Portal vein thrombosis: an emergency solution for blood flow in liver transplantation

Recipient portal vein thrombosis in liver transplantation is a contingency that increases surgical difficulty as well as patient morbidity and mortality. The aim of this paper is to demonstrate a surgical technique for reconstruction of portal blood flow in emergency situations of portal vein thrombosis with inadequate blood flow and a poor vascular bed for re-vascularization.     

Flow amperometric determination of pharmaceuticals with on-line electrode surface renewal

In this article, a flow system developed for the amperometric determination of a great variety of pharmaceuticals that are known to lead the rapid poisoning of the working electrode surface is described. The referred system was made up of two parallel flow channels that shared the voltammetric detector of tubular configuration, whose movement in the manifold followed the concept of multi-site location of detector. In this way, after each measurement, the conditioning of the working electrode was possible through the passage by its surface of a regeneration solution without implying the alteration of the carrier that flowed in the analytical channel of the manifold. The methodology proposed was evaluated through the determination of two drugs belonging to two distinct therapeutic groups: an antihypertensive (diltiazem) and a non-steroid anti-inflammatory (nimesulide). The results obtained after evaluation of various pharmaceutical formulations on the Portuguese market were in the case of diltiazem compared with those supplied by the reference US Pharmacopoeia XXIV method, with no statistically significant differences having been observed for a confidence interval of 95%. In the case of nimesulide, since no official reference method exists, a series of recovery experiments were proceeded with and a mean value of 101.1% with a R.S.D. of 0.7% was obtained.     

Temazepam,but not zolpidem,causes orthostatic hypotension in astronauts after spaceflight

Insomnia is a common symptom, not only in the adult population but also in many astronauts. Hypnotics, such as temazepam (a benzodiazepine) and zolpidem (an imidazopyridine), are often taken to relieve insomnia. Temazepam has been shown clinically to have hemodynamic side effects, particularly in the elderly; however, the mechanism is not clear. Zolpidem does not cause hemodynamic side effects. The purpose of this study was to determine whether the use of different hypnotics during spaceflight might contribute significantly to the high incidence of postflight orthostatic hypotension, and to compare the findings in astronauts with clinical research. Astronauts were separated into three groups: control (n = 40), temazepam (15 or 30 mg; n = 9), and zolpidem (5 or 10 mg; n = 8). In this study, temazepam and zolpidem were only taken the night before landing. The systolic and diastolic blood pressures and heart rates of the astronauts were measured during stand tests before spaceflight and on landing day. On landing day, systolic pressure decreased significantly and heart rate increased significantly in the temazepam group, but not in the control group or in the zolpidem group. Temazepam may aggravate orthostatic hypotension after spaceflight when astronauts are hemodynamically compromised. Temazepam should not be the initial choice as a sleeping aid for astronauts. These results in astronauts may help to explain the hemodynamic side effects in the elderly who are also compromised. Zolpidem may be a better choice as a sleeping aid in these populations.     

Use of admission Glasgow Coma Score, pupil size, and pupil reactivity to determine outcome for trauma patients

BACKGROUND: Determination of nonsurvival in trauma patients is difficult because valid prognostic indicators are lacking. It was hypothesized that patients presenting with a Glasgow Coma Score (GCS) of 3 as well as fixed and dilated (FD) pupils do not have a reasonable chance of survival. METHODS: From 1999 through 2001, adult trauma patients (age, >14 years) admitted with a GCS of 3 were reviewed. Patients receiving paralytic agents before initial assessment were excluded from analysis. Fixed and dilated pupils were defined as being 4 mm or more in diameter bilaterally and nonreactive to light. In this study, the FD patients were evaluated for survival, resuscitative measures, surgical procedures, length of hospital stay, and organ donation. The non-FD patients were evaluated for survival and length of hospital stay. RESULTS: Of the 137 patients evaluated with a GCS of 3, 104 had FD pupils and 33 did not. In the FD group, there were no survivors. On arrival, 28 (37.3%) of the patients were declared dead, and no further interventions were undertaken. Of the 76 patients (62.7%) who underwent further resuscitation, which included 53 surgical procedures, 30 died in the resuscitation bay, 39 within 24 hours, 4 within 48 hours, 2 within 72 hours, and 1 on day 6. There were 18 (23.7%) organ donors. Of the 33 patients without FD pupils, 11 (33%) survived to discharge (mean hospital stay, 21.4 days). Of the 22 nonsurvivors (67%), 10 died in the resuscitation bay, 8 within 24 hours, 1 within 48 hours, 1 on day 4, and 2 on day 6. CONCLUSIONS: Patients presenting with a GCS of 3 and FD pupils have no reasonable chance for survival. A significant percentage of these patients can be salvaged for organ donation. This information should be used in deciding to pursue aggressive resuscitation efforts and in discussing prognosis with family. Patients with a GCS of 3 who are not FD should be aggressively resuscitated because many of these patients survive to discharge.     

Modulation of endotoxin-induced endothelial activity by microtubule depolymerization

BACKGROUND: Endotoxin not only activates the Toll-mediated signaling pathway within endothelial cells that leads to neutrophil migration but also causes the polymerization of microtubules. The potential role of this polymerization event, however, is unknown. METHODS: Human umbilical vein endothelial cells stimulated with endotoxin were pretreated with or without the microtubule depolymerizing agent colchicine. Toll-mediated signaling events and protein production were in turn investigated by Western blot, gel shift, and enzyme-linked immunosorbent assay. Finally, neutrophil adhesion was assayed fluorometrically under the various conditions. RESULTS: Endotoxin led to activation of the various Toll-mediated pathways, production of intercellular adhesion molecule-1 and interleukin-8, and subsequent neutrophil adhesion. Pretreatment with colchicine led to selective inhibition of anti-dual phosphorylated extracellular signal-regulated kinase-1/2, anti-dual phosphorylated c-jun N-terminal kinase, and adaptor protein-1; selective enhancement of p38; and no effect on nuclear factor-kappaB. This selective modulation of intracellular signaling resulted in attenuated intercellular adhesion molecule-1, interleukin-8 and prostaglandin E2 production, but enhanced cyclooxygenase-2 expression. As a result, microtubule disruption led to a significant reduction in neutrophil adhesion. CONCLUSION: Microtubule formation is essential to optimal endotoxin-induced intracellular signaling through anti-dual phosphorylated extracellular signal-regulated kinase-1/2, anti-dual phosphorylated c-jun N-terminal kinase, and adaptor protein-1. Failure of these signaling events is associated with a marked reduction in the formation of a proadhesive phenotype that may prove to be beneficial in modulating neutrophil recruitment during sepsis.     

Synthesis and in vivo evaluation of novel radiotracers for the in vivo imaging of the norepinephrine transporter

The (R,R) and (S,S) enantiomers of 2-[(2-methoxyphenoxy)phenylmethyl]morpholine (MeNER) have been radiolabelled with carbon-11 in good yield and at high specific activity. These radiotracers are close analogues of reboxetine, a potent and selective ligand for the norepinephrine transporter (NET). They were examined as potential ligands for imaging NET in vivo by positron emission tomography (PET). The in vivo brain distribution of both [(11)C]-labeled enantiomers were evaluated in rats. Following tail-vein injection of the (R,R)-enantiomer regional brain uptake and washout of radioactivity was homogeneous at all time points examined (5-60 min). In contrast, administration of the (S,S)-enantiomer produced a heterogeneous distribution of radioactivity in brain with highest uptake in the hypothalamus, a NET rich region, and lowest uptake in the striatum, a brain region devoid of NET. Hypothalamus to striatum ratios of 2.5 to one were achieved at 60 min post injection of (S,S)-[(11)C]-MeNER. Pre-injection of the norepinephrine reuptake inhibitors, reboxetine or desipramine, reduced hypothalamus to striatum ratios to near unity while reuptake inhibitors of dopamine and serotonin had no significant effect on binding. In vitro autoradiography studies (rat brain slices) with (S,S)-[(11)C]-MeNER produced a regional distribution pattern that was consistent with the reported distribution of NET. (S,S)-[(11)C]-MeNER has the potential to be the first successful PET ligand to image NET.