Duration of treatment for candidemia and risk for late-onset ocular candidiasis.

PURPOSE: Few reports have been published on the optimal duration of treatment of ocular candidiasis. We have investigated the incidence of late-onset Candida chorioretinitis and endophthalmitis in patients with candidemia who did not initially receive an ophthalmologic examination. The aim was to determine the duration of initial antifungal treatment that may be sufficient to avoid this complication. METHODS: This was a long-term follow-up study of 144 patients with candidemia who survived for at least 60 days after the onset of candidemia. The frequency of early- and late-onset ocular complications due to candida infection and factors associated with ocular candidiasis were investigated. RESULTS: Fundoscopy was performed on 60 patients, revealing 12 cases of ocular candida infection (20 %). Risk factors were infection with Candida albicans compared to other Candida species (p = 0.021) and surgery due to solid tumor (p = 0.004). Only one case of late-onset ocular candidiasis occurred among the 84 candidemic patients who did not receive an initial ophthalmologic examination. For unknown reasons, this patient had received only 2 days of systemic antifungal treatment initially. CONCLUSIONS: No case of late-onset ocular candidiasis was detected in unexamined patients who received at least 14 days of antifungal treatment. Based on our results, it would appear that the recommended 2 weeks of treatment after the first negative blood culture are sufficient to avoid late-onset complications due to undiscovered Candida chorioretinitis in patients surviving for more than 60 days after the onset of candidemia.

FluoroSpot Analysis of TLR-Activated Monocytes Reveals Several Distinct Cytokine-Secreting Subpopulations.

Monocytes have long been considered a heterogeneous group of cells both in terms of morphology and function. In humans, three distinct subsets have been described based on their differential expression of the cell surface markers CD14 and CD16. However, the relationship between these subsets and the production of cytokines has for the most part been based on ELISA measurements, making it difficult to draw conclusions as to their functional profile on the cellular level. In this study, we have investigated lipoteichoic acid (LTA)- and lipopolysaccharide (LPS)-induced cytokine secretion by monocytes using the FluoroSpot technique. This method measures the number of cytokine-secreting cells on the single-cell level and uses fluorescent detection, allowing for the simultaneous analysis of two cytokines from the same population of isolated cells. By this approach, human monocytes from healthy volunteers could be divided into several subgroups as IL-1ß, IL-6, TNF-α and MIP-1ß were secreted by larger populations of responding cells (25.9-39.2%) compared with the smaller populations of GM-CSF (9.1%), IL-10 (1.3%) and IL-12p40 (1.2%). Furthermore, when studying co-secretion in FluoroSpot, an intricate relationship between the monocytes secreting IL-1ß and/or IL-6 and those secreting TNF-α, MIP-1ß, GM-CSF, IL-10 and IL-12p40 was revealed. In this way, dissecting the secretion pattern of the monocytes in response to TLR-2 or TLR-4 stimulation, several subpopulations with distinct cytokine-secreting profiles could be identified.

Activated protein C (Xigris) treatment in sepsis: a drug in trouble.

Drotrecogin alfa (activated) or recombinant human activated protein C (rhAPC) has been registered for use as adjuvant treatment in severe sepsis since 2001 under the trade name Xigris essentially based on the results from one large clinical trial (the PROWESS trial). In a recently published second randomized clinical trial (the ADDRESS trial), enrolling patients with severe sepsis but with less risk of death, no effect of the treatment was shown, not even a trend to a positive effect in the subgroup of patients with a high risk of death that would match the present prescription label for Xigris. In addition, a large randomized, placebo-controlled trial with rhAPC in paediatric sepsis has recently been terminated prematurely because of lack of efficacy. Altogether, the robustness of the data supporting the use of rhAPC in treating patients with severe sepsis may indeed be questioned. A confirmatory clinical trial is required before rhAPC can be used with confidence. The side-effects and the cost of rhAPC are well documented but its efficacy is not.

Different trends in antibiotic resistance rates at a university teaching hospital.

OBJECTIVES: To investigate long-term trends in antibiotic resistance of common bacterial species isolated at a university hospital and in its intensive care units (ICUs). METHODS: Levels of antibiotic resistance of common bacterial pathogens were investigated at the Karolinska Hospital during the 12-year period 1988-99. Resistance rates were analyzed for the entire hospital, as well as for ICUs combined. RESULTS: At the Karolinska Hospital, we found increased ciprofloxacin resistance among Escherichia coli isolates, from 0% in 1991 to 11% in 1999. In the ICUs, the corresponding increase was from 0% to 4.8% during the same period. Co-trimoxazole resistance levels increased from 7.5% to 14%, with lower levels for the ICUs. For ampicillin, cefuroxime, and gentamicin, the levels of resistance were similar in the whole hospital and in the ICUs. Among Pseudomonas aeruginosa isolates, imipenem resistance was higher in the ICUs. For ciprofloxacin, resistance increased from 2.5% in 1991 to 13% in 1999 in the whole hospital, with similar figures for the ICUs. CONCLUSION: The resistance rates at the Karolinska Hospital were still generally low, but were increasing for some antibiotic-microbe combinations. The results emphasize the importance of including all sectors of a hospital in resistance surveillance studies, and also the value of long surveillance periods.

Postoperative mediastinitis in cardiac surgery - microbiology and pathogenesis.

OBJECTIVE: During 1992-2000, postoperative mediastinitis developed after 126 (1.32%) of 9557 consecutive cardiac surgery procedures. The study was done to describe the variation in clinical characteristics and microbiological etiology in mediastinitis. METHODS: The records of 126 cases of postoperative mediastinitis were reviewed. RESULTS: The median time from operation to the development of mediastinitis was 7 days. Sternal dehiscence was seen in 86 patients (68%). Coagulase negative staphylococci (CNS) were isolated in 46% of the cases with a verified microbiological etiology, Staphylococcus aureus in 26% and gram-negative bacteria in 18%. CNS were more frequently isolated in patients with sternal dehiscence (44/80, 55%) than in patients with stable sternum (10/38, 26%) (P=0.003). However, S. aureus was more frequent in patients with stable sternum (18/38, 47%) than in patients with sternal dehiscence (13/80, 16%) (P<0.001). High body mass index was associated with coagulase negative staphylococci (P<0.001) and with sternal dehiscence (P=0.008). Chronic obstructive pulmonary disease was also associated with sternal dehiscence (P<0.001) and with coagulase negative staphylococci (P=0.04). Patients who had been reoperated before onset of mediastinitis tended to have an increased risk for a gram-negative etiology (32 vs. 15% in patients not reoperated, P=0.06). The overall 90-day all cause mortality in patients with mediastinitis was 19%. High age, need for reoperation before mediastinitis, and a long primary operation time was associated with increased mortality (P=0.02, P=0.007 and P=0.001, respectively). No specific bacterial etiology was associated with increased mortality nor was the presence of bacteriemia. CONCLUSIONS: Three different types of postoperative mediastinitis can be distinguished: (1) mediastinitis associated with obesity, chronic obstructive pulmonary disease, and sternal dehiscence, typically caused by coagulase negative staphylococci; (2) mediastinitis following peroperative contamination of the mediastinal space, often caused by S. aureus, and (3) mediastinitis mainly caused by spread from concomitant infections in other sites during the postoperative period, often caused by gram negative rods. The proposed classification of mediastinitis into three groups with different pathogenic mechanisms may be useful in understanding which prophylactic counter measures have the potentials to be effective in a given situation.

Fewer reoperations and shorter stay in the cardiac surgical ward when stabilising the sternum with the Ley prosthesis in post-operative mediastinitis.

OBJECTIVE: Using the Ley prosthesis, a 0.5mm thick titanium alloy plate for stabilising the sternum, is a new method in the treatment of mediastinitis after open-heart surgery. We report a retrospective analysis of our experience with this device. METHODS: One hundred consecutive cases of post-operative mediastinitis in the period 1992-1997 were reviewed. The primary procedure at reoperation for infection was as follows: 52 patients were treated with the Ley prosthesis and 48 patients underwent other conventional procedures. The choice of the surgical technique depended on the attending surgeon. The prosthesis was used more frequently in patients with sternal dehiscence (P<0.001) but otherwise patients' characteristics were similar in the two groups. As a control population for outcome data, 100 uninfected patients were matched with regard to operative procedure, age, sex and date of surgery. RESULTS: The median hospital stay was 48.5 days in the mediastinitis group vs. 14 days in the control group. The all-cause 90-day mortality in the mediastinitis group was 18% vs. 5% in the control group. The 52 patients treated with the Ley prosthesis had a median length of stay in the cardiac surgery ward for 29 days vs. 41.5 days in the mediastinitis group not treated with the prosthesis (P=0.013). However, when the total length of stay including hospitals outside the cardiac surgery ward was taken into account, the prosthesis did not reduce the length of stay. Only 8/52 patients treated with the prosthesis required further surgery vs. 23/48 patients who were not primarily treated with the prosthesis (P<0.001). The Ley prosthesis had no impact on mortality. CONCLUSION: The Ley prosthesis is a valuable adjunct to the treatment of mediastinitis after open-heart surgery. A shorter stay at the cardiac surgery ward and a reduced need for further surgical procedures were observed when using this prosthesis.

Randomized, placebo-controlled trial of the anti-tumor necrosis factor antibody fragment afelimomab in hyperinflammatory response during severe sepsis: The RAMSES Study.

OBJECTIVE: This study investigated whether treatment with the anti-tumor necrosis factor-alpha monoclonal antibody afelimomab would improve survival in septic patients with serum interleukin (IL)-6 concentrations of >1000 pg/mL. DESIGN: Multicenter, double-blind, randomized, placebo-controlled study. SETTING: Eighty-four intensive care units in academic medical centers in Europe and Israel. PATIENTS: A total of 944 septic patients were screened and stratified by the results of a rapid qualitative immunostrip test for serum IL-6 concentrations. Patients with a positive test kit result indicating IL-6 concentrations of >1000 pg/mL were randomized to receive either afelimomab (n = 224) or placebo (n = 222). Patients with a negative IL-6 test (n = 498) were not randomized and were followed up for 28 days. INTERVENTIONS: Treatment consisted of 15-min infusions of 1 mg/kg afelimomab or matching placebo every 8 hrs for 3 days. Standard surgical and intensive care therapy was otherwise delivered. MEASUREMENTS AND MAIN RESULTS: The study was terminated prematurely after an interim analysis estimated that the primary efficacy end points would not be met. The 28-day mortality rate in the nonrandomized patients (39.6%, 197 of 498) was significantly lower (p <.001) than that found in the randomized patients (55.8%, 249 of 446). The mortality rates in the IL-6 test kit positive patients randomized to afelimomab and placebo were similar, 54.0% (121 of 224) vs. 57.7% (128 of 222), respectively. Treatment with afelimomab was not associated with any particular adverse events. CONCLUSIONS: The IL-6 immunostrip test identified two distinct sepsis populations with significantly different mortality rates. A small (3.7%) absolute reduction in mortality rate was found in the afelimomab-treated patients. The treatment difference did not reach statistical significance.

Preoperative bacterial colonization of the upper airways does not predict postoperative airway infection in children.

The aim of this prospective non-interventional investigation was to study whether preoperative colonization of nasopharynx with potentially pathogenic airway bacteria carried an increased risk for the development of early postoperative bacterial airway infections after heart surgery in preschool children. Of the 91 patients studied, 62 (68%) were colonized preoperatively in the nasopharynx with Moraxella catarrhalis, Streptococcus pneumoniae, Haemophilus influenzae and/or Staphylococcus aureus. Nine children developed postoperative airway infections (four pneumonia, three bacterial bronchitis and two acute otitis media). Preoperative colonization was not significantly associated with increased risk for postoperative airway infection: 6/62 (10%) in colonized vs 3/29 (10%) in non-colonized children. Preoperative nasopharynx cultures in asymptomatic children should be avoided since it is unpleasant for the child, is not cost-effective, and may lead to unnecessary antibiotic treatment.

Mediastinitis after cardiovascular operations: a case-control study of risk factors.

BACKGROUND: An analysis of risk factors for postoperative mediastinitis can lead to a better understanding of the pathogenesis of this complication and to more effective preventive measures. METHODS: This case-control study of 37 patients and 74 matched controls evaluated 54 potential risk factors. RESULTS: Nine variables were significantly associated with increased risk of postoperative mediastinitis: total operation time (p = 0.0013), high body-mass index (p = 0.0033), use of beta-adrenergic drugs before the onset of infection (p = 0.0037), long cardiopulmonary bypass time (p = 0.0072), long aortic cross-clamp time (p = 0.0075), presence of diabetes (p = 0.0122), high body weight (p = 0.0130), and use and duration of temporary pacing wires (p = 0.0293 and p = 0.0241 respectively). In a conditional logistic regression analysis, use of beta-adrenergic drugs before the onset of infection (p = 0.0058; odds ratio 19.7; 95% confidence limits, 2.37 and 163.7) and body mass index (p = 0.0082; odds ratio 1.27; 95% confidence limits, 1.06 and 1.52) were independently associated with a significantly increased risk of postoperative mediastinitis. CONCLUSIONS: Obesity and use of beta-adrenergic drugs, which is indicative of obstructive respiratory problems, were the most important risk factors suggesting that mechanical strain on the sternotomy and sternal instability may precede infection. Targeted preventive measures for these groups could be justified.

Diagnosing sternal wound infections with 99mTc-labeled monoclonal granulocyte antibody scintigraphy.

BACKGROUND: Postoperative mediastinitis is a serious complication of thoracic operations. The diagnosis can sometimes be difficult, especially in cases with subacute clinical presentation. The aim of this study was to assess the clinical use of granulocyte scintigraphy and tomography in the diagnosis of postoperative wound infection and mediastinitis. METHODS: Twenty-nine patients after cardiothoracic operations were included, of whom 5 patients with a normal postoperative course formed the control group. We injected technetium 99m-monoclonal antigranulocyte antibodies and performed single-photon emission computed tomography after 4 and 20 hours. RESULTS: Twenty-three patients had both the early and the later scan; the remaining 6 had only the early scan. Seven scans indicated infection: 3 cases of mediastinitis, 2 cases of superficial wound infection, 1 case of infection in a synthetic aortic graft, and 1 case of osteitis. All were verified by bacterial culture. There was one false-negative scan; this patient had only the early registration and then was explored. CONCLUSIONS: This method when combined with the tomographic scan option is able to distinguish between deep and superficial infections. Two registrations must be made for optimal results.

Randomised, controlled trial of low-dose heparin for prevention of fatal pulmonary embolism in patients with infectious diseases. The Heparin Prophylaxis Study Group.

BACKGROUND: Fatal pulmonary embolism and other thromboembolic complications are common in hospital inpatients. However, there is little evidence on the routine use of pharmacological thromboprophylaxis in non-surgical patients. We assessed the efficacy and safety of low-dose heparin in the prevention of hospital-acquired, clinically relevant, fatal pulmonary embolism in patients with infectious diseases. METHODS: Our study used the postrandomisation consent design. 19,751 consecutive patients, aged 55 years or older, admitted to departments of infectious diseases in six Swedish hospitals, were screened for inclusion in the randomised, controlled, unblinded, multicentre trial. Of the eligible patients, 5776 were assigned subcutaneous standard heparin (5000 IU every 12 h) until hospital discharge or for a maximum of 3 weeks; 5917 were assigned no prophylactic treatment (control group). We sought consent only from the heparin group. Follow-up was for 3 weeks after discharge from hospital or for a maximum of 60 days from randomisation. The primary endpoint was necropsy-verified pulmonary embolism of predefined clinical relevance. FINDINGS: By intention-to-treat analysis mortality was similar in the heparin and control groups (5.3 vs 5.6%, p = 0.39) and the median time from admission to death was 16 days in both groups (IQR 8-31 vs 6-28 days). Necropsy-verified pulmonary embolism occurred in 15 heparin-treated and 16 control-group patients. There was a significant difference between heparin and control groups in median time from randomisation to fatal pulmonary embolism (28 [24-36] vs 12.5 [10-20] days, p = 0.007). This difference corresponds to the duration of heparin prophylaxis. Non-fatal thromboembolic complications occurred in more of the control than of the heparin group (116 vs 70, p = 0.0012). INTERPRETATION: Our findings do not support the routine use of heparin prophylaxis for 3 weeks or less in large groups of non-surgical patients. Further studies are needed to investigate whether heparin prophylaxis of longer duration may prevent fatal pulmonary embolism.

Plasma levels of cytokines in primary septic shock in humans: correlation with disease severity.

Thirteen patients (median age, 20 years) with life-threatening primary septic shock (10 meningococcal, 3 pneumococcal infections) were studied prospectively. All had a short history of sepsis (< or = 24 h) and no severe underlying disease. Two (15%) died. The logarithm of the initial plasma levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-6, IL-1 receptor antagonist (ra), and plasminogen activator inhibitor (PAI)-1 correlated significantly with APACHE II scores (r2 = .67, .57, .68, .81, and .68, respectively). The plasma levels of endotoxin, TNF-alpha, IL-1 beta, and PAI-1 decreased toward normal levels within the first 24 h of treatment, but IL-6 and IL-1ra levels remained high until clinical recovery. On admission, the molar excess of IL-1ra to IL-1 beta was > 2000-fold in 11 of the 13 patients. Acute plasmapheresis in 11 of the 13 patients significantly increased the plasma clearance of TNF-alpha (P = .02).

Endotoxaemia and inflammatory mediators in febrile patients with haematological disease.

OBJECTIVES: To study the pattern of plasma levels of endotoxin, tumour necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6) and C-reactive protein (CRP) in febrile neutropenic patients and to assess the potential diagnostic value of these analyses. DESIGN: Consecutive prospective study. SETTING: Patients treated at the haematology ward at Danderyd Hospital, Sweden. SUBJECTS: Ninety-four patients with fever and haematological disease entered the study (male/female: 59/35) with 176 febrile episodes. INTERVENTIONS: Blood samples were drawn at days 0, 1, 2 and 6 after onset of fever for analysis of, endotoxin, TNF-alpha, IL-6 and CRP. RESULTS: Infectious aetiology was established in 62.5% of the febrile episodes. Blood cultures showed significant growth in 71/176 (40.3%) febrile episodes. Nonbacteraemic bacterial infections were diagnosed in 34/176 (19.3%) episodes. Endotoxin was detected in plasma in 40% of febrile episodes regardless of aetiology. TNF-alpha was detected in 61% and IL-6 in 94% of all febrile episodes. The initial TNF-alpha and IL-6 levels were significantly higher in patients with Gram-negative bacteraemia than in patients with other causes of fever (P < 0.001). In episodes evaluated as successful after empirical antibiotic treatment, a significant (P < 0.001) decrease in CRP concentrations were found on day 6 after onset of fever. CONCLUSIONS: The sustained, low-grade endotoxaemia and persistently elevated levels of TNF-alpha and IL-6 found in febrile patients may reflect a failing mucosal barrier that allows endogenous bacterial products to reach the circulation. The diagnostic value of endotoxin, TNF-alpha, IL-6 and CRP to discriminate between bacteraemic and nonbacteraemic febrile episodes was very limited. The study supports the present policy of broad, empirical antibiotic treatment in patients with haematological disease and fever.

Plasmapheresis in the treatment of primary septic shock in humans.

14 patients (mean age 25.5 yrs) with life-threatening primary septic shock were eligible for treatment with acute plasmapheresis in a prospective study. They had a short history of sepsis and had no severe underlying disease. 10/14 patients had systemic meningococcal disease. All patients were severely ill with a mean APACHE II score of 25.0. 12/14 patients were treated with plasmapheresis exchanging 1 plasma volume within hours of admission. 11/14 patients survived without major sequelae and 3 (21%) died of irreversible septic shock. This mortality is lower than that predicted from the APACHE II scores (55.2%). A subgroup of plasmapheresis-treated patients with septic shock and extensive petechiae were compared to a historical control group. The mortality in the treatment group was 1/7 (14%) versus 8/21 (38%) in the control group. We conclude that acute plasmapheresis may be a therapeutic option in the early stages of severe primary non-surgical septic shock.

Effect of antithrombin concentrate on haemostatic variables in critically ill patients.

In a controlled pilot study of 32 critically ill patients, we have attempted prospectively to identify laboratory variables which can be used to select and monitor patients on antithrombin (AT) therapy. Patients with plasma AT levels less than 70% of normal were randomized to receive (AT group) or not to receive AT concentrate (non-AT group). The groups did not differ in median age, sex, median APACHE II and TISS scores, number of days spent in the Intensive Care Unit or mortality rate. At the time of inclusion all patients had activated coagulation and fibrinolysis demonstrated as high levels of soluble fibrin, thrombin-antithrombin complexes and fibrin-D-dimers (twice, four and ten times the upper reference range, respectively). In the AT group these levels decreased faster and the prothrombin complex concentration increased more rapidly to normal (i.e. the prothrombin time decreased). The level of C-reactive protein which was high in both groups on inclusion (139 and 98 mg/l, respectively) decreased by 40% in the AT group but did not change in the control group. Our study indicates that laboratory variables normalize faster in seriously ill patients who have activated coagulation and fibrinolysis when they receive AT concentrate and that the variables mentioned above seem to be useful for monitoring the treatment.

Hemostasis in Crohn's disease: low factor XIII levels in active disease.

Massive gastrointestinal hemorrhage sometimes occurs in Crohn's disease. To examine the possible role of acquired disorders of hemostasis contributing to such events, several laboratory indicators of hemostasis (APT time, Normotest, platelet count, bleeding time, fibrinogen, factor VIII activity, vWF:Ag, factor X, factor XIII, antithrombin III, fibrinopeptide A, and B beta(15-42] were studied in 10 patients with active Crohn's disease (Crohn's disease activity index (CDAI) greater than 150) and 10 patients with quiescent disease (CDAI less than 150). Marked thrombocytosis was seen in three patients with active disease. Factor VIII activity and fibrinogen levels were significantly elevated in patients with Crohn's disease (p less than 0.001), and the factor VIII activity levels were significantly higher (p less than 0.05) in the patients with active disease than in those with quiescent disease. Factor XIII levels were significantly lower (p less than 0.02) in patients with active disease. Three of the patients with active disease had factor XIII levels below the lower reference limit. The two patients with the lowest levels had hemorrhagic diarrhea and spontaneous bleeding from the rectal mucosa. Fibrinopeptide A and B beta(15-42) levels were significantly elevated in both groups. The other coagulation analyses were essentially normal in both patient groups. The results suggest that factor XIII deficiency acquired through gastrointestinal leakage may contribute to gastrointestinal hemorrhage in some patients with active Crohn's disease.

Prognostic evaluation in meningococcal disease. A retrospective study of 115 cases.

A retrospective study of the medical records of 115 consecutive cases of meningococcal disease with 11 fatalities was carried out in order to evaluate the power of 15 clinical and laboratory variables available on admission in predicting a fatal outcome. On linear discriminant analysis, six variables showed a significant discriminating power in predicting death: low systolic blood pressure, low platelet count, extensive petechiae, high body temperature, low CSF polynuclear cell count and absence of meningism. From a stepwise linear discriminant analysis, two alternative procedures for prognostic evaluation were derived. If a large high risk group is accepted which will include practically all patients at risk of death, a prognostic evaluation based only on systolic blood pressure on admission is sufficient. Alternatively, if unconventional, potentially hazardous therapy is considered for high risk patients, a small high risk group may be defined. Patients with systolic blood pressure less than 100 mm Hg, platelet count less than or equal to 125 X 10(9)/l and body temperature greater than 39 degrees on admission constitute a small group with a very high mortality. A similar risk group was defined if platelet count less than or equal to 125 X 10(9)/l was substituted for extensive petechiae. The advantage of the latter procedure is that only a simple bedside examination is required for the prognostic evaluation.

Fatal pulmonary embolism in hospitalized non-surgical patients.

A retrospective study of autopsy-verified fatal pulmonary embolism at a department of infectious diseases was carried out, covering a four-year period (1980-83). During that time 8 646 patients were hospitalized at the department and 221 patients died. In addition, 103 patients died within 30 days of discharge from the department. Pulmonary embolism was found at autopsy in 38 cases (autopsy rate 78%). In 16 of these patients, acute pulmonary embolism was a major contributing cause of death, otherwise the prognosis would have been favourable. All 16 patients were over 55 years old and all but one were over 65 years old. The incidence of hospital-acquired clinically relevant autopsy-verified fatal pulmonary embolism in these age groups was 0.4 and 0.5%, respectively. In patients with respiratory tract infections, the incidence was 0.7 and 0.8% in the respective age groups.

Further immunological studies of sera containing anti-mitochondrial antibodies, type M 5.

All of 15 sera containing anti-mitochondrial antibodies (AMA), type M 5, reacted in ELISA with ssDNA, whereas only four had anti-nuclear antibodies as demonstrated by immunofluorescence technique. Twelve of 15 had biological false-positive seroreaction for syphilis and seven of 11 cases investigated had a positive lupus anti-coagulant test. Cold agglutinins were present in 11 sera. Hyper-gamma-globulinaemia was not a prominent finding, but C4 values below the lower limit were common in spite of C3 within the normal range. Absorption of IgG fractions from three different sera with cardiolipin eliminated the reaction with ssDNA and mitochondria, supporting a certain degree of cross-reactivity among the antibodies. The presence of AMA, type M 5, seemed to discriminate a group of patients with symptoms often consistent with SLE although some of the most prominent findings were often absent.