Role of pentobarbitone anaesthesia and sympathetic tone in the haemodynamic effects of isosorbide dinitrate in rats with cirrhosis

The haemodynamic effects of nitrovasodilators and their mechanisms of action on portal hypertension remain unclear. The splanchnic and systemic haemodynamic response to the infusion of isosorbide dinitrate (100 μg/kg per min), a nitrovasodilator, was investigated in cirrhotic rats. The role of the conscious state in the haemodynamic response to isosorbide dinitrate was examined using rats that were anaesthetized with pentobarbitone. The role of sympathetic tone in the haemodynamic response to isosorbide dinitrate was examined using rats pretreated with the ganglion blocker hexamethonium. Isosorbide dinitrate had no haemodynamic effects in conscious, unblocked normal and cirrhotic rats. Isosorbide dinitrate had no haemodynamic effects in normal and cirrhotic rats treated with hexamethonium. In normal anaesthetized rats, isosorbide dinitrate significantly decreased systemic vascular resistance (414±25 vs 290±26 dyn.s/cm⁵ per 100 g). In cirrhotic anaesthetized rats, isosorbide dinitrate significantly decreased mean arterial pressure (98±6 vs 79±7 mmHg), systemic vascular resistance (318±30 vs 207±10 dyn.s/cm⁵ per 100 g), portal pressure (14.0±1.0 vs 11.3±0.9 mmHg) and portal territory vascular resistance (1362±163 vs 1031±182 dyn.s/cm⁵ per 100 g). In conclusion, this study shows that the portal hypotensive effects of isosorbide dinitrate depend upon the alterations of vascular tone by pentobarbitone.     

Infected Endocardial Pacemaker Electrodes: Successful Open Intracardiac Removal

The long-term results after open intracardiac removal of infected pacing electrodes are presented. Methods: between 1985 and 1990 open intracardiac removal of 19 infected pacing electrodes was performed in seven patients (six male and one femalel, with a mean age of 56 years. The indications were; persisting bacteremia in three; generator pocket infection in four; endocarditis in one; and ventricular tachycardia caused by retracted electrodes in one. All electrodes were fixed in the right heart and extraction by closed methods failed. Percutaneous catheter techniques were not applied in these seven patients. In five patients two ventricular electrodes had to be removed, and in two patients a single one. A total of seven atrial electrodes were removed in six patients (one electrode each in five patients; two electrodes in one patient). All atrial and two ventricular electrodes could be removed through a pursestring suture without use of a pump oxygenator. For the removal of ten ventricular electrodes in six patients (two electrodes each in four patients; 1 electrode each in two patients) a right-sided atriotomy was necessary with cardiopulmonary bypass (CPB). Simultaneously, five new pacing systems were implanted. Results; there were no early or late mortalities. In January 1991, all seven patients are alive and in a mean New York Heart Association Class 1,3 of heart failure after a mean interval of 33 months. In all cases the infection could be controlled with a simultaneous antimicrobial chemotherapy and the postoperative period was free of major complications. Conclusion; open intracardiac removal of retained pacing electrodes with or without use of CPB is a safe procedure without major complications. It is mandatory for all infected pacing electrodes that cannot be extracted by closed methods.     

Transradial Approach for Coronary Intervention: 25 Years for 25 Centimeters

The first series of transradial coronary angiograms was carried out by Lucien Campeau and published in 1989. The devices available at that time made the technique difficult to perform. Four years later, when stenting started being widely used with a significant rate of local complications induced by Coumadin treatment, F. Kiemeneij proposed the radial approach as a good alternative to the femoral approach to reduce the rate of local complications. Since then, the use of the radial approach has been increasing, though it remains limited. The first reason for this lies in the significant learning period that is all the longer as a low percentage of patients are treated via this approach. This is why we think it is preferable to perform at least 25% of all procedures, and especially coronary angiograms, through this approach before setting up a radial program. Patients with contraindications to the femoral approach (anticoagulation or GP IIb/IIIa inhibitors, obesity, aneurysm of the abdominal aorta, or vessel disease of the lower limbs, etc.) should be selected. The second reason is the small diameter of the radial artery that can generate a number of problems when large diameter guiding catheters are used (7Fr or 8Fr). However, the reduction in guiding‐catheter size, and the increasing use of 6Fr catheters should solve this problem. In our center, the femoral approach is usually selected when 7Fr or 8Fr catheters are used. It is to be noted that the radial approach is now widely used in some interventional cardiology centers where the learning period has been completed. With operator experience, puncture failure is extremely rare and the technical failure rate is around 1%, mainly due to the anatomic variations of the radial artery (antebrachial and humeral loops). Apart from the difficulties associated with the learning curve, the radial approach has few limitations. The procedure and x‐ray exposure times are slightly longer for coronary angiography but not for angioplasty. The risk of radial occlusion ranges from 2% to 5%, however, radial occlusion is asymptomatic in patients with a normal Allen's test. Conversely, the radial approach has many advantages. Patient comfort is significantly improved due to the ease of radial compression, ambulation is almost immediate, and the rate of local complications is almost nil. Same day discharge following coronary angiography and angioplasty can be considered. Finally, with the increasing use of GP IIb/IIIa inhibitors, sometimes in combination with thrombolysis in the treatment of myocardial infarction, the radial approach could become the preferred approach in this setting.     

Plasma concentrations of cyclic 3',5'-guanosine monophosphate in patients with cirrhosis: Relationship with atrial natriuretic peptide and haemodynamics

Little is known about the plasma concentrations of cyclic 3',5'-guanosine monophosphate (cGMP) in patients with cirrhosis. However, plasma cGMP concentrations provide information on cellular cGMP production by particulate guanylyl cyclases (which are stimulated by natriuretic peptides, such as atrial natriuretic peptide; ANP). In contrast, because intracellular cGMP elicits vasorelaxant mechanisms, plasma cGMP concentrations may be related to haemodynamic alterations in patients with cirrhosis. The aim of the present study was to measure plasma cGMP concentrations in patients with cirrhosis and controls and to examine the relationship between cGMP levels and plasma ANP concentrations and haemodynamic values. Plasma concentrations of cGMP and ANP and splanchnic and systemic haemodynamics were measured in 23 subjects; 13 subjects had cirrhosis and 10 were controls. All subjects had normal glomerular filtration. Plasma cGMP concentrations were significantly higher in patients (6.5±0.8 pmol/mL) than in controls (2.7±0.4 pmol/mL), while plasma ANP concentrations did not significantly differ between the two groups (127±22 and 123±27 pg/mL, respectively). In patients with cirrhosis, no significant correlation was found between plasma cGMP concentrations and plasma ANP concentrations, hepatic venous pressure gradient, cardiac output or systemic vascular resistance. In conclusion, in patients with cirrhosis, increased plasma cGMP concentrations may be due to an activation of particulate guanylyl cyclases by natriuretic peptides other than ANP. The present study suggests that plasma cGMP concentrations are not related to cirrhosis-induced haemodynamic alterations.     

Relationship between hepatic blood flow,liver tests,haemodynamic values and clinical characteristics in patients with chronic liver disease*

Although hepatic blood flow (HBF) has been measured in patients with liver disease for many years, the results of these studies have not provided clear information concerning the usefulness of this measurement. Hepatic blood flow was measured in 392 patients with either cirrhosis (n= 356) or hepatic fibrosis (n= 36). The control group included 59 subjects with normal liver architecture. Hepatic clearance of indocyanine green (ICG) was markedly reduced in patients with cirrhosis and hepatic fibrosis compared with controls (182±5, 276±22 and 421±25 mL/min, respectively). In patients with cirrhosis, ICG clearance and extraction were significantly correlated, but were not correlated to HBF. Although HBF did not differ between patients with cirrhosis and controls (1.26±0.04 vs 1.35±0.07 L/min, respectively), patients with hepatic fibrosis had lower HBF (1.04±0.07 L/min; P< 0.05). In patients with cirrhosis, no correlation was observed between HBF and cardiac output, mean arterial pressure, azygos blood flow, the hepatic venous pressure gradient or Pugh's score. However, a significant difference in HBF was observed in patients with and without hepatic encephalopathy (1.00±0.09 vs 1.28±0.03 L/min, respectively; P<0.05). In conclusion, the present study shows that, in patients with cirrhosis, HBF is normal and is not related to other haemodynamic values or liver tests. These results discourage the measurement of HBF in the evaluation of patients with cirrhosis.     

Biomarkers as non-invasive assessment of hepatic fibrosis in chronic hepatitis C

Abstract   Liver biopsy has been considered as the gold standard for assessing the stage and the grade of chronic liver diseases. Biopsy has a high sampling error (33% for fibrosis staging and 24% for necrosis staging), and intra- and interpathologist variability greater than 10%. Biochemical markers, particularly recent panels of markers (FibroTest-ActiTest) have good predictive values with a better benefit risk ratio and lower cost than liver biopsy. Discordances between biopsy and serological markers results can be either due to serological markers or to biopsy. Because of the improvement of biochemical markers, the limits and the risk of biopsy, liver biopsy should not be mandatory any longer in the management of patients with chronic liver hepatitis C.     

Selected Stro‐1‐enriched bone marrow stromal cells display a major suppressive effect on lymphocyte proliferation

Mesenchymal stem cells (MSCs) have an immunosuppressive effect and can inhibit the proliferation of alloreactive T cells in vitro and in vivo. Cotransplantation of MSCs and hematopoietic stem cells (HSCs) from HLA‐identical siblings has been shown to reduce the incidence of acute graft‐vs.‐host disease. MSCs are heterogeneous and data on the inhibitory effects of different MSC subsets are lacking. The antigen Stro1 is a marker for a pure primitive MSC subset. We investigated whether Stro‐1‐enriched induce a more significant suppressive effect on lymphocytes in a mixed lymphocyte reaction (MLR), and whether this action is related to a specific gene expression profile in Stro‐1‐enriched compared to other MSCs. We demonstrated that the Stro‐1‐enriched population elicits a significantly more profound dose‐dependent inhibition of lymphocyte proliferation in a MLR than MSCs. One thousand expanded Stro‐1‐enriched induced an inhibitory effect comparable to that of 10 times as many MSCs. Inhibition by Stro‐1‐enriched was more significant in contact‐dependent cultures than in noncontact‐dependant cultures at higher ratio. The Stro‐1‐enriched inhibitory effect in both culture types was linked to increased gene expression for soluble inhibitory factors such as interleukin‐8 (IL‐8), leukemia inhibitory factor (LIF), indoleamine oxidase (IDO), human leukocyte antigen‐G (HLA‐G), and vascular cell adhesion molecule (VCAM1). However, tumor growth factor‐β1 (TGF‐β) and IL‐10 were only up‐regulated in contact‐dependant cultures. These results may support using a purified Stro‐1‐enriched population to augment the suppressive effect in allogeneic transplantation.     

Severe childhood encephalopathy with dyskinesia and prolonged cognitive disturbances: evidence for anti‐N‐methyl‐d‐aspartate receptor encephalitis

Aim We report four cases of acquired severe encephalopathy with massive hyperkinesia, marked neurological and cognitive regression, sleep disturbance, prolonged mutism, and a remarkably delayed recovery (time to full recovery between 5 and 18mo) with an overall good outcome, and its association with anti‐N‐methyl‐d ‐aspartate (anti‐NMDA) receptor antibodies. Method We reviewed the four cases retrospectively and we also reviewed the literature. Results Anti‐NMDA receptor antibodies (without ovarian teratoma detected so far) were found in the two children tested in this study. Interpretation The clinical features are similar to those first reported in 1992 by Sebire et al., 1 and rarely recognized since. Sleep disturbance was not emphasized as part of the disorder, but appears to be an important feature, whereas coma is less certain and difficult to evaluate in this setting. The combination of symptoms, evolution (mainly seizures at onset), severity, paucity of abnormal laboratory findings, very slow recovery, and difficult management justify its recognition as a specific entity. The neuropathological substrate may be anatomically close to that involved in encephalitis lethargica, in which the same target functions (sleep and movement) are affected but in reverse, with hypersomnolence and bradykinesia. This syndrome closely resembles anti‐NMDA receptor encephalitis, which has been reported in adults and is often paraneoplastic.