Claes Söderström

Hepatocyte Growth Factor Levels in Cerebrospinal Fluid: A Comparison between Acute Bacterial and Nonbacterial Meningitis

The organotrophic functions of the hepatocyte growth factor (HGF) have been the subject of several studies. In the more recent studies, this function has been reported in the brain. In the present study, we have measured the levels of HGF in cerebrospinal fluid (CSF) and sera from 78 patients divided into 6 different groups according to central nervous system (CNS) infection and control. Quantitative measurements of HGF in the CSF and serum were performed by an enzyme-linked immunosorbent assay. Elevated values of CSF HGF were found in the patients with acute bacterial/probable bacterial meningitis (P<.001), compared with nonbacterial CNS infections and facial palsy, as well as with a control group without signs of CNS involvement. The values of CSF HGF were not correlated to blood-brain-barrier disruption in the groups. These observations might indicate an intrathecal production of HGF in acute bacterial/probable bacterial meningitis.

Vaccination responses to capsular polysaccharides of Neisseria meningitidis and Haemophilus influenzae type b in two C2-deficient sisters: alternative pathway-mediated bacterial killing and evidence for a novel type of blocking IgG.

Meningitis caused by Neisseria meningitidis serogroup W-135 was diagnosed in a 14-year-old girl with a history of neonatal septicemia and meningitis caused by group B streptococci type III. C2 deficiency type I was found in the patient and her healthy sister. Both sisters were vaccinated with tetravalent meningococcal vaccine and a conjugate Haemophilus influenzae type b vaccine. Three main points emerged from the analysis. First, vaccination resulted in serum bactericidal responses demonstrating anticapsular antibody-mediated recruitment of the alternative pathway. Second, addition of C2 to prevaccination sera produced bactericidal activity in the absence of anticapsular antibodies, which suggested that the bactericidal action of antibodies to subcapsular antigens detected in the sera might strictly depend on the classical pathway. A third point concerned a previously unrecognized type of blocking activity. Thus, postvaccination sera of the healthy sister contained IgG that inhibited killing of serogroup W-135 in C2-deficient serum, and the deposition of C3 on enzyme-linked immunosorbent assay plates coated with purified W-135 polysaccharide. Our findings suggested blocking to be serogroup-specific and dependent on early classical pathway components. Retained opsonic activity probably supported postvaccination immunity despite blocking of the bactericidal activity. The demonstration of functional vaccination responses with recruitment of alternative pathway-mediated defense should encourage further trial of capsular vaccines in classical pathway deficiency states.

Candida glabrata prosthesis infection following pyelonephritis and septicaemia.

Candida glabrata is a well-known cause of lower urinary tract infections. Systemic infections caused by this organism are less common, but have increased dramatically in recent years. Prosthesis infection caused by C. glabrata is extremely rare. We report a case of prosthesis failure due to C. glabrata 5 y after candidaemia and pyelonephritis caused by this organism. The same C. glabrata strain was isolated from both infections, as confirmed by the random amplified polymorphic DNA (RAPD) method.

Flucloxacillin-induced Cholestatic Liver Damage

Two female patients (75 and 68 yr old) developed jaundice 4 and 7 weeks respectively after treatment with flucloxacillin. Liver biopsies showed intrahepatic cholestasis. After cessation of the drug, the liver tests became normal.

Normal human serum depleted of Clq, factor D and properdin: its use in studies of complement activation

Normal human sera were depleted of Clq, factor D (D) and properdin (P) by a simple and reproducible procedure providing reagents for analysis of complement‐dependent functions. Classical pathway activity was restored with purified Clq, and alternative pathway activity with purified D and P. Since both activation pathways were abolished, antibodies and other components could be removed without loss of complement activity during immunoabsorption procedures. Synergism between the two pathways during haemolysis of rabbit erythrocytes was clearly demonstrated, and was also found on analysis of C3 cleavage in serum incubated with other alternative pathway activators such as zymosan and inulin. Experiments with a Neisseria meningitidis serogroup W‐135 strain isolated from a patient with inherited P deficiency showed that both pathways were capable of supporting antibody‐dependent killing of the bacteria in serum. The alternative pathway was possibly more efficient than the classical pathway in the assay system. In Clq,D,P‐depleted serum with high concentrations of anticapsular IgG antibodies, the addition of D alone resulted in efficient alternative pathway‐mediated killing. The alternative pathway was equally efficient in a Clq,D,P‐depleted serum with low concentrations of anticapsular antibody, but in this case the reaction required both D and P.

High serum hepatocyte growth factor levels in the acute stage of community-acquired infectious diseases

Acute serum levels of hepatocyte growth factor (HGF) were studied in 6 clinical groups with (i) gastroenteritis, (ii) skin and soft tissue infection, (iii) urinary tract infection, (iv) septicemia, (v) influenza, and (vi) chronic hepatitis C in comparison with a normal control group using an enzyme-linked immunosorbent assay method. We found that serum HGF levels were significantly higher in patients with acute infectious diseases (p <0.0001) compared to patients with chronic viral hepatitis and healthy controls. Serum HGF and CRP levels were correlated significantly (r = 0.65, p < 10-7). We conclude that serum HGF levels are elevated in patients with acute infectious diseases.

Hepatocyte growth factor (HGF) in patients with pneumonia : a comparison between survivors and non-survivors

Hepatocyte growth factor (HGF) is a multifunctional growth factor. After lung injury HGF is secreted in the lung and promotes reconstruction of the damaged organ. We measured, retrospectively, the serum HGF concentrations collected on admission in 55 patients with bacterial pneumonia, using an enzyme-linked immunosorbent assay (ELISA). The patients were divided into 3 groups: Group 1 was survivors with normal liver function (n = 14), Group 2 was survivors with abnormal liver function (n = 31) and Group 3 was non-survivors (n = 10). Median concentrations of HGF were elevated in Groups 1 and 2; and no statistically significant difference between these 2 groups was found. Group 3 had a median HGF concentration within the reference range, significantly lower than both Group 1 and Group 2. In addition LDH was significantly higher in non-survivors as compared with survivors. The combination of LDH and HGF concentrations discriminated between survivors and non-survivors (sensitivity 0.90 and specificity 0.96). The results support the hypothesis that increased levels of HGF might be a natural part of the healing process of lung injury, irrespective of liver involvement, and that patients without increased HGF levels, especially those with concomitant liver function impairment, may have a poor prognosis.

Septicaemia caused by unusual campylobacter species (C. laridis and C. mucosalis)

Two cases of campylobacter septicaemia are described. The first, caused by Campylobacter laridis was associated with gastroenteritis and occurred in a healthy individual. In the second case, a catalase negative species, C. mucosalis was isolated from blood in an immunocompromised patient with symptoms of pneumonia. Both campylobacter strains grew faintly under the routine culture conditions used. Improved diagnostic procedures for Campylobacter species may thus be warranted.

Another Swedish Family with Complete Properdin Deficiency: Association with Fulminant Meningococcal Disease in one Male Family Member

Inherited deficiency of the complement component properdin is described in a Swedish family without any previous history of meningococcal infections. The properdin-deficient index patient died from a fulminant infection caused by Neisseria meningitidis serogroup Y. Family investigation revealed properdin deficiency in the patients half-brother and in the maternal grandfather. The half-brother had a history of pneumococcal pneumonia and meningitis probably caused by Borrelia burgdorferi. Opsonic and bactericidal functions of serum were examined in the half-brother after immunization with tetravalent meningococcal vaccine. Vaccination promoted opsonization of N. meningitidis serogroups C and Y but not of serogroups A and W-135. The serum bactericidal activity increased against serogroup C and to some extent against serogroup W-135. This report emphasizes the importance of investigating the complement system even in families with single cases of fulminant meningococcal disease. Individuals with properdin deficiency might be protected from infection by immunization.

Hepatocyte Growth Factor may Act as an Early Therapeutic Predictor in Pneumonia

High serum levels of hepatocyte growth factor (HGF) may reflect the regenerative effect and enhanced local and systemic production of this cytokine after organ injuries. The possibility of using serial serum HGF values in order to predict the results of therapy for pneumonia was investigated in this study. In a prospective multicenter study we investigated the serum levels of HGF and CRP before and within 48 h after treatment in 70 patients with pneumonia. Serum levels of HGF before treatment were significantly higher than the HGF levels of a normal population (p < 0.0001). Within 48 h serum HGF levels had decreased significantly in those patients who ultimately responded to the initial antibiotic therapy (p < 0.0001). Serum HGF levels at 48 h were unchanged or increased in cases in whom the initial therapy was ineffective and had to be changed. CRP and HGF levels were significantly correlated. Using multivariate logistic regression analysis it was found that individual changes in acute serum HGF levels and serum HGF levels obtained within 48 h could predict the results of therapy at least as significantly (p < 0.003) as CRP (p = 0.05), although CRP levels were known and used by the physician to decide whether or not to change the initial therapy. We conclude that serial control of serum HGF levels can be used as an early indicator to predict the results of therapy during treatment of pneumonia.