A large multicenter study analysis of adverse events associated with single operator cholangiopancreatoscopy.

AIM: Cholangiopancreatoscopy (CP) is an endoscopic technique that allows for direct visualization of the biliary and pancreatic ducts using a narrow caliber endoscope that passes through the working channel of a duodenoscope directly into the bile and/or pancreatic ducts. Little data is available on the safety of CP. We performed a multicenter retrospective study to evaluate the frequency and severity of adverse events with single operator CP. METHODS: A multicenter retrospective study was conducted. RESULTS: A total of 282 single operator peroral CP procedures were performed in 224 patients (128 M, 96 F). Most procedures involved the performance of therapeutic maneuvers, with most cases including multiple therapeutic maneuvers. Cholangioscopic or pancreatoscopic-assisted tissue sampling was performed in 222 procedures. Thirty-seven patients underwent electrohydraulic lithotripsy (EHL) for the treatment of common bile duct stones. Adverse events in patients undergoing single cholangioscopy and pancreatoscopy included post-ERCP pancreatitis (N.=11, 3.9%, all mild), post-ERCP cholangitis (N.=4, 1.4%), bleeding (N.=3, 1%), and perforation (N.=2, 0.7%). CONCLUSION: Overall, our data shows that ERCP performed with single operator cholangioscopy or pancreatoscopy is safe with adverse events similar to that seen in large studies of ERCP performed without these additional techniques. Of note, vigorous irrigation of the bile ducts was not associated with increased rates of post-procedure cholangitis in our study.

Left ventricular mass as determined by magnetic resonance imaging in male endurance athletes.

Although many studies of the effect of dynamic exercise training on left ventricular (LV) mass have been reported, controversy continues to exist. Previous work has been criticized because of the techniques used for measuring LV mass, the variable level of training of the subjects recruited and the methods used to normalize the data. In an attempt to resolve this controversy, LV mass was determined using the very accurate and reproducible technique of magnetic resonance imaging (MRI). Highly trained competitive athletes including cross-country skiers, endurance cyclists and long distance runners (VO2max = 77 +/- 1, 72 +/- 2 and 75 +/- 2 ml (kg X min)-1, respectively) were examined. The data were normalized for body weight, body surface area and lean body mass. LV mass was significantly greater in skiers (239 +/- 9 g), runners (244 +/- 10 g) and cyclists (258 +/- 11 g) when compared with nonathletic control subjects (189 +/- 6 g) (p less than 0.001), which represents percent differences of 26, 29 and 37%, respectively. LV mass remained greater in the athletes, regardless of the method used to normalize the data. In addition, there was a good correlation between LV mass and VO2max (r = 0.80, p less than 0.001). It was concluded that LV mass is significantly greater in highly trained competitive endurance athletes and that normalizing LV mass with respect to body weight, body surface area or lean body mass does not alter this relation.

Influence of body size on oxygen consumption during bicycling.

Energy in bicycling is primarily expended to overcome air resistance, which is proportional to a cyclist's surface area (SA). Thus we hypothesized that large cyclists should have a lower O2 consumption normalized to body weight (VO2/BW) than small cyclists because of the former's lower SA/BW. We measured the VO2/BW of small (BW = 59.4 +/- 4.1 kg) and large (BW = 84.4 +/- 3.2 kg) cyclists while they bicycled on a flat road at 10, 15, and 20 mph. The large cyclists had a 22% lower VO2/BW than the small cyclists at all speeds. However, the SA/BW ratio of the large cyclists was only 11% lower than that of the small cyclists. We then photographically determined the frontal area (FA) of the cyclists in a racing posture, and found that the large cyclists had a 16% lower FA/BW ratio than the small cyclists. We conclude that large cyclists are at a distinct advantage, in terms of VO2/BW, while bicycling on level roads, and this advantage is principally due to their lower FA/BW ratio.

hNT neurons delay onset of motor deficits in a model of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron disease that manifests as a progressive muscular weakness leading to paralysis and death. Because of the diffuse nature of the motor neuron death, this disease is not considered a good candidate for treatment through neural transplantation. The purpose of this study was to show that transplantation of human neuron-like cells (hNT neurons) into the spinal cord of a transgenic ALS mouse model would improve motor deficits. The hNT neurons were transplanted bilaterally into L4-L5 spinal cord of the transgenic mice ( approximately 8 weeks of age), and the animals were evaluated on health and behavioral measures. The animals were perfused, and immunohistochemistry was performed to identify the transplanted cells. Transplantation of the hNT neurons into the spinal cord delayed the onset of motor behavioral symptoms. This was the first demonstration that even localized transplantation of neural cells directly into the parenchyma could improve motor function in an ALS model. Further study is needed to delineate the mechanism underlying these effects. This therapeutic approach has the potential to restore neural transmission, thereby improving quality of life for the ALS patient and possibly extend life expectancy.

In vitro and in vivo characterization of hNT neuron neurotransmitter phenotypes.

The hNT neuron exhibits many characteristics of neuroepithelial precursor cells, making them an excellent model to study neuronal plasticity in vitro and in vivo. These cells express a number of neurotransmitters in vitro, including dopamine, gamma-aminobutyric acid and acetylcholine. However, there have been few reports of the neurotransmitters that hNT neurons express in vivo. The present study examined whether hNT neurons express the same neurotransmitters in vivo as they do in vitro. First, the expression of tyrosine hydroxylase (TH), glutamic acid decarboxylase (GAD), choline acetyltransferase (ChAT) and the human specific nuclear marker NuMA by hNT neurons was confirmed. Nineteen normal animals were then transplanted with 80,000 hNT neurons aimed at the striatum, hippocampus or cerebral cortex. Five additional animals received injections of medium. All animals received daily intraperitoneal injections of cyclosporine (10 mg/kg) and survived 30 days. Sections through the transplants were examined for NuMA-positive hNT neurons, and for the presence of the three neurotransmitter markers: TH, GAD and ChAT. The hNT neurons were found in the striatum and cortex. Of the hNT neurons found within the rat striatum, 33% were ChAT-positive. In the cortex, only 4% of the neurons expressed ChAT. No GAD-positive hNT neurons were detected at either site. No NuMA-positive neurons were found in the hippocampus. The implanted hNT neurons did not induce activation of astrocytes as determined by immunocytochemistry for glial fibrillary acidic protein (GFAP). Moreover, no hNT neuron was found to express GFAP in vivo. Together, these data suggest that the hNT neurons engraft in the new host tissue, maintain their neuronal identity and may be guided in differentiation according to local environmental cues.

Plasma endothelin-1 during central hypovolaemia in man.

Endothelin-1 (ET-1) is a potent vasoconstricting peptide with effect on resistance as well as capacitance vessels. We followed ET-1 in arterial plasma together with heart rate (HR), central venous pressure (CVP), mean arterial pressure (MAP), and thoracic electrical impedance (TI) in seven men during central hypovolaemia induced by 50 degrees head-up tilt. During tilting plasma ET-1 increased from 1.1 +/- 0.2 to 1.4 +/- 0.3 pmol l-1 (mean +/- SE) concomitant with an increase in total peripheral resistance (TPR) (from 15 +/- 2 to 25 +/- 3 mmHg min l-1) (P < 0.01), and HR (from 67 +/- 2 to 94 +/- 5 beats min-1) (P < 0.01) while MAP remained unchanged. CVP decreased (from 1.8 +/- 0.9 to -1.6 +/- 1.0 mmHg) (P < 0.01) during tilting and remained unchanged during sustained tilt despite further reduction of central blood volume as recorded by TI. Presyncopal symptoms occurred after 28 +/- 6 min associated with decreases in HR (to 70 +/- 6 beats min-1), MAP (from 90 +/- 3 to 52 +/- 4 mmHg) and TPR (to 11 +/- 2 mmHg min l-1) (P < 0.01). At this time plasma ET-1 reached its highest level of 1.6 +/- 0.3 pmol l-1 (P < 0.01). Data show that head-up tilt is associated with increased plasma concentrations of ET-1 which may play a role in maintaining vascular tone in situations with a reduced central blood volume.

Intraspinal implantation of hNT neurons into SOD1 mice with apparent motor deficit.

INTRODUCTION: The aim of this study was to determine the effect of hNT neuron transplants on motor neuron function in SOD1 (G93A) mice when motor deficits were already apparent. METHOD: The hNT neurons were implanted into L(4)-L(5) segments of the ventral horn spinal cord of mice at 15-16 weeks of age: either G93A mice, transgenic mice carrying the normal allele for human SOD1 gene (hTg), or control wild type mice (wt). Behavioral tests (rotorod, beam balance, extension reflex, footprint) were performed prior to transplantation and at weekly intervals afterwards. RESULTS: HNT neuron transplantation in the SOD1 mice delayed disease progression for 3-4 weeks, although lifespan was not affected. CONCLUSION: These results suggest that hNT neuron transplantation may be a promising therapeutic strategy for ALS in the later phase of the neurodegeneration.

Estimation of human myocardial mass with MR imaging.

The accuracy and reproducibility of magnetic resonance (MR) imaging in the determination of left ventricular mass in humans was investigated. Left ventricular wall volume was measured from ten short-axis, end-diastolic MR images that spanned the left ventricle. Mass was estimated on the basis of average left ventricular wall volume and an assumed myocardial density. To establish the accuracy of the technique, the authors imaged ten cadaver hearts and compared true left ventricular weight with the mass estimate based on MR imaging findings. In vivo determination of left ventricular mass was evaluated in 40 subjects, with resultant calculated masses of 156.4-319.3 g. Intra- and interobserver variabilities of the technique were analyzed in ten subjects. Both the intra- (r = .96, standard error of estimate [SEE] = 11.1 g) and interobserver variabilities (r = .91, SEE = 17.8 g) were excellent. Eight subjects were imaged on two separate occasions to evaluate reproducibility of the technique and confidence limits for a given measurement. For these eight, there was good correlation between the two estimates (r = .93, SEE = 21 g). The authors conclude that MR imaging yields highly accurate and reproducible estimates of left ventricular mass in humans in vivo.

Intravenous versus intrastriatal cord blood administration in a rodent model of stroke.

Human umbilical cord blood (hUCB) is a rich source of hematopoietic stem cells that have been used to reconstitute immune cells and blood lineages. Cells from another hematopoietic source, bone marrow, have been found to differentiate into neural cells and are effective in the treatment of stroke. In this study, we administered hUCB cells intravenously into the femoral vein or directly into the striatum and assessed which route of cell administration produced the greatest behavioral recovery in rats with permanent middle cerebral artery occlusion (MCAO). All animals were immunosuppressed with cyclosporine (CSA). When spontaneous activity was measured using the Digiscan automated system, it was found to be significantly less when hUCB was transplanted 24 hr after stroke compared with nontransplanted, stroked animals (P < 0.01). Furthermore, behavioral recovery was similar with both striatal and femoral hUCB delivery. This is in contrast to the step test, in which significant improvements were found only after femoral delivery of the hUCB cells. In the passive avoidance test, transplanted animals learned the task faster than nontransplanted animals (P < 0.05). Together, these results suggest that hUCB transplantation may be an effective treatment for brain injuries, such as stroke, or neurodegenerative disorders. In addition, intravenous delivery may be more effective than striatal delivery in producing long-term functional benefits to the stroked animal.