[Field trial for eradication of methicillin- resistant Staphylococcus aureus (MRSA) in a pig breeding farm by bacteriophages]. / Feldversuch zur Eradikation von Methicillin-resistenten Staphylococcus aureus (MRSA) mittels Bakteriophagen in einem Schweinezuchtbetrieb.

INTRODUCTION: In recent years, Livestock Associated Methicillin-Resistant Staphylococcus aureus (LA-MRSA) are found frequently in pigs. The colonization of the care staff with LA-MRSA is strongly associated with the intensity and duration of animal contact and LA-MRSA herd prevalence. In human medicine, staphylococcal infections have been controlled successfully by topical or systemic administration of Staphylococcus - associated bacteriophages. Therefore, the present study investigated the effect of a bacteriophage cocktail on skin and mucosal colonization of pigs with MRSA in a pig farm with high MRSA prevalence. In a first experiment, the sows were washed with a bacteriophage cocktail and nose, mouth and vagina were rinsed before the sows were admitted to the farrowing house. Then, 10 ml of the bacteriophage cocktail was administered daily to the sows over the feed until weaning. The suckling piglets were sprayed and sampled twice a week during the suckling period and treated with the bacteriophage cocktail over the feed during the weaning period. In further experiments, the weaning room was nebulized three times a day with a bacteriophage cocktail and different concentrations of bacteriophages were added to the drinking water via Dosatron®. None of the experiments, however, showed an eradication of MRSA neither in nose nor in feces.

INTRODUCTION: Au cours des dernières années, des Staphylococcus aureus résistant à la méthicilline associé au bétail (LA-MRSA) ont été fréquemment trouvés chez les porcs. La colonisation du personnel soignant par des LA-MRSA est fortement corrélée à l'intensité et à la durée du contact avec les animaux et à la prévalence de LA-MRSA dans le troupeau. En médecine humaine, les infections à staphylocoques ont été contrôlées avec succès par l'administration topique ou systémique de bactériophages associés à Staphylococcus. C'est pourquoi la présente étude a étudié l'effet d'un cocktail de bactériophages sur la colonisation de la peau et des muqueuses des porcs atteints de SARM dans une exploitation porcine à forte prévalence de SARM. Dans une première expérience, les truies ont été lavées avec un cocktail de bactériophages et le nez, la bouche et le vagin ont été rincés avant leur admission dans le local de mise bas. Ensuite, 10 ml du cocktail de bactériophages ont été administrés quotidiennement aux truies sur l'aliment jusqu'au sevrage. Les porcelets allaitants ont été pulvérisés et échantillonnés deux fois par semaine pendant la période d'allaitement et traités avec le cocktail de bactériophages sur l'aliment pendant la période de sevrage. Dans d'autres expériences, le local de sevrage a été nébulisée trois fois par jour avec un cocktail de bactériophages et différentes concentrations de bactériophages ont été ajoutées à l'eau de boisson via Dosatron®. Cependant, aucune des expériences n'a montré d'éradication du SARM ni dans le nez ni dans les fèces.

Optimization of analgesia for piglet castration under isoflurane anaesthesia with parenteral butorphanol, meloxicam or intratesticular lidocaine.

INTRODUCTION: This blinded prospective study investigated analgesic effects of intramuscular (IM) butorphanol, meloxicam or intratesticular (IT) lidocaine for castration of 7-14 days old piglets under isoflurane anaesthesia. 66 piglets were randomly injected with: meloxicam IM (0.4 mg/kg; group M), butorphanol IM (0.2 mg/kg; group B), or both (group BM) 20 minutes prior to castration, or lidocaine IT (4 mg/kg (group ML4) or 8 mg/kg (group ML8)) together with meloxicam IM (0.4 mg/kg) under anaesthesia with 1.8% end-tidal isoflurane. Heart rate, respiratory rate, mean arterial blood pressure and end-tidal carbon dioxide were recorded. Anaesthesia quality was scored and postoperative behaviour assessed. As butorphanol caused unacceptable side effects, its use was stopped. Group M showed worse anaesthesia quality than ML4 and ML8 (higher incidence of movements: 11/17, 3/18 and 4/17, respectively). There were no significant differences between groups regarding parameters measured during castration. Postoperative behaviour did not differ between groups. For castration of 7-14 days old piglets under isoflurane anaesthesia, IT lidocaine provides an additional side effect free analgesia.

INTRODUCTION: Cette étude prospective en aveugle étudie l'effet analgésique de l'injection intramusculaire (IM) de butorphanol et de méloxicam ou de l'injection intra-testiculaire (IT) de lidocaïne pour la castration, sous anesthésie à l'isoflurane, de porcelets âgés de 7 à 14 jours. Soixante-six porcelets ont reçu de manière aléatoire soit du méloxicam IM (0.4 mg/kg; groupe M), soit du butorphanol IM (0.2 mg/kg; groupe B), soit les deux substances (groupe MB) 20 minutes avant la castration, soit de la lidocaïne IT (4 mg/kg (groupe ML4) ou 8 mg/kg (groupe ML8)) ainsi que du méloxicam IM (0.4 mg/kg), avec une anesthésie à l'isoflurane à 1.8% en fin d'expiration. Les fréquences cardiaques et respiratoires, la pression artérielle moyenne et le CO2 en fin d'expiration ont été documentés. La qualité de l'anesthésie a été estimée et le comportement post-opératoire observé. Le butorphanol a causé des effets secondaires inacceptables et son usage a été stoppé. Le groupe M montrait une plus mauvaise qualité d'anesthésie que les groupes ML4 et ML8 (plus grande incidence de mouvements : 11/17, 3/18 et 4/17). Les autres paramètres intra opératoires ne présentaient pas de différences significatives et on a pas constaté de différences entre les groupes dans la phase postopératoire. Pour la castrations de porcelets âgés de 7 à 14 jours sous anesthésie à l'isoflurane, l'utilisation intra testiculaire de lidocaïne représente une analgésie supplémentaire dépourvue d'effets secondaires.

Clinical Impact of the Current WHO Classification of Pituitary Adenomas.

WHO classifications should be used for comparing the results from different groups of pathologist and clinicians by standardized histopathological methods. Our present report describes the important parameters of pituitary adenoma pathology as demand of the WHO classification for correlation to endocrine data and prognosis. The combination of HE stain based structures with immunostainings for pituitary hormones allows subclassification of adenomas as the best method not only for correlations to clinical hyperfunctions but also for statements to the sensitivity of drug therapies (somatostatin analogs, dopamine agonists). GH-, PRL- and ACTH-secreting pituitary adenomas are further classified based on the size and number of their secretory granules by electron microscopy, or as is mostly the case nowadays by cytokeratin staining pattern, into densely and sparsely granulated. Granulation pattern may be considered for the prediction of treatment response in patients with GH-secreting adenomas, since the sparsely granulated subtype was shown to be less responsive to somatostatin analog treatment. For prognosis, it is important to identify aggressive adenomas by measurements of the Ki-67 index, of the number of mitoses, and of nuclear expression of p53. Among the criteria for atypical adenomas, high Ki-67 labeling index and invasive character are the most important adverse prognostic factors. Promising molecular markers have been identified that might supplement the currently used proliferation parameters. For defining atypical adenomas in a future histopathological classification system, we propose to provide the proliferative potential and the invasive character separately.

Emerging Histopathological and Genetic Parameters of Pituitary Adenomas: Clinical Impact and Recommendation for Future WHO Classification.

The review assesses immunohistochemical findings of somatostatin receptors and of metalloproteinases in different pituitary adenoma types and the significance of molecular genetic data. Current evidence does not support routine immunohistochemical assessment of somatostatin or dopamine receptor subtype expression on hormone-secreting or nonfunctioning pituitary adenomas. Further prospective studies are needed to define its role for clinical decision making. Until then we suggest to restrict membrane receptor profiling to individual cases or for study purposes. The problems of adenoma expansion and invasion are discussed. Despite partially contradictory publications, proteases clearly play a major role in permission of infiltrative growth of pituitary adenomas. Therefore, detection of at least MMP-2, MMP-9, TIMP-2, and uPA seems to be justified. Molecular characterization is important for familial adenomas, adenomas in MEN, Carney complex, and McCune-Albright syndrome and can gain insight into pathogenesis of sporadic adenomas.

Assessing pesticide risks to threatened and endangered species using population models: Findings and recommendations from a CropLife America Science Forum.

This brief communication reports on the main findings and recommendations from the 2014 Science Forum organized by CropLife America. The aim of the Forum was to gain a better understanding of the current status of population models and how they could be used in ecological risk assessments for threatened and endangered species potentially exposed to pesticides in the United States. The Forum panelists' recommendations are intended to assist the relevant government agencies with implementation of population modeling in future endangered species risk assessments for pesticides. The Forum included keynote presentations that provided an overview of current practices, highlighted the findings of a recent National Academy of Sciences report and its implications, reviewed the main categories of existing population models and the types of risk expressions that can be produced as model outputs, and provided examples of how population models are currently being used in different legislative contexts. The panel concluded that models developed for listed species assessments should provide quantitative risk estimates, incorporate realistic variability in environmental and demographic factors, integrate complex patterns of exposure and effects, and use baseline conditions that include present factors that have caused the species to be listed (e.g., habitat loss, invasive species) or have resulted in positive management action. Furthermore, the panel advocates for the formation of a multipartite advisory committee to provide best available knowledge and guidance related to model implementation and use, to address such needs as more systematic collection, digitization, and dissemination of data for listed species; consideration of the newest developments in good modeling practice; comprehensive review of existing population models and their applicability for listed species assessments; and development of case studies using a few well-tested models for particular species to demonstrate proof of concept. To advance our common goals, the panel recommends the following as important areas for further research and development: quantitative analysis of the causes of species listings to guide model development; systematic assessment of the relative role of toxicity versus other factors in driving pesticide risk; additional study of how interactions between density dependence and pesticides influence risk; and development of pragmatic approaches to assessing indirect effects of pesticides on listed species.

Acute myopericarditis associated with cat scratch disease in an adolescent.

Cat scratch disease is generally characterized by a self-limited chronic regional lymphadenopathy, but numerous other clinical manifestations involving a variety of organ systems have been reported. Cardiac involvement is unusual and when reported, it has been associated with culture-negative endocarditis in adults. We present the case of an adolescent male with typical cat scratch disease and associated myopericarditis.

Maximizing the extent of resection and survival benefit of patients in glioblastoma surgery: high-field iMRI versus conventional and 5-ALA-assisted surgery.

AIMS: A safe total resection followed by adjuvant chemoradiotherapy should be the primary goal in the treatment of glioblastomas (GBMs) to enable patients the longest survival possible. 5-aminolevulinic acid (5-ALA)- and intraoperative MRI (iMRI)-assisted surgery, have been shown in prospective randomized trials to significantly improve the extent of resection (EOR) and subsequently survival of patients with GBMs. No direct comparison of surgical results between both techniques has been published to date. We analyzed the additional value of iMRI in glioblastoma surgery compared to conventional surgery with and without 5-ALA. METHODS: Residual tumor volumes, clinical parameters and 6-month progression-free survival (6M-PFS) rates after GBM resection were analyzed retrospectively for 117 patients after conventional, 5-ALA and iMRI-assisted surgery. RESULTS: Mean residual tumor volume (range) after iMRI-assisted surgery [0.5 (0.0-4.7) cm(3)] was significantly smaller compared to the residual tumor volume after 5-ALA-guided surgery [1.9 (0.0-13.2) cm(3); p = .022], which again was significantly smaller than in conventional white-light surgery [4.7 (0.0-30.6) cm(3); p = .007]. Total resections were significantly more common in iMRI- (74%) than in 5-ALA-assisted (46%, p = .05) or white-light surgery (13%, p = .03). Improvement of the EOR by using iMRI was safely achievable as peri- and postoperative morbidities were comparable between cohorts. Total resections increased 6M-PFS from 32% to 45%. CONCLUSIONS: Analysis of residual tumor volumes, total resections and neurological outcomes demonstrate that iMRI may be significantly superior to 5-ALA and white-light surgery for glioblastomas at comparable peri- and postoperative morbidities. Longer 6M-PFS was observed in patients with total resections.

Long-term remission and recurrence rates after first and second transsphenoidal surgery for Cushing's disease: care reality in the Munich Metropolitan Region.

OBJECTIVE: Transsphenoidal surgery (TSS) presents the treatment of choice for Cushing's disease (CD). Remission and recurrence rates vary dependent on tumor size, extension, adenoma visibility on magnetic resonance imaging, and neurosurgical expertise. Other than published from single-surgeon neurosurgical series so far, we have aimed to describe long-term remission and recurrence rates of CD in a series incorporating different neurosurgeons, trying to reflect care reality in the Munich Metropolitan Region, which is accommodated by three tertiary university and multiple, smaller neurosurgical centers. DESIGN: We conducted a retrospective analysis of 120 patients who underwent first and 36 patients who underwent second TSS as treatment for CD between 1990 and 2012. METHODS: Patients were divided into three groups according to remission status. Potential risk factors for recurrence, pituitary function, and strategy in persistent disease were assessed. RESULTS: THREE OUTCOME GROUPS WERE IDENTIFIED ACCORDING TO REMISSION STATUS AFTER FIRST TSS (MEAN FOLLOW-UP 79 MONTHS): remission, 71% (85/120), disease persistence, 29% (35/120), and disease recurrence, 34% (29/85) (mean time to recurrence 54 months). After second TSS (n=36, mean follow-up 62 months), we documented remission in 42% (15/36), disease persistence in 58% (21/36), and disease recurrence in 40% (6/15) (mean time to recurrence 42 months). Postoperative hypocortisolism after first, though not after second, TSS was associated with a lower risk of suffering disease recurrence (risk=0.72; 95% CI 0.60-0.88; exact significance (two-sided) P=0.035). CONCLUSIONS: Our study shows higher recurrence rates of CD after first TSS than previously reported. Second TSS leads an additional 8% of the patients to long-term CD remission.

[Modern surgery of meningiomas affecting anterior visual pathways]. / Moderne Meningeomchirurgie im Bereich der vorderen Sehbahn.

Meningiomas are the most common form of primary intracranial tumors. If the anterior visual pathways are affected clinical visual compromise, visual field defects, oculomotor nerve disturbances or propotosis are predominant. Meningiomas of the anterior visual pathway remain therapeutically challenging due to the direct anatomical relationship to the circulus arteriosus cerebri, the cavernous sinus and cranial nerves. The therapy of choice is microsurgical resection. In many cases a curative approach can be achieved with modern surgical techniques and simultaneously maintaining patient quality of life. Problematic are cases in which resection would be associated with the risk of clinical impairment and in these cases radiotherapy is an important therapeutic option. In cases involving complex invasiveness an interdisciplinary treatment to control local clinical symptoms is favored.

[Meningiomas. Clinical case examples]. / Meningeome. Klinische Beispiele.

Using four case reports as examples the best treatment is discussed by considering the specific history and magnetic resonance imaging (MRI) findings. In many cases different therapeutic alternatives are possible for treatment of meningiomas.

Pituicytoma in a patient with Cushing's disease: case report and review of the literature.

Pituicytoma is an exceptionally rare low-grade glioma (WHO grade I) of the neurohypophysis and infundibulum. We are reporting the case of a 48-year-old man who presented with severe Cushing's syndrome. Endocrinological evaluation unequivocally confirmed pituitary-dependent Cushing's syndrome (=Cushing's disease). Cranial MR-imaging displayed a conspicuous area in the dorsal and basal pituitary gland and a minimal bulging of the pituitary gland paramedian of the pituitary stalk on the right side. Transsphenoidal inspection revealed a small tumor in the basal and dorsal pituitary gland. Surprisingly, the definite postoperative histopathological diagnosis of the removed tumor was pituicytoma and not pituitary adenoma. Hence, the microadenoma responsible for Cushing's disease was not yet removed and persistent hypercortisolism necessitated transsphenoidal re-operation. During re-operation, hemihypophysectomy was performed on the right side. The non-tumorous specimen of the adeno-hypophysis showed signs of Crooke's hyalinization consistent with Cushing's disease. Undetectable postoperative ACTH- and cortisol levels provided clear evidence that the underlying ACTH-source was successfully removed during re-operation. Coincidence of pituicytoma and pituitary-dependent Cushing's disease has not previously been reported.

Executive functions recover earlier than episodic memory after microsurgical transsphenoidal resection of pituitary tumors in adult patients--a longitudinal study.

Pituitary tumors may lead to cognitive dysfunction, and the most prevalent deficits are impaired memory and attention. To investigate whether memory and executive functions improve after surgical treatment we performed a prospective longitudinal study comprising 106 patients with pituitary tumors. Psychometric evaluation was performed with the d2-Letter Cancellation test, the Trail Making test, the Digit Span test and the Intelligence Structure test-Verbal Memory test at three timepoints: preoperatively, and at 3 months and 12 months after surgery. The preoperative and postoperative maximum suprasellar tumor extension and hormone status was assessed in all participants. The main finding was that concentration, working memory, and attentional speed improved significantly within the first 3 months after surgery (p<0.05), while improvement of episodic memory was not observed until 12 months after surgery (p<0.001). In the patients harbouring non-functioning adenomas, prolactinomas or other sellar lesions, the most important factor promoting improvement of neurocognitive function was the removal of the suprasellar tumor extension.

Histone acetylation patterns of typical and atypical pituitary adenomas indicate epigenetic shift of these tumours.

Pituitary adenomas are benign endocrine tumours of the anterior pituitary that are subclassified as typical (conventional) or atypical adenomas, with uncertain prognosis based on histopathological features. Clarifying epigenetic alterations of pituitary tumours, as well as the mechanisms underlying them, will hopefully open new windows to treatment and the classification of these tumours and maybe even prediction of patient survival. In the present study, using immunohistochemistry, we investigated the acetylation pattern of histone 3 lysine 9 (H3K9), an epigenetic marker of active chromatin state and gene transcription, in typical and atypical pituitary adenomas and the normal pituitary. We observed a significant increase in H3K9 acetylation from the normal pituitary to typical and atypical pituitary adenomas, which was associated with significant hyperacetylation of H3K9 in atypical adenomas (P < 0.0001). MIB-1 (Ki-67) overexpression was also highly associated with increased acetylation of H3K9, correlating prositively with tumour severity (P < 0.0001). p53 overexpression had a contributing effect on altered global H3K9 acetylation of atypical pituitary adenomas (P < 0.05). These data suggests that H3K9 acetylation status might serve as a relevant additional biomarker of tumour severity in pituitary adenomas, and also as a proper target for epigenetic-based therapies.

Demographic factors and the presence of comorbidities do not promote early detection of Cushing's disease and acromegaly.

OBJECTIVE: The aim of the study was to analyze the time-to-diagnosis interval in patients with Cushing's disease (CD) and acromegaly (AC), to assess factors that promote early disease detection and to investigate the medical fields diagnosing the pathologies. METHODS: 33 CD and 52 AC patients operated over 10 years received a self-designed disease-related questionnaire. Data about symptoms and their duration prior to diagnosis, education level, age, gender and place of residence (i. e. rural vs. urban, size of the city) were collected. RESULTS: The mean time-to-diagnosis interval was 6.0 years in CD and 5.8 years in AC patients. The vast majority of 67% of all investigated patients was diagnosed after they changed their primary health care provider or during a hospital stay owing to comorbidities caused by their underlying disease. Only 33% of all cases were diagnosed by their primary physician. In both groups neither gender, age, place of residence, education level, typical comorbidities (e. g. hypertension or diabetes) nor distinctive symptoms and bodily changes of the underlying disease (e. g. prognathism, acral enlargement, weight gain, buffalo hump) were significant factors promoting early detection. CONCLUSIONS: Apparently, patient-related factors do not affect the time-to-diagnosis interval, but rather the change of the primary health care provider. Knowledge of the disease among physicians is prerequisite to early detection. Due to the deleterious sequelae of delayed diagnosis, information programmes in the medical community are of paramount importance. Institution of screening programmes should be evaluated.

Are there gender-specific differences concerning quality of life in treated acromegalic patients?

OBJECTIVE: Acromegaly is associated with deleterious comorbidities that can remain irreversible even after successful cure has been achieved and lead to a persistently impaired Quality of Life (QoL). The aim of the study was to assess frequency and degree of persistent comorbidities and complaints after treatment of acromegaly and to investigate their impact on QoL. Another scope of interest was to determine gender-specific factors that influence perceived QoL in men and women. METHODS: We developed an Acromegaly Comorbidities & Complaints Questionnaire (ACCQ) consisting of 8 items (e. g. acral enlargement, joint complaints, hypertension, diabetes) known to affect QoL in order to assess frequency and degree of comorbidities. Additionally, the Acromegaly Quality of Life Questionnaire (AcroQoL) and the Short-form 36 (SF-36) questionnaire were handed out to 55 treated acromegalic patients. RESULTS: Both genders suffer from a lasting impairment in quality of life to a considerable degree. Complaints impairing manual skills (e. g. acral enlargement, arthralgias) were the most frequent findings (73% of all participants) in both genders. Multivariate analyses revealed that in men numbness of fingers and persistent joint-complaints were decisively responsible for impaired QoL. In women, it was the persistence of hypertension. CONCLUSIONS: Persistent joint complaints have adverse effects on QoL after treatment of acromegaly in men, possibly because they lead to impairment of manual motor skills and a handicap in their working life. Women seem to perceive late effects of hypertension as a manifest health threat.

Predictive factors for neurocognitive function and Quality of Life after surgical treatment for Cushing's disease and acromegaly.

BACKGROUND: Cushing's disease (CD) and acromegaly (AC) are associated with impairment in quality of life (QoL) and neurocognition that can persist after successful treatment. AIM: To investigate the influence of current disease status (remission vs no remission) on neurocognitive function and QoL in treated CD and AC patients and to determine predictive factors (e.g. demographic, clinical, neurosurgical, endocrinological) for post-operative neurocognition and QoL. SUBJECTS AND METHODS: Twenty-four CD and 37 AC patients underwent neuropsychological testing 1 to 10 yr following surgical therapy. Additionally, QoL was assessed. An overnight 2-mg dexamethasone suppression test in CD and IGF-I and GH levels in AC patients were assessed to determine current disease status. The results were compared with 28 sex-, education- and age-matched healthy controls (HC). RESULTS: Impaired QoL was more pronounced than neurocognitive decrease in both pathologies compared to HC. This finding was independent of the current status of disease. In AC, persistent comorbidities were associated with impaired QoL (p<0.05). Older age at operation in AC patients was a significant predictor for adverse effects on psychomotor speed and attentional functions (p<0.05). In CD persistent hypocortisolism, not hypercortisolism, had adverse effects on neurocognition (p<0.01). CONCLUSIONS: The current status of disease plays a subordinate role in postoperative outcome concerning QoL and neurocognition in either pathology. A possible explanation might be the considerably improved endocrinopathy after treatment compared to untreated patients, even if no cure is achieved. The lasting impairments might be explained by irreversible changes that have occurred during the active phase of the disease.