Chlamydophila pneumoniae in chronic rhinosinusitis.

CONCLUSIONS: The intracellular bacterium Chlamydophila pneumoniae (Cp) was infrequently found in nasopharynx and lacking in biopsies from the middle turbinate in chronic rhinosinusitis (CRS) patients. Compared with healthy controls, patients suffering from CRS had significantly higher and more prevalent antibody titers to Cp. However, an association between CRS and Cp could not be established. OBJECTIVES: To study the prevalence of Cp in CRS patients and in healthy controls to determine if an association exists between Cp and CRS. MATERIALS AND METHODS: PCR against Cp was run on middle turbinate biopsies and on throat and nasopharyngeal swabs from 25 CRS patients and from 10 healthy controls. Serum samples were tested for Cp-specific antibodies by the microimmunofluorescence method. Patients that tested positive for Cp or had high antibody titers were treated with antibiotics. RESULTS: Cp was found in nasopharyngeal samples from two patients but from none of the controls. Neither patients nor controls had Cp in biopsies from the middle turbinate. Antibody titers against Cp were significantly higher and more prevalent in patients than in controls. Seventeen patients were treated with antibiotics but only four of them recovered from sinusitis symptoms during the 2-year follow-up.

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.

Thallium-201 myocardial imaging at rest in male orienteers and other endurance athletes.

During the period 1979 to 1992, 16 sudden unexpected cardiac deaths were known to have occurred in young Swedish orienteers. Autopsy indicated myocarditis to be the most frequent finding, most often combined with extensive myocardial fibrosis. The aim of the present investigation was to explore whether young male orienteers show a higher frequency than other young elite endurance athletes (controls) in the occurrence of Thallium-201 myocardial perfusion defects at rest, suggestive of fibrosis evoked by myocarditis. Thallium-201 perfusion abnormalities at rest were more frequently found in the controls than in the orienteers (26% vs. 12%, p=0.03). Uneven Tl-201 perfusion was associated with left ventricular mass (r=0.32, r=0.24, p<0.01, p=0.02) and body weight (r=0.30, r=0.31, p<0.01, p=0.03) in orienteers and controls, respectively. Echocardiographic left ventricular wall motion abnormalities were found in 11 athletes (9 orienteers and 2 controls) but only two displayed an abnormal Thallium-201 perfusion scan at rest. Perfusion abnormalities at rest did not occur more frequently in the orienteers but were commonly found in both groups of apparently healthy athletes making it futile to discern abnormals from normals. Thallium-201 perfusion aberrations were not associated with left ventricular wall motion abnormalities obtained by echocardiography.

Wall motion abnormalities in male elite orienteers are aggravated by exercise.

During the period 1979-92, 16 (15 men and one woman) sudden unexpected cardiac deaths occurred among young Swedish orienteers. This finding indicated a sharp increase in the death rate of orienteers, and necropsy demonstrated that myocarditis was a common histopathological finding. Therefore, an extensive non-invasive cardiac investigation was performed. A total of 59 male élite orienteers (mean age 23 years) and 36 cross-country skiers and middle-distance runners (mean age 22 years), serving as controls, were examined by both echocardiography at rest and radionuclide ventriculography at rest and during exercise. Wall motion abnormalities were found in eight orienteers using echocardiography. The purpose of this study was to examine whether the group of orienteers with wall motion abnormalities found using echocardiography had a smaller increase in ejection fraction from rest to exercise using radionuclide ventriculography than the rest of the orienteers and the controls, indicating an aggravation of the wall motion abnormalities during exercise. There were no significant differences in the ejection fraction at rest between the groups. In the orienteers with wall motion abnormalities (group 1), 62% (five out of eight) had less than a 0.05 unit increase in left ventricular ejection fraction compared with 27% (14 out of 51) of the remaining orienteers (group 2) and 19% (7 out of 36) of the controls (group 3). A comparison of athletes in group 1 with those in groups 2 and 3 combined revealed a statistically significant difference (P < 0.05). The divergent response in left ventricular ejection fraction during exercise suggests an aggravation of the wall motion abnormalities with exercise. Both the echocardiographic and the radionuclide ventriculographic findings indicate that the orienteers in group 1 had concealed left ventricular damage.

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.

Assay of antibiotic susceptibility of Chlamydia pneumoniae.

It is well known that treatment of Chlamydia pneumoniae infections is difficult. High doses and prolonged treatment is often needed to achieve clinical cure despite good in vitro effect of the drugs used. We here discuss different methodological problems in the determination of MIC and MBC values of C. pneumoniae. The length of the preincubation time and the lack of fluctuation of the antibiotic concentrations may affect the outcome of the currently used assay.

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.

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.

Echocardiographic right and left ventricular measurements in male elite endurance athletes.

Echocardiography was used to assess normal values in the right and left ventricular cavity and wall in 127 male elite endurance athletes. M-mode and two dimensional measurements of left ventricle and left and right atria were also obtained. All subjects were high-performance orienteers, cross-country skiers and middle-distance runners. They all had a normal electrocardiogram at rest and no echocardiographic evidence of heart disease. With the use of multiple right ventricular cross-sections and two-dimensional measurements, we found a significantly greater right ventricular inflow tract and right and left atrial measurements in endurance athletes compared with earlier studies of normal, active subjects. The right ventricular free wall was slightly thicker than reported in normal active subjects but the differences were small. Left ventricular diastolic diameter was consistent with previous reports of endurance athletes. Of the 127 subjects, 13% had left ventricular wall thickness above 13 mm but none of the athletes had wall thickness above 15 mm. These data suggest that cardiac enlargement occurs symmetrically in both right and left cavities, probably reflecting increased haemodynamic loading, a mechanism by which athletes sustain a high cardiac output during exercise.

An increase in sudden unexpected cardiac deaths among young Swedish orienteers during 1979-1992.

BACKGROUND: Sixteen cases of sudden unexpected cardiac death, 15 males and one female, are known to have occurred among young Swedish orienteers from 1979 to 1992, of which seven cases occurred between 1989 and 1992. This is considered to be indicative of an increased death rate. RESULTS: Histopathological evaluation showed myocarditis in a higher than expected proportion of cases. In one such case, which we studied before the sudden unexpected death occurred, the victim had suffered a Chlamydia pneumoniae infection verified by serology, and a nucleotide sequence was found in the heart and lung by means of the polymerase chain reaction (PCR) that hybridized with a probe specific for that organism. Male Swedish orienteers do not, however, seem to have an increased rate of exposure to this agent. No further sudden unexpected deaths among young orienteers have occurred over the past 3.5 years. At the beginning of that period, attempts were made to modify training habits and attitudes.

Oral acyclovir as prophylaxis for bacterial infections during induction therapy for acute leukaemia in adults. The Leukemia Group of Middle Sweden.

We prospectively tested the hypothesis that prevention of herpes simplex virus infection with acyclovir might also reduce the incidence of bacterial infections in adult patients with acute leukaemia. During the first induction therapy a double-blind, randomized and placebo-controlled study was undertaken. Fifty-two patients were treated with 200 mg acyclovir orally four times daily throughout the induction period, whereas 55 patients received placebo. The groups were comparable with regard to age, cytotoxic chemotherapy and duration of neutropenia. Bacteraemias were significantly fewer in the acyclovir group (20 versus 41 episodes; P = 0.007). The number of isolated microorganisms causing bacterial or fungal infections was also lower during acyclovir prophylaxis (52 isolates, versus 93 isolates; P = 0.02). There was no significant difference between the groups with regard to the number of clinically documented infections or fevers of unknown origin. Herpes simplex virus isolations occurred only in the placebo group (P = 0.001). Thus, oral acyclovir prophylaxis was associated with reductions of all microbiologically documented infections suggesting that prevention of herpes simplex virus reactivation in acute leukaemia patients may reduce the occurrence of other infections.

Oral ketoconazole prophylaxis for Candida infections during induction therapy for acute leukaemia in adults: more bacteraemias.

We determined whether ketoconazole prophylaxis might reduce Candida colonization and infections in adult patients with acute leukaemia. During first-remission induction therapy 50 patients were treated with 200 mg ketoconazole administered orally daily, while 57 patients received placebo in a double-blind, randomized trial. The duration of severe neutropenia (granulocytes less than 0.1 x 10(9) l-1) represented 36% of the study period in the ketoconazole group and 26% in the placebo group (P = 0.043). Although fewer patients presented with positive Candida surveillance cultures and serological evidence of Candida infection in the ketoconazole group compared to the placebo group, two candidaemias and one Trichosporum fungaemia were observed in the ketoconazole group. Moreover, significantly more bacteraemias were noted in the ketoconazole group (n = 37) than in the placebo group (n = 21) (P = 0.004). Thus, although oral ketoconazole prophylaxis might be associated with less Candida colonization and fewer seroconversions, it also resulted in more bacteraemias and longer duration of severe neutropenia, suggesting that caution should be exercised when ketoconazole (or related drugs) is given to this group of immunocompromised hosts.

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.

Ceftazidime as initial therapy in febrile patients with acute leukemia during induction chemotherapy. Leukemia Group of Middle Sweden.

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.

UV irradiation of lymphocytes triggers an increase in intracellular Ca2+ and prevents lectin-stimulated Ca2+ mobilization: evidence for UV- and nifedipine-sensitive Ca2+ channels.

UV irradiation induces in vitro and in vivo immunosuppression. Because mobilization of intracellular calcium ([Ca2+]i) represents a central step in cell activation and immune response, we investigated the effect of UV irradiation on Ca2+ homeostasis. Using indo-1 and cytofluorometry, [Ca2+]i kinetics in UVC- or UVB-exposed human peripheral blood leukocytes (PBL) and Jurkat cells were determined in parallel with functional assays. Increases in [Ca2+]i were observed within 2-3 h of irradiation; these increases were UV-dose dependent and reached maxima of 240% and 180% above baseline level (130 nM) for UVB and UVC, respectively. The UV-induced [Ca2+]i rise was predominantly due to influx of extracellular calcium, and it was more pronounced in T than in non-T cells. Concurrent with [Ca2+]i shifts following UV treatment, there was a loss of ability to respond to phytohemagglutinin (PHA) or to proliferate or stimulate in mixed leukocyte culture. This loss of function appeared to be related not only to UV-induced calcium shifts, but also to effects of UV irradiation on the plasma membrane. No [Ca2+]i mobilization was induced by gamma irradiation, and gamma-irradiated cells showed a normal [Ca2+]i increase in response to PHA. UV-induced Ca2+ flux into the cells was blocked by nifedipine. These data indicate that UV and gamma irradiation have different effects on lymphocyte membranes and suggest that a disruption of Ca2+ homeostasis may be involved in UV-induced lymphocyte inhibition. The data suggest, furthermore, the presence of Ca2+ channels in lymphocyte membranes that are sensitive to UV irradiation and Ca2+ channel blockers such as nifedipine.

Central venous catheters in acute blood malignancies.

A one-year prospective study to evaluate the use of central venous catheters in intensive treatment of patients with acute blood malignancies was performed. Forty-seven catheters in 29 patients were studied. In spite of thrombocytopenia in several patients, no severe bleeding episodes were observed. Five patients with agranulocytosis had episodes of bacterial growth in the blood. Four patients had a clinical infection in the subcutaneous tunnel of the catheter. Bacterial growths on the tips of the catheters were found in three cases. Six patients died during the observation period, none of these was in remission. One of these patients had a growth of coagulase negative staphylococci in the blood, and another on the tip of the catheter, without any other known source of infection. The use of central venous catheters facilitates patient care and minimizes discomfort. It is associated with acceptable complications, necessitating meticulous insertion techniques, and careful daily care on the ward or at home.

The first human case of domestic Q fever in Sweden.

A case of Q fever in a 56-year-old man is reported. The patient had visited Mallorca six months prior to the present disease. Except for that he had not been outside Sweden for several years, thus being the first known case of Q fever acquired in this country.