Selective Mapping of Deep Brain Stimulation Lead Currents Using Acoustoelectric Imaging

We describe a new application of acoustoelectric imaging for non-invasive mapping of the location, magnitude and polarity of current generated by a clinical deep brain stimulation (DBS) device. Ultrasound at 1MHz was focused near the DBS device as short current pulses were injected across different DBS leads. A recording electrode detected the high-frequency acoustoelectric interaction signal. Linear scans of the US beam produced time-varying images of the magnitude and polarity of the induced current, enabling precise localization of the DBS leads within 0.70mm, a detection threshold of 1.75mA at 1 MPa and a sensitivity of 0.52 ± 0.07 μV/(mA*MPa). Monopole and dipole configurations in saline were repeated through a human skullcap. Despite 13.8-dB ultrasound attenuation through bone, acoustoelectric imaging was still >10dB above background with a sensitivity of 0.56 ± 0.10 μV/(mA*MPa). This proof-of-concept study indicates that selective mapping of lead currents through a DBS device may be possible using non-invasive acoustoelectric imaging.     

Aktuelle Daten und Trends zu Methicillin-resistenten Staphylococcus aureus (MRSA)

Nosocomial infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are a problem in hospital settings worldwide. The National Reference Centre for Staphylococci performs molecular typing on a representative sample set of MRSA isolates from German hospitals for assessing long-term trends thus following the dynamics of emergence and spread of MRSA clones. The article focuses on recent data concerning antibiotic resistance and epidemic MRSA in nosocomial settings and also reflects the impact of community-acquired MRSA and MRSA from zoonotic reservoirs. Identifying common and newly emerging clones is an on-going challenge in the changing epidemiology of MRSA and prevention of further spread needs molecular surveillance.     

Crystal structure of a eukaryotic zinc-dependent histone deacetylase, human HDAC8, complexed with a hydroxamic acid inhibitor

Histone deacetylases (HDACs) are a family of enzymes involved in the regulation of gene expression, DNA repair, and stress response. These processes often are altered in tumors, and HDAC inhibitors have had pronounced antitumor activity with promising results in clinical trials. Here, we report the crystal structure of human HDAC8 in complex with a hydroxamic acid inhibitor. Such a structure of a eukaryotic zinc-dependent HDAC has not be described previously. Similar to bacterial HDAC-like protein, HDAC8 folds in a single alpha/beta domain. The inhibitor and the zinc-binding sites are similar in both proteins. However, significant differences are observed in the length and structure of the loops surrounding the active site, including the presence of two potassium ions in HDAC8 structure, one of which interacts with key catalytic residues. CD data suggest a direct role of potassium in the fold stabilization of HDAC8. Knockdown of HDAC8 by RNA interference inhibits growth of human lung, colon, and cervical cancer cell lines, highlighting the importance of this HDAC subtype for tumor cell proliferation. Our findings open the way for the design and development of selective inhibitors of HDAC8 as possible antitumor agents.     

CTLA-4 exon 1 polymorphism in patients with autoimmune blood disorders

CTLA-4 is a CD28 homologue that plays an important role in negative regulation of T-cell responses. Its transient expression on the surface of activated T cells antagonizes the activating signals and terminates the T-cell response. An A to G polymorphism at position 49 of the CTLA-4 first exon has recently been associated with several autoimmune disorders. In the present study we have examined the prevalence of the A and G alleles of the CTLA-4 gene in 50 patients with autoimmune hemolytic anemia (AIHA), of which 20 had idiopathic AIHA and 30 had AIHA and chronic lymphocytic leukemia (CLL), and in 60 patients with immune thrombocytopenic purpura (ITP). Control subjects were 100 healthy individuals and 100 CLL patients without clinical evidence for an autoimmune disease. The G allele was present at a significantly higher frequency among the patients with AIHA (P = 0.003), whereas no difference was observed between patients with ITP and controls. The G allele frequency was highest among CLL patients who had developed AIHA. The obtained data indicate that the G allele of CTLA-4 predisposes to the development of AIHA, particularly among patients with CLL.     

Transmission of human immunodeficiency virus in a dental practice.

OBJECTIVE: To determine if patients of a dentist with the acquired immunodeficiency syndrome (AIDS) became infected with human immunodeficiency virus (HIV) during their dental care and, if so, to identify possible mechanisms of transmission. DESIGN: Retrospective epidemiologic follow-up of the dentist, his office practice, and his former patients. SETTING: The practice of a dentist with AIDS in Florida. PARTICIPANTS: A dentist with AIDS, his health care providers and employees, and former patients of the dentist, including eight HIV-infected patients. MEASUREMENTS: Identification of risks for HIV transmission (if present), degree of genetic relatedness of the viruses, and identification of infection control and other office practices. RESULTS: Five of the eight HIV-infected patients had no confirmed exposures to HIV other than the dental practice and were infected with HIV strains that were closely related to those of the dentist. Each of the five had invasive dental procedures, done by the dentist after he was diagnosed with AIDS. Four of these five patients shared visit days (P greater than 0.2). Breaches in infection control and other dental office practices to explain these transmissions could not be identified. CONCLUSION: Although the specific incident that resulted in HIV transmission to these patients remains uncertain, the epidemiologic evidence supports direct dentist-to-patient transmission rather than a patient-to-patient route.     

The effect of aspirin on the ventilatory response to exercise in chronic heart failure

INTRODUCTION: Patients with chronic heart failure (CHF) experience breathlessness and fatigue on exercise. One of the abnormalities seen on maximal exercise testing is an increased ventilatory response to exercise (VE/VCO(2) slope). The cause of this is unknown, but is likely to be due to a combination of interacting peripheral and central factors. Recent data have demonstrated a relation between VE/VCO(2) slope and prostaglandin levels in contracting muscles. The present study examined the influence of the presence of a potent non-selective prostaglandin inhibitor, aspirin, on the ventilatory response to exercise in a group of patients with CHF. METHODS: We investigated the ventilatory response to exercise of 120 consecutive patients in sinus rhythm attending a specialist heart failure clinic. We excluded those taking clopidogrel (six patients) and those on both warfarin and aspirin or taking other non-steroidal anti-inflammatory agents (five patients). The other 109 patients were grouped according to whether they were taking aspirin (n=52 (48%)) or not (n=57 (52%)). Each patient underwent echocardiography to assess left ventricular function, and exercise testing with metabolic gas exchange to derive peak oxygen consumption (pVO(2)) and the VE/VCO(2) slope. RESULTS: The groups were similar in terms of age, (67 (13) vs. 66 (12) years; P=0.34) drug use, heart failure aetiology, left ventricular function (ejection fraction; 33.3 (9.4) vs. 31.8 (9.9)%; P=0.05)) and exercise tolerance (pVO(2); 20.4 (5.3) vs. 19.9 (6.0); P=0.68, and VE/VCO(2) slope; 35.4 (6.2) vs. 35.7 (9.3); P=0.73). There was no difference in the ventilatory response to exercise or the symptoms of breathlessness between the two groups. CONCLUSIONS: Aspirin does not appear to affect exercise performance in CHF.