin and anionic phospholipids. The mode of presentation of prothrombin was found to greatly influence the reactivity of anti-prothrombin antibodies. In fact, when plain polystyrene plates were used to immobilize prothrombin, virtually no binding was observed. Conversely, when prothrombin was coated on high-activated PVC ELISA plates, 34 samples (58%) contained antibodies that recognize human prothrombin in solid phase. In particular, IgG antibodies were found in 21 plasmas and IgM in 22; both IgG and IgM isotypes were present in 9 of these cases. A higher prevalence was observed in the ELISA for the detection of the antibodies directed at the calcium-mediated complex of phosphatidylserine (PS)-bound prothrombin: 53 samples (90%), preadsorbed with cardiolipin liposomes to remove aCL antibodies, showed the presence of IgG and/or IgM anti-prothrombin antibodies. When the results were analyzed according to the immunoglobulin isotypes, 44 (75%) and 39 (66%) samples were found to contain IgG and IgM anti-prothrombin antibodies, respectively. Both IgG and IgM were present in the plasma of 30 patients. Only half of these samples reacted also with PVC-bound prothrombin. Apparently, the higher rate of positivity of the ELISA for the detection of antibodies to the complex of PS-bound prothrombin was not due to differences in the amount of antigen available in the 2 systems, as judged by binding experiments performed with a rabbit polyclonal anti-human prothrombin antiserum. Finally, the anticoagulant properties of 14 total IgG preparations (12 of them contained anti-prothrombin antibodies positive in both ELISA systems, whereas the other 2 cases reacted either with PVC-bound prothrombin only or with PS-bound prothrombin only) were evaluated by diluted Russell's Viper Venom Time and by diluted activated Partial Thromboplastin Time. To rule out the beta 2-glycoprotein I (beta 2-GPI)-dependent anticoagulant effect of the aCL antibodies contained in the preparations, the coagulation tests were performed in beta 2-GPI deficient plasma. Six preparations failed to show anticoagulant activity in both assay systems, suggesting that 2 types of IgG anti-prothrombin antibodies exist, that differ with respect to their anticoagulant properties. These findings suggest that anti-prothrombin antibodies resemble aCL antibodies with respect to the behaviour in "in vitro" coagulation reactions and underline the wide heterogeneity of antiphospholipid antibodies.     

Studies of immunoglobulins, bentonite flocculation and IgE, IgG and IgM antibodies in serum from patients with trichinosis

Serial serum samples were obtained from two patients from a family of four who ingested raw pork at a known time and in whom trichinosis developed. Single and occasionally two serum samples were obtained from other patients with proved trichinosis. Studies of these serum samples showed that elevations of serum immunoglobulin E (IgE) levels do occur but not in all serum samples and that even when these levels are elevated, they are not high enough to be of diagnostic value. This is also true for serum immunoglobulin M (IgM). Using a solid phase radioimmunoadsorbent test, IgE, IgG and IgM antibodies were detected in the serums. The IgE antibody activity appeared early but was not present in all samples. The IgM antibody activity appeared later than the IgE and IgG antibody activity, and there was a statistically significant correlation between IgM antibodies as determined by radioimmunoassay and the bentonite flocculation titers suggesting that the bentonite flocculation is due to IgM antibody. IgM antibodies detected by radioimmunoassay were positive in all serum samples from patients with trichinosis except for a sample obtained 3 days after the onset of symptoms. The early increase in IgG antibodies and the occurrence of these antibodies in all serum samples obtained more than 3 days after onset of symptoms suggest a potential diagnostic use if serial samples are available early in the course of the disease.     

Selected treatment strategies for septic shock based on proposed mechanisms of pathogenesis

PURPOSE: To review selected new therapies for septic shock designed to inhibit bacterial toxins or endogenous mediators of inflammation. DATA SOURCES: Scientific journals, scientific meeting proceedings, and Food and Drug Administration advisory committee proceedings. STUDY SELECTION AND EXTRACTION: Preclinical and clinical data from trials using core-directed antiendotoxin antibodies and anticytokine therapies for sepsis and studies in animal models of sepsis from our laboratory. RESULTS OF DATA SYNTHESIS: Ten clinical trials using core-directed antiendotoxin antibodies produced inconsistent results and did not conclusively establish the safety or benefit of this approach. Both anti-interleukin-1 and anti-tumor necrosis factor (TNF) therapies have been beneficial in some animal models of sepsis but did not clearly improve survival in initial human trials, and one anti-TNF therapy actually produced harm. Neutrophils, another target for therapeutic intervention, protect the host from infection but may also contribute to the development of tissue injury during sepsis. In a canine model of septic shock, granulocyte colony-stimulating factor increased the number of circulating neutrophils and improved survival, but an anti-integrin (CD11/18) antibody that inhibits neutrophil function worsened outcome. Nitric oxide, a vasodilator produced by the host, causes hypotension during septic shock but may also protect the endothelium and maintain organ blood flow. In dogs challenged with endotoxin, the inhibition of nitric oxide production decreased cardiac index and did not improve survival. CONCLUSIONS: No new therapy for sepsis has shown clinical efficacy. Perhaps more accurate clinical and laboratory predictors are needed to identify patients who may benefit from a given treatment strategy. On the other hand, the therapeutic premises may be flawed. Targeting a single microbial toxin such as endotoxin may not represent a viable strategy for treating a complex inflammatory response to diverse gram-negative bacteria. Similarly, the strategy of inhibiting the host inflammatory response may not be beneficial because immune cells and cytokines play both pathogenic and protective roles. Finally, our scientific knowledge of the complex timing of mediator release and balance during sepsis may be insufficient to develop successful therapeutic interventions for this syndrome.     

Anti-GQ1b IgG antibody activities related to the severity of Miller Fisher syndrome

The correlation between the activities of anti-GQ1b IgG antibodies in sera of patients with Miller Fisher syndrome and their clinical manifestations was investigated. The clinical severity was analyzed for 16 patients by scoring their symptoms during the peak of the clinical course and 4 weeks after onset. Serum samples were obtained from all the patients within the first 2 weeks of onset and from 12 of them 4 weeks after onset. Samples were immunostained by TLC after which antibody activities were measured by the ELISA. Anti-GQ1b IgG antibody activities reflect the severity of the patients' symptoms, especially ophthalmoplegia. Lessening of symptoms, expressed by the difference in MFS severity scores of the two tests, occurred with the marked decrease in antibodies. Results of cerebrospinal fluid and nerve conduction studies, performed during the first 2 weeks, showed no fluctuation with changes in the clinical symptoms or antibody activities.     

Epidemiology of sepsis and multiple organ dysfunction syndrome in children

STUDY OBJECTIVES: To determine the cumulated incidence and the density of incidence of systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, septic shock, and multiple organ dysfunction syndrome (MODS) in critically ill children; to distinguish patients with primary from those with secondary MODS. DESIGN: Prospective cohort study. SETTING: Pediatric ICU of a university hospital. PATIENTS: One thousand fifty-eight consecutive hospital admissions. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: SIRS occurred in 82% (n=869) of hospital admissions, 23% (n=245) had sepsis, 4% (n=46) had severe sepsis, 2% (n=25) had septic shock; 16% (n=168) had primary MODS and 2% (n=23) had secondary MODS; 6% (n=68) of the study population died. The pediatric risk of mortality (PRISM) scores on the first day of admission to pediatric ICU were as follows: 3.9 +/- 3.6 (no SIRS), 7.0 +/- 7.0 (SIRS), 9.5 +/- 8.3 (sepsis), 8.8 +/- 7.8 (severe sepsis), 21.8 +/- 15.8 (septic shock); differences among groups (p=0.0001), all orthogonal comparisons, were significant (p<0.05), except for patients with severe sepsis. The observed mortality for the whole study population was also different according to the underlying diagnostic category (p=0.0001; p<0.05 for patients with SIRS and those with septic shock, compared with all groups). Among, patients with MODS, the difference in mortality between groups did not reach significance (p=0.057). Children with secondary MODS had a longer duration of organ dysfunction (p<0.0001), a longer stay in pediatric ICU after MODS diagnosis (p<0.0001), and a higher risk of mortality (odds ratio, 6.5 [2.7 to 15.9], p<0.0001) than patients with primary MODS. CONCLUSIONS: SIRS and sepsis occur frequently in critically ill children. The presence of SIRS, sepsis, or septic shock is associated with a distinct risk of mortality among critically ill children admitted to the pediatric ICU; more data are needed concerning children with MODS. Secondary MODS is much less common than primary MODS, but it is associated with an increased morbidity and mortality; we speculate that distinct pathophysiologic mechanisms are involved in these two conditions.     

Immunotherapy of endotoxemia and septicemia

Neutralization of endotoxin (lipopolysaccharide, LPS) would be of considerable benefit in the treatment of Gram-negative sepsis. Administration of anti-LPS antibodies is an old approach which has been renewed by improvements in monoclonal antibody technology. The antibodies directed at the conserved core region of LPS or at the lipid A which have been studied in humans are discussed in this review. Some of these antibodies appeared to be protective in animal models or in clinical trials, but discrepant results have been reported and the mechanism of the postulated protection was not clarified. The polyclonal antibody preparations have given variable results in patients. The clinical studies of anti-lipid A monoclonal antibodies seemed promising because both antibodies appeared to protect subsets of patients. However, the studies gave discrepant results concerning the type of patients reported to benefit from the administration of these antibodies. One of these antibodies, E5, appeared to improve the survival of patients with Gram-negative sepsis provided they were not in shock, but a second trial failed to confirm this. The other antibody, HA-1A, appeared to protect patients with Gram-negative sepsis who were in refractory shock, but only when they were bacteremic. This antibody was recently released on the market in some european countries. However, the FDA agency decided that a confirmatory study should be done before it could consider to approve HA-1A because a careful reanalysis suggested that the observed differences were only of marginal statistical significance. Therefore, this type of treatment has not yet clearly been shown to benefit patients. More studies are needed to delineate the role of core LPS antibodies in the management of Gram-negative sepsis.     

Complement activation in septic shock due to gram-negative and gram-positive bacteria

Whole serum complement (CH50) and C3, C4, and C3PA plasma values were studied in 48 patients: 9 with nonseptic shock; 20 with sepsis; 14 with septic shock caused by gram-negative bacteria; 5 with septic shock caused by gram-positive bacteria. All were compared with a control group of 25 healthy individuals. Determinations were made upon admission and again 48 and 96 h later. No significant differences in complement values were found between the patients with nonseptic shock and the control group. In the patients with sepsis, decreased CH50 (p less than 0.001) and increased C3PA (p less than 0.02) values were observed, while C3 and C4 remained unaltered. In the patients with septic shock, markedly decreased levels of CH50, C3, and C4 were seen (p less than 0.001, and p less than 0.001, and p less than 0.001, respectively) without changes in C3PA levels. There were no differences between septic shock due to gram-negative and gram-positive bacteria, or between patients who died and those who survived. After 96 h, the altered values returned to the normal range. This underlines the transitory activation of the complement system through the classic pathway and suggests its possible role in the pathogenesis of septic shock in man.     

An improved enzyme linked immunosorbent assay for detection of anti-ranavirus antibodies in the serum of the giant toad (Bufo marinus)

An improved ranavirus antibody ELISA (R Ab ELISA) for the specific detection of anti-ranavirus antibodies in toad sera was developed. Sheep anti-epizootic haematopoietic necrosis virus (EHNV) was used as the antigen-capture antibody. EHNV was used as the antigen and sera from field and challenged toads were used to detect the virus. Rabbit anti-toad IgG and IgM were used to detect bound toad antibody. Pre-absorption of toad sera with a monoclonal antibody, raised against the 50 kDa EHNV protein, improved the specificity of the technique. A blocking ELISA, immunofluorescence and immuno-electron microscopy were used to confirm the validity of the ELISA. The assay has potential use in screening sera from Bufo marinus for the presence of antibodies against ranaviruses and to facilitate understanding of the humoral immunological response in toads during virus infection.     

Activation of the extrinsic coagulation pathway in patients with severe sepsis and septic shock

OBJECTIVES: To obtain systematic information on the extrinsic coagulation pathway, as well as to investigate the time course of the coagulation abnormalities in sepsis. DESIGN: Prospective observational study. SETTING: General intensive care unit. PATIENTS: Nineteen patients with the diagnosis of severe sepsis or septic shock and nine control patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Tissue factor antigen concentration (tissue factor antigen), prothrombin fragment F1+2, thrombin antithrombin III complex, fibrinopeptide A, D-dimer, and antithrombin III concentrations were measured on the day of diagnosis of severe sepsis and septic shock, and on days 1, 2, 3, and 4 after diagnosis. The concentrations of tissue factor antigen, prothrombin fragment F1+2, fibrinopeptide A, and D-dimer were significantly increased in patients with severe sepsis and septic shock compared with control subjects. However, the concentrations of thrombin antithrombin III complex showed no statistical differences between the septic patients and the control subjects. Significantly, low antithrombin III concentrations were observed in the septic patient groups compared with control subjects. With the exception of D-dimer, the concentrations of the hemostatic markers were similar between severe sepsis and septic shock patients. Significant correlations were noted between tissue factor antigen and the disseminated intravascular coagulation score (r2=.236, p< .0001) and the number of dysfunctioning organs (r2=.229, p=.035). CONCLUSIONS: We systematically elucidated coagulation disorders in newly defined sepsis. The extrinsic coagulation pathway is activated in patients with severe sepsis and septic shock. In these patients, enhanced thrombin generation and activation, and fibrin formation were demonstrated when compared with the control subjects. Furthermore, the thrombin generated appears not to be fully neutralized by antithrombin III.     

Sex-associated differences in cold-induced UCP1 synthesis in rodent brown adipose tissue

OBJECTIVE: To evaluate the usefulness of new ELISA for human parvovirus B19 (B19) antibodies and PCR for the diagnosis of acute onset of B19 polyarthritis. METHODS: We evaluated the reproducibility and sensitivity on the detection of anti-B19 antibody by ELISA using recombinant VP-1 and VP-2 (empty particle), and then studied for the prevalence of IgM and IgG B19 antibody in 125 samples for anti-B19 tests. The random study on anti-B19 antibody assay as well as PCR for B19-DNA was also performed in 130 cases with acute onset of arthritis excluding those with known origins, 224 with rheumatoid arthritis and 149 with other categories. RESULTS: The results by using B19-empty particle ELISA were reproducible and showed the assay was a sensitive way for clinical use. IgM anti-B19 antibodies were positive not only in all samples from erythema infectiosum, but also often in those from hemolytic anemia, pure red cell aplasia, fetal hydrops, hepatic injury, fever of unknown origin. Among 130 with acute onset of arthritis, 21 showed positive tests for IgM anti-B19 antibody and/or B19 DNA. On the other hand, 4 among 224 patients with rheumatoid arthritis were positive for IgM anti-B19 antibody, but all of 149 in control group were negative for IgM anti-B19 antibodies and for B19 DNA. CONCLUSION AND DISCUSSION: Anti-B19 ELISA using B19-empty particle which has been introduced as a routine test system, is a useful tool for the diagnosis of acute onset of B19 arthritis. An additional examination using PCR for B19 DNA may contribute for understanding persistent B19 polyarthritis or reactivation of B19 infection.     

Clinical factors relating to the presence of serum anti-GM1 and GD1b antibodies in demyelinating neuropathy--study using a multivariate analysis

We studied clinical factors relating to the presence of serum anti-GM1 and GD1b antibodies in patients with demyelinating neuropathy using a multivariate analysis. Sera were obtained from 46 patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and 33 with Guillain-Barré syndrome (GBS) and kept frozen at -20 degrees C until use. Anti-GM1 and GD1b IgM and IgG antibodies were measured by ELISA at serum dilution of 1:100 and considered to be positive when those values were more than the cut off values determined by means and standard deviations in 35 normal controls. Age, sex, duration, prodromal disease, neurological findings, concentration of CSF protein, nerve conduction, treatment, and outcome were investigated in all patients retrospectively. Multivariate logistic models using all those characteristics were used to clarify the clinical factors relating to the presence of anti-GM1 and GD1b antibodies. In CIDP, anti-GM1 antibodies associated with or without anti-GD1b antibodies were frequently seen in patients with motor dominant neuropathy than those with sensory dominant neuropathy (P = 0.007, odds ratio = 11.6). There was significant difference in anti-GM1 IgM antibodies (P = 0.003, odds ratio = 22.2), but no difference in IgG antibodies. Anti-GM1 antibodies were observed 5 (IgM, 5; IgG, 2) of 7 patients with pure motor neuropathy, 9 (IgM, 8; IgG, 4) of 17 with motor dominant neuropathy, 5 (IgM, 2; IgG, 3) of 16 with sensori-motor neuropathy, and none of 6 with sensory dominant neuropathy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Platelet lactate dehydrogenase activity in systemic lupus erythematosus: correlation with anticardiolipin antibodies

OBJECTIVE: To evaluate lactate dehydrogenase (LDH) activity in platelet subpopulations in systemic lupus erythematosus (SLE) and to correlate platelet LDH activity with concentrations of anticardiolipin antibody (aCL). METHODS: Twelve female patients with SLE and 12 age matched female control subjects were studied. Platelets were separated on the Percoll gradient, their density values controlled by density marker beads. LDH activity was measured after platelet lysis, expressed as nU/fl. ELISA were used to measure levels of IgG and IgM aCL. RESULTS: A significant increase of LDH activity with a significant correlation to IgG and IgM aCL were found in small, light platelets with a volume < 5 mu 3 compared to large, dense platelets and to controls. LDH activity did not correlate with immunoglobulin classes, anti-DNA antibodies, and complement fractions in small and large SLE platelets. CONCLUSION: Our data suggest a possible chronic activation of subpopulations of small platelets in patients with SLE independent of thrombotic process. Low levels of aCL can mediate small platelet activation. Quantitative and qualitative analysis of the small, light platelets can serve a clinical diagnostic purpose as an in vivo platelet activation index in SLE.     

The serological differentiation of acute and chronic schistosomiasis japonica using IgA antibody to egg antigen

Two groups of Schistosoma japonicum infected patients (acute and chronic) and non-infected individuals were studied using IgA antibody to egg antigen (SEA) and IgG and IgM antibodies to keyhole limpet haemocyanin (KLH). The means and standard deviation of the optical density in ELISA of acute, chronic and negative groups for IgA anti-SEA were 583 +/- 124.7, 98.2 +/- 78.8 and 82.2 +/- 39.3, respectively. There was a statistically significance between acute patients and chronic patients (P < 0.01). The means and standard deviation of IgG and IgM antibodies to KLH were 501.5 +/- 150.6, 113.0 +/- 79.1, 28.8 +/- 56.3 and 413.6 +/- 148.5, 70.2 +/- 14.8, 65.3 +/- 45.3, respectively. The detection results of IgA to SEA compared with the IgG and IgM to KLH did not demonstrate a significant difference (P < 0.01). The sensitivities of IgA to SEA and IgG and IgM antibodies to KLH for the detection of acute infection were 95.24%, 90.48% and 85.71%, respectively. Therefore, this study showed that the detection of IgA to SEA is also a useful new method for the serological differentiation of acute and chronic schistosomiasis japonica in humans.     

Humoral immune response against antigen 60 in BCG-vaccinated infants

An ELISA assay based on the A-60 antigen complex from Mycobacterium bovis BCG cytoplasm was used to detect anti-mycobacterial antibodies of different classes in the sera of 63 BCG-vaccinated infants during the 6-month post-vaccination period. The mean IgM and IgA levels increased, whereas the mean IgG level decreased after BCG vaccination. However, in a minority of cases only Ig levels were above the cut-off line: this was true for IgM in 11/63 (17%) cases and for IgA in 14/63 (22%) of cases but none of the tested infants was anti-A60 IgG ELISA positive. Fifty-two infants (83%) were tuberculin-positive eight weeks after vaccination, and no significant difference in mean antibody levels of tuberculin-positive and negative cases was observed, except for IgG (p < 0.05).     

The sepsis syndrome in a Dutch university hospital. Clinical observations

BACKGROUND: Most studies of the cause of sepsis syndrome focus on patients hospitalized in intensive care units. In this study, we analyzed the incidence, cause, and outcome of the sepsis syndrome in all hospitalized patients. METHODS: Clinical and microbiologic data were obtained for 382 patients (5.6% of all patients admitted) from whom blood was drawn for culture. RESULTS: The incidence of the sepsis syndrome was 13.6 per 1000 patients admitted (1.06 per 1000 hospital days), while the incidence of septic shock was 4.6 per 1000. The respiratory tract was the predominant infection site. Of all patients with sepsis syndrome, 38% (n = 35) had positive blood cultures. More than half of these cultures (13 [57%]) were caused by gram-positive microorganisms (excluding patients receiving selective decontamination of the digestive tract and those with intravascular device-related bacteremias). The mortality for patients with sepsis syndrome without shock was 28% (17/61), while for patients with septic shock, it was 55% (17/31). Patients with cardiovascular diseases had a significantly (P < .005) greater risk of dying during a sepsis syndrome episode than patients with other predisposing factors. Multivariate analysis of factors influencing outcome identified the development of shock and an immunocompromised state as being significantly associated with outcome in patients with sepsis syndrome. CONCLUSIONS: Patients fulfilling the criteria for the sepsis syndrome are at great risk of developing septic shock or multiple-organ failure and subsequently dying. In our hospital, the majority of bacteremic episodes were associated with gram-positive microorganisms.