The importance of tick-borne encephalitis virus RNA detection for early differential diagnosis of tick-borne encephalitis.

BACKGROUND: Tick-borne encephalitis virus (TBEV) is one of the most important causes of human viral infections of the central nervous system in Europe. Currently, the diagnosis of TBE is based on the demonstration of specific antibodies in patient's serum, which appear only several weeks after the infection. OBJECTIVE: To determine how successfully can viral RNA be detected by RT-PCR in the samples of body fluids of patients with TBE prior to and after the appearance of antibodies. STUDY DESIGN: Serum, whole blood and CSF samples from 34 patients with a serologically confirmed TBE were collected. Samples were tested for the presence of TBEV RNA by using RT-PCR method. RESULTS: Viral RNA was detected in all blood and serum samples collected before the development of antibodies. After the appearance of IgM antibodies, the number of positive samples dropped by at least one third. After the development of IgG antibodies, only 3% of serum and 16% of blood samples tested positive for viral RNA. Samples of cerebrospinal fluid were shown to be inappropriate for the molecular diagnosis of TBE using this assay, since only one sample (10%) that was collected in the sero-negative phase of disease was found positive by the PCR assay. CONCLUSIONS: RT-PCR is an efficient method for an early detection of TBEV in blood and serum samples collected prior to the appearance of antibodies. This method can be of valuable use for a differential diagnosis of TBEV infection in patients with febrile illness after a tick bite, particularly in regions where more than one tick-transmitted diseases are endemic.     

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Ohne Zusammenfassung     

First European Pediatric Case of Human Granulocytic Ehrlichiosis

Herein we report on the first confirmed pediatric case of acute human granulocytic ehrlichiosis in Europe. Presentation in this 11-year-old girl was comparable to clinical findings seen in adult European patients with human granulocytic ehrlichiosis; i.e., she had self-limited febrile illness with leukopenia, thrombocytopenia, and elevated serum C-reactive protein concentration. It is of interest that the patient not only had a fourfold change in antibody titer to Ehrlichia phagocytophila but also developed antibodies to Ehrlichia chaffeensis and that her PCR test result was positive on the third as well as on the 22nd day after the onset of illness, that is, 16 days after spontaneous defervescence.     

Mutational analysis of GJB1, MPZ, PMP22, EGR2, and LITAF/SIMPLE in Serbian Charcot-Marie-Tooth patients

We report the results of mutational analysis in the following genes: GJB1 , MPZ , PMP22 , EGR2 , and LITAF/SIMPLE in 57 Charcot-Marie-Tooth (CMT) patients of Serbian origin without the PMP22 duplication. We found 10 different mutations in 14 CMT patients: 6 mutations in GJB1 , 3 in MPZ , and 1 in PMP22 . Five of six GJB1 mutations are reported for the first time, and the most frequent one appears to be a founder mutation in the Serbian population. No mutations were found in EGR2 or LITAF . Thus, GJB1 mutation analysis should be done in patients without the PMP22 duplication and male-to-male transmission of CMT.     

Diagnostic Accuracy of Perioperative Measurement of Basal Anterior Pituitary and Target Gland Hormones in Predicting Adrenal Insufficiency After Pituitary Surgery

The insulin tolerance test (ITT) is the gold standard for diagnosing adrenal insufficiency (AI) after pituitary surgery. The ITT is unpleasant for patients, requires close medical supervision and is contraindicated in several comorbidities. The aim of this study was to analyze whether tumor size, remission rate, preoperative, and early postoperative baseline hormone concentrations could serve as predictors of AI in order to increase the diagnostic accuracy of morning serum cortisol.This prospective study enrolled 70 consecutive patients with newly diagnosed pituitary adenomas. Thirty-seven patients had nonfunctioning pituitary adenomas (NPA), 28 had prolactinomas and 5 had somatotropinomas. Thyroxin (T4), thyrotropin (TSH), prolactin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and insulin-like growth factor 1 (IGF-I) were measured preoperatively and on the sixth postoperative day. Serum morning cortisol was measured on the third postoperative day (CORT3) as well as the sixth postoperative day (CORT6). Tumor mass was measured preoperatively and remission was assessed 3 months after surgery. An ITT was performed 3 to 6 months postoperatively.Remission was achieved in 48% of patients and AI occurred in 51%. Remission rates and tumor type were not associated with AI. CORT3 had the best predictive value for AI (area under the curve (AUC) 0.868, sensitivity 82.4%, specificity 83.3%). Tumor size, preoperative T4, postoperative T4, and TSH were also associated with AI in a multivariate regression model. A combination of all preoperative and postoperative variables (excluding serum cortisol) had a sensitivity of 75.0% and specificity of 77.8%. The predictive power of CORT3 substantially improved by adding those variables into the model (AUC 0.921, sensitivity 94.1%, specificity 78.3%, PPV 81.9%, NPV of 92.7%). In a subgroup analysis that included only female patients with NPA, LH had exactly the same predictive value as CORT3. The addition of baseline LH to CORT3, increased sensitivity to 100.0%, specificity to 88.9%, PPV to 90.4%, and NPV to 100.0%.Besides CORT3, tumor size, thyroid hormones, and gonadotropins can serve as predictors of AI. LH in postmenopausal female patients with NPA has similar diagnostic accuracy as CORT3. Further studies are needed in order to validate the scoring system proposed by this study.     

Epidemiological, clinical and laboratory characteristics of patients with human granulocytic anaplasmosis in Slovenia

Human granulocytic anaplasmosis (HGA) has been recently recognized as an emerging tick-borne disease. Several reports indicate the presence of infection with Anaplasma phagocytophilum in Europe. Between January 1996 and December 2004, 24 adult patients with proven HGA were identified in a prospective study conducted at the Department of Infectious Diseases, University Medical Center Ljubljana, Slovenia, on the etiology of febrile illnesses occurring within 30 days after a tick bite. The diagnosis of acute HGA was established from seroconversion in 18 (75%) patients or at least a four-fold increase in antibody titers to A. phagocytophilum antigens in six (25%) patients and molecular identification of ehrlichial organisms in 15 (62.5%) patients. Clinical characteristics and laboratory findings were similar to those reported from the other European countries. All the patients had an acute febrile illness with headache, malaise, myalgia and/or arthralgia. Leukopenia was found in 16 (66.7%) patients, thrombocytopenia in 20 (83.3%), abnormal liver function test results in 23 (95.8%), elevated erythrocyte sedimentation rates in 18 (75%), and elevated concentration of C-reactive protein in 23 (95.8%). The disease course was relatively mild; none of the patients died and no long-term sequelae were found during a follow-up of one year even though only 15 (62.5%) were treated with doxycycline. At the examination one year after the first visit, 16/24 (66.7%) patients tested seropositive (> or =1 : 256) for A. phagocytophilum antibody, and two years after the first visit positive titers were still present in 10/18 (55.6%) patients.     

Clinical case report atypical myopathy in a young girl with 91 CTG repeats in DM1 locus and a positive DM1 family history

Myotonic dystrophy type 1 (DM1) is an autosomal dominant inheritable disease associated with an expansion of CTG repeats in the 3' UTR of the DMPK gene. The subject is an 11-year-old girl with atypical myopathy. Because the proband's family has a positive DM1 history, a molecular-genetic analysis for DM1 was performed. This study showed that proband had a small DMPK expansion (91 CTG repeats) although the observed myopathy would not normally be associated with DM1. These results show how the phenotypic manifestation of DM1 can have unusual symptoms with a completely unexpected relationship to genotype.     

Schizophrenia and polymorphic CAG repeats array of calcium-activated potassium channel (KCNN3) gene in Serbian population

KCNN3 might be a candidate gene for schizophrenia. The KCNN3 cDNA sequence contains two stretches of CAG trinucleotide repeats encoding two separate polyglutamine segments near the N-terminus of this channel protein. The second CAG repeat is highly polymorphic in the Caucasian population from both Europe and United States. The authors carried out a study to compare the allelic frequency distribution of the CAG repeat in KCNN3 gene in 55 Serbian schizophrenic patients and 46 controls. The data indicate a significant association between longer CAG repeats in second polymorphic KCNN3 region and schizophrenia in the Serbian population.