Hepatitis E, Helicobacter pylori and peptic ulcers in workers exposed to sewage: a prospective cohort study.

BACKGROUND: Workers exposed to sewage may have an increased risk of infection by Helicobacter pylori and hepatitis E virus (HEV). OBJECTIVES: To assess the incidence of clinical hepatitis E and peptic ulcers and the seroconversion rate of antibodies to H pylori and HEV in workers with and without sewage exposure. METHODS: 332 workers exposed to sewage and a control group of 446 municipal manual workers (61% participation rate) entered a prospective cohort study with clinical examination and determination of antibodies to H pylori and HEV (immunoglobulins G and A or G and M, respectively). Survival curves were examined with log rank tests and Cox regressions. Travelling to endemic areas, socioeconomic level, age, country of childhood, number of siblings, and personal protective equipment were considered as the main confounding factors. RESULTS: Incidence of clinical hepatitis E was not increased in sewage workers. One peptic ulcer and three eradications were recorded in sewage workers compared with no peptic ulcers and 12 eradications in control workers. Incidence rates of approximately 0.01, 0.10, and 0.15 seroconversion/person-year for hepatitis E, H pylori IgG and H pylori IgA, respectively, were found in both exposed and non-exposed workers. Survival curves did not show an increased risk in sewage workers and no association with any exposure indicator was found. Sensitivity analyses did not alter these results. CONCLUSIONS: Sewage does not appear to be a source of occupational infection by H pylori or HEV in trained sewage workers with personal protective equipment working in a region with good sanitation.

Mitogenic signal transduction in T lymphocytes in microgravity.

The activation by concanavalin A Con A of human peripheral blood lymphocytes (PBLs) in the presence of monocytes as accessory cells was investigated in cultures exposed to microgravity conditions in Spacelab. Activation of T cells was measured as incorporation of [3H]thymidine into DNA, secretion of interleukin-2 (IL-2), and interferon-gamma, and expression of IL-2 receptors. Whereas, as discovered in earlier experiments, the activation of resuspended T cells is strongly inhibited, activation of cells attached to microcarrier beads is more than doubled in microgravity. The results suggest that the depression of the activation in resuspended cells may be attributed to a malfunction of monocytes acting as accessory cells. In fact, although the ultrastructure of resuspended monocytes is not altered in microgravity, the secretion of IL-1 is strongly inhibited. Our data suggest that (1) IL-2 is produced independently of IL-1, (2) IL-1 production is triggered only when monocytes (and lymphocytes?) adhere to microcarriers, (3) the expression of IL-2 receptors depends on IL-1, and (4) provided sufficient IL-1 is available, activation is enhanced in microgravity. Finally, cultures of resuspended PBLs and monocytes in microgravity constitute a complete and natural system in which monocytes are not operational. This may be useful for studies of the role of accessory cells and cell-cell interactions in T lymphocyte activation.

IL-10 levels in cerebrospinal fluid and serum of patients with severe traumatic brain injury: relationship to IL-6, TNF-alpha, TGF-beta1 and blood-brain barrier function.

Controlling the extent of inflammatory responses following brain injury may be beneficial since posttraumatic intracranial inflammation has been associated with adverse outcome. In order to elucidate the potential role of anti-inflammatory mediators, the production of interleukin-10 (IL-10) was monitored in paired cerebrospinal fluid (CSF) and serum of 28 patients with severe traumatic brain injury (TBI) and compared to control samples. The pattern of IL-10 was analyzed with respect to the patterns of IL-6, tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta1 (TGF-beta1) in both fluids during a time period of up to 22 days. In parallel, the function/dysfunction of the blood-brain barrier (BBB) was monitored using the CSF-/serum-albumin quotient (Q(A)) and compared to intrathecal cytokine levels. Mean IL-10 concentration in CSF was elevated in 26 out of 28 TBI patients (range: 1.3-41.7 pg/ml) compared to controls (cut-off: 1.06 pg/ml), whereas only seven patients had elevated mean IL-10 concentration in serum (range: 5.4-23 pg/ml; cut-off: 5.14 pg/ml). The time course of IL-10 was similar in both fluids, showing a peak during the first days and a second, lower rise in the second week. Intrathecal IL-10 synthesis is hypothesized since CSF-IL-10 levels exceeded serum-IL-10 levels in most of the patients, IL-10-index (CSF/serum-IL-10/QA) was elevated in 23 individuals, and elevation of CSF-IL-10 showed to be independent from severe BBB dysfunction. Neither CSF nor serum IL-10 values correlated with the dysfunction of the BBB. IL-10, IL-6 and TGF-beta1 showed similar patterns in CSF over time, whereas rises of TNF-alpha corresponded to declines of IL-10 levels. Our results suggest that IL-10 is predominantly induced intrathecally after severe TBI where it may downregulate inflammatory events following traumatic brain damage.

S-100 beta reflects the extent of injury and outcome, whereas neuronal specific enolase is a better indicator of neuroinflammation in patients with severe traumatic brain injury.

It has been hypothesized that immunoactivation may contribute to brain damage and affect outcome after traumatic brain injury (TBI). In order to determine the role of inflammation after TBI, we studied the interrelationship of the immune mediators sICAM-1 and IL-6 with the levels of S-100beta and neuronal specific enolase (NSE), both recognized markers of brain damage. In addition, the extent and type of cerebral injury and the neurological outcome were related to these measured markers of injury. An evident elevation of S-100beta (range of means: 2.7-81.4 ng/mL) and NSE (range of means: 2.0-81.3 ng/mL) was observed in CSF of all 13 patients during the first 3 posttraumatic days and decreased over 2 weeks. In parallel, the production of sICAM-1 (range of means: 0.7-11.9 ng/mL) and IL-6 (range of means: 0.1-8.2 ng/mL) was also markedly enhanced in CSF. The CSF means of S-100beta and NSE per patient correlated with IL-6 (r = 0.60, p < 0.05; and r = 0.64, p < 0.05, respectively), whereas the corresponding means in serum showed a significant correlation only between NSE and IL-6 (r = 0.56, p < 0.05). Maximal CSF values of NSE and sICAM-1 correlated with each other (r = 0.57, p < 0.05). The contusion sizes assessed on the CT scans correlated with the means of S-100beta (r = 0.63, p < 0.05) and NSE (r = 0.71, p < 0.05) in CSF and with the mean of S-100beta in serum, although not statistically significant (r = 0.52, p = 0.06), but not with serum NSE. Interestingly, linear regression analysis demonstrated that means of S-100beta in CSF (r = 0.78, p = 0.002) and serum (r = 0.82, p < 0.001) correlated with the GOS. These results indicate that the elevation of these parameters in CSF depends on the extent of injury and that S-100beta may be a predictor of outcome after TBI, whereas NSE reflects better the inflammatory response.

Interleukin-6 and its soluble receptor in serum and cerebrospinal fluid after cerebral trauma.

Interleukin-6 (IL-6) and its soluble receptor (sIL-6-R) were measured in cerebrospinal fluid (CSF) and serum of 11 severely head injured patients for up to 3 weeks following trauma. IL-6 increased immediately after injury displaying much higher concentrations in CSF than in serum (n = 11). Differently, median levels of sIL-6-R remained in the normal ranges being 10 times higher in serum than in CSF. However, increased amounts over control levels were found in CSF (n = 7) and intrathecal release of sIL-6-R was also suggested (n = 7). Although no correlation with the extent of cerebral lesion or with clinical outcome was evident, elevation of sIL-6-R in CSF supports a pivotal role for IL-6/sIL-6-R complex in the injured brain.

Increased interleukin-12 levels in human cerebrospinal fluid following severe head trauma.

An overwhelming intracranial inflammatory response occurs as a consequence of severe head trauma, leading to cerebral edema and secondary brain injury. Cytokines are important mediators of post-traumatic cerebral inflammation. In the present study, levels of interleukin-12 (IL-12), a pro-inflammatory cytokine which activates cellular immune response mechanisms, were measured by ELISA in 140 matched serum and ventricular cerebrospinal fluid (CSF) samples from ten patients with severe traumatic brain injury. The mean IL-12 CSF levels were significantly elevated in all patients in the course of 14 days after trauma, compared to CSF samples from 15 control patients. Assessment of the IL-12 CSF/serum ratio and of the blood-brain barrier function, using the CSF/serum albumin ratio, suggest that elevated IL-12 CSF levels might be in part derived from intracerebral cytokine synthesis.

Clinical outcome and immunology of postoperative arginine, omega-3 fatty acids, and nucleotide-enriched enteral feeding: a randomized prospective comparison with standard enteral and low calorie/low fat i.v. solutions.

In a prospective randomized trial in patients undergoing major abdominal surgery, the impact of a new enteral formula supplemented with arginine, omega-3 fatty acids, and nucleotides (A, n = 14) on immunological parameters was compared with a standard enteral formula (B, n = 14) and a low calorie/low fat intravenous solution (C, n = 13). Four days postoperatively, a statistically significant decrease in total leukocyte count (A, 9.0 +/- 2.9; B, 8.0 +/- 2.4; C, 11.1 +/- 3.5 x 10(6) cells/mL; A versus C, B versus C; p < 0.05), higher percentage of lymphocytes (A, 14.3 +/- 4.9; C, 8.2 +/- 6.1; p < 0.05), and decreased median CRP levels (A, 80.4 [69.9]; B, 70 [74]; C, 88.5 [142] in mg/L; A versus C, p < 0.05; B versus C; p < 0.05) were observed in the enteral nutrition groups. The expression of activated surface antigen HLA-DR was diminished on CD14+ cells over 4 d (A, 58.2 [39.2]; B, 52.2 [36.2]; C, 76.6 [25.2] in %; A versus C, p < 0.05; B versus C, p < 0.05) and 8-10 d (A, 37.9 [31.4]; C, 58.5 [37.6]; p < 0.05) postoperatively. Significantly enhanced median phagocytic activity of CD14+ monocytes and granulocytes was observed in group C 8-10 days postoperatively (A, 83.3 [11.8]; B, 71.6 [34.1]; C, 87.4 [10.8]; A versus B, B versus C, p < 0.05; and A, 75.7 [10.0]; B, 69.0 [37.8]; C, 80.0 [10.1] in %, B versus C, p < 0.05, respectively). Postoperative hospital and intensive care unit stay was similar among the three groups; however, infectious complications were less frequent in group A (A versus C, p = 0.15). Thus, a modified enteral nutritional support and supplementation may influence the immune competence toward a more efficient defense response.

Hepatitis E, Helicobacter pylori, and gastrointestinal symptoms in workers exposed to waste water.

BACKGROUND: Workers exposed to sewage may have an increased risk of infection by Helicobacter pylori and hepatitis E virus (HEV). AIMS: To assess the prevalence of clinical hepatitis E (HE) and peptic ulcer disease as well as the seroprevalence of antibodies to H pylori and HEV in workers with and without sewage exposure and to look for symptoms due to exposure to endotoxin. METHODS: In the first year of a prospective cohort study 349 sewage exposed workers and 429 municipal manual workers (participation: 61%) underwent a complete medical examination. Travelling to endemic areas, socioeconomic level, age, country in which childhood was spent, and number of siblings were considered as the main confounding factors. RESULTS: Peptic ulcer disease and clinical HE did not occur more often in workers exposed to sewage. Prevalence of antibodies to HEV was 3.3% and overall prevalence of IgG antibodies to H pylori was 42% with large differences between subgroups. Logistic regression did not show an increased risk of seropositivity or antibodies to parietal cells in sewage exposed workers, but disentangling the effect of exposure from that of confounders was extremely difficult. No increase of symptoms due to exposure to endotoxin was found in sewage workers, with the exception of diarrhoea. CONCLUSIONS: No clear increased risk of infection by H pylori or by HEV in workers exposed to sewage was found in this cross-sectional study, but these results need to be confirmed by follow up.

Tumor necrosis factor alpha levels in cats experimentally infected with feline immunodeficiency virus: effects of immunization and feline leukemia virus infection.

Tumor necrosis factor alpha (TNF alpha) levels were determined by enzyme-linked immunosorbent assay (ELISA) and by cell culture bioassay in supernatants of lipopolysaccharide-stimulated feline monocyte cultures and in cat serum samples. There was a good correlation between the results obtained by the two methods. From the fact that TNF alpha was neutralized quantitatively by antibodies to human TNF alpha in feline monocyte supernatants and in feline sera, it was concluded that feline TNF alpha immunologically cross-reacts with human TNF alpha and that the human TNF alpha ELISA can be used to quantitate feline TNF alpha. During the first 6 months after experimental feline immunodeficiency virus (FIV) infection no differences in serum TNF alpha values were observed between infected and non-infected cats. TNF alpha levels increased significantly after primary vaccination with a feline leukemia virus (FeLV) vaccine in FIV infected cats over those in the non-infected controls. During secondary immune response TNF alpha levels rose transiently for a period of a few days in both the FIV positive and the FIV negative cats. After FeLV challenge, TNF alpha levels increased in all animals challenged with virulent FeLV for a period of 3 weeks. This period corresponded to the time necessary to develop persistent FeLV viremia in the control cats. It was concluded from these experiments that in the asymptomatic phase of FIV infection no increased levels of TNF alpha are present, similar to the situation in asymptomatic HIV infected humans. Activation of monocytes/macrophages in FIV infected cats by stimuli such as vaccination or FeLV challenge readily leads to increased levels of TNF alpha.

Expression pattern of cytokines in the different compartments of the feto-maternal unit under various conditions.

Concentrations of five cytokines, GM-CSF, G-CSF, IL-1, IL-6 and IL-8, were determined within five compartments under four different conditions: at the time of a Caesarean section performed between 25 and 38 weeks' gestational age in normal pregnancy without uterine contraction (n = 12), in normal pregnancy with labour already established (n = 8), in pregnancy complicated by amniotic infection (n = 11), or under the conditions of preeclampsia with fetal intrauterine dystrophy (n = 13), cytokine concentrations were determined in fetal arterial and venous blood, in amniotic fluid, and in retroplacentally obtained maternal blood and peripheral maternal blood. With dystrophy, the concentrations of GM-CSF, G-CSF and IL-1 were about 20-50% lower (P < 0.01) in the amniotic fluid, and IL-6 and IL-8 were elevated in maternal peripheral blood (P < 0.01) but not within maternal retroplacental blood. Thus, preeclampsia/intrauterine dystrophy is characterized by reduction of some cytokines within the amniotic fluid compartment and concomitant reactive augmentations of other cytokines within the maternal and fetal organism. With amniotic fluid infection, concentrations of G-CSF, IL-6 and IL-8 were elevated in all compartments (P < 0.001) but GM-CSF and IL-1 showed a significant rise only within amniotic fluid and retroplacental maternal blood (P < 0.001), a rise that was apparently not transmitted to peripheral maternal or fetal blood. Care was taken to exclude the presence of uterine contractions in the group of controls, because this condition by itself causes severe elevation of cytokine concentrations, which are pronounced within amniotic fluid.

[Relevant immunological profiles]. / Relevante Immunprofile.

In 1980 more than 200,000 immunological tests were performed in the Section of Clinical Immunology, Department of Medicine, University Hospital, Zurich (Switzerland), a fact which raises the question whether the results warrant the effort involved. To answer this question of clinical relevance, 4 disease complexes have been investigated: lupus erythematodes, systemic affections dominated by arthralgia, hepatitis and thyroiditis. The analysis shows that no single factor but only an optimized set of tests is capable of distinguishing between related diseases. Follow-up studies are of prime importance because the sequence of antigen expression and antibody responses provides valuable additional information. Laboratory results can be evaluated only in conjunction with the clinical picture.

[IgG-IgM cryoglobulinemia with a purpura-arthralgia-nephritis syndrome]. / IgG-IgM-Kryoglobulin ämie mit Purpura-Arthralgie-Nephritis-Syndrom.

The clinical and laboratory features in 7 patients with essential mixed cryoglobulinemia are presented. The clinical picture was characterized by arthralgia, purpura and glomerulonephritis (3 patients). The cryoprecipitate consisted of IgM and IgG, the IgM being monoclonal (3 patients) with anti-IgG activity. Depressed C4 and/or C3 values were detected in 5 patients and were not correlated with the presence of nephritis. The IgM levels were elevated in 5 patients. The possibility that the disorder represents an immune complex mediated vasculitis is supported by the ability of the cryoglobulins to activate the complement system and by the detection of immunoglobulins and/or complement in the vasculitic lesions in the glomerula or the skin. Treatment by plasma exchange, steroids and azathioprine or cyclophosphamide was followed by a definite improvement in the purpura and the arthralgia, whereas the proteinuria, microhematuria and hypocomplementemia were not affected by therapy.

CA 242 is a new tumor marker for pancreatic cancer.

BACKGROUND: The tremendous progress in imaging techniques over the past few years has not resulted in an earlier diagnosis of pancreatic cancer (PC). The search for a noninvasive diagnostic tool, capable of early diagnosis, led to the development of a series of tumor markers. This article discusses the evaluation of the latest one--CA 242--and its comparison with established markers such as CA 19.9, CA 50, and carcinoembryonic antigen (CEA). METHODS: The markers were tested in preoperative serum samples collected from 300 patients and 30 healthy controls between April 1986 and May 1991. There were 68 patients with ductal carcinoma of the pancreas, 24 with other pancreatic tumors, 57 with acute pancreatitis, 29 with chronic pancreatitis (CP), 90 with benign disease of the upper gastrointestinal tract, and 32 with malignant disease. The test for CA 242 consisted of a DELFIA research kit (WALLAC OY, Turku, Finland) with a cutoff level of 20 U/ml. The other markers were tested with commercially available kits. RESULTS: Sensitivities for PC in this population, with other malignant neoplasms accounting for 16% of the group, were 66.2%, 70.6%, and 70.6% for CA 242, CA 19.9, and CA 50, respectively (90% specificity level). The best results were achieved with the combination of CA 242 and CA 50, reaching a sensitivity of 75.0%. The differential diagnosis between PC and CP could be made with a sensitivity of 64.7%, 79.4%, and 77.9%, respectively, for the three markers. CONCLUSIONS: The authors conclude that, on its own, CA 242 does not improve the sensitivities reached with CA 19.9 and CA 50, but the combination does achieve both a higher sensitivity and specificity.

[Serum immunoglobulins during immunosuppressive therapy following kidney transplantation]. / Serumimmunglobuline unter immunsuppressiver Therapie nach Nierentransplantation.

Immunoglobulins IgG, IgA and IgM and the complement factor C'3 were measured in the serum of 103 kidney allograft recipients. As compared to those in 50 patients on hemodialysis treatment, 100 hospitalized patients and 100 blood donors, the mean values for IgA, IgG and C'3 were significantly decreased. IgM was higher than in blood donors. The longitudinal profile in 6 transplant patients showed remarkably stable immunoglobulin concentrations. No association between low IgG levels and infections or rejection episodes was observed.

Immunological abnormalities and HLA antigen frequencies in IgA deficient patients with epilepsy.

Twenty-three epileptics with constitutional factors for seizures and low IgA serum concentrations were studied. Imbalance of the IgG subclasses was often observed, the IgG4 being undetectable in 13 (65%) patients. The percentage of circulating lymphocytes positive for surface immunoglobulins was normal except for slightly increased values for IgA in six (28.5%) patients. Of the epileptics, 48% showed subnormal proportions of lymphocytes forming spontaneous rosettes. There was a distinct trend for HLA-A2 antigen in the patients tested.

[The tumor markers CA 19.9, Ca 50 and CEA in the differential diagnosis of pancreatic carcinoma]. / Die Tumormarker CA 19.9, CA 50 und CEA in der Differentialdiagnose des Pankreaskarzinoms.

The tumour markers CA 19.9, CA 50 and CEA were measured preoperatively in 178 patients with symptoms of the upper abdomen and in 30 healthy individuals. Raising the cutoff of CA 19.9 and CA 50 and combining the three markers resulted in a sensitivity of 81.5% and a specificity of 86.7%. With increasing local tumour size and tumour spread, a non-significant tendency to greater tumour marker concentrations was observed. The tumour markers tested proved of great value in differentiating between pancreatic cancer and chronic pancreatitis. Sensitivity and specificity in this context were 81.5% and 100% respectively. In postoperative follow-up and in evaluation of new therapy regimens we recommend CA 19.9 as the marker most closely related to tumour progression or recurrence.

IgA deficiency, epilepsy, and hydantoin medication.

Serum-immunoglobulin concentrations were measured in 364 patients with epilepsy. On dividing the patients into those treated with or without hydantoins, and according to possible aetiological factors, a characteristic pattern emerged. Irrespective of the treatment given, the mean values of IgA were significantly reduced in patients in whom constitutional factors were apparent, including those with familial prevalence of seizures. While IgA was rarely found below 0-6 mg/ml, a limit chosen to define IgA deficiency in patients not treated with hydantoins, the IgA level was subnormal in 20-25% of the patients treated with such drugs. In contrast, the mean concentration of IgA was normal and no individual subnormal values were observed in epileptic patients treated with or without hydantoins whose disease was thought to be secondary to traumatic or infectious events or to metabolic disturbances. The data suggest that epilepsy with constitutional characteristics might predispose to low IgA, but that IgA deficiency only occurs when hydantoins are given. Whether this postulated predisposition is relevant to the aetiology or pathogenesis of epilepsy remained unresolved.

[Prevalence and significance of ant-HCV-antibodies in ambulatory patients with raised transaminases]. / Prävalenz und Bedeutung von Anti-HCV-Antikörpern bei ambulanten Patienten mit erhöhten Transaminasen.

From November 1989 to April 1990 we analyzed prospectively the prevalence of anti-hepatitis C virus antibodies and the possible mode of infection in 90 outpatients with repeatedly elevated alanine-aminotransferase levels. The clinical and serological course of these patients was evaluated after 1, 3 and 6 months. Initially, 24 patients (26.6%) were positive for anti-HCV antibodies, but subsequently only 14 of these patients (15.5%) were positive in the follow-up tests. 9 patients (10%) showed no antibodies against HCV in control evaluations and one patient dropped out of the investigation. The 9 patients with a negative result in the control tests had median relative anti-HCV concentrations of 2.0 (range 1.2-4.1) in contrast to 5.5 (range 1.6-256.5) in the 14 patients with a confirmed anti-HCV test (p less than 0.001). None of those 9 patients had received blood transfusions, 7 had consumed drugs intravenously and only 2 had no specific risk for HCV infection. The consistently anti-HCV positive patients had median alanine-aminotransferase levels between 115 and 200 U/l, whereas the levels in initially anti-HCV positive and subsequently negative patients ranged from 75-90 U/l. The initial prevalence of anti-HCV antibodies in 26.6% of our patients is related to the high rate of either false positive results or sero-conversion in 38% of this group. We recommend cautious interpretation of anti-HCV test results with relative anti-HCV concentrations less than or equal to 2 in equivocal clinical situations.