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A M Lebech

Publications and source records attributed to A M Lebech.

At least 19 recordsLinked to original sources

[Leukocyte scintigraphy: indications and diagnostic value].

Leukocyte scintigraphy is a diagnostic method that allows visualisation of pathological accumulation of leukocytes. Some important indications are reviewed with special emphasis on the diagnostic value and possible limitations. Leukocyte scintigraphy is valuable for diagnosing osteomyelitis in bones with a pre-existing pathology, but probably not in chronic or vertebral osteomyelitis. The test is also valuable for detection of intra-abdominal abscess and vascular graft infection. Fever of unknown origin represents a diagnostic challenge. Although the sensitivity of leukocyte scintigraphy is only modest in this context, it seems to be a valuable addition to other tests performed in these patients.

Abdominal Abscess↗

Diagnostic value of PCR for detection of Borrelia burgdorferi DNA in clinical specimens from patients with erythema migrans and Lyme neuroborreliosis.

BACKGROUND: The aim of the study is to evaluate the diagnostic sensitivity of a 16S ribosomal RNA-based PCR on clinical specimens from patients with erythema migrans (EM) and neuroborreliosis and to compare the sensitivities with those obtained by in vitro culture and serological testing. A semiquantitative detection system, representing the input amount of specific DNA and thus the density of spirochetes in clinical specimens, indicated the preferred clinical sample to obtain for PCR testing. METHODS AND RESULTS: Skin biopsy and urine samples from 31 patients with EM and cerebrospinal fluid (CSF) and urine samples from 30 patients with neuroborreliosis were investigated. Borrelia burgdorferi DNA was detected in 71% of the skin biopsy specimens and 13% of the urine samples from patients with EM. Forty-one percent of the patients with EM were found to have B burgdorferi-specific antibodies in serum, and B burgdorferi was cultured in 29% of the EM specimens. For patients with neuroborreliosis, the diagnostic sensitivities in CSF and urine samples were 17% and 7%, respectively. Specific intrathecal antibody production was found in 90% of the patients, and 87% showed elevated B burgdorferi antibodies in serum. In general, PCR of skin biopsy samples yielded very high amounts of amplicons versus low amounts for CSF and urine samples. CONCLUSIONS: PCR of skin biopsy specimens is currently the most sensitive and specific test for the diagnosis of patients with EM, superior to culture and serological testing. For B burgdorferi-specific CSF disgnosis in patients with neuroborreliosis, the measurement of specific intrathecal antibody synthesis is superior to PCR. However, in patients with a short duration of disease (<14 days), PCR may be a useful diagnostic supplement. PCR of urine samples cannot be recommended at the present time for routine diagnosis of patients with EM or neuroborreliosis.

Adolescent↗

Immunoserologic evidence of Human Granulocytic Ehrlichiosis in Danish patients with Lyme neuroborreliosis.

Human Granulocytic Ehrlichiosis (HGE) is a recently described human illness in the US which manifests as fever, myalgia and headache combined with pancytopenia and elevated concentrations of hepatic transaminases. Genetic analyses indicate that the agent of HGE appears to be an Ehrlichia species that is closely related to E. equi and E. phagocytophila. Ixodes dammini and I. scapularis were identified as potential vectors of HGE. Ixodes ticks are also the vector of Borrelia burgdorferi, the agent of Lyme borreliosis. The presence of antibodies against Ehrlichia in 132 sera from Danish patients with definite Lyme neuroborreliosis were examined in order to provide immunoserologic evidence of this infection in Denmark. Patients with Lyme neuroborreliosis were chosen as a test cohort, as these patients had been infested by a tick sufficient for transmission of B. burgdorferi. All had cerebrospinal fluid lymphocytic pleocytosis. As controls, serum samples from 50 healthy Danish blood donors were included. Of the 132 patients with Lyme neuroborreliosis, 5 (3.8%) reacted with the E. equi antigen substrate at titres 1:128. None of the blood donors were found seropositive for E. equi. At least 2 of the patients found seropositive for HGE constituted probable cases of HGE with E. equi antibody titres of at least 80 combined with fever, headache and myalgias. However, in no cases were we able to detect the presence of the HGE agent in the serum by PCR. We conclude that human exposure to granulocytic Ehrlichiae species may also occur in Europe, although further studies will be necessary to document active infection with these potential pathogens.

Adult↗

Lyme carditis: a clinical presentation and long time follow-up.

The acute disease and a follow-up carried out up to 7 years after definite Lyme carditis in 6 patients is described. At the time of diagnosis all 6 patients had 2-3 degrees AV block, 4 patients presented with syncopes, and 1 revealed episodes of non-sustained ventricular tachycardia. The diagnosis of Lyme carditis was confirmed by Borrelia burgdorferi-specific IgM and IgG antibody determinations in consecutive serum samples. All patients were treated with antibiotics. At follow-up, a clinical examination, a 2D and M-mode echocardiogram, and an exercise test did not reveal sequelae to Lyme carditis.

Adult↗

[Toxoplasmosis-chorioretinitis: clinical course and treatment of seven patients].

Toxoplasmosis is a major and preventable cause of severe visual loss and blindness in young people. Ocular toxoplasmosis is the leading cause of posterior uveitis and in most cases it represents a late manifestation of a congenital infection. The clinical picture and anti-Toxoplasma therapy of seven patients referred to the Department of Infectious Diseases, Hvidovre Hospital is described. All patients had clinical ocular toxoplasmosis at initial examination with unilateral focal necrotizing retinitis associated with typical old, pigmented scars. All patients had anti-toxoplasmosis IgG antibodies. After anti-Toxoplasma therapy with sulfadiazine, pyrimethamine and corticosteroid the ocular lesions were healed to atrophic scars and the inflammatory activity disappeared. We conclude that when the clinical picture is compatible with toxoplasmosis, antibodies to Toxoplasma gondii are demonstrated and there is no other diagnosis, anti-Toxoplasma treatment should be considered. It is important to inform pregnant women about prophylactic measures, and to perform a serological screening of newborns, since treatment of congenital toxoplasmosis from birth improves the prognosis.

Adolescent↗

Evolution of the Borrelia burgdorferi outer surface protein OspC.

The genes coding for outer surface protein OspC from 22 Borrelia burgdorferi strains isolated from patients with Lyme borreliosis were cloned and sequenced. For reference purposes, the 16S rRNA genes from 17 of these strains were sequenced after being cloned. The deduced OspC amino acid sequences were aligned with 12 published OspC sequences and revealed the presence of 48 conserved amino acids. On the basis of the alignment, OspC could be divided into an amino-terminal relatively conserved region and a relatively variable region in the central portion. The distance tree obtained divided the ospC sequences into three groups. The first group contained ospC alleles from all (n = 13) sensu stricto strains, the second group contained ospC alleles from seven Borrelia afzelii strains, and the third group contained ospC alleles from five B. afzelii and all (n = 9) Borrelia garinii strains. The ratio of the mean number of synonymous (dS) and nonsynonymous (dN) nucleotide substitutions per site calculated for B. burgdorferi sensu stricto, B. garinii, and B. afzelii ospC alleles suggested that the polymorphism of OspC is due to positive selection favoring diversity at the amino acid level in the relatively variable region. On the basis of the comparison of 16S rRNA gene sequences, Borrelia hermsii is more closely related to B. afzelii than to B. burgdorferi sensu stricto and B. garinii. In contrast, the phylogenetic tree obtained for the B. hermsii variable major protein, Vmp33, and 18 OspC amino acid sequences suggested that Vmp33 and OspC from B. burgdorferi sensu stricto strains share a common evolutionary origin.

Amino Acid Sequence↗

Comparison of in vitro culture, immunohistochemical staining, and PCR for detection of Borrelia burgdorferi in tissue from experimentally infected animals.

An avidin-biotin-amplified immunophosphatase staining method with a purified polyclonal rabbit anti-Borrelia burgdorferi hyperimmune serum was developed for identification of B. burgdorferi in tissue specimens. The diagnostic efficacy was compared with those of in vitro culture and PCR with fresh and fixed, paraffin-embedded tissues. A nested PCR assay was developed for identification of a 276-bp fragment of the B. burgdorferi flagellin gene. The diagnostic sensitivities of the different techniques were evaluated with spleen, renal, and urinary bladder tissues from eight experimentally infected gerbils. A systemic infection was verified by positivity of 23 of 24 (96%) organ cultures. B. burgdorferi was visualized immunohistochemically in 9 of 23 (39%) of the specimens. Among these nine specimens, an average of 33% of the 15 sections examined were positive. The spirochetes accumulated in discrete clusters and were associated with focal lymphocytic infiltration. The diagnostic sensitivity obtained by PCR with fixed, paraffin-embedded tissue was 21%, considerably lower than that with fresh tissue (71%). Thus, the reliable demonstration of B. burgdorferi by immunohistochemical staining is possible but extremely laborious, and considering the fact that the density of B. burgdorferi in human tissue is even lower than that in experimentally infected animals, the method is not useful in a clinical setting. It may, however, still be valuable in pathogenetic research. Detection of B. burgdorferi DNA by PCR should be performed with fresh tissue specimens and not with fixed, paraffin-embedded specimens.

Animals↗

Taxonomic classification of 29 Borrelia burgdorferi strains isolated from patients with Lyme borreliosis: a comparison of five different phenotypic and genotypic typing schemes.

Twenty-nine European and North American Borrelia burgdorferi strains isolated from patients with Lyme borreliosis, were investigated by restriction fragment length polymorphism (RFLP) of two phylogenetically highly conserved chromosomal genes encoding flagellin (fla) and the p60 common antigen (CA), as well as of the plasmid-borne outer surface protein A (ospA) gene. RFLP of the ospA, fla and CA gene revealed five, two and four distinct subspecies-specific patterns, respectively. RFLP classification of the B. burgdorferi strains was compared with four different classification schemes proposed by others: (i) molecular mass profile of OspA and OspB (Adam et al. [1]); (ii) OspA serotyping (Wilske et al. [34]); (iii) genomic fingerprinting on the central region of the B. burgdorferi fla gene (Picken [24]) and (iv) 16S rRNA signature nucleotide analysis (Marconi and Garon [19]). Results obtained with the different methods correlated highly. All strains classified as B. burgdorferi sensu stricto and B. afzelii could be unequivocally identified as one distinct group by all five typing methods. B. garinii isolates, however, were more heterogeneous and according to RFLP of the CA and ospA gene fell into either two or three subgroups. The agreement of the different approaches supports the recent concept that B. burgdorferi sensu lato strains should be delineated to three genomic groups and that B. burgdorferi sensu lato is clonal. All 12 US strains were B. burgdorferi sensu stricto, whereas the 17 European isolates belonged to any of three genospecies. Among European B. burgdorferi isolates there was an association between B. burgforferi genospecies and the clinical manifestation of Lyme borreliosis. B. afzelii strains were found to predominate in 11 skin isolates (75%), whereas all 6 cerebrospinal fluid isolates from patients with neuroborreliosis were B. garinii. These findings support the concept of a strain-dependent organotropism of B. burgdorferi.

Animals↗

Serological follow-up after treatment of patients with erythema migrans and neuroborreliosis.

To investigate the duration and kinetics of immunoglobulin M (IgM) and IgG antibodies against Borrelia burgdorferi in serum after treatment of Lyme borreliosis, consecutive serum samples from 30 seropositive patients with erythema migrans and 91 seropositive patients with neuroborreliosis were analyzed with a capture IgM enzyme-linked immunosorbent assay (ELISA) and an indirect IgG ELISA, both using B. burgdorferi flagella as the antigen. All the patients improved after treatment: 97 patients had a complete clinical recovery, while 24 patients had sequelae. The results showed that patients with erythema migrans and early neuroborreliosis more often initially had highly elevated IgM optical density (OD) values and low IgG OD values against B. burgdorferi, while the opposite was found in patients with late neuroborreliosis. During follow-up, the majority of patients had developed negative or significantly declining IgM ODs after 1 to 1.5 years but persistently positive IgM ODs were found up to 17 months after treatment of erythema migrans and 3 years after treatment of neuroborreliosis. IgG antibody levels declined more slowly and remained elevated to a larger extent, but more than half of the patients had developed negative IgG ODs within 5 years after therapy. However, positive IgG OD values were found after 9 to 10 years for patients treated for neuroborreliosis as well as erythema migrans. Both IgM and IgG antibodies against B. burgdorferi may persist for months to years after successful treatment of Lyme borreliosis. Consequently, a single serum sample with antibodies against B. burgdorferi must always be carefully evaluated and correlated to clinical symptoms.

Adult↗

Serological follow-up after treatment of Borrelia arthritis and acrodermatitis chronica atrophicans.

To study the serological response to Borrelia burgdorferi after treatment of late Lyme borreliosis, consecutive serum samples from 20 patients with Borrelia arthritis and 21 with acrodermatitis chronica atrophicans were analysed with capture IgM ELISA and indirect IgG ELISA, both using B. burgdorferi flagella as antigen. Seven patients had positive IgM OD values, whereas all 41 had positive IgG OD values before therapy. In the majority, highly elevated IgG OD values were seen. All patients improved after antibiotic therapy, 32 recovering completely, while 9 had sequelae. At follow-up after 6 months to 5 years, 4/7 patients became negative IgM ELISA, whereas 3 still had slightly elevated IgM OD values 6 months, 1 year and 4.5 years, respectively, after therapy. Only one patient became negative in IgG ELISA during follow-up, although a significant decline in IgG OD values was seen in 22 of the remaining 40 initially IgG-positive patients. The serological response after successful treatment of Borrelia arthritis and acrodermatitis chronica atrophicans may persist for several years even with highly elevated IgG OD values in patients who have recovered completely.

Acrodermatitis↗

[Complications of second-look surgery for ovarian cancer].

All complications were registered in 139 consecutive second-look operations for ovarian cancer. Forty-one complications were registered in 33 patients, none lethal. The most frequent complications were anaemia requiring blood-transfusion (10.7%) and acute cystitis (4.3%). Other complications were seen with frequencies between 0.7 to 2.8 percent. No differences with respect to complications were found between patients with residual tumour versus those without, nor between patients where only biopsies were taken versus those who had organs removed. Although the patients were in clinical complete remission, 53% were found to have residual disease at second-look operation.

Adolescent↗

Polymorphism in ospC gene of Borrelia burgdorferi and immunoreactivity of OspC protein: implications for taxonomy and for use of OspC protein as a diagnostic antigen.

The nucleotide sequences of the ospC gene from five Danish human Borrelia burgdorferi isolates representing all three B. burgdorferi genospecies (B. burgdorferi sensu stricto, Borrelia garinii sp. nov., and group VS461) and from the American type strain B31 were determined and compared with the published ospC sequence from the German B. burgdorferi isolate PKo (R. Fuchs, S. Jauris, F. Lottspeich, V. Preac-Mursic, B. Wilske, and E. Soutschek, Mol. Microbiol. 6:503-509, 1992). The ospC gene was present in all isolates, regardless of the presence or absence of its product, OspC. The deduced amino acid sequences of OspC from the seven isolates were aligned and revealed pairwise sequence identities ranging from 60.5 to 100%. Differences were scattered throughout the amino acid sequences. A phylogenetic tree was constructed and revealed three distinct phenotypic groups OspCI to OspCIII corresponding to the three delineated genospecies. Immunoblot analysis revealed that the seven OspC proteins tested have both common and specific epitopes. There is significant epitope diversity, since even polyclonal antisera showed serotype-restricted specificity. Therefore, a serodiagnostic assay for Lyme borreliosis utilizing OspC as a test antigen should include all three OspC phenotypes in order to obtain a species-wide sensitivity.

Amino Acid Sequence↗

Borrelia burgdorferi-specific intrathecal antibody production in neuroborreliosis: a follow-up study.

We used a capture ELISA with biotinylated Borrelia burgdorferi flagella as antigen to analyze the kinetics of intrathecal antibody production against B burgdorferi in 27 patients with neuroborreliosis. All patients had lymphocytic pleocytosis, 13/27 had intrathecal specific IgM production, and 26/27 had intrathecal IgG synthesis against B burgdorferi before therapy. All patients improved after antibiotic treatment. At follow-up, 11 months to 8 years later (median, 1 1/2 years), 20 patients had had a complete clinical recovery, and seven suffered from sequelae. One patient without sequelae had persistent specific intrathecal IgM synthesis. Ten of 20 patients without sequelae and five of seven patients with sequelae had persistent intrathecal IgG production against B burgdorferi. None of the 16 patients with persistent specific intrathecal antibody synthesis had pleocytosis at follow-up. Therefore, intrathecal immunoglobulin production against B burgdorferi, especially IgG, may persist for years after treatment of neuroborreliosis without clinical signs of active disease.

Adolescent↗

The clinical and epidemiological profile of Lyme neuroborreliosis in Denmark 1985-1990. A prospective study of 187 patients with Borrelia burgdorferi specific intrathecal antibody production.

This prospective study reports the clinical and epidemiological features of 187 consecutive patients with neuroborreliosis recognized in Denmark over the 6-yr period, 1985-1990. Only patients with intrathecal Borrelia burgdorferi specific antibody synthesis were included. In 1990 regional incidences varied between 5.7 and 24.1 per million. Ninety-four percent of the patients had early (second stage) neuroborreliosis. The most common manifestation was a painful lymphocytic meningoradiculitis (Bannwarth's syndrome) either with paresis (61%) or as a radicular pain syndrome only (25%). Central nervous system (CNS) involvement in early neuroborreliosis was rare; 4% had signs of myelitis and only one patient had acute encephalitis. Children showed a different course of the disease. Six percent of the patients suffered a chronic course with a disease duration between 6 mths and 6 yrs either as chronic lymphocytic meningitis (1.6%) or as third stage chronic encephalomyelitis (4.3%). Meningeal signs were rare despite pronounced inflammatory cerebrospinal fluid (CSF) changes (median cell count 160/microliters; median protein concentration 1.13 g/l). High dose i.v. penicillin G was administered to 91% of the patients. Based on the clinical outcome and normalization of CSF no treatment failures were recognized. The final morbidity after a median follow-up of 33 mths was low; disabling sequelae were reported in nine patients, mainly those with previous CNS involvement. We conclude that neuroborreliosis is a common and characteristic neurological disorder. The diagnosis should be based on the demonstration of inflammatory CSF changes and B. burgdorferi specific intrathecal antibody production.

Aged↗

Detection of Borrelia burgdorferi DNA in urine samples and cerebrospinal fluid samples from patients with early and late Lyme neuroborreliosis by polymerase chain reaction.

A polymerase chain reaction (PCR) was developed for use in the identification of a 248-bp fragment of the Borrelia burgdorferi flagellin gene in urine and cerebrospinal fluid (CSF) from patients with Lyme neuroborreliosis. The specificities of the PCR products were confirmed by DNA-DNA hybridization with an internal probe. The assay had a detection limit of 10 in vitro-cultivated B. burgdorferi. The PCR assay seemed to be species wide as well as species specific, since DNA from all 21 B. burgdorferi isolates from humans tested but not from Borrelia hermsii or Treponema pallidum could be amplified. We tested 10 consecutively diagnosed patients with untreated neuroborreliosis. There was lymphocytic pleocytosis and intrathecal B. burgdorferi-specific antibody synthesis in the CSF of all patients. Urine and CSF samples were investigated by PCR before, during, and up to 8.5 months after therapy. B. burgdorferi DNA was detected in urine samples from nine patients; five patients, including two patients with chronic neuroborreliosis, were PCR positive prior to treatment, whereas urine samples from the remaining four patients obtained 3 to 6 days after the onset of therapy became PCR positive. All urine samples obtained greater than 4 weeks after therapy were negative by PCR. PCR of CSF was less sensitive, and samples from only four patients, including one with chronic neuroborreliosis, were positive. We conclude that urine is a more suitable sample source than CSF for use in B. burgdorferi DNA detection by PCR. Normalization of inflammatory CSF changes and the negative PCR results during follow-up even in patients with chronic neuroborreliosis do not point to a persistent infection. The future role of PCR as a diagnostic tool for Lyme neuroborreliosis is still uncertain.

Adolescent↗

Roxithromycin in Lyme borreliosis: discrepant results of an in vitro and in vivo animal susceptibility study and a clinical trial in patients with erythema migrans.

A new semisynthetic macrolide roxithromycin was evaluated for its potential use in the treatment of Lyme borreliosis. Using a macro-dilution broth technique, Borrelia burgdorferi was shown to be susceptible to roxithromycin with a minimal bactericidal concentration (MBC) of 0.06-0.25 microgram/ml. A systemic B. burgdorferi infection was established in gerbils; a dosage of greater than or equal to 25 mg/kg/day roxithromycin for 10 days eliminated the infection. A single blind, randomized multicenter study was performed to evaluate the efficacy of roxithromycin 150 mg b.i.d. versus phenoxymethyl-penicillin 1 g b.i.d. for 10 days in patients with uncomplicated erythema migrans. The study was interrupted when 19 patients had enrolled because of five treatment failures. All 5 patients had received roxithromycin; three patients had persisting or recurrent erythema migrans, one developed a secondary erythema migrans-like lesion and severe arthralgia and one developed neuroborreliosis. B. burgdorferi was isolated from skin biopsies after roxithromycin therapy from two patients with persistent erythema migrans and both isolates were still highly susceptible to roxithromycin (MBC = 0.03 microgram/ml). No treatment failures were seen in 10 patients treated with phenoxymethyl-penicillin. Roxithromycin is thus not recommended for treatment of Lyme borreliosis.

Adult↗

Lyme neuroborreliosis: a new sensitive diagnostic assay for intrathecal synthesis of Borrelia burgdorferi--specific immunoglobulin G, A, and M.

An antibody capture enzyme-linked immunosorbent assay was developed to measure directly intrathecal immunoglobulin (Ig) G, A, and M synthesis specific for Borrelia burgdorferi. Purified, biotin-avidin-peroxidase-labeled B. burgdorferi flagella was used as test antigen. Paired cerebrospinal fluid and serum specimens from 100 patients with clinically definite neuroborreliosis and 35 control subjects with neurological diseases were examined. Significant B. burgdorferi-specific intrathecal IgG, A, and M production was found in 89%, 65% and 67% of patients with neuroborreliosis. Local synthesis of specific IgA was only seen in patients with significant local IgG synthesis. Antibody production in cerebrospinal fluid began by 2 weeks after onset of neurological symptoms. At the end of the second week specific IgM, IgG, or both, was detected in 88% of the patients. Specific IgG synthesis was present in all patients by 6 weeks after onset. Specific local IgM synthesis usually disappeared by 3 to 6 months after therapy, whereas specific IgG synthesis persisted after recovery. Even in patients with a severely altered blood-brain barrier, the assay discriminated between intrathecal antibody synthesis and antibody leakage from serum. The assay makes diagnostic measurement of B. burgdorferi-specific intrathecal antibody synthesis reliable, rapid, and accessible as a routine serological test.

Antibodies, Bacterial↗