The role of the p75 neurotrophin receptor in cholinergic dysfunction in Alzheimer's disease.

Degeneration of basal forebrain cholinergic neurons is a common feature of Alzheimer's disease and is proposed to be an early and key event in the condition's etiology. This review discusses recent findings that strongly link the p75 neurotrophin receptor (p75(NTR)) to both cholinergic neuron degeneration and the production of toxic forms of amyloid-beta (Abeta), which is found deposited as amyloid plaques in the brains of Alzheimer's disease patients. Although elucidating the underlying molecular mechanisms and the clinical significance of these findings will require further experimentation, a number of possible scenarios and future research directions are presented.

Atrial electrical remodeling by rapid pacing in the isolated rabbit heart: effects of Ca++ and K+ channel blockade.

INTRODUCTION: Electrical remodeling describes atrial electrophysiologic changes that occur following atrial fibrillation. The mechanism(s) responsible for this phenomenon is not well understood. The purpose of this study was to examine the effects of rapid atrial pacing on atrial action potential duration, conduction time and refractoriness in the isolated rabbit heart. The effects of Ca++ and K+ blockade in this model were also studied. METHODS AND RESULTS: Monophasic action potential recordings were made from 12 epicardial atrial sites in 50 isolated perfused rabbit heart preparations. These recordings were analyzed for activation time (AT), 90% action potential duration (APD) and conduction times (CT) measured at a 250 msec cycle length. Atrial effective refractory periods (ERP) were determined at a 200 msec cycle length. All measurements were made at baseline and repeated after 2 hours of biatrial pacing at 250 msec (control group, n = 10) or 2 hours of rapid biatrial pacing (approximately 80 msec) in 4 groups: rapid pacing alone (rapid pacing group); rapid pacing in the presence of 0.1 mM verapamil (verapamil group) for L-type Ca++ channel blockade; rapid pacing with 1 mM 4-aminopyridine (4-AP group) for K+ channel blockade; and rapid pacing with 50 microM nickel chloride (Ni++ group) for T-type Ca++ channel blockade (n = 10 each group). All baseline and post pacing measurements were taken in the presence of Ca++ or K+ blockers for the respective groups. After rapid atrial pacing alone the average APD shortened by 8.2 +/- 10.4 msec compared to 3.6 +/- 12.5 msec shortening for control group (p = 0.002). The shortening of APD was uniform at all recording sites. For the rapid pacing group, CT was unchanged for right to left atrial conduction but shortened significantly for left to right atrial conduction (26.8 +/- 1.9 msec at baseline to 22.3 +/- 4.1 msec post pacing, p = 0.005). Conduction times were unchanged in the control group. The dispersion of repolarization was unchanged by rapid pacing alone. The decrease in APD from baseline to post rapid pacing was similar to the control group for those hearts treated with verapamil and 4-AP (1.5 +/- 12.3 and 4.7 +/- 10.4 msec, respectively, both p > or = 0.18 vs control group). The decrease in APD was significantly greater for the Ni++ group (11.8 +/- 14.3 msec) than for either the control group or rapid pacing group (both p < or = 0.023). The dispersion of repolarization was increased only in the 4-AP group post rapid pacing (41.7 +/- 6.2 msec at baseline to 53.5 +/- 9.6 msec post pacing, p = 0.01). ERPs were unchanged in any of the 5 groups except for a decrease in left atrial ERP in the Ni++ group after rapid pacing (98 +/- 14 msec at baseline to 88 +/- 8 msec post rapid pacing, p = 0.005). CONCLUSIONS: In the isolated rabbit heart model: 1) atrial APD is shortened after rapid pacing; 2) the shortening of APD is attenuated by verapamil and 4-AP but exaggerated by Ni++; 3) atrial conduction times are shortened in a direction specific manner after rapid pacing; and 4) shortening of ERP in this model is measured only in the presence of Ni++. These findings suggest that both L-type Ca++ and 4-AP sensitive channels may participate in atrial electrical remodeling.

Patients' desire for peri-operative information: Jamaican attitudes.

The desire for peri-operative information has been examined in patients from other countries. This study was undertaken to assess the peri-operative information needs in Jamaican patients and to compare them to those from other populations. A questionnaire examining the desire for information about impending anaesthesia was administered to 93 patients awaiting elective surgery at the University Hospital of the West Indies. Responses were assessed across age and gender, and were compared to results from five industrialized countries. Although Jamaican patients expressed a desire for information concerning anaesthesia and surgery, they did not regard it as their right to get information, and this was the most important factor in the Jamaican sample providing a significantly less positive response than patients from other nations (p < 0.01 versus each country). Information priority was given to practical aspects of anaesthesia and post-operative outcome-mobility, pain, and the consumption of food and drink. Meeting the anesthetist was high on the list of desires. Female patients were 1.9 (Confidence Interval 1.4, 2.5) times more likely to express a positive desire for information. There were no age-related differences.

Paravertebral anaesthesia for breast surgery an initial experience at the University Hospital of the West Indies.

Paravertebral blockade (PVB) is a regional anaesthetic technique that allows the injection of local anaesthetic agents into the paravertebral space. It has been used for acute and chronic pain relief and as an anaesthetic technique for unilateral surgery of the chest, breast, shoulder, kidney, and inguinal region. Paravertebral blockade has been performed on a limited basis for breast surgery at the University Hospital of the West Indies (UHWI) since 1998. This retrospective review was undertaken to report the initial experience with this block. We reviewed the notes of all patients who were given a PVB alone, or in combination with general anaesthesia (GA). Twenty-one patients had P VB: twenty females and one male, with age range of 24 to 90 years. Six were attempted with PVB alone, but two of these needed supplementation with a GA. Fifteen were done in combination with GA. No complications were recorded The initial experience shows that the performance of PVB is both possible and safe; it may offer an alternative to GA for breast surgery. A randomized prospective study is underway to allow a detailed comparison between the two methods.

The influence of immediate knee flexion on blood loss and other parameters following total knee replacement.

In an initial randomised controlled trial (RCT) we segregated 180 patients to one of two knee positions following total knee replacement (TKR): six hours of knee flexion using either a jig or knee extension. Outcome measures included post-operative blood loss, fall in haemoglobin, blood transfusion requirements, knee range of movement, limb swelling and functional scores. A second RCT consisted of 420 TKR patients randomised to one of three post-operative knee positions: flexion for three or six hours post-operatively, or knee extension. Positioning of the knee in flexion for six hours immediately after surgery significantly reduced blood loss (p = 0.002). There were no significant differences in post-operative range of movement, swelling, pain or outcome scores between the various knee positions in either study. Post-operative knee flexion may offer a simple and cost-effective way to reduce blood loss and transfusion requirements following TKR. We also report a cautionary note regarding the potential risks of prolonged knee flexion for more than six hours observed during clinical practice in the intervening period between the two trials, with 14 of 289 patients (4.7%) reporting lower limb sensory neuropathy at their three-month review.

Cloning and characterization of an orphan seven transmembrane receptor from Schistosoma mansoni.

A partial cDNA sequence was obtained from the human blood fluke, Schistosoma mansoni using a signal sequence trap approach. The full-length cDNA was cloned and termed Sm-7TM. The corresponding open reading frame had 7 membrane spanning domains and shared identity with a small, novel group of seven transmembrane (7TM) receptors from vertebrates and invertebrates, including the human ee3 receptor - a heptahelical protein implicated in neuronal signalling. Phylogenetic analysis of this novel family showed that the Sm-7TM ORF formed a clade with exclusively invertebrate sequences. Based on topology modelling with ee3, Sm-7TM was predicted to possess an intracellular C-terminal tail, which was expressed as a soluble thioredoxin fusion protein (Sm-7TMC) in Escherichia coli and purified using metal ion-affinity chromatography. A polyclonal antiserum against this domain was used to detect Sm-7TM in detergent-soluble parasite extracts and to immunolocalize the receptor to the tegument of adult S. mansoni.

(+-)-N6-endonorbornan-2-yl-9-methyladenine (N-0861) and its enantiomers: selective antagonists of A1-adenosine receptors in guinea pig isolated atria.

Adenosine and its metabolically stable analog 5'-N-ethylcarbox-amidoadenosine (NECA) induce negative inotropic, chronotropic and dromotrpic actions in the heart through activation of A1-adenosine receptors and relaxation of vascular smooth muscle through activation of A2-adenosine receptors. In vitro studies were carried out in order to determine the potency of the antagonist (+-)-N6-endonorbornan-2-yl-9-methyladenine (N-0861) and its two component enantiomers, WRC-0006(+) and WRC-0007(-), at the A1 receptors in the guinea pig atria and the A2 receptors in the guinea pig aorta. N-0861 competitively antagonized the negative inotropic responses induced by NECA in the eletrically paced left atrium (pKB = 6.24) and the negative chronotropic responses induced by NECA in the spontaneously beating right atrium (pKB = 6.29). WRC-0007 was 4-fold more potent (pKB = 6.51) than WRC-0006 (pKB = 5.86) at antagonizing the A1-adenosine receptors in the guinea pig left atrium. N-0861, WRC-0007 and WRC-0006 at high concentrations (> 3 x 10(-5) M) produced direct relaxations of the guinea pig aorta that masked to a small extent the A2 receptor antagonism by these compounds. The affinities of the antagonists for the A2 receptor in the aorta were calculated using the method of pharmacological resultant analysis. N-0861 was 47-fold less potent at the A2 receptor (pKB = 4.57) than it was at the A1 receptor. WRC-0006 was 2-fold more potent (pKB = 4.81) than WRC-0007 (pKB = 4.52) at the A2-adenosine receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Sonographic assessment of infrarenal inferior vena caval dimensions.

The dimensions of the infrarenal inferior vena cava during quiet respiration, single leg lifting, and breath-holding were assessed using sonography in 156 patients. Sonographic assessment of infrarenal inferior vena caval dimensions was feasible in 69% of patients. Measurements during breath-holding were significantly greater than during quiet respiration (P < 0.001) and leg lifting (P < 0.005), although in approximately one quarter of the patients the mean calculated diameter was greatest during quiet respiration. we conclude that sonographic assessment of infrarenal inferior vena caval dimensions is feasible, but it should be performed during quiet respiration and breath-holding to allow for variation with different respiratory maneuvers.

Initial evaluation of a continuous speech recognition program for radiology.

The aims of this work were to measure the accuracy of one continuous speech recognition product and dependence on the speaker's gender and status as a native or nonnative English speaker, and evaluate the product's potential for routine use in transcribing radiology reports. IBM MedSpeak/Radiology software, version 1.1 was evaluated by 6 speakers. Two were nonnative English speakers, and 3 were men. Each speaker dictated a set of 12 reports. The reports included neurologic and body imaging examinations performed with 6 different modalities. The dictated and original report texts were compared, and error rates for overall, significant, and subtle significant errors were computed. Error rate dependence on modality, native English speaker status, and gender were evaluated by performing ttests. The overall error rate was 10.3 +/- 3.3%. No difference in accuracy between men and women was found; however, significant differences were seen for overall and significant errors when comparing native and nonnative English speakers (P = .009 and P = .008, respectively). The speech recognition software is approximately 90% accurate, and while practical implementation issues (rather than accuracy) currently limit routine use of this product throughout a radiology practice, application in niche areas such as the emergency room currently is being pursued. This methodology provides a convenient way to compare the initial accuracy of different speech recognition products, and changes in accuracy over time, in a detailed and sensitive manner.

Patients' desire for peri-operative information: Jamaican attitudes

The desire for peri-operative information has been examined in patients from other countries. This study was undertaken to assess the peri-operative information needs in Jamaican patients and to compare them to those from other populations. A questionnaire examining the desire for information about impending anaesthesia was administered to 93 patients awaiting elective surgery at the University Hospital of the West Indies. Responses were assessed across age and gender, and were compared to results from five industrialized countries. Although Jamaican patients expressed a desire for information concerning anaesthesia and surgery, they did not regard it as their right to get information, and this was the most important factor in the Jamaican sample providing a significantly less positive response than patients from other nations (p < 0.01 versus each country). Information priority was given to practical aspects of anaesthesia and post-operative outcome-mobility, pain, and the consumption of food and drink. Meeting the anesthetist was high on the list of desires. Female patients were 1.9 (Confidence Interval 1.4, 2.5) times more likely to express a positive desire for information. There were no age-related differences.

Paravertebral anaesthesia for breast surgery an initial experience at the University Hospital of the West Indies

Paravertebral blockade (PVB) is a regional anaesthetic technique that allows the injection of local anaesthetic agents into the paravertebral space. It has been used for acute and chronic pain relief and as an anaesthetic technique for unilateral surgery of the chest, breast, shoulder, kidney, and inguinal region. Paravertebral blockade has been performed on a limited basis for breast surgery at the University Hospital of the West Indies (UHWI) since 1998. This retrospective review was undertaken to report the initial experience with this block. We reviewed the notes of all patients who were given a PVB alone, or in combination with general anaesthesia (GA). Twenty-one patients had P VB: twenty females and one male, with age range of 24 to 90 years. Six were attempted with PVB alone, but two of these needed supplementation with a GA. Fifteen were done in combination with GA. No complications were recorded The initial experience shows that the performance of PVB is both possible and safe; it may offer an alternative to GA for breast surgery. A randomized prospective study is underway to allow a detailed comparison between the two methods