D2 lymphadenectomy in the management of gastric cancer

Background Gastric carcinoma is a significant cause of death in Ireland. Surgery offers the best option of cure, but the five-year survival following resection remains dismal at 10–15%. Experience from Japan and from some Western units suggest that an extended (D2) lymphadenectomy in association with gastrectomy increases the prospect of cure, but concern about the morbidity and mortality of this operation and lack of evidence from randomised studies has limited its acceptance. Aims This study reports the experience of a specialist upper gastrointestinal unit with D2 gastrectomy in a four-year audit. Methods Sixty-two resections were performed for gastric cancer. Results Nineteen patients were deemed unsuitable for the D2 procedure and underwent a more limited lymphadenectomy (DO or D1). Forty-three patients underwent D2 resection, 12 with an oesophagogastrectomy, 22 with total gastrectomy and nine with a sub-total distal resection. Eight patients undergoing D2 resection had extended resections, five with splenectomy and three with a distal pancreatectomy. Post-operative complications occurred in 31% of patients. Thirty-day and 90-day mortality were zero. Median survival was 822 days in the D2 group (range 120–1,320). Conclusions These results show that a D2 gastrectomy can be performed with a low morbidity and mortality and a median survival of greater than two years.     

ENDOTHELIAL CELL CULTURE AND SEEDING OF PROSTHETIC VASCULAR GRAFTS: AN EXPERIMENTAL STUDY

Current synthetic vascular prostheses do not acquire lining of vascular endothelium in humans or dogs. Endothelial seeding of vascular grafts has been proposed as a means of reducing the thrombogenicity of these grafts. We examined feasibility of cultivating endothelial cells (EC) by tissue culture technique and their subsequent seeding onto small diameter polytetra fluoroethylene (PTFE) grafts. Twenty adult dogs underwent common carotid artery interposition with 4 mm PTFE grafts. Ten dogs received seeded and the remaining ten received unseeded grafts. Grafts were removed at 4 and 12 weeks and their gross/morphological features compared. Cumulative patency rates for seeded grafts were 70% as compared to unseeded ones 30%. Seeded grafts were completely surfaced with a mono-layer of endothelium by 4 weeks. Small graft patency appears to be related to the establishment of an endothelial surface, the development of which is clearly facilitated by seeding with autogenous endothelium.KEY WORDS: Endothelial cell seeding, Vascular grafts     

Cloning of cDNA coding for connective tissue activating peptide III from a human platelet-derived lambda gt11 expression library

We report here the cloning of the cDNA coding for platelet connective tissue-activating peptide-III (CTAP-III) from a lambda gt11 expression library prepared using messenger RNA (mRNA) isolated from human platelets. The open reading frame of the clone coded for a protein with 128 amino acid residues. Since the precursor of CTAP-III, platelet basic protein (PBP is 94 amino acids long, the 5'-translated region of the cDNA codes for a leader sequence 34 amino acids long. This leader sequence, like the sequence of mature CTAP-III, shows significant homology to the sequence of platelet factor 4 (PF4), the only other platelet specific alpha-granule protein cloned until now, from a human erythroleukemic (HEL) cell line-derived cDNA library. These leader sequences are probably critical for targeting such proteins to the alpha-granule. Northern blot hybridization with platelet and megakaryocyte mRNA shows a single species mRNA of approximately 0.8 kb, suggesting that the corresponding cDNA is full length. The cloning of platelet specific CTAP-III provides additional evidence for the platelet specificity of the cDNA library used.     

Roles of mGluR5 in synaptic function and plasticity of the mouse thalamocortical pathway

The group I metabotropic glutamate receptor 5 (mGluR5) has been implicated in the development of cortical sensory maps. However, its precise roles in the synaptic function and plasticity of thalamocortical (TC) connections remain unknown. Here we first show that in mGluR5 knockout (KO) mice bred onto a C57BL6 background cytoarchitectonic differentiation into barrels is missing, but the representations for large whiskers are identifiable as clusters of TC afferents. The altered dendritic morphology of cortical layer IV spiny stellate neurons in mGluR5 KO mice implicates a role for mGluR5 in the dendritic morphogenesis of excitatory neurons. Next, in vivo single-unit recordings of whisker-evoked activity in mGluR5 KO adults demonstrated a preserved topographical organization of the whisker representation, but a significantly diminished temporal discrimination of center to surround whiskers in the responses of individual neurons. To evaluate synaptic function at TC synapses in mGluR5 KO mice, whole-cell voltage-clamp recording was conducted in acute TC brain slices prepared from postnatal day 4–11 mice. At mGluR5 KO TC synapses, N -methyl- d -aspartate (NMDA) currents decayed faster and synaptic strength was more easily reduced, but more difficult to strengthen by Hebbian-type pairing protocols, despite a normal developmental increase in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-mediated currents and presynaptic function. We have therefore demonstrated that mGluR5 is required for synaptic function/plasticity at TC synapses as barrels are forming, and we propose that these functional alterations at the TC synapse are the basis of the abnormal anatomical and functional development of the somatosensory cortex in the mGluR5 KO mouse.     

Pharmacokinetic and pharmacodynamic aspects of concomitant mibefradil-digoxin therapy at therapeutic doses.

This study investigated the effect of mibefradil on digoxin pharmacokinetics an pharmacodynamics. Following a loading dose of digoxin (0.375 mg, three times, day 1), 0.375 mg was administered once daily to 40 healthy subjects (days 2-15). Mibefradil was administered daily at 50 mg, 100 mg, or 150 mg (days 9-15). With co-administration of 50 mg or 100 mg mibefradil (the recommended doses), mean digoxin Cmax values increased 1.19- and 1.32-fold, respectively; Cmin values were 0.95- and 1.04-fold, respectively; mean AUC0-24 h increased 1.05- and 1.11-fold, respectively; and the total amount of digoxin excreted in urine remained unchanged. Digoxin monotherapy produced modest but transient prolongations of PQ interval, small decreases in heart rate, and no changes in blood pressure. With the addition of mibefradil, no effects on trough blood pressure or cardiac index were observed, but there was a further increase in PQ interval and decrease in heart rate. In a previous study, mibefradil had no significant effect on trough plasma digoxin concentration in patients with congestive heart failure and ischemia. Therefore, while the vast majority of patients should not need their digoxin dosages adjusted when given mibefradil, an occasional patient may require dose reductions based on clinical response and plasma digoxin.     

腘绳肌腱重建前交叉韧带移植肌腱的固定

目的:腘绳肌腱重建前交叉韧带曾出现过多种固定器材,分析近年来关于腘绳肌腱重建前交叉韧带的文献资料,了解肌腱固定方式的发展趋势。资料来源:通过计算机检索Medline1995-01/2006-09有关腘绳肌腱重建前交叉韧带移植肌腱固定方式的文献,检索词为“anteriorcruciate ligament,reconstruction,hamstring”,限定文章语言种类为English;另外检索中文期刊全文数据库2000-01/2006-03有关腘绳肌腱重建前交叉韧带移植肌腱固定方式的文献,检索词为“前交叉韧带,重建术,腘绳肌腱”,限定文章语言种类为中文。资料选择:选取有关腘绳肌腱重建前交叉韧带的文章,纳入标准:①随机或自身前后对照的临床研究。②观点明确。③有关于固定方式的评论。排除标准:①综述。②重复性研究。资料提炼:共检索到60篇关于腘绳肌腱重建前交叉韧带的文章,选择其中符合标准的33篇进行综合分析。资料综合:固定方式经历了一个由皮质骨外固定到骨隧道内固定的演变过程,Transfix是目前较为理想的固定方式,肌腱结嵌压固定是最新出现的一种固定方式,其临床效果尚需进一步验证。在固定位置的选择上,多数学者认为应该遵循等距重建。通过对固定方式的比较发现,隧道内固定能减轻术后骨隧道的扩大程度。结论:腘绳肌腱重建前交叉韧带的固定方法越来越趋于隧道内固定,并朝着利于腱骨愈合、减轻骨隧道扩大的方向发展。在固定位置的选择上,学者们尚无统一的意见,其趋势可能是向解剖固定发展。