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11 patients with bacterial meningitis, examined during the course of the disease for immunoglobulin (Ig) abnormalities in the cerebrospinal fluid (CSF), all had an increased CSF IgM index equal to (CSF/serum IgM):(CSF/serum albumin), indicating intrathecal IgM production. Seven patients had a slightly increased CSF IgG index, and 7 a slightly increased IgA index. Six of the 11 patients had an increased IgM index in the presence of normal indices for IgG and IgA. Follow-up revealed the return of these values to normal. Four patients had identical oligoclonal IgG bands in the CSF and serum, probably representing a systemic immune response, but in only one case were oligoclonal bands suggestive of intrathecal IgG production found. No oligoclonal IgA response was demonstrable in the 4 patients examined. Antigen-immunofixation or antigen-absorption studies revealed evidence of a specific, intrathecal IgG antibody response in only 2 patients, while a search for IgG antibodies against aetiologically unrelated bacterial and viral antigens was negative. With the exception of IgM production, therefore, a humoral intrathecal immune response is less common in bacterial than in aseptic meningitis.

A simplified enzymatic method for determination of serum 3 alpha-hydroxy bile acids (3 alpha-HBA) has been evaluated. Analytical precision was low in the normal range but satisfactory for elevated values. The fasting upper reference value was 8.0 mumol/l. In 12 healthy subjects serum 3 alpha-HBA levels were measured after oral loads (125, 250, 500, and 1000 mg) of unconjugated chenodeoxycholic acid (CDA). After the 125-mg CDA loading dose no significant increase in serum 3 alpha-HBA was observed, but with the 250 mg CDA loading dose serum 3 alpha-HBA levels were elevated at 30, 60, and 120 min. The loading doses of 500 mg and 1000 mg CDA produced significant increases in serum 3 alpha-HBA levels throughout the observation period (3 h). When sera with increased serum bile acids were analyzed by radioimmunoassay for CDA, the results correlated well with those obtained enzymatically. The usefulness of the simplified method is evident in this situation, and we also find it useful for serum bile acid determination after an oral bile acid loading test with CDA. The method is easy to perform and requires only standard laboratory equipment.

The occurrence of viral antibodies in relation to IgG separated by thin-layer polyacrylamide gel isoelectric focusing was studied in CSF and serum from 24 patients with mumps meningitis by immunofixation with viral antigens and autoradiography. Eleven of the patients displayed on the autoradiograms evidence of locally in the central nervous system synthesized mumps virus antibodies which were related to oligoclonal IgG bands in all 5 patients who displayed this CSF abnormality, otherwise to polyclonal IgG bands. Local synthesis of mumps virus antibodies was detectable in 43% of specimens obtained 1–13 days after onset, and in 75% obtained 27–47 days after onset. Only one patient displayed local synthesis of antibodies to other viruses (measles and herpes simplex) which could then be traced to polyclonal IgG bands.

With the use of enzyme-linked immunosorbent assay (ELISA) for demonstration of specific viral antibodies in 21 patients with mumps meningitis (MM), 19 (91%) displayed evidence for synthesis within the central nervous system (CNS) of IgG antibodies and 11 (52%) of IgM antibodies. Only one MM patient did not show local antibody production, but he had high mumps IgM titers in serum. Elevated IgG and IgM indices reflecting local IgG and IgM production, were found in 4 (19%) and 17 (81%) of the patients, respectively, and frequently did not coincide with local synthesis of specific antibodies. None of 21 control patients with acute aseptic meningitis of other etiology showed evidence for a local antibody response against mumps. In one of the MM patients, local production of measles IgM antibodies was demonstrated, reflecting an IgM response within the CNS against an antigen unrelated to the disease. This study concludes that in less serious CNS infections, such as MM, highly sensitive methods as ELISA are needed to demonstrate intrathecal specific viral immune response.

Oligoclonal immunoglobulins (Ig) demonstrble as bands by agarose-gel electrophoresis of CSF were characterized in ten patients with aseptic meningitis. Oligoclonal CSF IgG was found in all patients, IgM was found in two. The oligoclonal Ig was more often of lambda light-chain type than of kappa type. In four patients, oligoclonal Ig bands contained kappa and lambda light chains simultaneously. In two patients, bands consisting of free lambda light chains were found. On repeated investigations more than one year later in three cases, the oligoclonal IgG was of the same light-chain type. The immune response within the CNS in aseptic meningitis seems to be dominated by synthesis of IgG with lambda light chains.

Three different bile acid provocation tests--an intravenous stimulation with cholecystokinin (CCK), a test meal, and an oral bile acid load of 500 mg chenodeoxycholic acid (CDA)--were compared in 12 healthy subjects. Blood samples were drawn every 30 min for 3 h, and serum bile acids (SBA) were measured by an enzymatic method (Enzabile). The CCK stimulation gave significant SBA elevations only at 30 min. After the test meal and the CDA loading tests SBA elevations were observed from 30 min and throughout the observation period. Maximal increases were obtained at 120 min after the test meal but already at 30 min after the CDA loading test. We conclude that among these three bile acid provocation tests the oral CDA loading test is to be preferred because it gives marked and rapid elevation of SBA in all subjects and is independent of bile acid pool size and normal function of the gallbladder.

A case of septicemia and meningitis caused by Fusobacterium aquatile is described. The insidious onset of the megningitis and occurrence of multiple cranial nerve affections were outstanding features. In spite of adequate antibiotic treatment the course was protracted, and the outcome was permanent damage to 3 of the affected cranial nerves.

Virus-induced proliferation of cerebrospinal fluid (CSF) lymphocytes and blood lymphocytes was studied in patients with mump meningitis and in patients with aseptic meningitis of other etiology. In four out of five patients with mump meningitis the proliferation of CSF lymphocytes after mumps virus stimulation was higher than obtained with the corresponding number of blood lymphocytes. No proliferation was registered when lymphocytes from patients with other aseptic meningitis were stimulated with mumps virus. These data indicate the occurrence in CSF of lymphocytes specifically sensitized against mumps virus in patients with mumps meningitis.

The cell responses to different polyclonal lymphocyte activating substances were studied in 15 patients with aseptic meningitis by analysis of lymphocyte proliferation. the in vitro response to phytohaemagglutinin (PHA), concanavalin A (Con A) and poke weed mitogen (PWM) was investigated in blood and CSF lymphocytes simultaneously. the blood lymphocytes responded stronger than the corresponding number of CSF lymphocytes. These cells were, however, always capable of a response, suggesting that they were immunologically competent. No predominance of either PHA or Con A populations of T lymphocytes could be demonstrated in CSF compared to blood by this technique. When culture conditions were changed from the optimal cell or mitogen concentrations, the decrease in proliferation of the CSF lymphocytes was more pronounced than that of blood lymphocytes.

Cerebrospinal fluid (CSF) lymphocytes from two patients with tuberculous meningitis proliferated stronger than the corresponding peripheral blood lymphocytes (PBL) when stimulated with tuberculin purified protein derivative (PPD) in the lymphocyte transformation test after 3 days of culture. This might indicate an accumulation of specifically primed lymphocytes within the central nervous system. CSF lymphocytes and PBL from nine of ten patients with acute aseptic meningitis investigated as controls showed no or low responses when stimulated with. PPD, whereas the remaining patient displayed a significant proliferation of CSF lymphocytes, which was more pronounced than that of PBL. Stimulation with the mitogens phytohaemagglutinin, concanavalin A, and pokeweed mitogen gave lower proliferation of CSF lymphocytes compared with PBL in tuberculous and aseptic meningitis. Evaluation of the proliferative response of CSF lymphocytes compared with PBL on stimulation with PPD might be a useful complement in the diagnosis of tuberculous meningitis.

At our hospital 15 cases of leukaemic reticuloendotheliosis and 4 cases of legionnaires' disease have been diagnosed. 3 patients had both diseases. The clinical findings are reported. It is probable that patients with leukaemic reticuloendotheliosis have an increased susceptibility to Legionnaires' disease. Possible reasons for the decreased resistance are discussed.

The concentrations of complement factors C3 and C4 were quantified by single radial immunodiffusion in unconcentrated cerebrospinal fluid (CSF) and in serum from 38 patients up to 2 months after onset of acute aseptic meningitigs (AM). Elevated absolute concentrations were found in CSF in 26 and 35 patients, respectively, and in serum in 8 and 31, respectively. Elevation of the CSF C3 index, equal to (CSF/serum C3):(CSF/serum albumin), and of the corresponding CSF C4 index were found in 16 and 7 patients, respectively, as evidence of intrathecal synthesis. Only minor differences of the frequencies of elevated CSF C3 and C4 indices were encountered over the course of AM up to 2 months after onset. The occurrence of intrathecal C3 and C4 synthesis in AM is proposed as reflecting activation of hitherto unknown significance within the central nervous system.

B and T cells were defined in cerebrospinal fluid (CSF) and blood of 18 multiple sclerosis (MS), five optic neuritis, and 17 mumps meningitis patients by counting immunoglobulin-bearing lymphocytes for B cells, and the capacity of rosette formation with sheep erythrocytes of T-cell determination. Patients with MS and mumps meningitis had significantly higher T-cell values in CSF compared to blood, while the B cell value was significantly lower in CSF in mumps meningitis only. MS patients also displayed significantly lower B-cell values in blood compared to mumps meningitis patients and blood donors. No significant differences were observed between MS patients in exacerbation and in remission.

Therapy with balanced amino acid solution enriched in branched amino acids has been reported to favourably influence hepatic encephalopathy due to liver cirrhosis. We here report the same favourable effect in 3 patients aged 29, 30 and 41 yr with hepatic coma at least in part induced by acute viral hepatitis. The patients regained consciousness within 8, 12 and 12 h, respectively. The treatment was continued for 9, 6 and 5 days, respectively.

By means of a microculture technique and calculation of incorporation of 14C-thymidine, cerebrospinal fluid (CSF) lymphocytes from multiple sclerosis (MS) patients showed low or absent proliferation when stimulated with phytohaemagglutinin, concanavalin A, or pokeweed mitogen, in contrast to peripheral blood lymphocytes (PBL) obtained simultaneously and investigated in parallel. A lower proliferation of CSF lymphocytes compared with PBL was also found in acute aseptic meningitis, although it has been reported that CSF lymphocytes show greater proliferation than PBL when specifically stimulated. The low proliferation of MS CSF lymphocytes on mitogen stimulation may be a consequence of prolonged sensitization to an as yet unidentified antigen. The proliferation of MS CSF lymphocytes was not improved by adding irradiated PBL, making helper cell insufficiency less likely. MS CSF had no inhibitory effect on proliferation of PBL, arguing against an inhibitory effect of soluble factors in the CSF as an explanation for the depressed response of CSF lymphocytes.

Fasting and postprandial serum bile acids were determined before and after reduced caloric intake in patients with Gilbert's syndrome. Cholic and chenodeoxycholic acid were determined by radioimmunoassay. In all patients there was a pronounced increase in serum bilirubin (mean increase, 140%) after caloric restriction. However, both fasting and postprandial levels of serum bile acids were within the normal range before and after reduced caloric intake. The results indicate that different mechanisms are involved in the hepatic uptake and secretion of bile acids and bilirubin. Moreover, the results show that determinations of serum bile acids can be used to assess liver function in patients with Gilbert's syndrome irrespective of the degree of hyperbilirubinemia.

Ornithosis is a notifiable disease in Sweden since 1954. In 1981 and 1982 a sharp increase in the number of notifications occurred. Since then the number has declined but is still high. A changed epidemiology characterized by no history of bird contact and no common source, raised the suspicion of a new agent. Serological data now suggest that the epidemic was to a substantial part due to Chlamydia pneumoniae (strain TWAR) (48% of the patients during 1981-1982 compared to 9% during 1984-1987). During recent years TWAR infections have thus become uncommon but reappearance can be expected in the near future. The clinical picture as well as the complications appear to be very similar in infections caused by C. pneumoniae and C. psittaci.

Agarose gel electrophoresis and subsequent immunofixation revealed one or more bands consisting of IgG, IgA, IgM free Lambda chains and free Kappa chains in 39, 1, 1, 7 and 0, respectively, of 39 consecutive multiple sclerosis CSF specimens. A predominance of IgG Kappa bands was found in 30 of them, of IgG lambda bands in 5. 27 CSF specimens also displayed IgG Kappa and Lambda present in the same band, probably due to microheterogeneity.

The phytohaemagglutinin (PHA) response of lymphocytes from seven patients with natural rubella infection was investigated during the acute, early and late convalescence stages of the disease. When the lymphocytes were cultured in autologous serum, a moderate depression of the response, following stimulation with PHA in both optimal and suboptimal concentrations was obtained two weeks after the onset of exanthema (early convalescence). Two months later (late convalescence), the lymphocyte stimulation response had returned to almost normal values. On the other hand, lymphocytes incubated in pooled homologous serum reacted normally to PHA in optimal concentrations at all three stages. Determination of T- and B-lymphocytes did not reveal any change in the relative proportion of T-lymphocytes during the course of the disease. However, in late convalescence, a significant decrease in the relative number of B-lymphocytes was recorded.

The frequencies of the HLA antigens A3, B7, and Dw2, previously related with multiple sclerosis, were investigated in 26 patients with acute aseptic meningitis and oligoclonal immunoglobulins in cerebrospinal fluid (CSF), but not in serum when investigated by agarose gel electrophoresis. HLA antigen frequencies were similar in patients with aseptic meningitis and controls. The oligoclonal immune response within the central nervous system in aseptic meningitis is not associated with the same HLA antigens found in patients with multiple sclerosis.

Two cases of infection of the central nervous system (CNS) with Haemophilus parainfluenzae — a 12-month-old girl with meningitis and a 17-month-old girl with brain abscess—are reported. Both infants had long-standing upper respiratory infection before CNS disease. Both recovered after treatment.

To the Editor.— As many as 50% of patients are admitted to the hospital because of adverse drug reactions; up to 18% of hospitalized patients suffer from side effects of drugs, which sometimes may be fatal. 1 Over 20 years, metronidazole has earned a reputation of being remarkably safe, although in recent years doses and duration of treatment have gradually increased, for example, when treating Crohn's disease. 2 Adverse reactions have mostly been mild and reversible, such as nausea, vomiting, fever, urticaria, and metallic taste, but sometimes can be more severe, such as polyneuropathy, mental confusion, convulsions, and leukopenia. Recently, cases of serum sickness and meningitis have been described. We report a case of pneumonitis caused by metronidazole. 2 Report of a Case.— A 42-year-old woman was admitted to the hospital for the first time on Aug 3,1985. She had a known pollen allergy, but no known hypersensitivity to drugs.