Vasospasm of the basilar artery following spontaneous SAH-clinical observations and implications for vascular research.

The basilar artery (BA), as a reference vessel for laboratory investigations of cerebral vasospasm (CVS) in many experimental models, warrants a sufficient blood supply despite hemodynamic changes during CVS. In a prospective evaluation study, we analyzed  patients who were admitted to our department with subarachnoid hemorrhage (SAH) for the occurrence and sequelae of CVS. Specifically, we sought to identify patients with CVS of the BA. As per institutional protocol, all patients with CVS detected in the posterior circulation had magnetic resonance imaging (MRI) examinations instead of CTA. Between January and December 2016, 74 patients were treated for spontaneous SAH. CVS occurred in 45 (61%) patients, and 31 (42%) patients developed associated cerebral infarctions (CI). CVS was significantly associated with CI (p < 0.0001; OR 44). In 18 (24.3%) patients, CVS significantly affected the basilar artery. Poor admission clinical state, younger age, and treatment modalities were significantly associated with BACVS. BACVS was more often detected in patients with severe CVS (p < 0.046; OR 4.4). Patients with BACVS developed cerebral infarction in a frequency comparable to other patients with CVS (61% vs. 70%, p = 0.7), but none of these infarctions occurred in the brain stem or pons even though vessel diameter was dramatically reduced according to CT- and/or MR-angiography. BACVS does not appear to be followed by cerebral infarction in the BA territory, presumably due to a vascular privilege of this vessel and its perforating branches. In contrast, brain ischemia can frequently be observed in the territories of other major arteries affected by CVS.

Comparison of carotid and basilar bifurcation aneurysms versus non-T-angled bifurcations: the geometry is associated with the outcome.

Patients with ruptured aneurysms of carotid bifurcation artery seem to suffer less often from cerebral vasospasm and early brain injury and have a better clinical outcome. Aim of our study was to identify differences in clinical course and outcome in aneurysms of terminus segments (carotid bifurcation artery and basilar tip) compared to aneurysms of other aneurysm locations except carotid bifurcation artery and basilar tip. Patients with SAH were entered into a prospectively collected database (1999 to June 2014). A total of 471 patients ('T-shaped' aneurysms n = 63, 'non-T-shaped' aneurysms n = 408) were selected. Outcome was assessed by modified Rankin Scale (mRS) 6 months after SAH. Mean age was 53.75 years. Statistically, analysis showed a significant better outcome in 'T-shaped' aneurysms (p = 0.0001) and a significant lower mortality rate (p = 0.02) despite higher rates of Fisher 3 bleeding pattern and CVS. In 'T-shaped' aneurysms, no prognostic factors for outcome could be detected. In 'non-T-shaped' aneurysms admission status (p < 0.0001), early hydrocephalus (p < 0.0001), shunt-dependence (p = 0.001), and the occurrence of severe CVS (p = 0.01) statistically were factors influencing patients' outcome. Multivariate analysis showed 'non-T-shaped' aneurysms itself as independent prognostic factor for patients' outcome. Despite same rate of poor admission status, early hydrocephalus and shunt dependence 'T-shaped' aneurysms have a highly significantly better. Pathophysiological mechanism actually is not understood. Further studies are necessary to identify, which factors lead to the decreased outcome in "non-T-shaped"- aneurysms.

Decision-making in a patient with cardiac arrest due to venous thromboembolism within 24 h after glioblastoma resection.

In the fulminant VTE form with cardiac arrest, systemic thrombolysis remains the most effective therapy. However, several contraindications restrict the use such as intracranial neoplasm or a recent history of intracranial surgery. Here, we report the case of a 59-year-old man who underwent glioblastoma resection and suffered from a fulminant pulmonary embolism with cardiac arrest. After CPR, continuous tPA infusion via an endovascularly placed pulmonary catheter was maintained over a period of 8 h. In this case, we report on our decision-making process and the use of local thrombolysis as a successful therapy in a patient with multiple contraindications.

Differential up-regulation of neurotrophin receptors and functional activity of neurotrophins on peripheral blood eosinophils of patients with allergic rhinitis, atopic dermatitis and nonatopic subjects.

BACKGROUND: Recent studies suggest that neurotrophins have a pivotal role in neuroimmune interactions. Indeed, in contrast to nonatopic subjects (NA), neurotrophins have been shown to be increased in atopic diseases such as allergic rhinitis (AR) and atopic dermatitis (AD). AIM: The aim of the study was to assess the functional role of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin (NT)-3 and -4 and the expression of pan-neurotrophin receptor (p75(NTR)) and tyrosine kinase (trk)A, -B and -C on peripheral blood eosinophils in AR, AD and NA. METHODS: Peripheral blood eosinophils of patients with AR, AD and NA were purified by CD16 negative selection (purity>98%). Neurotrophin receptor expression was analysed by FACS analysis. Apoptosis test (FACS analysis) and chemotactic index (modified Boyden chamber assay) were assessed after stimulation with BDNF, NT-3/-4 and NGF. RESULTS: The expression of trkA-C and p75(NTR) was significantly higher in AD>AR>NA (P<0.05-0.001). Apoptosis was significantly inhibited by BDNF, NGF, NT-3 in AD (P<0.05-0.001), by NT-3/-4 and NGF in AR (P<0.05-0.01) and by NT-3 (P<0.05-0.01) in NA eosinophils. Chemotaxis was significantly induced by BDNF and NT-3/4 (P<0.01-0.001) in AD peripheral blood eosinophils. CONCLUSION: Neurotrophin receptor expression and neurotrophin functional activity was greatest in AD>AR>NA. AD eosinophils are pre-activated and may therefore better respond to neurotrophins. With this study, we provide new pathophysiologic insights into atopic diseases with a functional role of neurotrophins in peripheral blood eosinophils in AD and AR.

Modulation of neurotrophin and neurotrophin receptor expression in nasal mucosa after nasal allergen provocation in allergic rhinitis.

BACKGROUND: Patients with allergic rhinitis (AR) feature both allergic airway inflammation and a hyperresponsiveness to nonspecific stimuli which is partly neuronally controlled. Still, it is unclear whether or not neurotrophins are involved in airway pathophysiology of AR and in nasobronchial interaction. METHODS: Nine AR patients with mono-allergy to grass pollen and nine healthy controls underwent nasal allergen provocation (NP). Serum samples, nasal and bronchial biopsies were taken before (T(0)) and 24 h after (T(24)) NP. Pan-neurotrophin receptor p75(NTR), tyrosine kinase A (trkA), trkB, nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) were assessed with immunohistochemistry, and NGF and BDNF levels with ELISA. RESULTS: At T(24), BDNF and NGF were upregulated in nasal mucosa (P < 0.05) and increased in the peripheral blood of AR compared with T(0). The increase in nasal BDNF expression correlated positively with the maximum increase in total nasal symptom score in AR (P = 0.02). p75(NTR) was expressed on peripheral nerves and epithelial layer, trkA on endothelial cells, and trkB on mast cells. trkB + mast cells significantly decreased after NP in AR (P < 0.01). NP did not modulate p75(NTR) and trkA expression in nasal mucosa and had no effect on the expression of neurotrophins and receptors in bronchial mucosa. CONCLUSION: This study shows that neurotrophins and their receptors are expressed in human airways. Allergic rhinitis was characterized by a modulation of BDNF, NGF, and trkB in nasal mucosa after NP and a correlation of nasal BDNF with the maximal increase of total nasal symptom score. Therefore, our data suggest that neurotrophins participate in upper-airway pathophysiology in AR, whereas their role in nasobronchial interaction remains unclear.

Circulating levels of brain-derived neurotrophic factor correlate with disease severity in the intrinsic type of atopic dermatitis.

BACKGROUND: Recent studies have shed light on the complex regulation of genetic, environmental, immunologic and pharmacologic factors, which contribute to the development of atopic dermatitis (AD). However, it is still unclear to which extent neuroimmune mediators have a role in AD. AIMS OF THE STUDY: To assess peripheral neurotrophin levels and their correlation with scoring atopic dermatitis (SCORAD) scores in both the intrinsic and extrinsic types of AD compared with patients with psoriasis and nonatopic healthy subjects. METHODS: Levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were assessed in peripheral blood with enzyme-linked immunosorbent assay. Based on IgE-mediated sensitization, AD was divided into the extrinsic and intrinsic type. Severity of AD was assessed with SCORAD score and with psoriasis area and severity index (PASI) in patients with psoriasis. RESULTS: Brain-derived neurotrophic factor and NGF were detectable in all the subjects studied. However, the levels of both neurotrophins were significantly higher in patients with extrinsic and intrinsic types of AD compared with patients with psoriasis and nonatopic healthy subjects (NGF: P < 0.001, BDNF: P < 0.001). NGF and BDNF levels were similar in the intrinsic and extrinsic type of AD. There was a significant correlation between BDNF and SCORAD score only in patients with the intrinsic type of AD (r = 0.57, P < 0.05). CONCLUSIONS: This study shows for the first time that NGF and BDNF are increased in both, the extrinsic type and the intrinsic type of AD. This finding points to a similar pathophysiologic background implicating a neuroimmune network in both variants of this chronic inflammatory skin disease. Future studies are needed to show the direct mechanisms of neurotrophin action in chronic inflammatory skin.

[Risk of postoperative hemorrhage in tonsillectomy. A comparison between general anesthesia and local anesthesia]. / Nachblutungsrisiko bei Tonsillektomie. Ein Vergleich zwischen Vollnarkose und lokaler Betäubung.

BACKGROUND: Postoperative bleeding after tonsillectomy is still a life-threatening problem. The incidence of postoperative bleeding, as well as many factors (kind of surgery, hemostasic problems) affecting this risk have been investigated. A possible factor that has not been well studied is the used anaesthetic procedure. METHODS: A prospective study was completed comparing the risk of postoperative bleeding in patients operated in local vs. general anaesthesia. RESULTS: The study enrolled 1063 patients, who consecutively underwent tonsillectomy. In 16 (4.12%) of 388 patients operated under general and 51 (7.55%) of 675 patients operated under local anaesthesia postoperative bleeding occurred. After local anaesthesia postoperative bleeding was seen mainly at the day of operation (46 of 51), there was no late bleeding after the 6th postoperative day. After general anaesthesia in 6 of 16 cases postoperative bleeding occurred after the 6th postoperative day. DISCUSSION: Postoperative bleeding occurs more frequent in patients who underwent tonsillectomy in local anaesthesia. The risk of late postoperative bleeding however is higher with tonsillectomy in general anaesthesia.

[MRI of aseptic osteonecrosis in children and adolescents with acute lymphoblastic leukemia]. / Kernspintomographie von aseptischen Osteonekrosen bei Kindern und Jugendlichen mit einer akuten lymphoblastischen Leukämie.

PURPOSE: To evaluate the incidence, localisation, and course of symptomatic aseptic osteonecrosis (AON) in children undergoing treatment for acute lymphoblastic leukemia (ALL). METHODS: 72 MRI examinations obtained from 26 children with bone pain selected from a group of 121 children with ALL were evaluated retrospectively. The area of the AON was determined by computer assisted planimetry. Follow-up examinations after 2-5 years were considered. RESULTS: 10/121 (8.3%) of the children had symptomatic AON, the number of lesions varied between 1 and 24 per child. 62/66 lesions were localized within the lower extremities. 58% of the AON were positioned in the epiphysis and 42% in the meta- and diaphysis. The mean area of AON was 7.6 cm2 with a range of 0.5 to 50 cm2. Follow-up examinations revealed a regression in 19 AON, no change in 43 and a progression in 4 lesions. AON within the epiphysis with joint involvement or lesions greater than 9 cm2 more frequently showed a progression of AON with final joint destruction. An elevated risk for AON was seen in children older than 10 years and in children with intensified chemotherapy due to high-risk ALL. CONCLUSION: AON is a common complication in ALL-children under chemotherapy. Most frequently, the course is benign but large AON with joint involvement have an elevated risk for progression of AON with final joint destruction.

Intestinal T lymphocytes of different rat strains in immunotoxicity.

In order to study the intestinal mucosal immune cells, with emphasis on single T lymphocytes, an inventory was made of single and organized lymphocytes in the epithelium and lamina propria of the small intestines of untreated Wistar, Fischer 344, and Lewis rats. The single and organized lymphocytes were examined microscopically. In addition, the single lymphocytes in the epithelium (IEL) and lamina propria (LPL) were analyzed by flow cytometry. Next, the use of flow cytometry analysis was explored to detect changes in the IEL T-lymphocyte population in subacute oral studies with the immunomodulating agents azathioprine and hexachlorobenzene. Untreated random-bred Wistar rats exhibited a large interindividual variability in IEL composition, while the variability was small in inbred Fischer 344 and Lewis rats. The explorative study with the 2 model immunomodulating compounds demonstrated that hexachlorobenzene increased the number of intraepithelial T lymphocytes with CD8+ phenotype at the cost of T cells with CD4+ phenotype in Lewis rats. Azathioprine did not induce distinct effects on the percentages of IEL. The data indicate that the intraepithelial lymphocytes in the intestines are a potential target for orally administered immunomodulating compounds and should therefore receive more attention in toxicologic pathology studies.

Aseptic osteonecrosis in children with acute lymphoblastic leukemia.

Joint destruction caused by aseptic osteonecroses (AONs) is a severe complication in acute lymphoblastic leukemia (ALL). Here, factors were determined that influence the occurrence and clinical course of AON in ALL patients. Clinical data of 121 patients were correlated with the occurrence of AON. Magnetic resonance imaging was performed in patients with bone pain. Areas of AONs were correlated with the clinical course of AON. Ten patients presented with clinical symptoms of AON and 9 of 10 patients were graded as high-risk ALL compared with 46 of 111 patients without AON (chi 2, P < .05). In 10 ALL patients 66 AONs were identified by MRI. In some patients up to 14 different AON sites were observed. The courses of AONs varied in individual patients, suggesting that necrosis-specific factors might be responsible. A size above 900 mm2 was significantly associated with progressive AON (P < .01). The more intensive treatment regimen in high-risk ALL patients might contribute to the development of AON. The clinical course of AON, however, is determined by necrosis-specific factors such as a large size. These data could help in developing therapeutic strategies for the prevention of progressive AON.

Patients' attitudes toward advance directives and end-of-life treatment decisions.

Much of the patient education about advance directives described in the literature involves explaining the purpose of advance directives to patients and guiding them through the process of issuing a directive. However, well over half of the subjects in this study claimed to know enough about the directives to issue one, and almost all subjects expressed a preference for issuing directives when healthy. Although health care agencies that wish to adhere to the PSDA must continue to ask all patients if they have issued an advance directive, aggressive patient education programs that press hospitalized patients to consider issuing an advance directive may be perceived by patients as coercive and uncaring. Patient education may be more likely to achieve the goals of the PSDA if it is provided before hospitalization and if patients are encouraged to discuss their care preferences with family members who would be in a position to speak for them at the end of life. Further study of the few patients who choose to issue an advance directive would be informative. When and why they chose to issue the directive should be explored. Patients who report issuing an advance directive but do not provide their physician or hospital with a copy of the directive upon admission should also be studied to determine if this represents a desire not to activate the directive during the current admission or simply confusion about the disposition of this document. Finally, most studies of advance directives have been cross-sectional. Longitudinal study of patients who issue advance directives are needed to determine the effectiveness of these documents in influencing the end-of-life treatment that patients receive.

Critical elements of transition from NICU to home and follow-up.

The continued expansion of NICU's and the subsequent increase in the survival rate of infants and children with special health care needs warrants an examination of the variables that contribute to a successful transition from hospital to home. While best practices have been identified for both families and professionals, many of the 1150 NICU's across the country are not in a position to implement such practices, primarily because of fiscal and time constraints. This article presents an overview of a project designed to identify and facilitate critical elements of transition that can be implemented at minimum cost for all families transitioning from hospital to home care in Connecticut. The identified elements include: (a) the use of a parent to parent support network, (b) the use of a standard discharge summary form to enhance communication among family and care providers, (c) the use of a continuing care plan to facilitate the accessibility of community services, and (d), the identification of on-going training activities for both families and providers.

Parent-to-parent teaching.

The effectiveness of using parents as interventionists for their children and other parents was examined. A multiple baseline design was employed to measure the effects of specific intervention techniques on teaching skills of three parents of toddler-aged children with Down syndrome. The first parent was trained by a professional interventionist on the use of the techniques. This parent then trained a second parent, who then trained a third parent. A fidelity-of-implementation measure indicated that the parents implemented the training procedures appropriately when training another parent. The effectiveness of the intervention techniques was measured through an observational code that assessed parent and child behavior during teaching sessions. Results suggest that training had a functional effect on the parents' use of the selected intervention techniques. The intervention also had a functional effect on the children's percentage of correct responding during the teaching session.

The effect of weight lifting exercise on heart rate and metabolism in experienced weight lifters.

Fifteen experienced weight lifters were investigated to examine the effects of weight exercise with variable intensity on heart rate and changes in arterial glucose, lactate and pyruvate, as well as serum total lipids, beta-lipoproteins, triglycerides, glycerol and free fatty acids. The highest value of heart rate were reached during repetitions (ca. 150 beats/min), during single maximal contraction only 120--130 beats/min. No important changes were found in lipid substrates or glucose, while lactate (x max: 4 mmol/l) and urivate (x max: 0.11 mmol/l) increases were moderate. This type of training may be useful in the clinical rehabilitation of the locomotor system but it lacks importance for preventive or rehabilitation therapy of the cardiovascular system.

[Comparison of vaginal cytologic effects and blood elimination curves of different oestrogen drugs (author's transl)]. / Vergleichende Betrachtung von vaginalzytologischen Indexverläufen und Bluteliminationskurven bei verschiedenen Ostrogenen.

With different oral oestrogens it was studied, if relations are existing between pharmacokinetic and vaginal effect. By means of Karyopycnotic Index and Dynamic Oestrogenicity Index the cytological effect was quantified from a single dose of oestradiol valerianate, mestranol, ethinyloestradiol and 3 depot oestrogens proved on postmenopause women and compared with adequate pharmacocinetical investigations. The courses of oestrogen levels did not correlate with indices. Both methods of investigation do not compensate, but complete one another. Depotoestrogens and short acting oestrogens are distinguishable with regard to proliferation maxium and steepness of index decline.