Quality of life after single-incision laparoscopic cholecystectomy: A randomized,clinical trial

Background

Controversy continues as to whether single-incision laparoscopic cholecystectomy, with the somewhat larger incision at the umbilicus, may lead to a worse postoperative quality of life and more pain compared with the more classic 4-port laparoscopic cholecystectomy. The aim of this study was to compare single-incision and 4-port laparoscopic cholecystectomy from the perspective of quality of life.

Genetic variations of HSD11B2 in hypertensive patients and in the general population, six rare missense/frameshift mutations.

Mutations in the gene encoding 11beta-hydroxysteroid dehydrogenase type 2, HSD11B2, cause a rare monogenic juvenile hypertensive syndrome called apparent mineralocorticoid excess (AME). In AME, defective HSD11B2 enzyme activity results in overstimulation of the mineralocorticoid receptor (MR) by cortisol, causing sodium retention, hypokalemia, and salt-dependent hypertension. Here, we have studied whether genetic variations in HDS11B2 are implicated in essential hypertension in Japanese hypertensives and the general population. By sequencing the entire coding region and the promoter region of HDS11B2 in 953 Japanese hypertensives, we identified five missense mutations in 11 patients (L14F, n = 5; R74H, n = 1; R147H, n = 3; T156I, n = 1; R335H, n = 1) and one novel frameshift mutation (4884Gdel, n = 1) in a heterozygous state, in addition to 19 genetic variations. All genetic variations identified were rare, with minor allele frequencies less than 0.005. Four of 12 patients with the missense/frameshift mutations showed renal failure. Four missense mutations, L14F, R74H, R147H, and R335H, were successfully genotyped in the general population, with a sample size of 3,655 individuals (2,175 normotensives and 1,480 hypertensives). Mutations L14F, R74H, R147H, and R335H were identified in hypertensives (n = 6, 8, 3, and 0, respectively) and normotensives (n = 8, 12, 5, and 0, respectively) with a similar frequency, suggesting that these missense mutations may not strongly affect the etiology of essential hypertension. Since the allele frequency of all of the genetic variations identified in this study was rare, an association study was not conducted. Taken together, our results indicate that missense mutations in HSD11B2 do not substantially contribute to essential hypertension in Japanese.     

Immunohistochemical analysis of TrkA neurotrophin receptor expression in human non-neuronal carcinomas

The Trk family of tyrosine protein kinase receptors plays a significant role in the development and maintenance of neural tissues. It has been recently shown that Trk receptors are also expressed by a wide range of normal non-neuronal tissues in humans in a cell type-specific manner. In the present study, the expression patterns of TrkA in 337 non-neuronal invasive carcinomas of 15 different human tissues were investigated immunohistochemically. Overall, 133 (39%), 101 (30%) and 103 (31%) tumors exhibited strong, moderate and no TrkA Immunoreactivity, respectively. Esophageal and thyroid carcinomas expressed high levels of TrkA, whereas the levels in gastric and colon cancers were low. TrkA expression was detected not only in carcinomas originating from TrkA-positive normal counterpart tissues, Including the esophagus, breast, lung and uterus, but also in those from TrkA-negative tissues/cells of the thyroid, liver and ovary. Immunostaining for nerve growth factor-β, the specific ligand for TrkA, in esophageal and breast carcinomas demonstrated its immunoreactivity in stromal fibroblasts and some TrkA-expressing tumor cells. These results suggest that paracrine/autocrine regulation via stromal/tumoral NGF-tumoral TrkA interaction may be involved In the growth of certain non-neuronal carcinomas.     

Induction of endothelium-dependent relaxation in the rat aorta by IRL 1620, a novel and selective agonist at the endothelin ETB receptor.

1. The effects of a novel and selective agonist at the endothelin ETB receptor, IRL 1620 (Suc-[Glu9, Ala11,15] endothelin-1 (8-21)), were examined in the isolated aorta of the rat. 2. IRL 1620 (1-300 nM) changed neither the resting tone nor the cytosolic Ca2+ level ([Ca2+]i) of the aorta without endothelium. In the presence of endothelium, however, IRL 1620 increased endothelial [Ca2+]i with little effect on the muscle tone. In the absence of external Ca2+, IRL 1620 still induced a transient increase in endothelial [Ca2+]i. 3. Noradrenaline (100 nM) increased both muscle [Ca2+]i and tension. IRL 1620 (1-300 nM) relaxed the muscle with an increase in endothelial [Ca2+]i only in the presence of endothelium. An inhibitor of nitric oxide synthase, 100 microM NG-monomethyl-L-arginine, inhibited the relaxant effect of IRL 1620 but not the increase in endothelial [Ca2+]i. 4. In resting and noradrenaline-stimulated aorta, the effects of IRL 1620 were inhibited by a selective antagonist of the ETB receptor, IRL 1038 (0.3-3 microM), although a selective antagonist of the ETA receptor, BQ-123 (3 microM), was ineffective. Verapamil (10 microM) did not alter the effects of IRL 1620. 5. A muscarinic receptor agonist, carbachol (1 microM), also induced endothelium-dependent relaxation with an increase in endothelial [Ca2+]i. However, the effects of carbachol were not inhibited by the ETB antagonist, IRL 1038 (3 microM).(ABSTRACT TRUNCATED AT 250 WORDS)     

Prenatal diagnosis of Werdnig Hoffmann disease in China

Objective To establish a means for prenatal prediction of spinal muscular atrophy (SMA) through survival motor neuron (SMN) gene deletion analysis and genetic counseling in families with a child affected with SMA.
Methods Genetic analysis for prenatal prediction of Werdnig-Hoffmann disease was performed in a at risk Chinese family by polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) in SMN gene exons 7 and 8.
Results The pregnancy was positive for the homozygous deletion of the SMN gene, thus the fetus was diagnosed as being affected and the pregnancy was terminated.
Conclusion This approach is fast and reliable for DNA-based prenatal diagnosis of Werdnig-Hoffmann disease.     

Initial steroid bolus injection promotes vigorous CD8+ alloreactive responses toward early graft acceptance immediately after liver transplantation in humans.

We have found that steroid bolus withdrawal prior to graft reperfusion increased the incidence of acute cellular rejection (ACR). This study aims to clarify how initial steroid bolus (ISB) injection at reperfusion influences the kinetics of CD8(+) alloreactive immune responses immediately after living donor liver transplantation (LDLT). A total of 49 hepatitis C virus (HCV)-infected recipients were classified into 3 groups according to hierarchical clustering by preoperative CD8(+)CD45 isoforms. The naive T cell proportion was considerably higher in Group I than in Groups II and III, whereas Group II recipients had the highest effector memory (EM) T cells and Group III the highest effector T cells. The frequency of ACR was significantly higher in recipients without ISB than in those with ISB. In particular, the ACR rates were the highest in Group II without ISB. Following ISB, the proportion of effector T cells was promptly upregulated within 6 hours after graft reperfusion, simultaneously with the upregulation of CD27(-)CD28(-) subsets, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha and perforin expression, which significantly correlated with increasing interleukin (IL)-12 receptor beta 1 cells. These were then downregulated to below preoperative levels by tacrolimus (Tac) administered at 24 hours. These changes did not occur in the absence of ISB. In Group II without ISB, the downregulation of IL-12Rbeta1(+) cells was the greatest, consistent with the highest rates of ACR and mortality (60%). In conclusion, ISB must be done in place, especially in Group II with preexisting high EM T cells, to enable the development of early allograft acceptance.