Perioperative monitoring of the electrocardiogram during cerebral aneurysm surgery

Electrocardiographic (ECG) abnormalities occur frequently following a subarachnoid hemorrhage and may also occur intraoperatively and postoperatively in patients undergoing neurovascular procedures. The aim of this study was to assess the relationship between ECG changes and the neurological status of the patient, the size and the location of the aneurysm, and the influence of these changes on the cardiac and neurological outcome. The preoperative ECG was analyzed in 270 patients. Forty-five patients had intraoperative Holter monitoring. An immediate postoperative ECG was recorded in 120 patients and 60 patients had three consecutive postoperative ECGs. Preoperatively, 52% of the patients had an abnormal ECG and the incidence was highest in patients with a poorer neurological status. Most of the ECG changes involved the T wave or the ST segment. Intraoperative and postoperative changes occurred in 35 and 65% of the patients, respectively, and were independent of the studied factors. There were no documented cardiac events. The presence of an abnormal preoperative ECG did not influence the neurological outcome of the patient, but fluctuating postoperative changes were associated with a worse outcome.     

Elevated tonic extracellular dopamine concentration and altered dopamine modulation of synaptic activity precede dopamine loss in the striatum of mice overexpressing human α-synuclein

Overexpression or mutation of α-synuclein (α-Syn), a protein associated with presynaptic vesicles, causes familial forms of Parkinson's disease in humans and is also associated with sporadic forms of the disease. We used in vivo microdialysis, tissue content analysis, behavioral assessment, and whole-cell patch clamp recordings from striatal medium-sized spiny neurons (MSSNs) in slices to examine dopamine transmission and dopaminergic modulation of corticostriatal synaptic function in mice overexpressing human wild-type α-Syn under the Thy1 promoter (α-Syn mice). Tonic striatal extracellular dopamine and 3-methoxytyramine levels were elevated in α-Syn mice at 6 months of age, prior to any reduction in total striatal tissue content, and were accompanied by an increase in open-field activity. Dopamine clearance and amphetamine-induced dopamine efflux were unchanged. The frequency of MSSN spontaneous excitatory postsynaptic currents (sEPSCs) was lower in α-Syn mice. Amphetamine reduced sEPSC frequency in wild types (WTs) but produced no effect in α-Syn mice. Furthermore, whereas quinpirole reduced and sulpiride increased sEPSC frequency in WT mice, they produced the opposite effects in α-Syn mice. These observations indicate that overexpression of α-Syn alters dopamine efflux and D2 receptor modulation of corticostriatal glutamate release at a young age. At 14 months of age, the α-Syn mice presented with significantly lower striatal tissue dopamine and tyrosine hydroxylase content relative to WT littermates, accompanied by an L-DOPA-reversible sensory motor deficit. Together, these data further validate this transgenic mouse line as a slowly progressing model of Parkinson's disease and provide evidence for early dopamine synaptic dysfunction prior to loss of striatal dopamine.     

The release of platelet-activating factor into plasma during allergen-induced bronchoconstriction

Plasma histamine and platelet-activating factor (PAF) were measured in six subjects with mild seasonal asthma before and after allergen-induced bronchoconstriction, and in six other patients with asthma before and after methacholine-induced bronchoconstriction. A significant increase in plasma histamine and PAF levels was found in patients with mild seasonal asthma after allergen-induced bronchoconstriction but not in patients with asthma after bronchoconstriction induced by methacholine. There was a significant correlation between the baseline plasma PAF levels and the degree of bronchial hyperresponsiveness to methacholine. These findings suggests that PAF may be an important mediator in the pathogenesis of asthma and bronchial hyperresponsiveness.     

Ataxia telangiectasia: more variation at clinical and cellular levels

Ataxia telangiectasia (A‐T) is a rare recessively inherited disorder resulting in a progressive neurological decline. It is caused by biallelic mutation of the ATM gene that encodes a 370 kDa serine/threonine protein kinase responsible for phosphorylating many target proteins. ATM is activated by auto(trans)phosphorylation in response to DNA double strand breaks and leads to the activation of cell cycle checkpoints and either DNA repair or apoptosis as part of the cellular response to DNA damage. The allelic heterogeneity in A‐T is striking. While the majority of mutations are truncating, leading to instability and loss of the ATM protein from the allele, a significant proportion of patients carry one of a small number of mutations that are either missense or leaky splice site mutations resulting in retention of some ATM with activity. The allelic heterogeneity in ATM, therefore, results in an equally striking clinical heterogeneity. There is also locus heterogeneity because mutation of the MRE11 gene can cause an obvious A‐T like disorder both clinically and also at the cellular level and mutation of the RNF168 gene results in a much milder clinical phenotype, neurologically, with the major clinical feature being an immunological defect.     

Mechanism of persistent infection associated with peritoneal implants.

The ability of rabbits to clear an intraperitoneal injection of Pseudomonas aeruginosa in the presence or absence of a surgically implanted peritoneal device was investigated. Sham-operated rabbits without an implant eliminated a P. aeruginosa challenge of 5 x 10(6) cfu/ml; lavage fluid and peritoneal tissues became culture-negative within 96 h. However, peritonitis developed in rabbits that were given the same number of bacteria in the presence of an implant; high bacterial counts were recovered from the lavage fluid and the device itself. Scanning and transmission electronmicroscopy revealed bacterial biofilms on the surface of the device. Insertion of pre-colonised devices demonstrated a rapid multiplication of sessile organisms within the resulting bacterial biofilm. Counts reached a plateau of about 1 x 10(7) cfu/cm2 of Silastic by day 16 and fluctuated around this level until the end of the study. Pre-immunisation with formalin-killed whole cells of P. aeruginosa did not reduce this bacterial growth despite high levels of specific IgG. The results confirm the failure of peritoneal defences to clear an infection in the presence of an implant following either challenge with planktonic bacteria or insertion of a pre-colonised device, and demonstrate the rapid development of bacterial biofilms on the surface of the implant which appear to protect the bacteria from host defences, even when primed by pre-immunisation.     

Localization of neurotensin-like immunoreactive amacrine cells in the larval tiger salamander retina

Summary Light microscopic immunocytochemistry was used to localize the populations of NT-like immunoreactive amacrine cells in the larval tiger salamander retina. Seventy-nine percent of NT-immunostained cells observed in transverse cryo-prepared sections were classified as Type 1 amacrine cells. Another 6% were classified as Type 2 amacrine cells, while 15% of the NT-cells had their cell bodies situated in the ganglion cell layer and were tentatively designated as displaced amacrine cells. Each type of NT-like immunoreactive cell was observed in the central and peripheral retina. NT-immunostained processes were observed to ramify in sublayers 3 and 5 of the inner plexiform layer. An examination of retinal whole mounts revealed that NT-amacrine cells were distributed throughout the center and periphery of the retina at a density of 82 ± 24 cells/ mm². The dendritic fields of NT-immunostained amacrine and displaced amacrine cells were observed to be either symmetrically or asymmetrically distributed about their somas. Symmetrical dendritic fields were generally oval-shaped and ranged in diameter from 250 to 500 m (major axis) by 150 to 250 m (minor axis). Asymmetrical dendritic fields were observed to encompass one-half or less of an imaginary circle surrounding their soma of origin and were orientated in all directions. The processes forming asymmetrical dendritic fields ranged from 75 to 260 m in length. Furthermore, partial overlap was often observed between the dendritic fields of adjacent NT-amacrine cells.     

Activation of human B lymphocytes by 8' substituted guanosine derivatives

The 8-substituted guanosine derivatives (8-sGs), mercaptoguanosine and bromoguanosine, are shown to induce immunoglobulin production and proliferation in a subset of normal human B lymphocytes. Limiting dilution analysis indicated that the 8-sG-responsive B cell pool is approximately 10 times larger than that activated by pokeweed mitogen (PWM), 10 times smaller than that activated by Epstein-Barr virus (EBV), and contains approximately equal proportions of cells committed to the expression of IgG, IgA or IgM isotypes. Although some B cells seem able to respond to 8-sGs in the absence of T helper cells, maximal immunoglobulin production is only observed in the presence of T cells. The 8-sG response pattern of human B lymphocytes appeared similar but not identical to that reported for rodent cells. The mitogenic 8-sGs are unique activators as they bypass surface membrane interactions obligatory for other agents including anti-IgM, Staphylococcus aureus particles, PWM, and EBV.