CENTRAL NEUROGENIC NEUROPROTECTION: PROTECTION OF BRAIN FROM FOCAL ISCHEMIA BY CEREBELLAR STIMULATION

Electrical stimulation of the cerebellar fastigial nucleus (FN) elevates regional cerebral blood flow (rCBF) independently of cerebral metabolism (rCGU) throughout brain. One hour of FN stimulation also reduces, by up to 50%, the volume of the focal ischemic infarction produced by occlusion of the middle cerebral artery in rat. Protected areas correspond to the ischemic penumbra. Neuroprotection, while reversible, persists for weeks after 1h of stimulation. It cannot be attributed to increasing rCBF and/or reducing rCGU to improve matching of flow and metabolism. Conditional stimulation of FN initiates long-lived inhibition of expression of peri-infarction depolarizing waves, possibly by altering potassium-channel function and suppresses induction of inducible nitric oxide synthase (iNOS) and ICAM in cerebral microvessels. The brain contains intrinsic networks which may protect the brain from ischemic injury, possibly by producing widespread and longterm suppression of electrical excitability and/or and expression of proinflammatory molecules.     

A rapid method for harvesting autologous red cells from patients with hemoglobin S disease

Red cells from patients with sickle cell disease (HbSS and HbSC) are more resistant to lysis in hypotonic NaCl solutions than normal (HbAA) red cells. Taking advantage of this inherent resistance to osmotic stress, patient red cells (HbSS or HbSC) were rapidly isolated from donor red cells (HbAA or HbAS) by washing with hypotonic (0.3%) NaCl. The hypotonic method of washing provides a previously unavailable means for obtaining autologous HbSS or HbSC red cells from samples containing transfused donor red cells. Once isolated, these red cells can be used for phenotyping, autoadsorption, or evaluation of positive direct antiglobulin tests.     

Measurements of in vivo intra-articular gentamicin levels from antibiotic loaded articulating spacers in revision total knee replacement

Previous in vitro studies have found high levels of antibiotic release in the days immediately following implantation of antibiotic loaded articulating spacers. However there are relatively few data describing the elution profile beyond this immediate period. This study was designed to measure if gentamicin levels continue to be clinically therapeutic after an extended period following in vivo implantation. Twelve patients received a gentamicin loaded articulating spacer between a 1st and 2nd stage revision total knee arthroplasty. At the 2nd stage procedure synovial fluid and blood samples were collected and assayed for the presence of gentamicin. The second stage revision occurred at a median of 99 days following spacer insertion. The median intra-articular gentamicin levels were 0.46 mg/L (0.24 to 2.36 mg/L) which would be considered therapeutic. There were no cases of reinfection. In this study, preformed articulating spacers containing gentamicin provided therapeutic concentrations in the synovial fluid surrounding the joint throughout the period of implantation. These data confirm the observations from in vitro studies, where a prolonged elution profile was observed for such spacers.     

Rate and determinants of antiviral treatment initiation for patients with HBeAg-negative chronic hepatitis B

Most clinic attenders with chronic hepatitis B (CHB) are serum HBeAg-negative, and a minority will require suppressive antiviral treatment. Expert guidelines propose schedules for the monitoring of untreated patients, but the recommended frequency of patient review does not reflect recognised demographic determinants of HBeAg-negative chronic hepatitis. Also, the impact of patient ethnicity on risk has not been defined. The aim of our study was to determine the rates and determinants of antiviral treatment initiation in a large multi-ethnic cohort of CHB patients attending a single centre. We undertook a retrospective study using entirely electronic sources of patient information. Treatment initiation dates were identified from electronic pharmacy records. Crude and time-dependent statistical analyses were undertaken to identify rate and risk factors for treatment initiation. Treatment was initiated for 232/1256 (18.5%) patients with rates of 23.2% and 33.2% at 5 and 10 years. An increased risk of treatment was associated with male sex (RR 1.803), older age at presentation (RR 1.027 per year increase) and with non-Black ethnicity (RR 1.654). Patient sex, baseline age and ethnicity also determined risk for treatment in the subset of patients with normal serum ALT and low HBV DNA at baseline, though overall treatment rate in this group was low (only 2% per annum). Thus, patient demographics permit risk stratification for treatment initiation and could determine to a significant extent the frequency of review required for untreated HBeAg-negative patients. Black ethnicity is associated with a significant reduction in risk of treatment initiation.