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Biomedical subjects

G Dobler

Publications and source records attributed to G Dobler.

At least 19 recordsLinked to original sources

A new Puumala hantavirus subtype in rodents associated with an outbreak of Nephropathia epidemica in South-East Germany in 2004.

A micro-epidemic of hantavirus infections occurred in Lower Bavaria, South-East Germany, starting in April 2004. While only three cases were registered from 2001 to 2003, a dramatically increased number of clinically apparent human hantavirus infections (n=38) was observed in 2004, plus seven additional cases by June 2005. To determine the reservoir responsible for the infections, a total of 43 rodents were trapped in Lower Bavaria. Serological and genetic investigations revealed that Puumala virus (PUUV) is dominant in the local population of bank voles. Partial PUUV S segment nucleotide sequences originating from bank voles at four different trapping sites in Lower Bavaria showed a low divergence (up to 3.1%). This is contrasted by a nucleotide sequence divergence of 14-16% to PUUV strains detected in Belgium, France, Slovakia or North-Western Germany. PUUV sequences from bank voles in Lower Bavaria represent a new PUUV subtype which seems to be responsible for the observed increase of human hantavirus infections in 2004-2005.

Animals↗

Rickettsia spp. in Ixodes ricinus ticks in Bavaria, Germany.

This study aims to provide information on the occurrence of spotted fever rickettsiae in Ixodes ricinus ticks in southern Germany. A total of 2,141 I. ricinus ticks was collected in Bavaria. Pools of 5-10 ticks were studied by a PCR targeting the rickettsial citrate synthase gene gltA. The average prevalence rate was 12% (257 of 2,141). Sequencing data exclusively identified Rickettsia helvetica DNA. Results and other data demonstrate the possible role of R. helvetica in I. ricinus as a source of human infections in southern Germany.

Animals↗

[The elderly traveler].

In recent years, the number of senior citizen travelers has been increasing. As a result of this trend, the general practitioner is every more frequently being confronted with the problem of counseling his elderly patients. A particularly important point is that underlying illnesses and long-term medication must be adapted to the destination, traveling time and style of traveling. Since considerable immunization deficits can be found among senior citizens, the application of prophylactic vaccination prior to the jou rney presents an ideal opportunity to bring the patient's immunization status up to date in terms of generally recommended vaccinations. Should chemoprophylaxis be necessary, consideration must always be given to drug interactions. By making appropriate recommendations in terms of health-related and destination-related dos and don'ts, the risk of developing health problems while traveling can be minimized.

Age Factors↗

Effects of alpha1-adrenoceptor antagonists on cultured prostatic smooth muscle cells.

BACKGROUND: alpha1-adrenoceptor (alpha1-AR) antagonists, used to relieve the lower tract urinary symptoms (LUTS) in benign prostate hyperplasia (BPH) patients, are thought to act in inhibiting the contraction of stromal smooth muscle. An attempt was made using new technology to visualize and quantify the effect of alpha1-AR antagonists in a cell culture model of prostatic smooth muscle cells (SMC). METHODS: Prostatic smooth muscle cells cultured from human prostate tissue were treated with alpha1-AR agonists and antagonists. The effects on cell growth, cell contraction, differentiation status, and apoptosis were determined by means of an MTT cell viability assay, time-lapse video microscopy, RT-PCR analysis, and FACS analysis of annexin V/propidium iodide-stained cells, respectively. RESULTS: Prostatic smooth muscle cells derived from prostate tissue expressed SMC-specific markers. They showed spontaneous contractions, and phenylephrine increased the percentage of contracting cells by 3-fold. alpha1-AR antagonists inhibited spontaneous as well as phenylephrine-induced contractions. Long-term treatment with doxazosin induced differentiation tended towards a contractile phenotype, as indicated by an increase of the ratio of smooth muscle heavy chain myosin subtypes SM2/SM1. There was, however, no effect on cell growth. High concentrations of antagonist (100 microM) induced apoptosis in about 80% of the treated SMC. This effect was not cell-type-specific and was also seen in skin fibroblasts and immortalized prostate epithelial cells. CONCLUSION: In an easy-to-handle cell culture model of prostatic smooth muscle cells, the effects of alpha1-AR antagonists on cell contraction, growth, and differentiation can be investigated. The results indicate that in addition to inhibition of cell contraction, alpha1-AR antagonists have the potential to induce apoptosis.

Adrenergic alpha-1 Receptor Antagonists↗

Serological investigations of red foxes (Vulpes vulpes L.) for determination of the spread of tick-borne encephalitis in Northrhine-Westphalia.

Serum samples from 786 red foxes shot between January 1995 and August 1996 in the southern half of Northrhine-Westphalia, located in western Germany, were tested for the presence of antibodies against tick-borne encephalitis (TBE) virus using the Immunozym FSME IgG All Species-ELISA (Immuno, Heidelberg, Germany) as a screening test: 759 sera were negative, 23 (2.9%) were borderline, and four (0.5%) were positive. Nine of the 27 ELISA reactive sera were confirmed by the TBE Western-Blot (Immuno, Heidelberg, Germany). Furthermore these 27 sera were tested for neutralizing antibodies by means of a plaque reduction neutralization test (PRNT) against TBE and West Nile viruses. Only one single serum was found to have a neutralization titre (+1:800 PRNT80) against TBE virus. All other 26 sera were negative for neutralizing antibodies against TBE or West Nile virus. Since the titre of the single serum is low, it can be interpreted that if TBE virus is present, its prevalence is extremely low. Northrhine-Westphalia is not classified as a TBE-endemic area. Further calculated serological testing of game and virological investigation of collected ticks in the affected area seem to be meaningful and necessary.

Animals↗

[Persistent arthralgias in Ross-River-Virus disease after travel to the South Pacific].

HISTORY AND CLINICAL FINDINGS: A 57-year-old patient presented with malaise and severe persistent arthralgia of the left shoulder. He reported an acute illness with fever, generalized myalgia and arthralgias of the large joints which had started one month earlier during his flight back to Germany after a two weeks trip to the South Pacific. Physical examination showed extensive pain on palpation of the glenohumeral and acromioclavicular joints with impairment of active and passive mobility. Investigation of the cervical spine was normal. INVESTIGATIONS: Apart from elevated C-reactive protein and erythrocyte sedimentation rate levels, routine laboratory investigations were normal including negative immunodiagnostic tests for autoantibodies and various global infections that may be associated with arthritis. Immunofluorescence tests showed significant levels of specific IgM- and IgG-antibodies against Ross River virus (RRV) but not against other arboviruses endemic in the South Pacific and Australia (Dengue, West Nile, Chikungunya, Sindbis, Barmah Forest). This was confirmed by a positive RRV neutralisation test. Attempts at virus isolation and detection of viral RNA by PCR were not successful. TREATMENT AND COURSE: Symptomatic treatment with high doses of diclofenac quickly led to pain relief, and arthralgias receded within 10 days after begin of treatment. However, several bouts of arthralgia of the left shoulder and left knee occurred during a period of 4 months. CONCLUSIONS: Because of the current epidemiological situation in the South Pacific and Australia, infections by arboviruses like RRV should be considered in travellers returning from these areas with severe and persistent arthralgia of unknown origin, even in the absence of fever and other symptoms of acute infection.

Alphavirus Infections↗

Thunderclap headache caused by Erve virus?

Systematic studies of a possible human neuropathogenicity of the Erve virus have not yet been carried out. In a randomized, blind study 166 patients with viral encephalitis, 46 patients with cerebral hemorrhage, 72 patients with "thunderclap" headache, and 205 healthy blood donors were examined by indirect immunofluorescence for Erve virus antibodies. None of the patients with encephalitis, two patients with cerebral hemorrhage (4.3%), 10 patients with thunderclap headache (13.9%; p < 0.0001), and two blood donors (1.0%) exhibited antibodies against the Erve virus. These results suggest a human pathogenicity of the Erve virus for the first time.

Adult↗

Evidence of dengue virus infection in a german couple returning from hawaii

Dengue is an acute, mosquito-transmitted viral disease characterized by fever, arthralgia, myalgia, rash, nausea, and vomiting and caused by any of four different serotypes of the virus (DEN-1, DEN-2, DEN-3, and DEN-4).1 The disease is endemic in most tropical areas of the world and has been reported in international travelers returning from such areas.2 The incidence of epidemic and endemic dengue has increased substantially in the Americas since 1977, and various epidemics have occurred.1-4

Journal Article↗

Prevalence of infection with dengue virus among international travelers.

BACKGROUND: Dengue has been recognized as a potential hazard to tourists. A prospective, controlled study in the outpatient clinic of a German infectious disease clinic was conducted to assess the prevalence of dengue virus infection among international travelers. METHODS: Serum samples from 130 patients with signs or recent history clinically compatible with dengue (fever, headache, muscle and joint pain, or rash), 95 matched controls with diarrhea, and 26 patients who never visited a country endemic for dengue were investigated. RESULTS: Nine (6.9%) of the 130 patients with compatible symptoms and 1 (1%) of the 95 controls with diarrhea developed rising antibody titers against dengue virus. Of these 10 patients with probable dengue infection, 6 had been to Thailand, 2 to Malaysia, and 1 each to Indonesia and Brazil. CONCLUSIONS: Infection with dengue virus appears to be a realistic threat to travelers to Southeast Asia. Symptoms commonly associated with dengue, such as fever, myalgia, arthralgia, and vomiting, can be helpful for diagnosis when present, but the absence of typical symptoms does not exclude infection.

Acute Disease↗

Clinical value of specific intrathecal production of antibodies.

The production of intrathecal antibodies is considered a highly specific marker for an infection of the central nervous system (CNS), e.g. borreliosis or tick-borne encephalitis (TBE). To investigate the validity of this assumption, we examined records of patients who had been hospitalized between 1989 and 1995, who were tested for borreliosis (n = 8003) and TBE (n = 904) and whose cerebrospinal fluid (CSF) had subsequently tested positive for intrathecal production of antibodies. The time period between the beginning of the symptoms and the time of the CSF examination ranged from one day to six weeks. Seventy-seven patients showed a production of intrathecal antibodies against Borrelia burgdorferi. Three of these patients were false positives with no history and no clinical signs of neuroborreliosis. In two cases, this was due to a non-specific cross-reaction caused by a preceding infection with syphilis. The third false positive was possibly caused by an earlier administration of immunoglobulins. Three patients showed a production of intrathecal antibodies against TBE virus. Two of these patients were false positives. In one case, we suspect that the production of intrathecal antibodies was caused by a non-specific immune reaction during an acute neuroborreliosis. One year earlier, the patient had contact with TBE virus through a vaccination against TBE. The cause of the second false positive is unclear, the clinical findings, acute encephalitis and the serological analysis suggest a cross-reaction with a virus similar to TBE. A specific intrathecal production of antibodies is not a proof for an infection of the CNS. In unclear cases, one should carry out a Western blot analysis or, if one suspects a case of TBE, a neutralization test.

Adult↗

[Cross reactions of patients with acute dengue fever to tick-borne encephalitis].

Sera from 20 patients with acute dengue fever were tested on their cross reactivities to other flaviviruses, especially against tick-borne encephalitis (TBE). One of the test systems used, indirect immunofluorescence (IIFT), was shown to exhibit strong cross reactivity. The reactivity pattern of sera from patients with pre-existing vaccine-induced antibodies against TBE or yellow fever was found similar to dengue secondary antibody response. In plaque reduction neutralization tests (PRNT) no cross reactions between different flaviviruses were found. The results show that PRNT is the most specific test system for differentiation of flavivirus antibodies.

Acute Disease↗

Arboviruses causing neurological disorders in the central nervous system.

Arthropod-borne viruses are important causes of diseases of the central nervous system. In addition to the tick-borne encephalitis viruses, other arboviruses in Europe are known to cause neurological disorders. Among them are West Nile, California group, Bhanja, Erve, Kemerovo group, Eyach, and Thogoto viruses. The ecologies and epidemiologies of these viruses are presented and their medical importance as travel-related diseases is discussed.

Animals↗

Hepatitis C and arboviral antibodies in the island populations of Mauritius and Rodrigues.

A serological survey for antibodies to hepatitis C virus (HCV), dengue viruses (DEN), West Nile virus (WN), and sindbis virus (SIN) was carried out in sera of selected groups of the population of the Islands of Mauritius (n = 449) and Rodrigues (n = 115), Indian Ocean. 8.3% of 564 sera were positive for anti-HCV. In Mauritius, 2.1% of sera of healthy individuals were found with anti-HCV. The highest prevalence was found in sexually transmitted disease (STD) patients and prison inmates with 46.2% and 43.8%, respectively. None of the sera from blood donors sampled from Rodrigues Island had anti-HCV. Antibodies to arboviruses were detected in sera of individuals from both islands. Anti-DEN IgG was detected in 3.8% of sera from Mauritius and 0.9% from Rodrigues. Anti-WN IgG was detected in 2.2% of sera from Mauritius and 0.9% from Rodrigues. All sera from Rodrigues were without anti-SIN IgG, 1.1% of those from Mauritius were positive. This suggests that arboviruses occur on these islands.

Adult↗

Identification of molecular defects causing congenital adrenal hyperplasia by cloning and differential hybridization of polymerase chain reaction-amplified 21-hydroxylase (CYP21) genes.

Congenital adrenal hyperplasia (CAH), one of the most common autosomal recessive disorders, is caused primarily by defects in the gene encoding steroid 21-hydroxylase, CYP21B. The molecular diagnosis of CAH, important for prenatal diagnosis, carrier detection, and a better understanding of the various clinical CAH forms, is complicated by the close proximity of a highly similar pseudogene, CYP21A, containing (and probably donating, by gene conversion-like events) most of the defects underlying CAH. In this study, we describe an efficient strategy to identify molecular defects causing CAH: polymerase chain reaction-amplified CYP21 loci are cloned and hybridized to a set of oligonucleotides, allowing rapid and allele-specific identification of all known CYP21B mutations relevant to 21-hydroxylase function. Possible new mutations can be identified by subsequent nucleic acid sequencing provided they reside within the cloned CYP21B fragment (from the TATA box to the 8th of the 10 CYP21B gene exons). Using this method, the CYP21B gene mutations of a heterozygous carrier and 25 CAH patients have been identified by oligonucleotide hybridization. All disease haplotypes seem to have been generated by recombinational events involving the CYP21A pseudogene. In 5 individuals, these data were subsequently verified by nucleic acid sequencing. The procedure can be used for diagnostic applications and may facilitate identification of new CYP21B defects.

Adrenal Hyperplasia, Congenital↗