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A Meyer-Lindenberg

Publications and source records attributed to A Meyer-Lindenberg.

At least 19 recordsLinked to original sources
PubMed2006

Impact of complex genetic variation in COMT on human brain function.

Catechol-O-methyltransferase (COMT) has been shown to be critical for prefrontal dopamine flux, prefrontal cortex-dependent cognition and activation. Several potentially functional variants in the gene have been identified, but considerable controversy exists regarding the contribution of individual alleles and haplotypes to risk for schizophrenia, partly because clinical phenotypes are ill-defined and preclinical studies are limited by lack of adequate models. Here, we propose a neuroimaging approach to overcome these limitations by characterizing the functional impact of ambiguous haplotypes on a neural system-level intermediate phenotype in humans. Studying 126 healthy control subjects during a working-memory paradigm, we find that a previously described risk variant in a functional Val158Met (rs4680) polymorphism interacts with a P2 promoter region SNP (rs2097603) and an SNP in the 3' region (rs165599) in predicting inefficient prefrontal working memory response. We report evidence that the nonlinear response of prefrontal neurons to dopaminergic stimulation is a neural mechanism underlying these nonadditive genetic effects. This work provides an in vivo approach to functional validation in brain of the biological impact of complex genetic variations within a gene that may be critical for its clinical association.

Adult↗
PubMed2006

Morphology of canine placental sites after induced embryonic or fetal death.

Although spontaneous and medically induced canine embryonic or fetal death and "resorption" are clinically well documented, morphological studies of these processes are still missing. The objective of this study was therefore a detailed morphological investigation of canine placental sites after embryonic or fetal death. In five pregnant beagle bitches, embryonic or fetal death was induced by cloprostenol and cabergoline or by aglepristone. Two dogs served as untreated controls. Between Days 30 and 33 of gestation, the bitches were ovariohysterectomized, placental sites were fixed and examined by different methods. Morphological features of placental sites after both treatments were similar, finally leading to a complete disappearance of the placental labyrinth. Although there was an increase in the number of cells in the glandular chambers (superficial endometrial glands) expressing lysozyme after induced fetal death, signs of phagocytosis were absent in these cells, and no increased infiltration of maternal stroma by macrophages (compared to normal placental sites at the same time of gestation) occurred. We inferred that fetal and placental tissues were lysed, but no phagocytosis by genuine or "functional" macrophages was detectable. Further investigations are needed for a more detailed understanding of the morphological processes occurring after embryonic or fetal death in the dog.

Animals↗
PubMed2006

Co-existence of ununited anconeal process and fragmented medial coronoid process of the ulna in the dog.

OBJECTIVES: To determine the incidence of fragmented medial coronoid process of the ulna in dogs with ununited anconeal process. The efficacy of presurgical radiography to diagnose the co-existence of these diseases was also investigated. METHODS: One hundred and fifty-five joints from 137 dogs with ununited anconeal process were included in the study. For the radiographic examinations, an extended mediolateral projection and a craniolateral-caudomedial oblique projection of each elbow joint were taken before surgery. Inspection of the medial part of the joint was carried out either by arthrotomy or arthroscopy. RESULTS: Seventy-two per cent of the dogs were German shepherd dogs. In 25 joints (16 per cent) a fragmented medial coronoid process was diagnosed and removed via arthrotomy or arthroscopy. The co-existence of a fragmented medial coronoid process was diagnosed correctly in only 13 cases (52 per cent) by radiography. In five of these cases with advanced osteoarthritis, the fragment was directly visible because of its dislocation. Compared with published information, the occurrence of ununited anconeal process with fragmented medial coronoid process is noted more frequently in the present study. CLINICAL SIGNIFICANCE: It can be summarised that if ununited anconeal process is present, it is not usually possible to clearly identify fragmented medial coronoid process by radiography. Therefore, it is important to be able to inspect the medial aspect of the joint concerned during surgery.

Animals↗
PubMed2006

[Determination of the elastic properties of the compact bone in the femur of dogs].

Total hip endoprotheses are a good possibility for treatment degenerative wear and pathologic damage of the hip joint in man as well as in dogs. However, aseptic loosening of the protheses, especially in the area of the shaft, is still a problem in conventional total hip endoprotheses. The purpose of the present study was to use the finite-element-analysis (FEA), to enhance endoprothetic design and to prevent loosening of protheses. In order to simulate the femur of the dog for numerical analysis, a material law for the compacta in the femur of the dog was developed. The elastic properties of the compacta were experimentally determined by using compression tests of bone samples of euthanised dogs. The results show constant denseness and a constant axial elastic modul in the compacta.

Animals↗
PubMed2006

[Examination of the density of the brain parenchyma in different dog breeds using quantitative computed tomography].

In the present study quantitative computed tomography was used to analyze the absorption density in different localisations of the brain parenchyma comparatively in five different dog breeds. The breeds German Shepherd Dog, Dachshund, Boxer, Labrador Retriever and Miniature Poodle were chosen as representatives of different skull shapes and sizes. The mean absorption density for the German Shepherd Dog was 35.8 HU in the cerebellum, 28.5 - 34.8 HU in several locations of the cerebrum, 39.6 HU in the brain stem and 40.8 HU in the hypophyseal region. In the Dachshund, the mean density was 33.8 HU (cerebellum), 34.3 - 44.2 HU (several locations of the cerebrum), 33.3 HU (brain stem) and 38.6 HU (hypophyseal region). The Boxer showed a mean density of 38.7 HU in the cerebellum, 30.2 - 40.8 HU in several locations of the cerebrum, 35.6 HU in the brain stem and 33.1 HU in the hypophyseal region. The mean absorption density in the Labrador Retriever was 37.2 HU in the cerebellum, 29.4 - 32.9 HU (several locations of the cerebrum), 34.7 HU in the brain stem and 47.5 HU in the hypophyseal region. In the Miniature Poodle the mean density was 33.6 HU (cerebellum), 34.9 - 45.5 HU (several locations of the cerebrum), 32.7 HU (brain stem) and 32.4 HU (hypophyseal region). The study showed that the absorption density of the cerebrum, the brain stem and of the hypophyseal region partly were influenced by the different dog breeds. In the cerebellum no difference of density could be seen in the different breeds. The standardised values for the data of absorption densities of the brain parenchyma are the base for further examinations of dogs with clinical CNS diseases.

Animals↗
PubMed2006

[Influence of different surface machining treatments of resorbable implants made from different magnesium-calcium alloys on their degradation--a pilot study in rabbit models].

To examine the influence of different surface machining treatments of resorbable implants 3x5 mm cylinders of magnesium-calcium-alloys with plane, rough or sand blasted surface and different concentrations of calcium (0.4 %, 0.8 %, 1.2 % und 2.0 %) were implanted into the distal femur condylus of 18 New Zealand White Rabbits. They were placed into the spongy-cortical passage. During six weeks the animals were examined daily and x-rayed weekly. After euthanasia the bone was explanted and scanned in a microcomputed tomograph. The implants were well tolerated by the rabbits, neither lameness nor signs of pain occured. Wound healing was mostly without complications. Eight of 36 implants (22 %) showed dehiscence of suture within first ten days, whereby implants made of 1,2 % MgCa were mainly affected (six of 12 cases, 50 %). At the place of insertion all implants induced obvious callus genesis which could be seen in MgCa 1,2-cylinders with plane surface and MgCa 0,8-cylinders with rough and sand blasted surface the most. Influence of different calcium concentrations on degradation behaviour could not be discovered. They showed different stages of resorption. Concerning the different surface machining treatments sand blasted implants showed the highest degree of degradation which could be seen by the totally loss of structure in micro-computed examinations. These implants also showed in six of 36 cases a clinical occurrence of gas production. Rough implants showed an irregular degradation with high degree of resorption of some implants and signs of degradation only in the border area of others. Cylindricity maintained in plane implants. They showed loss of structure only in border areas.

Alloys↗
PubMed2005

[One decade of functional imaging in schizophrenia research. From visualisation of basic information processing steps to molecular-genetic oriented imaging].

Modern neuroimaging techniques such as magnetic resonance imaging (MRI) and positron emission tomography (PET) have contributed tremendously to our current understanding of psychiatric disorders in the context of functional, biochemical and microstructural alterations of the brain. Since the mid-nineties, functional MRI has provided major insights into the neurobiological correlates of signs and symptoms in schizophrenia. The current paper reviews important fMRI studies of the past decade in the domains of motor, visual, auditory, attentional and working memory function. Special emphasis is given to new methodological approaches, such as the visualisation of medication effects and the functional characterisation of risk genes.

Biomarkers↗
PubMed2005

In vivo corrosion of four magnesium alloys and the associated bone response.

Degrading metal alloys are a new class of implant materials suitable for bone surgery. The aim of this study was to investigate the degradation mechanism at the bone-implant interface of different degrading magnesium alloys in bone and to determine their effect on the surrounding bone. Sample rods of four different magnesium alloys and a degradable polymer as a control were implanted intramedullary into the femora of guinea pigs. After 6 and 18 weeks, uncalcified sections were generated for histomorphologic analysis. The bone-implant interface was characterized in uncalcified sections by scanning electron microscopy (SEM), element mapping and X-ray diffraction. Results showed that metallic implants made of magnesium alloys degrade in vivo depending on the composition of the alloying elements. While the corrosion layer of all magnesium alloys accumulated with biological calcium phosphates, the corrosion layer was in direct contact with the surrounding bone. The results further showed high mineral apposition rates and an increased bone mass around the magnesium rods, while no bone was induced in the surrounding soft tissue. From the results of this study, there is a strong rationale that in this research model, high magnesium ion concentration could lead to bone cell activation.

Absorbable Implants↗
PubMed2004

Immunohistochemical characterization of inflammatory cell populations and adhesion molecule expression in synovial membranes from dogs with spontaneous cranial cruciate ligament rupture.

This study describes the distribution of CD4+ and CD8alpha+ T lymphocytes, B lymphocytes, macrophages, MHC class II antigens, immunoglobulin (IgG, IgM, IgA)-containing cells and of adhesion molecules belonging to the CD11/CD18 family in synovial membrane biopsies from 28 dogs with spontaneous rupture of the cranial cruciate ligament (CCL). Synovial membranes from 11 dogs without evidence of joint lesions were used as control tissues. The main cell types in synovial membranes from dogs with CCL rupture were B lymphocytes and plasma cells belonging to the IgG isotype. The severity of inflammatory cell infiltration in CCL cases was positively correlated with the expression of adhesion molecules. Double immunofluorescence labelling of frozen sections revealed that in the inflamed synovium of dogs with CCL rupture numerous dendritic cells expressing MHC class II antigen and canine CD1c were present. The findings further support the view that in the synovium of dogs with CCL rupture an immunologic response is going on in which dendritic cells are possibly involved by presenting hitherto unknown antigens to T lymphocytes.

Animals↗
PubMed2004

Oligodendroglioma in the cervical spinal cord of a dog.

A 7-year-old male castrated Yorkshire Terrier dog developed slowly progressive neurologic disturbances consisting of difficulties in moving the neck, lack of proprioception, and tetraparesis 4 months prior its death. Neurologic examination, computer tomography, and myelography resulted in the tentative diagnosis of intramedullary cervicothoracic spinal cord lesion. At necropsy, an intramedullary cervical spinal cord mass between C5 and C6 was noticed. Histologically, cells of this well-demarcated, nonencapsulated neoplasm were arranged in sheaths or cords separated by a fine fibrovascular stroma. The polygonal to round tumor cells were characterized by moderate pale, basophilic, and vacuolar cytoplasm and round to slightly oval, centrally located nuclei with fine-stippled heterochromatin, a single nucleolus, and a very low mitotic activity. Tumor cells lacked glial fibrillary acidic protein, vimentin, factor VIII-related, and cytokeratin antigen expression. Histologic and immunohistochemical findings led to the diagnosis of a cervical spinal cord oligodendroglioma.

Animals↗
PubMed2003

Analysis of systematic effects on congenital sensorineural deafness in German Dalmatian dogs.

We have analysed the systematic influences, phenotypic colour markers and the additive genetic variation for congenital sensorineural deafness (CSD) in German Dalmatian dogs in order to help elucidate the importance of phenotypic breed characteristics for genetic differences of CSD. Linear animal models using restricted maximum likelihood methods were employed to estimate variance components. Data were obtained from all three German Dalmatian kennel clubs associated with the German Association for Dog Breeding and Husbandry (VDH). CSD was recorded by standardized protocols for brainstem auditory-evoked response (BAER). The material included 1899 German Dalmatian dogs from 354 litters in 169 different kennels. BAER testing results were from the years 1986 to 1999. Pedigree information was available for up to seven generations. The animal model regarded the fixed effects of sex, coat colour, eye colour, presence of patches, litter size, percentage of examined puppies per litter, kennel club, and inbreeding coefficient. The common environment of the litter and kennel as well as the additive genetic effect of the animal were taken into account as randomly distributed effects. The fixed effects of eye colour, percentage of puppies examined per litter and kennel club were significant in the mixed model analysis. A significant proportion of additive genetic variation could be shown despite corrections for phenotypic colour variants. The heritability estimate for CSD in German Dalmatian dogs was h(2)=0.27+/-0.07. The additive genetic correlation of CSD with presence of blue eyes was r(g)=0.53+/-0.41 and with presence of patches r(g)=-0.36+/-0.24. We concluded that additional genes other than those associated with phenotypic colour markers in German Dalmatian dogs significantly contribute to the occurrence of CSD.

Animals↗
PubMed2003

The use of botulinum toxin A for treatment of possible essential blepharospasm in a dog.

A 3-year-old Great Dane with bilateral possible essential blepharospasm resulting in ocular complications is described. Conservative treatment was not successful and the disease was treated with local injections of botulinum toxin A into the orbicularis oculi muscle. Blepharospasm disappeared completely 5 to 6 days after injection and did not reappear until 3 to 4 months later, at which time the injection was repeated. After several treatments over a period of more than 3 years no side effects have occured. Botulinum toxin A appeared to be effective in the treatment of essential blepharospasm in this dog.

Animals↗
PubMed2002

Prevalence of fragmented medial coronoid process of the ulna in lame adult dogs.

Over a period of three years, a diagnosis of fragmented medial coronoid process of the ulna was confirmed by arthroscopy in 263 dogs, in 69 of which both elbow joints were affected, giving a total of 332 affected joints; 39 of the joints were also affected by osteochondrosis dissecans of the trochlea of the humerus. More than half of the dogs (51.7 per cent) were over one year old when first examined. In 259 (78 per cent) of the joints there were radiographic changes of secondary osteoarthrosis of different severity, but the other 73 (22 per cent) had no signs of osteophytosis except for a mild sclerosis. Among these 73 there were 14 joints in 13 dogs between 19 and 36 months old and 11 joints in 10 dogs over three years old. A further 12 joints in 11 dogs over three years old showed only mild arthrosis. In five of the 11 joints of the dogs over three years old which had no radiological signs of arthrosis, the fragment was already dislocated. Among the dogs over 18 months old with no arthrosis and the dogs over three years old with mild arthrosis, the most commonly affected breeds were the Bernese mountain dog, rottweiler and boxer.

Animals↗
PubMed2002

Caudomedial approach for removal of an ununited anconeal process and assessment of the medial coronoid process of the ulna.

A caudomedial approach that allows the removal of an ununited anconeal process (UAP) is described. Intraoperative examination of the medial part of the joint to diagnose a fragmented coronoid process (FCP) is also possible using the same approach. Sixty-two joints (53 dogs) with UAP and various degrees of arthrosis were included in the study. In all joints the UAP could be removed via the caudomedial approach and the medial coronoid process could be inspected after extending the incision of the joint capsule distally. In eight cases a FCP was diagnosed and removed either by the caudomedial or by a medial approach. The results of the present study show that an UAP can occur simultaneously with a FCP in the same joint and that inspection of the medial part of the joint is useful.

Animals↗
PubMed2002

Concentration of enrofloxacin and its metabolite ciprofloxacin in canine matrices of the locomotor system.

Due to its pharmacodynamic and pharmacokinetic properties, the use of enrofloxacin may be indicated in canine osteomyelitis, but there is insufficient data on its distribution within the musculoskeletal tissues. The dogs used in this study were 31 regular veterinary orthopaedic patients. Four hours after their oral or subcutaneous treatment with 10 mg/kg enrofloxacin (Baytril; Bayer, Leverkusen, Germany) once daily for 1 or 3 days, the concentration of enrofloxacin and its main metabolite ciprofloxacin was quantified in plasma, bone, musculature and other matrices of the locomotor system by high pressure liquid chromatography with fluorescence-detection after homogenization and solid phase extraction of the samples. By oral or subcutaneous administration of enrofloxacin once daily for 3 days, higher concentrations of the active constituents in the samples were achieved than by single treatment. Nevertheless, even after single injection, minimal inhibitory enrofloxacin concentrations of up to 0.5 microg ml or microg/g sample against most pathogens of osteomyelitis were exceeded. In the musculature, on average, higher concentrations of active constituents were detected than in less perfused matrices (bones and synovial membranes) at sampling time. The enrofloxacin diffusion into inflamed bone was higher compared with mechanically damaged bone, whereas for ciprofloxacin it was lower. In conclusion, a dosage of 10 mg/kg enrofloxacin is sufficient to exceed the minimal inhibitory concentrations in osteomyelitic bone against most pathogens that are sensitive in vitro, but clinical efficacy remains to be evaluated.

Administration, Oral↗
PubMed2001

Evidence for abnormal cortical functional connectivity during working memory in schizophrenia.

OBJECTIVE: Disturbed neuronal interactions may be involved in schizophrenia because it is without clear regional pathology. Aberrant connectivity is further suggested by theoretical formulations and neurochemical and neuroanatomical data. The authors applied to schizophrenia a recently available functional neuroimaging analytic method that permits characterization of cooperative action on the systems level. METHOD: Thirteen medication-free patients and 13 matched healthy comparison subjects performed a working memory (n-back) task and sensorimotor baseline task during positron emission tomography. "Functional connectivity" patterns, reflecting distributed correlated activity that differed most between groups, were extracted by a canonical variates analysis. RESULTS: More than half the variance was explained by a single pattern showing inferotemporal, (para-)hippocampal, and cerebellar loadings for patients versus dorsolateral prefrontal and anterior cingulate activity for comparison subjects. Expression of this pattern perfectly separated all patient scans from comparison scans, thus showing promise as a trait marker. This result was validated prospectively by successfully classifying unrelated scans from the same patients and data from a new cohort. An additional 19% of variance corresponded to the pattern activated by the working memory task. Expression of this pattern was more variable in patients during working memory but not the control condition, suggesting inability to sustain a task-adequate neural network, consistent with the disconnection hypothesis. CONCLUSIONS: Pronounced disruptions of distributed cooperative activity in schizophrenia were found. A pattern showing disturbed frontotemporal interactions showed promise as a trait marker and may be useful for future investigations.

Adult↗
PubMed2001

In vitro efficacy of chemotherapeutics as determined by 50% inhibitory concentrations in cell cultures of mammary gland tumors obtained from dogs.

OBJECTIVE: To determine the 50% inhibitory concentration (IC-50) of carboplatin, cisplatin, and doxorubicin in cell cultures of mammary gland tumors obtained from dogs and to assess whether in vitro efficacy was within the range of clinically relevant concentrations, SAMPLE POPULATION: 30 mammary gland tumors excised from dogs. PROCEDURE: Cell cultures were established from the 30 tumors. Cultures then were treated with carboplatin, cisplatin, or doxorubicin. Growth inhibition of cultures was assessed via DNA measurement 24, 48, and 72 hours after treatment. The IC-50 values were calculated by use of linear interpolation. RESULTS: Cultures varied in their pattern of susceptibility. Doxorubicin induced significantly lower IC-50 values than the platinum derivatives. Cisplatin and carboplatin had comparable effects. The IC-50 values for carboplatin and doxorubicin were in the range of clinically relevant concentrations, but only part of the cisplatin cultures had IC-50 values within clinically relevant concentrations. We did not detect differences in the in vitro susceptibility among subtypes of tumors (ie, adenocarcinoma, solid carcinoma, malignant mixed tumor). CONCLUSION AND CLINICAL RELEVANCE: The IC-50 values determined in this study allowed assessment of in vitro drug efficacy of chemotherapeutics in cultures of mammary gland tumors obtained from dogs. Variations in susceptibility were evident and emphasize the importance of assessing susceptibility and resistance patterns for each tumor. Prospective studies to assess direct correlations between in vitro and in vivo efficacy must be performed to determine the clinical predictive value of this in vitro chemosensitivity assay for treatment of dogs with mammary gland tumors.

Adenocarcinoma↗