Metalloproteinase levels are decreased in symptomatic carotid plaques

BACKGROUND: Matrix metalloproteinase enzymes (MMP) have been identified in carotid atherosclerotic plaques, but their role in the development of clinical symptoms remains ill defined. We correlated the activity and levels of metalloproteinase enzymes and their inhibitors in human carotid plaques to ischemic neurologic events. METHODS: Carotid plaques were collected at the time of endarterectomy from 23 patients with carotid stenosis. Sixteen patients were asymptomatic and 7 patients had symptoms of stroke or transient ischemic attack within 6 weeks of surgery. Protein was extracted from the plaques, proteolytic activity was determined by gelatin zymography, and pro-MMP and tissue inhibitor of metalloproteinase (TIMP) enzyme content were measured by ELISA assay. Macrophage accumulation in the plaque was determined using immunohistochemistry. RESULTS: Plaques from symptomatic patients had decreased proteolytic activity on substrate gel zymography at the 62- and 92-kDa regions (corresponding to active MMP-2 and pro-MMP-9). A decrease in pro-MMP-9 (8.21 +/- 2.35 vs 17.42 +/- 3.14 ng, P < 0. 05) and an increase in TIMP-2 protein (12.62 +/- 0.58 vs 10.56 +/- 0. 77 ng, P < 0.05) were noted on ELISA in plaques from symptomatic patients. No difference was noted in macrophage accumulation in the plaques between the two groups. CONCLUSIONS: Plaques from patients who present with ischemic neurologic symptoms have decreased proteolytic activity associated with decreased pro-MMP-9 and increased TIMP-2 protein levels. These data suggest that metalloproteinase enzymes are not responsible for plaque instability in the carotid circulation and may in fact promote plaque stability.     

Comparison of radioiodinated TOC,TOCA and Mtr-TOCA: the effect of carbohydration on the pharmacokinetics

Although somatostatin-based peptide receptor imaging (sst-PRI) and peptide receptor radiotherapy (sst-PRRT) of human endocrine tumours and their metastases has become a valuable method, the experience with radiohalogenated sst-directed peptides has so far been disappointing. To extend the broad spectrum of radiohalogens with suitable radionuclide properties for sst-PRI and PRRT, new strategies in ligand development are required. The major drawbacks to be overcome include fast hepatic uptake, high abdominal background activity and low tumour uptake. Recently we introduced radiolabelled glycated octreotides as a new series of sst-binding radiotracers with excellent physicochemical characteristics. In this study we compared [(125)I]Tyr(3)-octreotide ([(125)I]TOC, ( 1)), [(125)I]Tyr(3)-octreotate ([(125)I]TOCA, ( 2)) and a carbohydrated octreotide derivative, maltotriose-[(125)I]Tyr(3)-octreotate ([(125)I]Mtr-TOCA, ( 3)) to evaluate the effect of single C-terminal oxidation and simultaneous N-terminal carbohydration. The biodistribution was compared in nude mice bearing AR42J tumour xenografts. Compared with ( 1), activity uptake of ( 2) and ( 3) at 1 h was decreased in intestine [36% ( 2), 72% ( 3)], liver [62% ( 2), 79% ( 3)] and kidney [34% ( 2), 41% ( 3)], respectively. Blood clearance was fast for all compounds investigated. Using ( 1) as reference, tumour uptake of ( 2) and ( 3) was 3.8- and 4.3-fold higher at 1 h p.i. At 1 h the tumour-to-blood ratio of ( 3) was 28.2+/-7.3, and the tumour-to-muscle ratio, 147+/-48. Specificity of tumour uptake was demonstrated in AR42J tumour-bearing mice by pretreatment with 0.8 mg TOC/kg 5 min prior to injection of ( 3). In cells transfected with sst1-sst5, the binding profile of I-Mtr-TOCA revealed a very high affinity and selectivity for sst2. In a first scintigraphic [(123)I]Mtr-TOCA study of a patient with a carcinoid of the small intestine with known peritoneal carcinomatosis and a solitary liver metastasis, all tumour tissues, including the liver metastasis, were well defined and clearly visible as soon as 30 min p.i. Based on these encouraging findings we conclude that carbohydration is a powerful strategy for the development of new radiolabelled sst-binding peptides and may represent a general method to improve pharmacokinetics of other peptide radioligands. [(123)I]Mtr-TOCA is a very promising new candidate for sst-directed PRI.     

Computer-aided intrapatient comparison of brain SPECT images: the gray-level normalization issue applied to children with epilepsy.

A tool was developed for automated intrapatient comparison of brain SPECT images, with specific emphasis on gray-level normalization. METHODS: Ictal and interictal (99m)Tc-ethyl cysteinate dimer SPECT images were acquired for 6 children with partial epilepsy (age range, 2-10 y). For each patient, 3-dimensional rigid geometric ictal-to-interictal image registration optimizing different classic criteria (correlation coefficient, ratio uniformity) in a multiscale translation-rotation 6-parameter space was first performed. Gray-level normalization was then performed with different methods, using a 1- or 2-parameter linear model. In the 1-parameter case, the scaling factor was equal to the interictal-to-ictal ratio of the maximum, mean, or median values calculated within different reference volumes (whole brain or cerebellum) or obtained by linear regression between ictal and interictal counts in the brain or by maximizing a robust criterion, the number of deterministic sign changes in the subtraction images. In the 2-parameter case, the scaling factor and additive constant were estimated using these last 2 methods. For each patient, registration validity and normalization plausibility were assessed by considering the correlation scatterplot together with the different normalization lines and by comparing interictal and registered normalized ictal images using a twin display (with isocontours) in the 3 orthogonal planes. Three-dimensional volumes of interest could be selected on coupled interictal-subtraction images for further focused numeric comparison. RESULTS: After a satisfactory and stable geometric registration with both criteria, the different normalization methods led to similar subtraction images for 5 of 6 patients, except the maxima ratio, which gave noticeably different results in 2 patients. For the remaining patient, with highly dissimilar ictal-interictal images, the maxima ratio normalization was obviously wrong and the other 1-parameter methods probably better depicted the data than did the 2-parameter methods. CONCLUSION: When comparing intrapatient brain SPECT images, one should be aware of the potential impact of the gray-level normalization method on clinical interpretation. For ictal-interictal images, simple robust scaling should be recommended. In particular, image maximum should generally not be considered a valid reference, and no additive constant is needed in the linear gray-level normalization model.     

Extra corporal membrane oxygenation in general thoracic surgery: a new single veno-venous cannulation

Extracorporeal membrane oxygenation (ECMO) is used in severe respiratory failure to maintain adequate gas exchange. So far, this technique has not been commonly used in general thoracic surgery. We present a case using ECMO for peri-operative airway management for pulmonary resection, using a novel single-site, internal jugular, veno-venous ECMO cannula.     

Unusual case of closed rupture of both extensor tendons of the index finger

Extensor tendon rupture is a common condition following penetrating injuries, whereas closed rupture is rare unless in a mallet finger. We describe an unusual case of closed rupture of both extensor tendons to the index finger. The extensor indicis proprius and extensor digitorum longus were avulsed proximal to the extensor retinaculum in a 23-year-old male patient due to forced hyperflexion of his index finger. Investigation was done in the Department of Orthopaedic Surgery at the Notre Dame Des Secours University Hospital, Byblos Lebanon.     

慢性阻塞性肺病稳定期患者家庭无创正压通气疗效分析

目的 研究慢性阻塞性肺病(COPD)稳定期患者长期家庭无创正压通气(NIPPV)治疗的意义.方法 回顾性分析2006～2007年法国Croix Rousse医院住院随访的接受NIPPV治疗的COPD稳定期慢性呼吸衰竭患者46例,比较患者治疗前和治疗后1、3、6、12、24和36个月的动脉血气变化;治疗前和治疗后6、12、24和36个月的肺功能改变.结果 患者应用NIPPV 1、3、6、12、24和36个月后的PaCO2较使用前皆显著下降(P均<0.05);1、3、12和36个月后的PaO2较使用前都显著升高(P均<0.05);而6、12、24和36个月后的肺功能第一秒用力呼气容积/用力呼气肺活量(FEV1/FVC)、FEV1占预计值%和FVC指标无明显改善,无统计学差异.结论 COPD稳定期长期家庭NIPPV治疗可改善血气、呼吸困难、头痛症状和提高生活质量,但在改善肺功能、延长生存期和降低死亡率方面的作用还有待进一步证实.     

<Emphasis Type=Italic>Mycobacterium tuberculosis</Emphasis> complex drug resistance pattern and identification of species causing tuberculosis in the West and Centre regions of Cameroon

Background  

Data on the levels of resistance of Mycobacterium tuberculosis complex (MTBC) strains to first line anti-tuberculosis drugs in Cameroon, and on the species of MTBC circulating in the country are obsolete. The picture about 10 years after the last studies, and 6 years after the re-organisation of the National Tuberculosis (TB) Control Programme (NTBCP) is not known.     

Culture-independent species typing of neotropical Leishmania for clinical validation of a PCR-based assay targeting heat shock protein 70 genes

PCR-restriction fragment length polymorphism analysis of heat shock protein 70 genes discriminates most neotropical Leishmania species, as well as Trypanosoma cruzi. The assay, combined with capillary electrophoresis in a microchip device, may be applied directly on clinical samples with a high sensitivity, hence supporting clinical and epidemiological monitoring of leishmaniasis.