Measurement of antibody responses to pneumolysin--a promising method for the presumptive aetiological diagnosis of pneumococcal pneumonia.

An enzymeimmunoassay (EIA) for measuring antibodies to pneumococcal pneumolysin has been developed. The method was used to study the possible pneumococcal aetiology of pneumonia in 159 mostly elderly patients admitted to hospital because of a positive chest X-ray. The results obtained with the assay were compared to those obtained by other diagnostic methods, namely blood culture, detection of pneumococcal antigen in urine and demonstration of an antibody response to pneumococcal C-polysaccharide and capsular polysaccharides. Antibody response to pneumolysin was found in 32 of 39 (82%) patients with pneumococcal pneumonia aetiologically diagnosed presumptively by other methods. In addition, the EIA for pneumolysin antibodies was positive in 31 patients without evidence of pneumococcal aetiology by other methods. The clinical and laboratory investigations of these patients supported the presumption of bacterial infection. We conclude that the EIA we have developed for measuring pneumolysin antibodies is a promising, sensitive method for the presumptive aetiological diagnosis of pneumococcal pneumonia. The assay is simple to perform because only one antigen is needed and measurement of IgG antibodies alone seems to be enough for aetiological diagnosis.

Changes in serum lipoprotein pattern induced by acute infections.

To study the effects of acute infections on serum lipids and lipoproteins we measured the concentration and composition of different lipoproteins, apoproteins A-I, A-II, and B, and the activities of plasma postheparin lipolytic enzymes, lipoprotein lipase (LPL) and hepatic lipase (HL) during acute and convalescence phase and after complete recovery in 72 infectious patients (33 with viral infection and 39 with bacterial infection). The mass concentrations of both low density lipoprotein (LDL) (P less than .001) and high density lipoprotein (HDL)2 (P less than .002) were reduced during acute infections due to the lowering of their cholesterol, phospholipid, and protein contents. The reduction of LDL cholesterol was maximal at the acute stage of infection (change -15%, P less than .001) while the reduction of HDL2 cholesterol was maximal during the convalescence (change -35%, P less than .001). During acute infections LDL became triglyceride-enriched (11.8 v 8.6%, P less than .0001) but cholesterol-poor (36.6 v 39.3%, P less than .0001). The ratio of HDL cholesterol/LDL cholesterol was significantly reduced during the convalescence (0.42 +/- 0.15 v 0.53 +/- 0.19, P less than .0001). The concentrations of apo A-I and apo A-II were decreased during acute infections (changes -22%, P less than .001, and -16%, P less than .001, respectively). The very low density lipoprotein (VLDL) was 18% higher during the convalescence period than after the recovery due to the elevations of VLDL triglycerides, cholesterol, and phospholipids. The activity of LPL was reduced both in the acute and convalescence phase, whereas that of HL was reduced only in the acute phase of infections.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum lipids in pneumonia of different aetiology.

The changes in serum triglycerides, cholesterol and high density lipoprotein (HDL) cholesterol were followed in patients with pneumonia caused by different bacteria or viruses as well as in those with no defined aetiology. In the acute phase of the disease there was: 1) a fall in serum triglycerides in patients with bacteremic pneumococcal disease and in patients with no defined aetiology (p less than 0.01 and less than 0.005, respectively). 2) a reduction in cholesterol in all aetiological groups (p less than 0.001) except for those with viral pneumonias, where only 4 patients were studied, and 3) a fall in HDL cholesterol in all the groups (at least at p less than 0.05) except in those with virus infection. 4) In bacteraemic pneumococcal disease the cholesterol level (mean 2.6, SEM 0.3 mmol/l) was lower than that in the other groups (at least at p less than 0.05). In the acute phase there was a tendency to a negative correlation of erythrocyte sedimentation rate and of C-reactive protein with serum cholesterol and/or HDL cholesterol. Changes in serum lipids in various infections deserve further pathophysiological investigation.

The aetiology of pneumonia. Application of bacterial serology and basic laboratory methods.

The aetiology of community-acquired pneumonia was studied by use of new bacterial and established viral serological methods besides blood culture in 162 patients. Evidence for a specific aetiology was obtained in 79 patients (49.4%). The pneumococcus was the most common aetiological agent, identified in 25.6% of cases. Other bacteria, Haemophilus influenzae, Branhamella catarrhalis, Neisseria meningitidis and Chlamydia spp. were demonstrated in 23.5%, Mycoplasma pneumonia in 1.2% and viruses in 7.4% patients. In 58% those with viral pneumonia there was evidence of mixed infection with bacteria. The predictive value of rapid laboratory tests, erythrocyte sedimentation rate, white blood cell count and C-reactive protein (CRP), was evaluated in relation to the aetiological diagnosis. They all differentiated viral from bacterial pneumonia, with CRP having the best predictive value. On the basis of these tests, most cases in which our serological tests remained negative would appear to have a bacterial aetiology also.

Serum angiotensin converting enzyme in pneumonias.

Serum concentrations of angiotensin converting enzyme (ACE) were studied in pneumonias caused by different pathogens and in cases in which the aetiology could not be defined. In all aetiological groups, except in viral pneumonia, there was a significant increase in ACE during recovery (p less than 0.001). In several patients the lowest values during the acute phase of disease and the highest values during recovery were outside the reference limits. In cases with known aetiology the highest ACE values and the difference between the lowest and the highest values correlated positively with C-reactive protein concentrations at admission (p less than 0.001). The pathophysiology behind the fluctuations of the ACE concentrations is unknown.

Effect of bacterial lipopolysaccharide on serum lipids and on the development of aortic atherosclerosis in rabbits.

The effect of repeated intravenous administration of bacterial lipopolysaccharide (LPS) on serum lipids and on aortic atherosclerosis was studied in rabbits on basal diet and on hypercholesterolemic diets containing 0.15-1.0% cholesterol. LPS (10 or 100 ng/kg body weight) was administered 3 times per week for 3 or 6 weeks. No difference was observed in serum lipid levels or in aortic atherosclerosis between LPS- and saline-treated animals. These observations do not support the hypothesis that LPS has an effect on the progression of atherosclerosis.

Serum lipids in viral and bacterial meningitis.

The changes in serum triglycerides (Tg), cholesterol and high density lipoprotein (HDL) cholesterol were examined in 17 patients with viral (VM) and in 7 patients with bacterial (BM) meningitis. In VM, there were low values of cholesterol (p less than 0.001) and HDL cholesterol (p less than 0.01) on admission to hospital and a rise in Tg after 1 week (p less than 0.01). In BM, caused in 4 cases by meningococci and in 3 cases by various streptococci, both cholesterol and HDL cholesterol were decreased during the acute phase (p less than 0.001 and less than 0.02, respectively). Corresponding changes were observed when the meningococcal cases were treated as a separate group (p less than 0.02 and less than 0.05, respectively). On admission cholesterol and HDL cholesterol levels in BM were lower than those in VM (p less than 0.05 in each case). In VM, the changes in serum lipids did not correlate with the changes of protein and glucose levels or leucocyte counts in cerebrospinal fluid (CSF). In BM, protein concentration in CSF correlated negatively with serum Tg (p less than 0.01) and positively with HDL cholesterol (p less than 0.05); glucose concentration in CSF correlated positively with Tg (p less than 0.01). Our results emphasize the need for further investigation of the pathophysiological role of lipids in various infections.

Carcinoembryonic antigen (CEA) in blood in cases of pneumonia.

Serum levels of carcinoembryonic antigen (CEA) were analysed in patients with pneumonia of different etiology. Significant (p less than 0.01) increases in blood CEA levels occurred in all groups of pneumonia of bacterial etiology, i.e., pneumococcal, gram-negative or chlamydial. In viral pneumonia similar increases were observed, but the changes were not statistically significant, probably due to the small number of patients. In pneumonia of unknown etiology CEA behaved as in bacterial pneumonias. Maximal values between 5 and 15 micrograms/l CEA were common in pneumonia, the basal level usually being less than 5 micrograms/l. The severity of pneumonia, as judged by maximal erythrocyte sedimentation rate, correlated weakly with CEA levels in the bacterial group (p less than 0.05). In pneumonias of unknown etiology white blood cell counts and C-reactive protein levels correlated significantly with maximal CEA (p less than 0.01). In conclusion we have demonstrated, that in pneumonias of different etiology strongly but transiently increased blood CEA levels are the rule. The severity of pneumonia is not clearly correlated with CEA levels.

Effect of bacterial lipopolysaccharide on serum high density lipoprotein cholesterol in rabbits.

The effect of bacterial lipopolysaccharide (LPS) on serum lipids was examined in rabbits. LPS was prepared from the smooth Salmonella typhimurium LT2 strain and given intravenously at a dose of 100 ng/kg b.wt. There were no significant changes in serum triglyceride or cholesterol levels in 1-3 days after the administration of LPS. There was, however, a decrease in serum high density lipoprotein (HDL) cholesterol, which was greatest after 2 days (P less than 0.001). Simultaneously, the HDL/total cholesterol ratio decreased (P less than 0.005).

Fever of unknown origin: a follow-up investigation of 34 patients.

34 patients hospitalized for fever of unknown origin (FUO) were subjected to a follow-up investigation on the average 5 yr after the hospital stay. Two patients had died of a disease related to FUO: one had adenocarcinoma with an unknown primary site and the other a supposed autoimmune disease. In one case the cause of FUO was a periappendicular abscess. A woman continued to have periods of fever with high ESR. In the remaining 30 cases the cause of FUO had apparently been a self-limited, benign disease. In contrast to an earlier series from our clinic, no cases of tuberculosis were revealed.

High density lipoprotein cholesterol in haemorrhagic hyperlipidaemia in rabbits.

The effects of repeated bleeding (15 ml/day/kg b.wt. on 3 consecutive days) on plasma lipids, especially on high density lipoprotein (HDL)-cholesterol were studied in rabbits. As a result of the bleeding, plasma triglycerides (TG) increased from a mean of 0.61 (SD range 0.34-1.09) mmol/l to 2.86 (1.16-7.12) mmol/l (P less than 0.02). Plasma total cholesterol (TC) increased from 1.4 +/- 0.5 (SD) mmol/l to 2.0 +/- 0.5 mmol/l. The concentration of HDL-cholesterol, however, decreased from 0.72 +/- 0.16 mmol/l to 0.48 +/- 0.23 mmol/l (P less than 0.02). The HDL-cholesterol/TC ratio decreased from 0.57 +/- 0.17 to 0.29 +/- 0.15 (P less than 0.05). In connection with the haemorrhagic hyperlipidaemia a negative correlation (P less than 0.01) appeared between plasma TG and HDL-cholesterol. It is concluded that hypoxia, being the primary cause of haemorrhagic hyperlipidaemia, may be one factor regulating HDL-cholesterol concentrations and thereby possibly the development of atherosclerosis.

Effect of immune complexes on plasma HDL-cholesterol in rabbits.

The effect of immune complexes on plasma lipids, especially on high density lipoprotein (HDL) cholesterol, was studied in rabbits. In rabbits immunized twice with bovine serum albumin (BSA) with an interval of about 6 weeks, a significant decrease in plasma HDL-cholesterol (P less than 0.01) and in the HDL/total cholesterol ratio (P less than 0.02) was found 6 days after the second BSA injection. As a result of repeated bleedings commenced 6 days after the second BSA injection, the changes in plasma triglycerides (TG) and total cholesterol (TC) were similar to those found previously in non-immunized rabbits. In contrast to the findings in non-immunized rabbits, no significant decrease in HDL-cholesterol was found as a consequence of the bleedings, but a negative correlation (P less than 0.05) between plasma TG and HDL-cholesterol appeared. It is concluded that immune complexes may affect plasma HDL-cholesterol concentrations and thereby possibly also the development of atherosclerosis.

Effects of immune complexes on plasma triglycerides in rabbits.

The effect of immune complexes on plasma lipids, especially triglycerides (TG) was studied in rabbits. After a single intravenous dose of bovine serum albumin (BSA), serological aberrations suggestive of immune complexes appeared around the 14th day. Changes in the plasma TG or cholesterol values were not observed within a follow-up period of 4 weeks. However, reimmunization with a second dose of BSA 2 months later led to a significant decrease in plasma TG (P less than 0.01). In fat tolerance tests TG emulsion was given intravenously to rabbits immunized 14 days earlier with BSA. The elimination curve of exogenous TG (followed for 100 men) was in its first phase exponential and in it second phase linear in all experimental groups. The significance of the second phase, however, has to be interpreted with some caution because of the possible recirculation of TG into the blood stream. In the rabbits immunized with one dose of BSA the fractional removal rate of TG did not differ from that of the controls. However, in the rabbits reimmunized with a second dose of BSA 2 months later the fractional removal rate of TG was greater than in the controls (P less than 0.01). It was concluded that immune complex lesions under certain circumstances may affect the TG metabolism. The mechanism concerned may be increased permeability of the injured vascular endothelial cells, possibly through the increased release of lipoprotein lipase (LPL).

Immunity to diphtheria in Helsinki in 1975.

To determine the status of the population's immunity to diphtheria, the Schick test was performed on 489 and the diphtheria antitoxin level determined in 404 hospital patients, all residents of Helsinki. A low ("unprotective", less than 0.01 IU/ml) antitoxin level was found in not more than 5% among persons under 20. The highest percentage, 48%, was found in the 50--59 years age group. A low antitoxin level was more common among women than men in those over 40 years of age. Taking into consideration the age structure of the population of Helsinki in 1975, 23% of the population had an antitoxin level less than 0.01 IU/ml. The percentage of Schick-positives among different age groups was almost the same as the percentage of low antitoxin levels. Of 100 serum samples from military recruits coming from different regions of the country, 15% had an antitoxin level below 0.01 IU/ml.

The removal of exogenous triglycerides in haemorrhagic hyperlipidaemia in rabbits.

Bleedings (15 ml/day/kg b.wt.) on two consecutive days caused a threefold increase in plasma triglycerides (TG) in rabbits. Both in normal and in haemorrhagic rabbits the elimination of injected TGs (fat emulsion) was exponential, the fractional removal rate in the haemorrhagic group being slower than normal. In order to rule out the possible effect of the TG pool in haemorrhagic rabbits and the possible changes in endogenous TGs during the test, the TGs were fractionated by the polyvinylpyrolidone density gradient method. Again, both in normal and in haemorrhagic rabbits the elimination of exogenous TGs was exponential, the removal rate of haemorrhagic animals being retarded. Accordingly, the changes in endogenous TGs were negligible. The results are regarded as indicative of an elimination defect as one factor in the pathogenesis of haemorrhagic hyperlipidaemia.

Cerebrospinal fluid lysozyme in bacterial and viral meningitis.

The concentration of lysozyme (LZM) in cerebrospinal fluid was determined in 25 patients with bacterial meningitis, in 18 patients with viral meningitis and in 25 control patients who had other fibrile illnesses. The concentration of LZM was less than 1.5 microgram/ml in all control patients, and slightly to markedly raised in 10 patients with viral meningitis and in 11 out of 13 patients with untreated bacterial meningitis. The concentration of LZM was significantly different in the viral and bacterial meningitis patients (p less than 0.001). Most raised concentrations of cerebrospinal fluid LZM persisted for at least one week after the start of antibiotic treatment. The concentrations of LZM correlated well with concentrations of lactic dehydrogenase. These results show that the determination of cerebrospinal fluid LZM is a useful tool in the differential diagnosis of meningitis, particularly when the prehospital treatment with antibiotics may be responsible for a diagnostically misleading negative bacterial culture of the cerebrospinal fluid and altered cerebrospinal fluid cytology.