Christina Nyström-Rosander

High incidence of Chlamydia pneumoniae in sclerotic heart valves of patients undergoing aortic valve replacement

Chlamydia pneumoniae has previously been demonstrated in the atherosclerotic lesions of various arteries, including the coronary arteries, and has been proposed to play a role in the pathogenesis of atherosclerosis. A prospective study of the incidence of C. pneumoniae in the sclerotic valves of patients undergoing aortic valve replacement because of aortic stenosis and in the aortic valves of cases dying of non-cardiac reasons and undergoing forensic autopsy was undertaken. The results were correlated to serological markers of past (IgG) or persistent (IgA) C. pneumoniae infection. C. pneumoniae, as determined by the polymerase chain reaction (PCR), was detected in the aortic valve in 19/39 (49%) patients and in 1/11 (9%) autopsy controls (p = 0.018) and confirmed by electron microscopy in one patient. There was no significant difference in the incidence rate of IgG or IgA antibody positivity between PCR-positive and PCR-negative cardiac patients. These results extend the hypothesis of a pathogenic role of C. pneumoniae in atherosclerosis to include also aortic valve sclerosis.

First Documented Case of Human Babesiosis in Sweden

A 34-year-old splenectomized man presented with fever, myalgia and dysuria. His condition rapidly deteriorated, he became anuric and developed severe haemolytic anaemia, thrombocytopenia and fibrinolysis. Peripheral blood smears revealed intra-erythrocytic parasites consistent with Babesia divergens in 40% of the erythrocytes. The diagnosis was confirmed by gerbil inoculation and by a significant rise in antibody titer. Blood exchange transfusion reduced the number of babesia infected erythrocytes to 1%. Parenteral therapy with a combination of quinine and clindamycin eradicated parasitaemia after 10 days of treatment and the patient rapidly improved. Renal failure necessitated haemodialysis for one month, whereafter the patient made a full recovery. Human babesiosis is a rare disease, but with a potential fatal outcome and should be considered as a diagnostic alternative in splenectomized and otherwise immunocompromised individuals with severe febrile illnesses.

Chlamydophila pneumonia: Specific mRNA in aorta ascendens in patients undergoing coronary artery by-pass grafting

The objective of this prospective study was to investigate if Chlamydophila pneumoniae (Cp)-specific DNA and mRNA are present in tissue samples from the wall of aorta ascendens in patients undergoing by-pass surgery for coronary artery disease (CAD) that includes stable angina pectoris (SAP, 25 patients) and acute coronary syndrome (ACS, 19 patients). Viable Cp was detected in 8/44 (18%) patients using reversed transcriptase PCR (RT-PCR) against bacterial mRNA with detection of cDNA using real-time PCR against the MOMP gene. Cp DNA was detected by nested PCR in 22/44 (50%) patients and by real-time PCR in 13/44 (30%) patients. In total, 24/44 (55%) patients were positive for Cp nucleic acid in any PCR. Antibodies to Cp were detected in 13/24 (54%) Cp PCR-positive and in 15/20 (75%) Cp PCR-negative patients. Nested PCR was run on throat swabs from all patients. No significant differences were noted between SAP and ACS patients regarding PCR results or serology. It has been suggested that Cp may be a ‘silent passenger’ picked up by the atherosclerotic plaque. Our findings of viable and metabolically active bacteria in aortic tissue add further support to the hypothesis that Cp may have an active role in the pathogenesis of atherosclerosis.

Antibodies to Chlamydia pneumoniae in Young Swedish Orienteers

During 1992-93 sera from 1790 Swedish elite orienteers were tested for antibodies to Chlamydia pneumoniae. The reason for this was that a cluster of 16 cases of sudden unexpected cardiac death had occurred among Swedish orienteers and DNA from C. pneumoniae had been found in the myocarditic heart and in the lung in 1 of 2 deceased athletes in whom testing was feasible; in addition, C. pneumoniae IgG was found in all 5 cases where serum was available. Among the orienteers, the prevalence rates of IgG antibodies in males and females were 54% (n = 1194) and 50% (n = 596), respectively. The corresponding figures for 319 male and female blood donors were 60% (n = 169) and 53% (n = 150), respectively. These differences are not statistically significant. Male orienteers had a lower prevalence of IgA antibodies than male blood donors (19% and 26%, respectively; p < 0.05), while no such difference was found in females (16% and 18%). The prevalence of IgM antibodies was < 1% in all groups. Neither the performance level of the orienteers nor the place of residence affected the antibody prevalence. In conclusion, Swedish orienteers do not show a higher prevalence of antibodies to C. pneumoniae than healthy blood donors.During 1992-93 sera from 1790 Swedish elite orienteers were tested for antibodies to Chlamydia pneumoniae. The reason for this was that a cluster of 16 cases of sudden unexpected cardiac death had occurred among Swedish orienteers and DNA from C. pneumoniae had been found in the myocarditic heart and in the lung in 1 of 2 deceased athletes in whom testing was feasible; in addition, C. pneumoniae IgG was found in all 5 cases where serum was available. Among the orienteers, the prevalence rates of IgG antibodies in males and females were 54% (n = 1194) and 50% (n =596), respectively. The corresponding figures for 319 male and female blood donors were 60% (n = 169) and 53% (n =150), respectively. These differences are not statistically significant. Male orienteers had a lower prevalence of IgA antibodies than male blood donors (19% and 26%, respectively; p < 0.05), while no such difference was found in females (16% and 18%). The prevalence of IgM antibodies was < 1% in all groups. Neither the performance level of the orienteers nor the place of residence affected the antibody prevalence. In conclusion, Swedish orienteers do not show a higher prevalence of antibodies to C. pneumoniae than healthy blood donors.

Susceptibility of Chlamydia pneumoniae to azithromycin and doxycycline : Methodological aspects on the determination of minimal inhibitory and minimal bactericidal concentrations

An in vitro assay for measuring and comparing the efficacy of different antimicrobial agents against Chlamydia pneumoniae was developed. Azithromycin, a representative of the new azalide group of antibiotics, and doxycycline were evaluated with respect to their antibacterial effect and capacity for intracellular killing under different experimental conditions. For both study drugs, the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) values increased significantly with longer bacterial preincubation time. The effect of different exposure times of antibiotics on the bacteria was also studied.

Ceftazidime as Initial Therapy in Febrile Patients with Acute Leukemia during Induction Chemotherapy

We studied the efficacy of ceftazidime as initial monotherapy in 82 adult patients with acute leukemia who developed 123 febrile episodes during induction chemotherapy. 88% of the patients survived their febrile episode(s), whereas 10% died of infection. When assessed at 72 h after initiation of treatment (early evaluation), 43/123 episodes (35%) had been successfully treated with ceftazidime. These 43 favourable responses were seen in 15/47 (32%) microbiologically documented infections, 20/46 (43%) clinically defined infections, and 8/30 (27%) fever of unknown origin (FUO). At the resolution of fever (late evaluation) 115 episodes were evaluable, and 48% had responded successfully to ceftazidime. Successful treatment was most frequently observed in FUO, 18/29 (62%). In contrast, only 19/44 (43%) microbiologically documented infections and 18/42 (43%) clinically defined infections were cured during ceftazidime treatment. In bacteremia the response rate was only 8/26 (31%). Thus, this study shows that although ceftazidime can be safely used for initial empirical monotherapy in neutropenic leukemia patients, the need for therapy modification is high and few patients with serious infections are cured with ceftazidime alone.

Iron Homeostasis in Tissues Is Affected during Persistent Chlamydia pneumoniae Infection in Mice

Chlamydia pneumoniae (C. pneumoniae) may be a mediator in the pathogenesis of atherosclerosis. For its growth C. pneumoniae depends on iron (Fe), but how Fe changes in tissues during persistent infection or affects bacterial replication in tissues is unknown. C. pneumoniae-infected C57BL/6J mice were sacrificed on days 4, 8, 20, and 40. Mice had bacteria in the lungs and liver on all days. Inflammatory markers, chemokine Cxcl2 and interferon-gamma, were not affected in the liver on day 40. The copper (Cu)/zinc (Zn) ratio in serum, another marker of infection/inflammation, increased on day 4 and tended to increase again on day 40. The Fe markers, transferrin receptor (TfR), Hepcidin (Hamp1), and ferroportin 1 (Fpn1), increased in the liver on day 4 and then normalized except for TfR that tended to decrease. TfR responses were similar to Fe in serum that increased on day 4 but tended to decrease thereafter. In the liver, Fe was increased on day 4 and also on day 40. The reappearing increases in Cu/Zn on day 40 concomitant with the increase in liver Fe on day 40, even though TfR tended to decrease, and the fact that viable C. pneumoniae was present in the lungs and liver may indicate the early phase of activation of recurrent infection.

Trace Element Changes in Thoracic Aortic Dissection

Thoracic aortic dissection is a life-threatening condition with an incompletely understood pathogenesis. Trace elements are essential for the functioning of different processes in the body, including the immune system and associated responses to infection/inflammation. Because inflammation may be part of the pathogenesis of thoracic aortic dissection, we investigated whether trace element changes associated with inflammation occur in serum and tissue samples during the disease. The study included 21 patients undergoing surgery for thoracic aortic dissection, 10 forensic autopsy specimens for tissue controls and 23 healthy blood donors for serum controls. Levels of magnesium (Mg), calcium (Ca), vanadium (V), manganese (Mn), iron (Fe), cobalt (Co), copper (Cu), zinc (Zn), arsenic (As), selenium (Se), cadmium (Cd) and mercury (Hg) were measured in the aortic tissue and serum by inductively coupled plasma-mass spectrometry (ICP-MS). In the serum, Ca, V, Cu and Zn decreased, whereas Fe increased. In the tissue, Cu and Zn decreased and Fe tended to increase. The Cu/Zn ratio in the serum, a marker of infection/inflammation, did not change in the patients. Concerning trace element changes in the serum and tissue, our data do not support the hypothesis that inflammation is involved in the pathogenesis of thoracic aortic dissection.

An echocardiographic study comparing male Swedish elite orienteers with other elite endurance athletes.

Between 1979 and 1992, there were 16 known cases of sudden unexpected cardiac death among young Swedish orienteers, whose autopsies showed myocarditis to be a common finding. Therefore, 96 elite orienteers and 47 controls underwent echocardiography, showing left ventricular wall motion abnormalities in 9% of the orienteers compared with 4% in the controls.

Cholesterol uptake in the mouse aorta increases during Chlamydia pneumoniae infection

&NA; Chlamydia pneumoniae has been suggested as a stimulator of the atherosclerotic process. Mice fed a normal diet were infected intranasally with C. pneumoniae and given one intraperitoneal injection of 14C‐cholesterol tracer per day for 12 days. Bacteria were demonstrated in the aorta in the early phase of infection and in lungs and liver throughout the study period of 20 days. 14C‐cholesterol was not affected in the heart but increased in the blood, liver and aorta on day 4 when the infection was clinically most severe. Furthermore, on day 20 14C‐cholesterol tended to be increased in the aorta. Accordingly, copper‐ and zinc levels and expressions of the infection biomarkers Cxcl2 and Ifng increased in the liver on day 4 with a tendency of increased of copper, zinc and Ifng on day 20. In mice where bacteria could be cultivated from the lungs, expressions of cholesterol transporters Abca1 and Idol were both increased in the liver on day 4. The increased levels of 14C‐cholesterol in blood and aorta together with increased Abca1 and Idol in the liver during C. pneumoniae infection in mice fed a normal diet suggest that this pathogen may have a role in the initiation of the atherosclerotic process. &NA; Graphical Abstract Figure. Cholesterol metabolism is affected during the acute phase of Chlamydia pneumoniae infection in mice which supports the involvement of this common respiratory bacterium in the development of atherosclerosis.