Distribution of azithromycin into brain tissue, cerebrospinal fluid, and aqueous humor of the eye.

To measure the concentrations of azithromycin in the central nervous system, 20 patients with brain tumors (group I) received a single 500-mg oral dose of azithromycin either 24, 48, 72, or 96 h prior to the tumor removal operation and 10 patients with cataracts undergoing surgery (group II) and 7 patients scheduled to undergo lumbar puncture (group III) received the same dose of azithromycin 24 h prior to the operation or procedure. Serum from all patients, brain tissue from group I, aqueous humor from group II, and cerebrospinal fluid from group III were assayed for azithromycin concentration. The mean concentrations of azithromycin in brain tissue 24, 48, 72, and 96 h after administration were 2.63 +/- 2.58, 3.64 +/- 3.81, 0.74 +/- 0.37, and 0.41 micrograms/g, respectively. In contrast, the concentrations of azithromycin in cerebrospinal fluid and aqueous humor of the eye were very low or undetectable. Therefore, these data show that azithromycin appears to be widely distributed into brain tissue but not into cerebrospinal fluid or aqueous humor of the eye.     

Schwere Atemdepression durch unkorrekt verschlossene Pharmacia CADD-PCA-5200-Pumpe

CASE REPORT: We report a case of severe respiratory depression during postoperative patient-controlled analgesia (PCA) in a 14-year-old boy. The medication cassette of a Pharmacia CADD-PCA 5200 was not properly connected, which led to a free-flow infusion of about 85 mg piritramide (strong mu-opioid agonist) within 15 min; the patient lost consciousness and developed apnea. He was successfully treated with artificial ventilation via ambu-bag and 0.2 mg naloxone i. v. The incident occurred approx. 2 h after the start of postoperative medication, when other infusions (suspended above the PCA device level) had been stopped, making the free-flow opioid infusion possible. As the PCA device was in a bedside pump enclosure, the disconnection was not immediately apparent. DISCUSSION: Although PCA is considered a safe method, it can have potentially lethal complications: Technical problems or serious handling errors involve the risk of large volumes of analgesics being infused within a very short time. Therefore, we recommend apparative monitoring (e. g., pulse oximetry) as a necessary condition for the safe use of PCA.     

Lack of efficacy of high-dose verapamil in preventing brain damage in baboons and pigs after prolonged partial cerebral ischemia

There has been mounting speculation that calcium antagonists may be useful in reducing or preventing brain damage after cardiopulmonary resuscitation. To test the clinical usefulness of these agents in averting such damage, high-dose verapamil was administered to baboons and pigs after partial cerebral ischemia for varying periods of time. In Group A baboons and pigs, the major aortic branches supplying the carotid and vertebral circulations were clamped for periods ranging from 15 to 150 minutes, and neurological recovery was observed. In Group B, verapamil hydrochloride 0.7 mg/kg was given by intravenous infusion after similar periods of arterial occlusion. The administration of verapamil did not lead to any clinically improved neurological outcome. The use of verapamil after prolonged periods of partial cerebral ischemia did not improve neurological recovery in baboons and pigs.     

The clinical spectrum of anxiety in Parkinson's disease

Anxiety is common in Parkinson's disease (PD), and contributes to increased disability and poorer quality of life. In spite of its significant impact, the symptomatology, chronology, and neurobiology of anxiety in PD are all poorly understood, and this hinders accurate diagnosis and development of effective treatment strategies. This review investigates and updates literature related to the clinical spectrum of anxiety in PD. The reported prevalence of anxiety in PD varies considerably, with emerging interest in the frequency of the DSM‐IV residual category of “Anxiety disorder, not otherwise specified” (Anxiety disorder NOS), which is observed in up to 25% of PD patients. By design, there are no standardized diagnostic criteria for Anxiety disorder NOS, because this is the category applied to individuals who do not meet diagnostic criteria for any other current anxiety disorder. Anxiety rating scales incompletely capture anxiety symptoms that relate specifically to PD symptoms and the complications arising from PD therapy. Consequently, these scales have been deemed inappropriate for use in PD, and there remains a need for the development of a new PD‐specific anxiety scale. Research establishing accurate symptom profiles of anxiety in PD is sparse, although characterizing such symptomatology would likely improve clinical diagnosis and facilitate targeted treatment strategies. Research into the neurobiological and psychological underpinnings of anxiety in PD remains inconclusive. Anxiety can precede the onset of PD motor symptoms or can develop after a diagnosis of PD. Further investigations focused on the chronology of anxiety and its relationship to PD diagnosis are required. © 2014 International Parkinson and Movement Disorder Society     

Relationship of muscle sympathetic nerve activity to insulin sensitivity

Purpose

An association between insulin resistance and activation of the sympathetic nervous system has been reported in previous studies. However, potential interactions between insulin sensitivity and sympathetic neural mechanisms in healthy people remain poorly understood. We conducted a study to determine the relationship between sympathetic activity and insulin resistance in young, healthy humans.

Methods

Thirty-seven healthy adults (18–35 years, BMI <28 kg m^?2) were studied. Resting muscle sympathetic nerve activity (MSNA) was measured with microneurography and insulin sensitivity of glucose and free fatty acid metabolism was measured during a hyperinsulinemic-euglycemic clamp with two levels of insulin.

Results

During lower doses of insulin, we found a small association between lower insulin sensitivity and higher MSNA (P < 0.05) but age was a cofactor in this relationship. Overall, we found no difference in insulin sensitivity between groups of low and high MSNA, but when women were analyzed separately, insulin sensitivity was lower in the high MSNA group compared with the low MSNA group of women.

Conclusions

These data suggest that MSNA and insulin sensitivity are only weakly associated with young healthy individuals and that age and sex may be important modifiers of this relationship.     

Do current therapeutic anti-Aβ antibodies for Alzheimer’s disease engage the target?

Reducing amyloid-β peptide (Aβ) burden at the pre-symptomatic stages of Alzheimer’s disease (AD) is currently the advocated clinical strategy for treating this disease. The most developed method for targeting Aβ is the use of monoclonal antibodies including bapineuzumab, solanezumab and crenezumab. We have synthesized these antibodies and used surface plasmon resonance (SPR) and mass spectrometry to characterize and compare the ability of these antibodies to target Aβ in transgenic mouse tissue as well as human AD tissue. SPR analysis showed that the antibodies were able to bind Aβ with high affinity. All of the antibodies were able to bind Aβ in mouse tissue. However, significant differences were observed in human brain tissue. While bapineuzumab was able to capture a variety of N-terminally truncated Aβ species, the Aβ detected using solanezumab was barely above detection limits while crenezumab did not detect any Aβ. None of the antibodies were able to detect any Aβ species in human blood. Immunoprecipitation experiments using plasma from AD subjects showed that both solanezumab and crenezumab have extensive cross-reactivity with non-Aβ related proteins. Bapineuzumab demonstrated target engagement with brain Aβ, consistent with published clinical data. Solanezumab and crenezumab did not, most likely as a result of a lack of specificity due to cross-reactivity with other proteins containing epitope overlap. This lack of target engagement raises questions as to whether solanezumab and crenezumab are suitable drug candidates for the preventative clinical trials for AD.     

Screening for Depression and High Utilization of Health Care Resources Among Patients in Primary Care

The study aims to evaluate the prevalence of depression and the severity of depressive symptoms among primary care patients, who are high utilizers (HU) of health care resources. A cross-sectional, two-stage design was applied to screen for depression using the Brief Psychiatric Health Questionnaire and the Diagnostic Expert System for Psychiatric Disorders. A total of 38 primary care physicians accredited to practice in Berlin and Potsdam in Germany participated in the study. A total of 1,775 patients participated, 507 were identified as HU, 182 (36 %) of these were depressed compared to 81 (11 %) of the typical utilizers (p < 0.001). The depression score was higher and acute suicidality was more prevalent in HU than in typical utilizers (p < 0.001). Our results suggest that HU represent a population with a high prevalence of depression in primary care and should be considered for routine depression screening.