药物涂层支架与金属裸支架对稳定型心绞痛患者局部冠状动脉循环组织因子水平早期影响的比较

目的比较药物涂层支架（DES）与金属裸支架（BMS）置入前后冠状动脉循环内局部血浆组织因子（TF）水平的变化,探讨DES对血浆TF水平的早期改变及其对急性支架内血栓（AST）形成的意义。方法入选稳定型心绞痛患者26例,按标准方法行冠状动脉造影证实有冠状动脉狭窄均在70%以上。其中15例置入DES（DES组）,11例置入BMS（BMS组）。全部患者术前给予阿司匹林、氯吡格雷口服,支架置入前静脉给予低分子质量肝素。PCI术中冠状动脉内血样采集顺序依次为：支架置入前后冠状动脉入口处（ostium）用引导导管,支架置入后15 min通过血栓吸引器穿过病灶在病灶下方（beyond the lesion）采血。血浆TF水平检测采用酶联免疫双抗体夹心法（ELISA）。结果PCI术前26例患者在冠状动脉入口处与病灶下方冠状动脉循环内的TF基线水平比较差异无统计学意义（31.50±7.05 ng/L比31.40±7.30 ng/L,P=0.748）,但高于正常参考值3倍;支架置入后15min在冠状动脉入口处（29.60±6.96 ng/L比31.50±7.05 ng/L,P=0.135）与病灶下方（30.70±7.70 ng/L比31.40±6.30 ng/L,P=0.230）冠状动脉循环内的TF水平与术前比较,差异亦无统计学意义。术后15min,DES组和BMS组冠状动脉入口处（31.20±4.37 ng/L比30.70±5.39 ng/L,P=0.674）及病灶下方（31.60±5.39 ng/L比29.00±7.96 ng/L,P=0.789）TF水平差异均无统计学意义。结论稳定型心绞痛患者冠状动脉循环血内存在大量的TF。DES和BMS两种支架均不引起冠状动脉内局部、早期血浆TF水平的改变。     

The significance of vasitis nodosa

Vasitis nodosa is an infrequently recognized, benign disorder that may be confused with malignancy of the vas deferens. A review of 30 patients with vasal masses removed during vasovasostomy revealed 20 men with vasitis nodosa. Of the patients 15 had vasal masses on physical examination, 1 of which was painful. Of the 20 patients with vasitis nodosa 14 had associated granulomatous inflammation. Vasitis nodosa is notably more common than has been reported previously and has been associated with spontaneous recanalization of the vas deferens following vasectomy.     

Psychiatric implications of presymptomatic testing for Huntington's disease

Responses of 69 at-risk individuals suggest that potential for psychiatric problems exists for those testing positive for the Huntington Disease gene and for their relatives. Their families were found to have high rates of psychiatric dysfunctions and suicide. Poorly developed social support networks and the psychological defensive strategies of many at-risk people may also contribute to post-test psychiatric morbidity. The active involvement of mental health professionals is emphasized.     

Neck contracture as a rare complication of cervical soft tissue expansion

An unusual complication using an inflatable silicon implant for removing postburn scarred tissue of the neck and face is described. The appearance of a fibrotic band along the inflating tube caused neck contructure. The purpose of this article is to present this uncommon complication and to emphasize the technical error when using the tissue expander in the neck region.     

Embryonic spinal cord neurons develop preferential cholinergic projections to sympathetic ganglia explanted from appropriate levels of the neuraxis

To determine whether cholinergic spinal cord neurons can develop preferential projections in vitro within sympathetic ganglia (SGs) of appropriate levels of the neuraxis, organotypic explants of fetal mouse spinal cord (E13) from cervical, thoracic (upper and lower) and lumbar segments were co-cultured with either pairs of neonatal SGs: the rostral superior cervical ganglion (SCG) or a caudally located upper lumbar ganglion (LG). After 3.5-4 weeks of co-culture, levels of the enzyme, choline acetyltransferase (ChAT), were measured in individual spinal cord explants and SCGs or double LGs (to match the target mass of a single SCG). Interaction was assumed to occur primarily between an SCG or LG doublet and the adjacent ipsilateral half of the co-cultured cord segment. An index of cholinergic interaction was defined as the ganglion ChAT activity per unit ChAT activity in half co-cultured cord segment. The index of interaction with the SCG was highest with the T1/T2 (1.4) as compared with the T10/T11 (0.79), L1/L2 (0.38) and C2/C3 (0.11) segments. In contrast, the index of cholinergic interaction with double LGs was highest with the more caudally located T10/T11 (0.62) cord segment as compared with the rostral T1/T2 (0.33), cervical C2/C3 (0.2) and lumbar L1/L2 (0.17) segments. Ganglion compound action potentials evoked in LGs by stimulation of the ipsilateral portion of T10/T11 cord were blocked by the ganglionic antagonist, hexamethonium, as previously observed in co-cultures of SCGs with T1/T2 cord. These results indicate that pools of preganglionic neurons in thoracic cord segments can develop in vitro preferential cholinergic projections within SGs of appropriate position. Cervical and lumbar cord segments which contain a preponderance of somatic motoneurons over preganglionic neurons did not interact as effectively with either type of SG. The preferential cholinergic projections from rostral thoracic cord explants within co-cultured SCGs and from caudal thoracic cord explants within co-cultured SCGs and from caudal thoracic cord explants within LGs may reflect some degree of positional preference intrinsic to embryonic spinal cord neurons and/or their appropriate target SGs, consistent with the positional specificity expressed by preganglionic neurons and SGs in situ.     

Biodegradable PLGA microparticles for sustained release of a new GnRH antagonist: part II. In vivo performance.

Poly (DL-lactide-co-glycolide) microparticles (MP) containing a highly potent peptidic gonadotropin releasing hormone antagonist (degarelix) of interest in the prostate cancer indication were screened for biological performance. Efficacy was tested in a castrated male rat model at 3 doses (0.4, 1.0 and 1.5 mg/kg) and assessed as inhibition of luteinizing hormone (LH) secretion. When increasing the dose, onset of inhibition was faster, inhibition was more intense, and duration of action was prolonged. The MP type was also highly influent. If spray-dried and microextrusion particles exhibited comparable potencies, double emulsion microspheres were significantly less potent, both for onset and duration of inhibition. Interestingly, for the latter type it was found that the degarelix fraction released upon reconstitution in the solution for injection was significantly lower (max 0.3%), in comparison to spray-dried MP (max 2%) or microextrusion (max 4%). With the three types of particles, increasing peptide content was detrimental for duration of action, but only little difference was noticed between particles based on different polymers. At 1.5 mg/kg, LH inhibition was achieved over 36 days with spray-dried MP based on 75/25 lactate/glycolate copolymer. This was superior by 1 week to the performance of unformulated degarelix given at the same dose.     

Serum alpha-fetoprotein: changes associated with acute and chronic ethanol ingestion in the resting and regenerating rat liver

The effect of acute and chronic ethanol consumption on serum alpha-fetoprotein was studied in adult male rats with resting and regenerating livers. Unlike many hepatotoxins, ethanol consumed over both the long and short term suppressed serum alpha-fetoprotein concentrations (p less than 0.05). This suppression was not due to increased degradation, since the half-life of alpha-fetoprotein was not significantly altered by chronic ethanol treatment. However, liver cytosolic alpha-fetoprotein was markedly increased after ethanol consumption, suggesting the presence of impaired secretion or mobilization from the liver cells. During liver regeneration following partial hepatectomy, alpha-fetoprotein increased in both the control (390 ng-hr/ml) and ethanol-treated animals (288 ng-hr/ml). At no time did the ethanol animal values equal the control levels. The change in serum alpha-fetoprotein showed an inverse exponential correlation with the amount of liver removed at hepatectomy and a positive correlation with the amount of nuclear DNA present at sacrifice. However, in the ethanol-treated animals it required the removal of 1.9 times as much liver to stimulate the same degree of liver regeneration as in the controls (p less than 0.001). A significant inverse correlation was observed between 3H-thymidine uptake and the areas under the alpha-fetoprotein time curves in the controls (p less than 0.001). In the ethanol groups the correlation was not statistically significant (p less than 0.2). It is concluded that although changes in serum alpha-fetoprotein may be associated with liver injury and regeneration, they are not a direct result of the regenerative process. The direct correlation with available nuclear DNA indicates the need for existing cells to hypertrophy and produce the alpha-fetoprotein. The depression associated with acute and chronic ethanol ingestion appears to reflect a direct effect of ethanol on protein synthesis and/or release.     

HIV-1 viremia prevents the establishment of interleukin 2-producing HIV-specific memory CD4+ T cells endowed with proliferative capacity

CD4+ T cell responses are associated with disease control in chronic viral infections. We analyzed human immunodeficiency virus (HIV)-specific responses in ten aviremic and eight viremic patients treated during primary HIV-1 infection and for up to 6 yr thereafter. Using a highly sensitive 5-(and-6)-carboxyfluorescein diacetate-succinimidyl ester-based proliferation assay, we observed that proliferative Gag and Nef peptide-specific CD4+ T cell responses were 30-fold higher in the aviremic patients. Two subsets of HIV-specific memory CD4+ T cells were identified in aviremic patients, CD45RA- CCR7+ central memory cells (Tcm) producing exclusively interleukin (IL)-2, and CD45RA- CCR7- effector memory cells (Tem) that produced both IL-2 and interferon (IFN)-gamma. In contrast, in viremic, therapy-failing patients, we found significant frequencies of Tem that unexpectedly produced exclusively IFN-gamma. Longitudinal analysis of HIV epitope-specific CD4+ T cells revealed that only cells that had the capacity to produce IL-2 persisted as long-term memory cells. In viremic patients the presence of IFN-gamma-producing cells was restricted to periods of elevated viremia. These findings suggest that long-term CD4+ T cell memory depends on IL-2-producing CD4+ T cells and that IFN-gamma only-producing cells are short lived. Our data favor a model whereby competent HIV-specific Tcm continuously arise in small numbers but under persistent antigenemia are rapidly induced to differentiate into IFN-gamma only-producing cells that lack self-renewal capacity.     

Plethysmographic dynamic indices predict fluid responsiveness in septic ventilated patients

Objectives In septic patients, reliable non-invasive predictors of fluid responsiveness are needed. We hypothesised that the respiratory changes in the amplitude of the plethysmographic pulse wave (ΔP_PLET) would allow the prediction of changes in cardiac index following volume administration in mechanically ventilated septic patients. Design Prospective clinical investigation. Setting An 11-bed hospital medical intensive care unit. Patients Twenty-three deeply sedated septic patients mechanically ventilated with tidal volume ≥ 8 ml/kg and equipped with an arterial catheter and a pulse oximetry plethysmographic sensor. Interventions Respiratory changes in pulse pressure (ΔPP), ΔP_PLET and cardiac index (transthoracic Doppler echocardiography) were determined before and after volume infusion of colloids (8 ml/kg). Measurements and main results Twenty-eight volume challenges were performed in 23 patients. Before volume expansion, ΔPP correlated with ΔP_PLET (r ² = 0.71, p < 0.001). Changes in cardiac index after volume expansion significantly (p < 0.001) correlated with baseline ΔPP (r ² = 0.76) and ΔP_PLET (r ² = 0.50). The patients were defined as responders to fluid challenge when cardiac index increased by at least 15% after the fluid challenge. Such an event occurred 18 times. Before volume challenge, a ΔPP value of 12% and a ΔP_PLET value of 14% allowed discrimination between responders and non-responders with sensitivity of 100% and 94% respectively and specificity of 70% and 80% respectively. Comparison of areas under the receiver operator characteristic curves showed that ΔPP and ΔP_PLET predicted similarly fluid responsiveness. Conclusion The present study found ΔP_PLET to be as accurate as ΔPP for predicting fluid responsiveness in mechanically ventilated septic patients. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. This work was performed in the Medical Intensive Care Unit, Centre Hospitalier, Belfort, France. Funding: No external funding