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Biomedical subjects

J Breuer

Publications and source records attributed to J Breuer.

At least 19 recordsLinked to original sources
PubMed2006

Further characterization of a rat model of varicella zoster virus-associated pain: Relationship between mechanical hypersensitivity and anxiety-related behavior, and the influence of analgesic drugs.

Persistent herpes zoster-associated pain is a significant clinical problem and an area of largely unmet therapeutic need. Progress in elucidating the underlying pathophysiology of zoster-associated pain and related co-morbidity behavior, in addition to appropriately targeted drug development has been hindered by the lack of an appropriate animal model. This study further characterizes a recently developed rat model of zoster-associated hypersensitivity and investigates (a) response to different viral strains; (b) relationship between viral inoculum concentration ('dose') and mechanical hypersensitivity ('response'); (c) attenuation of virus-associated mechanical hypersensitivity by clinically useful analgesic drugs; and (d) measurement of pain co-morbidity (anxiety-like behavior) and pharmacological intervention in the open field paradigm (in parallel with models of traumatic peripheral nerve injury). Varicella zoster virus was propagated on fibroblast cells before s.c. injection into the glabrous footpad of the left hind limb of adult male Wistar rats. Control animals received injection of uninfected fibroblast cells. Hind-limb reflex withdrawal thresholds to mechanical, noxious thermal and cooling stimuli were recorded at specified intervals post-infection. Infection with all viral strains was associated with a dose-dependent mechanical hypersensitivity but not a thermal or cool hypersensitivity. Systemic treatment with i.p. morphine (2.5 mg/kg), amitriptyline (10 mg/kg), gabapentin (30 mg/kg), (S)-(+)-ibuprofen (20 mg/kg) and the cannabinoid WIN55,212-2 (2 mg/kg) but not the antiviral, acyclovir (50 mg/kg), was associated with a reversal of mechanical paw withdrawal thresholds. In the open field paradigm, virus-infected and nerve-injured animals demonstrated an anxiety-like pattern of ambulation (reduced entry into the central area of the open arena) which was positively correlated with mechanical hypersensitivity. This may reflect pain-related co-morbidity. Further, anxiety-like behavior was attenuated by acute i.p. administration of gabapentin (30 mg/kg) in nerve-injured, but not virus-infected animals. This model will prove useful in elucidating the pathophysiology of zoster-associated pain and provide a tool for pre-clinical screening of analgesic drugs.

Amines↗
PubMed2006

Reactivation of 2 genetically distinct varicella-zoster viruses in the same individual.

Varicella-zoster viruses recovered from 2 episodes of herpes zoster in an immunocompetent man were found to be different genotypes. The fact that the 2 isolates came from the same individual was confirmed by DNA fingerprinting. Immunity following chickenpox may not always protect against systemic reinfection. This finding raises questions about varicella-zoster virus pathogenesis and may have an impact on public health policy.

Adult↗
PubMed2006

The syndrome of right isomerism -- prenatal diagnosis and outcome.

OBJECTIVE: To evaluate the accuracy of the prenatal diagnosis of right isomerism and to assess possible diagnostic and prognostic markers. METHODS: Retrospective review of all cases of right isomerism identified between 1989 and 2003 in two tertiary referral centres in Germany. RESULTS: Among 21 foetuses, 16 had a correct prenatal diagnosis of right isomerism. 19 showed different types of viscerocardiac heterotaxy, 12 of them in combination with juxtaposition of vena cava inferior and aorta. 20 had cardiac defects, with a high prevalence of atrioventricular septal defect (CAVSD) (62 %), right outflow tract obstruction (48 %), anomalous pulmonary venous return (33 %) and double outlet right ventricle (29 %). 4 out of 6 cases with total anomalous pulmonary venous return were overseen on prenatal ultrasound. Only 6 children survived. The highest loss occurred in the neonatal period. Two out of 6 survivors underwent single ventricle palliation, while another two had a biventricular repair. One child is awaiting mitral valve replacement. The remaining case has no cardiac defect and lives with supraventricular re-entry tachycardia. Only the presence of CAVSD was significantly correlated with non-survival (p < 0.05). CONCLUSIONS: The prenatal diagnosis of right isomerism remains a difficult task. Important sonographic markers are viscerocardiac heterotaxy, complex cardiac malformations and juxtaposition of vena cava inferior and aorta. Special attention has to be paid to the pattern of pulmonary venous drainage, as it is often misdiagnosed. The mortality in neonates is high, especially in the presence of CAVSD. Survivors suffer from significant morbidity.

Adolescent↗
PubMed2006

Use of genomic analysis of varicella-zoster virus to investigate suspected varicella-zoster transmission within a renal unit.

BACKGROUND: The source of hospital-acquired chickenpox infection may be presumed from a known exposure, but has not been previously proven using genomic analysis. OBJECTIVE: Investigation of suspected VZV transmission was done using single nucleotide polymorphism genomic analysis. STUDY DESIGN: Comparison was made of viral isolates from two patients with chickenpox on the same ward who were not known to have had direct contact. RESULTS: An identical genotype in the variable R1 region of the VZV was isolated from the two patients. CONCLUSION: Inapparent hospital-acquired transmission was the most likely route of infection.

Acyclovir↗
PubMed2006

Intrapericardial teratoma in the newborn--3D-echocardiography and course of disease.

Intrapericardial teratoma is a rare tumour which may become life threatening when it causes mediastinal compression. Early sonographic detection and careful evaluation is necessary for further management. In this paper, we present a case with a large intrapericardial teratoma diagnosed in utero (25 + 0 weeks). After birth, 3D-echocardiography was particularly helpful in obtaining a comprehensive view of the three-dimensional structure of this complex tumour, in order to determine tumour extension and attachment before surgical excision. This case illustrates the opportunities which new, noninvasive echocardiographic tools create to aid therapeutic management and surgical therapy of critically ill patients.

Adult↗
PubMed2006

Ruptured sinus of Valsalva aneurysm in two patients with subarterial ventricular septal defect.

Rupture of a sinus of Valsalva aneurysm (SVA) is a rare, but life-threatening, event and requires immediate recognition and intervention. We present two previously healthy and physically active patients who were 12 and 33 years of age when rupture of a right coronary SVA into the right ventricle occurred. A subarterial ventricular septal defect (VSD) was detectable in both patients. Cardiac surgery involved VSD closure as well as reconstruction of the aortic valve. Considering complications of subarterial VSD, such as aortic cusp prolapse, aortic insufficiency or SVA, we suggest close follow-up and surgical closure of the VSD in case of any aortic valve deformity.

Adult↗
PubMed2006

Prenatal diagnosis and therapy of upper extremity vascular malformation causing high cardiac output and Kasabach-Merritt sequence: a report of two cases.

We present two cases of upper extremity vascular malformation causing a high output state in the prenatal period. One fetus responded well to transplacental digitalis treatment. Both newborns had a Kasabach-Meritt sequence including anemia and thrombocytopenia. Postpartum treatment included successful interventional occlusion of the main feeding arteries and subsequent surgical removal of the tumor.

Anemia↗
PubMed2006

Right aortic arch detected in fetal life.

OBJECTIVE: To evaluate the prenatal distribution, associated conditions and outcome of the different types of right aortic arch (RAA) detected in fetal life. METHODS: This was a retrospective review of all cases of RAA detected prenatally between 1998 and 2005 in two tertiary referral centers. RESULTS: In the study period 71 cases of RAA were detected; 26 (37%) had RAA with aberrant left subclavian artery, 23 (32%) had RAA with mirror-image branching, 20 (28%) had RAA of unknown type and two (3%) had double aortic arch. While 20/26 cases with RAA and aberrant left subclavian artery were isolated findings, all 23 cases with RAA and mirror-image branching were associated with cardiac defects, namely tetralogy of Fallot (43%) or pulmonary atresia with ventricular septal defect (22%). Of the 20 cases with RAA, 19 of unknown type were associated with heterotaxy syndromes and had additional cardiac malformations and ambiguities of the situs. The two cases with DAA were isolated findings. Seven cases in our series (10%) had a microdeletion 22q11 and these were significantly associated with extracardiac malformations. The outcome in our series depended solely on the associated cardiac and extracardiac malformations, with the exception of one infant with isolated DAA, in whom a surgical correction was warranted. CONCLUSIONS: RAA detected in fetal life is associated frequently with other cardiac/non-cardiac malformations, heterotaxy syndromes and microdeletions 22q11. The associated conditions vary depending on the branching type of the brachiocephalic vessels and the presence of extracardiac malformations.

Adult↗
PubMed2006

Imaging characteristics of hepatocellular carcinoma using the hepatobiliary contrast agent Gd-EOB-DTPA.

PURPOSE: To evaluate the ability of contrast-enhanced magnetic resonance imaging (MRI) with Gd-EOB-DTPA in comparison with non-enhanced imaging and spiral computed tomography (CT) to provide additional information for classification and characterization of hepatocellular carcinoma. MATERIAL AND METHODS: Forty patients with histopathology-proven hepatocellular carcinoma were selected for this subgroup analysis from a phase-III multicenter study in 235 patients with known or suspected liver lesions. The primary analysis was comparison of the proportion of hepatocellular carcinoma correctly classified and characterized by combined pre-/post-contrast MRI compared with pre-contrast MRI alone or with spiral CT. All images were evaluated on site, and in a blinded reading by three independent readers off site. RESULTS: In the on-site evaluation, the lesions were correctly classified as a malignant tumor with combined MRI in 90.3%, with pre-contrast imaging alone in 82.9% and with spiral CT in 87.8% (n.s.). The proportion of correct characterization (lesion type diagnosis) with combined MRI was 85.4%, 75.6% for pre-contrast imaging, and 77.5% for spiral CT (n.s.), respectively. In the blinded reading, one reader showed a significant increase in the proportion of correctly characterized lesions by 27% (P<0.05). The other two readers showed a reduction in the proportion of correct characterization by 12% and 15%, respectively (n.s.). CONCLUSION: With regard to lesion classification, no difference was found between combined pre-/post-contrast MRI and spiral CT. A non-significant trend in favor of Gd-EOB-DTPA-enhanced MRI with regard to characterization of hepatocellular carcinoma was found, although the CT scans were not optimized as the MRI scans.

Adult↗
PubMed2006

Performance of a time-resolved fluorescence immunoassay for measuring varicella-zoster virus immunoglobulin G levels in adults and comparison with commercial enzyme immunoassays and Merck glycoprotein enzyme immunoassay.

Highly sensitive and specific, quantitative assays are needed to detect varicella-zoster virus (VZV) immunoglobulin G in human sera, particularly for determining immune status and response following vaccination. A time-resolved fluorescence immunoassay (TRFIA) has been developed, and its performance was compared to that of two commercial enzyme immunoassays (EIAs) and Merck glycoprotein EIA (gpEIA). The TRFIA had equivalent sensitivity (97.8%) and high specificity (93.5%) in relation to gpEIA. A commercial (Behring) EIA compared favorably with TRFIA in terms of sensitivity (98.4%) but had lower specificity (80.7%). Another commercial EIA (Diamedix) had high specificity (97.1%) but low sensitivity (76.4%) compared to TRFIA if equivocal test results were treated as negative for VZV antibody. A novel feature of the TRFIA was that the cutoff was generated using population mixture modeling and was expressed in mIU/ml, as the assay was calibrated using the British standard VZV antibody.

Adult↗
PubMed2006

Genotyping of varicella-zoster virus and the discrimination of Oka vaccine strains by TaqMan real-time PCR.

Single nucleotide polymorphisms (SNPs) in five genes have been used to identify four major subtypes of wild-type varicella-zoster virus (VZV) A, B, C, and J. Additional SNPs, located in the IE62 major transactivating gene can be used to differentiate the Oka vaccine strain (vOka) from wild-type VZV. Primer-probe sets for the detection of the five polymorphic loci were designed by Applied Biosystems for the ABI 7900HT platform. Probes for each allele were labeled with VIC or 6-carboxyfluorescein fluorogenic markers. Each primer-probe set was validated to establish assay sensitivity and specificity using VZV DNA of predetermined copy number and genotype. Further evaluation was carried out using DNA samples from the vesicle fluid or skin swab of the rash of adult patients with herpes zoster or rashes due to vOka. Assay sensitivity ranged from 10 and 10(8) copies/ml of VZV DNA (equivalent to 2 to 20 copies per reaction). Statistical analyses showed that for each genotype, a set of two probes clearly differentiated the nucleotide present (allele) at that locus (P < 0.0001). It was possible to determine the genotype of wild-type VZV using one of four SNP assays and also to differentiate wild type from vOka using a single SNP assay. The assay can be used for diagnostic and epidemiological studies of VZV, including the differentiation of vOka from wild-type strains, investigation of breakthrough infections, and varicella outbreaks following immunization.

Chickenpox Vaccine↗
PubMed2005

Door-opening motion can potentially lead to a transient breakdown in negative-pressure isolation conditions: the importance of vorticity and buoyancy airflows.

A patient with severe chickenpox was admitted to a negative-pressure isolation room. He remained sedated, intubated and mechanically ventilated throughout his admission. He was managed only by nurses immune to chickenpox. A non-immune male nurse occasionally handed equipment through the doorway, without entering the room. Ten days later, he also developed chickenpox. Sequencing of viruses from the patient and nurse showed the same rare genotype, indicating nosocomial transmission. An experimental model demonstrated that, despite negative pressure, opening the door could have resulted in transport of infectious air out of the isolation room, leading to a breakdown in isolation conditions.

Air Pressure↗
PubMed2005

The cost-effectiveness of antenatal varicella screening with post-partum vaccination of susceptibles.

Varicella infection during pregnancy or around the time of birth can result in serious complications for the mother and/or her child. However, infection during pregnancy is relatively rare as most women are infected during childhood. Immigrant mothers from certain tropical countries are at increased risk of infection, as these countries appear to have lower rates of infection during childhood. We used a cohort model to assess the potential costs and benefits of screening first-time pregnant mothers and then vaccinating those who are susceptible. The model was stratified by age and country of birth (Bangladesh or UK). The strategies evaluated were: (a) an initial verbal screen followed by a serological screen for those with a negative or uncertain history; (b) universal serological screening; and (c) the current strategy which is to treat cases as they arise. Post-partum vaccination was given to those who screen negative for VZV antibodies. The model suggested that the screening and vaccination strategies prevent cases in women compared with the current strategy. Verbal followed by serological screening may be cost-saving to the NHS for both UK- and Bangladesh-born women. Universal screening is more costly but more effective than verbal screening, and it may be cost-effective to universally screen younger immigrant mothers.

Adolescent↗
PubMed2005

Long term cardiac follow up of severe twin to twin transfusion syndrome after intrauterine laser coagulation.

OBJECTIVE: To assess long term changes in cardiac morphology and function in survivors of severe twin to twin transfusion syndrome (TTTS) after intrauterine laser coagulation of placental anastomoses. DESIGN: Prospective follow up of fetuses with severe TTTS treated by laser coagulation of intrauterine placental anastomoses. Fetal echocardiography and Doppler studies of feto-placental haemodynamic function were performed at the time of laser coagulation (median gestational age of 21.7 weeks). Postnatal cardiac follow up included a detailed echocardiographic study of systolic and diastolic cardiac function at a median age of 21.1 months. SETTING: Paediatric cardiology unit. PATIENTS: 89 survivors from 73 consecutive pregnancies with severe TTTS. RESULTS: Before laser treatment, 28 of 51 (54.9%) recipient twins had typical signs of cardiac dysfunction due to volume overload and 9 of 38 (23.7%) donors had absent or reversed end diastolic flow in the umbilical artery. Echocardiography was normal in 87.6% of the survivors (34 of 38 donors, 44 of 51 recipients). The prevalence of congenital heart disease and particularly of pulmonary stenosis, which was recorded only in recipients, was increased in comparison with the general population (congenital heart disease, 10 of 89 (11.2%) v 0.3%; pulmonary stenosis, 4 of 51 (7.8%) v 0.03%). Findings before laser treatment were not correlated with the development of structural heart disease. CONCLUSIONS: Despite the high rate and severity of prenatal cardiac overload in recipients, the majority of cases of TTTS are normalised after laser treatment. However, given the increased prevalence of congenital heart disease and in particular pulmonary stenosis, intrauterine and postnatal follow up is warranted.

Child, Preschool↗
PubMed2005

Three- and four-dimensional freehand fetal echocardiography: a feasibility study using a hand-held Doppler probe for cardiac gating.

OBJECTIVE: To evaluate the clinical feasibility of the signal from a hand-held Doppler probe as a real-time tracking signal for dynamic three-dimensional (3D) (so-called four-dimensional (4D)) fetal echocardiography in a random patient cohort. METHODS: Seventy fetuses, with and without congenital heart disease, at various gestational ages (mean, 25 weeks; range, 18-38 weeks) were investigated using freehand 3D echocardiography. Time gating was achieved concurrently by obtaining a Doppler signal of the fetal heart without further signal averaging. In 10 fetuses, Doppler gating was compared to cardiotocogram (CTG)-gated 3D echo using signal averaging. Gray-scale and color Doppler dynamic 3D displays and multiplanar views were assessed according to their ability to accurately depict cardiac gating and cardiac morphology. RESULTS: In 68/70 fetuses, valid Doppler-based trigger signals were obtained. Correct cardiac gating was achieved in 231/275 (84%) 4D datasets. Doppler tracing of the fetal heart allowed beat-to-beat triggering without the necessity for signal averaging. Doppler gating detected rapid changes in the fetal heart rate more reliably than CTG gating, but was more sensitive to acoustic interference between the gating and echo-transducer when color-coded Doppler imaging was used. Image quality was highly dependent on random motion and the acoustic window. A total of 171/231 (74%) correctly gated datasets successfully demonstrated clinically useful 4D images of the fetal heart. The reconstruction of 3D and multiplanar views provided additional views not obtainable by two-dimensional imaging. CONCLUSION: These results show that a hand-held Doppler probe can be used as a reliable online gating source for 4D fetal echocardiography.

Adult↗
PubMed2005

Atrioventricular block detected in fetal life: associated anomalies and potential prognostic markers.

OBJECTIVES: To assess the spectrum of anomalies associated with fetal heart block and to identify possible prognostic markers. METHODS: Retrospective review of all cases of second- or third-degree heart block identified in two tertiary referral centers in Germany (Bonn and Lübeck) and one in the USA (Baltimore). RESULTS: Sixty fetuses with heart block were identified in the study period. Thirty-two had complex cardiac malformations, 31 of them associated with left isomerism. The outcomes of these fetuses were 22 terminations of pregnancy (TOP), three intrauterine fetal deaths (IUFD), three neonatal deaths (NND), two childhood deaths (CD) and there were two survivors. In 20 cases without complex cardiac malformations maternal antinuclear-antibodies were detected. Their outcomes were 2 TOP, 1 IUFD, 1 NND and 16 survived. The remaining eight cases had neither complex cardiac malformations nor associated maternal antibodies. Their outcomes were 1 TOP, 2 IUFD, 2 NND and 3 survived. After exclusion of terminated cases, hydrops as well as the presence of cardiac defects was significantly associated with non-survival (P < 0.01). The cardiothoracic circumference ratio was significantly higher in hydropic fetuses and significantly negatively correlated with survival in immune-mediated cases (P < 0.01). Atrial and ventricular frequencies and their evolution did not accurately predict fetal or neonatal outcome. Sympathomimetic treatment in seven cases was not associated with favorable fetal outcome in cases of hydrops or cardiac malformations. CONCLUSIONS: The most important marker predicting adverse outcome in cases of heart block is fetal hydrops, followed by the association with complex cardiac malformations. Cases without cardiac malformations have a significantly better prognosis, especially in the absence of severe cardiomegaly.

Adult↗