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Biomedical subjects

L Lindquist

Publications and source records attributed to L Lindquist.

At least 37 records · Page 2Linked to original sources

Incidence and prognosis of meningitis due to Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis in Sweden.

The incidence, concomitant conditions and case fatality rate of Haemophilus influenzae (Hi) and pneumococcal meningitis and of invasive meningococcal infections were studied retrospectively in Sweden (population 8.4 million) for the years 1987-89, the period before vaccination against Hi type b started. A total of 1,019 cases with culture-verified infection were found. The incidence rates per 100,000 per year were 1.8 for Hi meningitis, 1.2 for pneumococcal meningitis and 1.0 for invasive meningococcal infections. The age-specific incidence was highest in the 3-23 months age group for the 3 bacterial species. Pneumococcal meningitis was common in individuals > or = 60 years and meningococcal infections in the age-group 10-24 years. A serious concomitant condition was known in 57% of all patients with pneumococcal meningitis while this was uncommon for the other organisms. The case fatality rate was 2% for Hi meningitis, 24% for pneumococcal meningitis and 10% for meningococcal infections. All 81 pneumococcal isolates which had been serotyped belonged to serotypes in the 23-valent pneumococcal vaccine. Of the meningococcal isolates, 65% belonged to serogroup B. In conclusion, the high incidence of Hib meningitis justifies general Hib vaccination. Development of a vaccine against N. meningitidis group B should have high priority. Furthermore, improved pneumococcal vaccines are needed for patients with predisposing conditions. The currently available pneumococcal polysaccharide vaccine seems to be underused.

Adolescent↗

No findings of enteroviruses in Swedish patients with chronic fatigue syndrome.

Enteroviruses have been proposed to cause an immune complex disease in the chronic fatigue syndrome. Altogether 34 patients with the chronic fatigue syndrome, according to criteria of the Centers for Disease Control, USA, were studied evenly over the seasons for the possible presence of a chronic enterovirus infection. In 11 patients, 1-5 faecal samples were collected at about 6 month intervals for virus isolation before and after acid treatment, followed by ultracetrifugation at pH 3 to dissolve possible enterovirus-antibody complexes. Another 14 fecal samples were subjected to routine virus isolation alone. Seven pairs of serum-cerebrospinal fluid samples were analysed for cross-reactive IgG antibody activity to enteroviruses. In 29 patients a muscle biopsy was collected for enterovirus polymerase chain reaction (PCR). We were unable to identify enteroviruses in any of these samples by any of these techniques. Our study does not confirm evidence for persistent enterovirus infection in the chronic fatigue syndrome.

Acids↗

Intrathecal production of neopterin and beta 2 microglobulin in tick-borne encephalitis (TBE) compared to meningoencephalitis of other etiology.

To study the pathophysiology of tick-borne encephalitis (TBE), the kinetics of neopterin and beta 2 microglobulin (beta 2M) production were measured in sequential, cerebrospinal fluid (CSF) and serum samples in 133 patients with aseptic meningoencephalitis (TBE, n = 72; non-TBE, n = 61). Intrathecal production of neopterin was demonstrable in all patients. Neopterin levels in CSF were elevated already at day 2: geometric mean value in TBE 36 nmol/l (range 1-253), in the non-TBE group 29 nmol/l (0.2-96). At day 9 and week 6 the neopterin level was significantly higher in TBE (86 (19-725) and 17 (4-122) nmol/l) than in non-TBE (28 (5-109) and 3 (0.2-58) nmol/l) (p < 0.001). After 1 year CSF levels were within the normal range. The beta 2M response in CSF followed the pattern of neopterin. The intensity and duration of neopterin and beta 2M was not correlated to the clinical course. Neopterin seems to be a more sensitive indicator of intrathecal T-cell response and inflammatory reaction than beta 2M. The results indicate that a long-lasting strong inflammatory reaction is of pathophysiological significance in TBE.

Adolescent↗

Prevention of chemotherapy-induced ulcerative mucositis by transforming growth factor beta 3.

Mucositis is a common, dose-limiting complication in patients receiving cancer chemotherapy, which appears to be a consequence of the rate of epithelial proliferation. The beta transforming growth factors have been shown to be negative regulators of epithelial cell proliferation. Here we show that transforming growth factor beta 3 administration reduced proliferation of oral epithelium in vitro and in vivo. Topical application of transforming growth factor beta 3 to the oral mucosa of the Syrian golden hamster prior to chemotherapy significantly reduced the incidence, severity, and duration of oral mucositis, reduced chemotherapy-associated weight loss, and increased survival.

Animals↗

Structure of the O antigen of Escherichia coli K-12 and the sequence of its rfb gene cluster.

Escherichia coli K-12 has long been known not to produce an O antigen. We recently identified two independent mutations in different lineages of K-12 which had led to loss of O antigen synthesis (D. Liu and P. R. Reeves, Microbiology 140:49-57, 1994) and constructed a strain with all rfb (O antigen) genes intact which synthesized a variant of O antigen O16, giving cross-reaction with anti-O17 antibody. We determined the structure of this O antigen to be -->2)-beta-D-Galf-(1-->6)-alpha-D-Glcp- (1-->3)-alpha-L-Rhap-(1-->3)-alpha-D-GlcpNAc-(1-->, with an O-acetyl group on C-2 of the rhamnose and a side chain alpha-D-Glcp on C-6 of GlcNAc. O antigen synthesis is rfe dependent, and D-GlcpNAc is the first sugar of the biological repeat unit. We sequenced the rfb (O antigen) gene cluster and found 11 open reading frames. Four rhamnose pathway genes are identified by similarity to those of other strains, the rhamnose transferase gene is identified by assay of its product, and the identities of other genes are predicted with various degrees of confidence. We interpret earlier observations on interaction between the rfb region of Escherichia coli K-12 and those of E. coli O4 and E. coli Flexneri. All K-12 rfb genes were of low G+C content for E. coli. The rhamnose pathway genes were similar in sequence to those of (Shigella) Dysenteriae 1 and Flexneri, but the other genes showed distant or no similarity. We suggest that the K-12 gene cluster is a member of a family of rfb gene clusters, including those of Dysenteriae 1 and Flexneri, which evolved outside E. coli and was acquired by lateral gene transfer.

Acetylation↗

Inhibition of leukocyte rolling with polysaccharide fucoidin prevents pleocytosis in experimental meningitis in the rabbit.

Inflammatory recruitment of leukocytes into the cerebrospinal fluid (CSF) during bacterial meningitis has been shown to contribute significantly to the neurological damage commonly associated with this serious disease. In this study we tested whether or not inhibition of leukocyte rolling, a precondition for firm leukocyte adhesion to vascular endothelium in vivo, may reduce CSF leukocyte recruitment and associated inflammatory changes in rabbits with experimental meningitis. As documented by intravital microscopy of small venules in the rabbit mesentery and tenuissimus muscle, leukocyte rolling was rapidly and profoundly reduced by intravenous treatment with the polysaccharide fucoidin, a homopolymer of sulfated L-fucose known to block the function of the leukocytic "rolling receptor" L-selectin. Moreover, fucoidin treatment dramatically reduced the accumulation of both leukocytes and plasma protein in the CSF of rabbits challenged intrathecally with pneumococcal antigen. These main findings thus illustrate that inhibition of leukocyte rolling, an early and obligatory step in the process of leukocyte extravasation, may be an effective therapeutic approach to attenuate leukocyte-dependent central nervous system damage in bacterial meningitis.

Animals↗

Comparison of intravenous penicillin G and oral doxycycline for treatment of Lyme neuroborreliosis.

To compare the efficacy of oral doxycycline and IV penicillin G for the treatment of neuroborreliosis, we randomized consecutive patients with Lyme neuroborreliosis to receive either IV penicillin G (3 g q 6 h) or oral deoxycycline (200 mg q 24 h) for 14 days. All patients had antibodies against Borrelia burgdorferi in serum, CSF, or both, or had a positive CSF culture. Twenty-three patients randomized to penicillin G and 31 patients to doxycycline were included in the study. All patients improved during treatment, and there were no significant differences between the two treatment groups in patient scoring, CSF analysis, or serologic and clinical follow-up during 1 year. There were no treatment failures, although one patient in each treatment group was re-treated because of residual symptoms. In conclusion, oral doxycycline is an adequate and cost-effective alternative to IV penicillin for the treatment of Lyme neuroborreliosis.

Administration, Oral↗

Purification, characterization and HPLC assay of Salmonella glucose-1-phosphate thymidylyl-transferase from the cloned rfbA gene.

We here report on the purification and characterization of glucose-1-phosphate thymidylyl-transferase, the first of four enzymes committed to biosynthesis of dTDP-L-rhamnose from Salmonella enterica strain LT2. The purification was greatly facilitated by the cloning of the rfbA gene encoding this enzyme. Pure enzyme was obtained by 109-fold enrichment in three chromatography steps. The glucose-1-phosphate thymidylytransferase catalyzes a reversible bimolecular group transfer reaction and kinetic measurements indicate that it acts by a 'ping-pong' mechanism. The Km values for dTTP and alpha -D-glucose 1-phosphate in the forward reaction are 0.020 mM and 0.11 mM, respectively. In the reverse reaction the Km values for dTDP-D-glucose and diphosphate are 0.083 mM and 0.15 mM, respectively. The enzyme also accepts UTP and UDP-D-glucose and alpha-D-glucosamine 1-phosphate is accepted equally as well as alpha-D-glucose 1-phosphate. The NH2-terminal sequence of glucose-1-phosphate thymidylyl-transferase agrees with the sequence predicted from the nucleotide sequence of the orf6.1 gene of the rfb gene cluster. The SDS/PAGE estimated subunit mass of 31 kDa agrees well with that calculated from the amino acid composition deduced from the nucleotide sequence of the orf6.1 gene (32453 Da).

Amino Acid Sequence↗

Serum C-reactive protein in the differential diagnosis of acute meningitis.

The ability of serum C-reactive protein (S-CRP) to differentiate between acute bacterial and viral meningitis was evaluated in 235 patients, both children and adults. The patients underwent lumbar puncture due to suspected central nervous system (CNS) infection. In patients with bacterial meningitis, 7/60 (12%) had S-CRP concentrations below 50 mg/l. Of these patients, 4 were children below 6 years of age, all with symptoms of meningitis for less than 12 h before admission and 3 adults of whom 1 had symptoms of meningitis for less than 12 h. In patients with viral meningitis, 15/146 (10%) had S-CRP concentrations above 50 mg/l. Only 3 children below 6 years of age with viral meningitis had S-CRP concentration above 20 mg/l, but none exceeded 50 mg/l. An S-CRP value above 50 mg/l in patients with CSF pleocytosis usually indicates bacterial etiology. However, S-CRP values above 50 mg/l may occasionally be seen in viral meningitis. In children younger than 6 years of age a discriminatory level for S-CRP of 20 mg/l can be used to distinguish between bacterial and viral meningitis, but for older patients a discriminatory level of 50 mg/l is more appropriate. If the duration of the illness is less than 12 h, S-CRP concentrations below the discriminatory levels are of limited diagnostic value.

Acute Disease↗

Value of cerebrospinal fluid analysis in the differential diagnosis of meningitis: a study in 710 patients with suspected central nervous system infection.

A prospective study to determine the value of cerebrospinal fluid analysis in the differential diagnosis of meningitis was performed in 710 consecutively observed patients, both children and adults, who underwent lumbar puncture due to suspected central nervous system infection. Diagnoses included acute or presumed bacterial meningitis (n = 79), acute or presumed viral meningoencephalitis (n = 218), acute unclassified meningitis (n = 6), other infections of the central nervous system (n = 37), non-infectious neurological diseases (n = 76) and control patients (n = 294). The sensitivity, specificity and predictive values were determined for cerebrospinal fluid white blood cell count, total protein, lactate, glucose and C-reactive protein levels as well as the blood/cerebrospinal fluid glucose ratio. Determination of cerebrospinal fluid levels of lactate (greater than or equal to 3.5 mmol/l) was found to be superior to the other tests. The C-reactive protein level gave no additional diagnostic information when the lactate level was determined. The white blood cell count, and total protein and glucose levels were often unreliable tools for differential diagnosis, largely due to low sensitivity at realistic discriminatory limits. The study confirms that no cerebrospinal fluid test is fully reliable in distinguishing bacterial meningitis from other forms of meningitis.

Adolescent↗

Quantitation of C-reactive protein in cerebrospinal fluid and serum by zone immunoelectrophoresis assay (ZIA).

The zone immunoelectrophoresis assay (ZIA) for C-reactive protein (CRP) determinations is easy to perform and requires only small amount of antiserum, e.g., 25-100 and 0.5-1.0 microliter anti-CRP antibody/20 serum and CSF samples, respectively. For quantitating CSF-CRP the immunoprecipitates formed were stained using alkaline phosphatase-conjugated secondary antibodies and the lowest standard concentration used was 30 micrograms/l. The immunoprecipitates formed when measuring CRP in serum were stained by Coomasie brilliant blue R250 with a detection limit of about 300 micrograms/l. CRP was determined in cerebrospinal fluid in 27 patients with bacterial meningitis (range less than 0.03-23.0 mg/l) and in 25 patients with viral meningitis (range less than 0.03-0.23 mg/l). CRP was quantitated in 52 sera by both the CRP ZIA method (y) and by electroimmunoassay (x). The correlation coefficient was r = 0.992 with the regression line y = 1.024 x + 0.855.

C-Reactive Protein↗

Experimental meningitis in the rabbit. I. Arterial blood pressure and acid-base balance during halothane anesthesia and in situ freezing of the brain.

Effects of halothane/N2O anesthesia and in situ freezing of the brain on mean arterial blood pressure (MABP), pH, pCO2 and pO2 were evaluated in rabbits with either Streptococcus pneumoniae or Escherichia coli meningitis. Prior to anesthesia infected rabbits had, compared to controls, significantly lower values for MABP and pCO2, either with a compensated (S. pneumoniae group) or decompensated (E. coli group) metabolic acidosis. In most animals a slight additional decrease in MABP was observed during anesthesia. With maintained pre-anesthetic hypocapnia no further disturbance in acid-base balance occurred during anesthesia. After one minute of freezing MABP increased towards preanesthetic levels. We conclude that the technique for in situ freezing of the brain under halothane/N2O anesthesia may be applied for studies of cerebral metabolism in rabbit with experimental meningitis.

Acid-Base Equilibrium↗

Experimental meningitis in the rabbit. II. Cerebral energy metabolism in relation to increased cerebrospinal fluid concentrations of lactate.

We have analyzed cerebral energy metabolism in rabbits with Streptococcus pneumoniae or Escherichia coli meningitis aiming at an increased understanding of the cerebrospinal fluid (CSF) lactacidosis observed in this disease. After intracisternal inoculation of bacteria the lactate concentration in the CSF increased to 9.7 +/- 0.7 (mean +/- SE) mmol/l compared to control values of 3.2 +/- 0.2 mmol/l. Simultaneously sampled brain tissue from parietal cortex, caudate nucleus, and thalamus showed no increase in lactate concentrations. The high-energy phosphate content decreased only marginally, phosphocreatine levels by 11-17% in the cortex and in the caudate nucleus, and adenosine triphosphate concentrations by 15%, but only in the caudate nucleus. Our results indicate that the CSF lactate increase in bacterial meningitis is not primarily linked to cerebral lactacidosis. The decreased concentrations of high-energy phosphates in diseased animals need further study but may be due to increased intracranial pressure and reduced capillary blood flow.

Animals↗