Serological markers of Chlamydia pneumoniae infection in men and women and subsequent coronary events; the Scottish Heart Health Study Cohort.

AIMS: To investigate the relationship between serum markers of Chlamydia pneumoniae infection and subsequent coronary events. METHODS AND RESULTS: In a nested case-control study, based on the Scottish Heart Health Study cohort, we estimated IgG, IgA and IgM antibodies to C. pneumoniae, and circulating immune complexes containing C. pneumoniae antigen in baseline serum samples from 217 cases experiencing a subsequent coronary event during follow-up (mean 7.5 years) and from their matched controls. In men, the proportion of specimens positive for IgG, IgA and IgM antibodies showed no case-control differences (80% vs 80%, 57% vs 53% and 3% vs 3%, respectively). The odds ratio for a coronary event was 1.00 (95% confidence interval 0.59-1.69) for the presence of IgG antibodies to C. pneumoniae; 1.21 (0.76-1.92) for IgA and 0.75 (0.17-3.35) for IgM. Similar results were seen in women. The proportion of specimens with circulating immune complexes with C. pneumoniae antigen also showed no case-control differences (12% vs 12%, both sexes combined) with an odds ratio of 1.00 (0.57-1.76). CONCLUSION: Prior infection with C. pneumoniae, as estimated by these markers, does not appear to be a risk factor for subsequent coronary heart disease.

Impact of an infection consultation service for bacteraemia on clinical management and use of resources.

Since 1993, the infection consultation service for bacteraemia has seen 310 patients in the Medical and Surgical Directorates at Ninewells Hospital and Kings Cross Hospital. A random sample of 100 was audited. Case-notes were incomplete for five patients, leaving 95 fully-audited patients. Clinical outcome measures were death from infection, and readmission within 2 weeks of discharge. Initial treatment was inconsistent with antibiotic policy in 46 patients (48%). Antibiotic treatment was changed in 37 (80%) of these patients: increased in intensity in 19 (41%) and decreased in 18 (39%). Changes were also made in 30 (61%) of the 49 patients whose initial treatment was consistent with sepsis policy-increased in seven (14%) and decreased in 23 (47%). Median daily antibiotic costs were lowered in patients whose initial treatment was consistent with sepsis policy (pounds 10.10 vs. pounds 7.28, p = 0.0274). However, in the other patients, savings were balanced by increases (p = 0.7696). Consultation required one consultant session per week (3.5 h) and the audit required an additional 16 consultant sessions. Seven patients died, but only one death was directly related to infection. Six patients were readmitted to hospital within 2 weeks, in three due to recurrence of infection. Changes to treatment were recommended in the majority of patients, regardless of whether initial treatment complied with the sepsis policy. The service primarily redistributed resources rather than reducing costs. A fully audited service requires considerable consultant time, but we believe such time is well spent.

The potential role of Clostridium perfringens alpha toxin in the pathogenesis of acute pancreatitis.

BACKGROUND: Clostridium perfringens is a bowel commensal that can colonise the biliary tract. It produces the alpha toxin (phospholipase C), which can induce spontaneous tissue necrosis. AIMS: To investigate whether there is any evidence that Clostridium perfringens alpha toxin can be detected in acute pancreatitis. METHODS: Serum samples from 21 patients with acute pancreatitis and 22 controls were assayed for C perfringens phospholipase C as well as anti-phospholipase C IgG and IgM; IgG and IgM anti-toxins were measured by enzyme linked immunosorbent assay. RESULTS: In normal healthy controls there is a very high level of natural anti-toxin of both the IgG and IgM class. Of the 21 patients with acute pancreatitis alpha toxin was detected in five (23.8%). Levels of both IgG and IgM anti-toxin were significantly reduced in acute pancreatitis. CONCLUSIONS: The results suggest that there is an abnormality of the immune status to C perfringens alpha toxin in patients with acute pancreatitis. This may be the result of a release of alpha toxin, although it is difficult to state whether this is a primary or secondary phenomenon in these patients. These preliminary results merit further investigation.

The role of a nested polymerase chain reaction in the diagnosis of Pneumocystis carinii pneumonia.

Aim-To compare the techniques and results of a nested PCR and an immunofluorescence assay (IFA) for the detection of Pneumocystis carinii infection; to consider the role of the nested PCR in the diagnosis of P carinii pneumonia (PCP).Methods-Serial dilutions of two known P carinii positive samples were tested by IFA and PCR to determine their relative sensitivities. Seventy eight respiratory samples (15 from 11 patients with HIV infection/acquired immunodeficiency syndrome (AIDS) and 63 from 42 patients with other forms of immunodeficiency) were tested using both assays, and the costs and technical requirements of each assay were assessed.Results-The PCR had a greater relative sensitivity over the IFA of 2 x 10(1) to 2 x 10(3) fold in a postmortem lung sample and 2 x 10(5) to 2 x 10(6) fold in a bronchoalveolar lavage sample from a patient with PCP. P carinii was detected in all 15 samples from the patients with HIV/AIDS by both IFA and PCR. Of the 63 samples from the patients with immunodeficiencies other than HIV/AIDS, the PCR was more sensitive than IFA.Conclusions-The nested PCR is a more sensitive assay than the IFA. It may be useful in the diagnosis of PCP in patients with immunodeficiencies other than HIV/AIDS. Similarly, PCR may be of benefit for this patient group as less invasive specimens are needed. PCR has an increasing role to play in the diagnosis of PCP in the routine laboratory.

Evidence that oilseed rape (Brassica napus ssp. oleifera) causes respiratory illness in rural dwellers.

A study of 25 residents in a small Scottish village over a two-year period investigated respiratory symptom reporting in the presence or absence of oilseed rape. Symptom reporting in the year when oilseed rape virtually surrounded the village, varied during the growing season of the crop and was at its highest coincident with peak flowering. At the same period of the following year when the crop was absent, symptom reporting was significantly lower. The symptoms which correlated most strongly with peak oilseed rape flowering were sneezing, cough, headache, eye irritation and the total of these and other symptoms. Increased symptoms were reported by 12 of the participants though only seven of these were judged to be atopic. The symptoms did not correlate with levels of oilseed rape pollen but there is no clear evidence as to which of the other factors associated with the crop might be the cause.

Development of an ELISA assay for Clostridium perfringens phospholipase C (alpha toxin).

A new method for the assay of Clostridium perfringens alpha toxin (phospholipase C) is described using a sandwich ELISA. This assay has been shown to be quantitative, to have a high specificity for the toxin and is capable of detecting purified Clostridium perfringens phospholipase C at concentrations of as little as 0.005 units/ml in cooked meat culture medium.

Antigenic heterogeneity of strains of Saccharomyces cerevisiae and Candida albicans recognised by serum antibodies from patients with Crohn's disease.

The antigenic heterogeneity of twelve strains of Saccharomyces cerevisiae and serovar A and B strains of Candida albicans was investigated by cross-absorption of serum antibodies from a patient with Crohn's disease. On the basis of common antibody absorption patterns, eleven of the yeast strains were divided into Group 1 (five S. cerevisiae), Group 2 (two C. albicans, one S. cerevisiae) and Group 3 (three S. cerevisiae). The remaining three S. cerevisiae strains (Group 4) showed unique absorption patterns. The antigenic relationship between S. cerevisiae and C. albicans was further studied by cross-absorption of sera from eight patients with Crohn's disease. This confirmed a limited degree of cross-reaction between most strains of S. cerevisiae and C. albicans, but C. albicans serovar B significantly absorbed antibodies to more S. cerevisiae strains than did C. albicans serovar A. The results demonstrate considerable antigenic heterogeneity of S. cerevisiae and suggest that the elevated serum antibody levels to S. cerevisiae found in Crohn's disease are directed against multiple antigens.

The effect of dietary yeast on the activity of stable chronic Crohn's disease.

The effect of dietary yeast on the activity of stable Crohn's disease was assessed in 19 patients. During the 1st month patients continued their usual diet (base-line period), but during the next 2 months dietary yeast was excluded except that during 1 month patients took baker's yeast capsules while for the other month they took placebo capsules. The patients' mean Pettit Crohn's disease activity index (CDAI) while taking baker's yeast (mean, 107.9; SE, 6.1) was significantly greater than during yeast exclusion (mean, 102.1; SE, 5.7; p less than 0.05). The mean of each patient's maximum CDAI during yeast exclusion (mean, 107.1; SE, 5.7) was significantly lower than those during the base-line (mean, 115.2; SE, 6.1; p less than 0.05) and baker's yeast inclusion periods (mean, 113.9; SE, 6.7; p less than 0.05). Patients with elevated yeast antibodies tended to develop a higher CDAI while receiving baker's yeast (13 of 15). These results suggest that dietary yeast may affect the activity of Crohn's disease.

Dextran antibodies, complement conversion and circulating immune complexes after intravenous iron dextran therapy in dialysed patients.

Serum immune complexes, plasma dextran antibodies and percentage conversion of complement have been measured in 20 dialysed patients before and after an intravenous infusion of iron dextran providing 600 mg elemental iron. Complement conversion was unmeasurable and there were no changes in circulating immune complexes. The presence of dextran antibodies in nine patients before the infusion was not related to prior exposure to iron dextran. They became undetectable in these patients within hours after the infusion, reappearing 1 month later in three. Two of three patients reporting mild aches and shivers on the day following the infusion had no detectable dextran antibodies. An adverse reaction involving inflamed joints occurred 1-2 days after a second infusion given to one of the patients studied above. The parameters under study were again measured and did not appear to relate to the reaction. The presence of dextran antibodies does not preclude the giving of iron dextran to patients on dialysis, and the immune complex and complement systems remain undisturbed by iron dextran infusions.

The role of the spleen in the immune response following naturally acquired exposure to encapsulated bacteria.

Female New Zealand White Rabbits following splenectomy (n = 9), splenectomy with 50% splenic autotransplantation (n = 8) and sham laparotomy (n = 9) have been serially exposed to type 2 Streptococcus pneumoniae and Haemophilus influenzae by aerosol inhalation. Animals were sampled for 3 weeks after exposure and the IgG and IgM type-specific antibody response measured by enzyme-linked immunosorbent assay. Haemophilus influenzae initiated a substantial anti-haemophilus IgG response which was not diminished by splenectomy. The anti-haemophilus IgM response was present in sham-operated animals, absent following splenectomy, and partially restored by splenic autotransplantation. Type 2 Streptococcus pneumoniae induced a minimal IgG and IgM antibody response in all animals irrespective of the presence or absence of a spleen. The results support the role of the spleen in mediating IgM production against polysaccharide encapsulated bacteria. The differential degree of immune response produced by the two organisms may explain in part the differential frequency with which these two organisms infect man following splenectomy.

Antibody to selected strains of Saccharomyces cerevisiae (baker's and brewer's yeast) and Candida albicans in Crohn's disease.

IgG serum antibody was measured by ELISA in patients with Crohn's disease (15), ulcerative colitis (15), and in normal controls (15) to 12 strains of Saccharomyces cerevisiae (baker's and brewer's yeast) and to the two major serotypes of the commensal yeast Candida albicans. Antibody to 11 of the 12 strains of S cerevisiae was raised in patients with Crohn's disease but not in patients with ulcerative colitis when compared with controls (p less than 0.001). The pattern of antibody response to these 11 strains was variable, however, suggesting the likelihood of antigenic heterogeneity within the species. Antibody to C albicans was not significantly different in patient and control groups. The specificity of this unusual antibody response in Crohn's disease for S cerevisiae suggests that it is not simply the result of a generalised increase in intestinal permeability. Furthermore, because brewing and baking strains detected the response, the relevant antigen(s) are presumably common in the diet. Hypersensitivity to dietary antigens may be involved in the pathogenesis of Crohn's disease, and the role of S cerevisiae requires further investigation.