JNK1 contributes to metabotropic glutamate receptor-dependent long-term depression and short-term synaptic plasticity in the mice area hippocampal CA1

Several recent reports implicate an important role played by c-Jun N-terminal kinases (JNKs) in long-term potentiation (LTP). However, little is known about how the isoforms of JNKs participate in synaptic plasticity. Here we showed that short-term synaptic plasticity was impaired in the hippocampal area CA1 of JNK1-deficient (JNK1-/-) mice; these mice showed normal LTP in response to a strong tetanus and no alteration of N-methyl-D-aspartate receptor-dependent long-term depression (LTD) in the hippocampus. However, LTD induced either by group I metabotropic glutamate receptors (mGluRs) agonist dihydroxyphenylglycine or by paired-pulse low-frequency stimulation was absent in both the JNK1-/- slices and in JNK inhibitor anthrax [1, 9-cd] pyrazol-6(2H)-1 (SP600125)-pretreated slices. Induction of mGluR-dependent LTD resulted in an increase in phosphorylation of JNK1 substrates, including p-c-Jun and p-ATF2 in wild-type (WT) mice, and these increases failed to occur in the JNK1-/- or SP600125-pretreated mice. These results demonstrated that JNK1 played a crucial role in the short-term synaptic plasticity and mGluR-dependent LTD, whereas hippocampus LTP was not affected by JNK1 deficiency.     

Influence of VEGF-A gene variation and protein levels in breast cancer susceptibility and severity

Vascular endothelial growth factor-A (VEGF-A) plays an important role in tumour angiogenesis and cancer progression. VEGF gene variation may influence VEGF levels and therefore cancer susceptibility and progression. We studied the role of VEGF single nucleotide polymorphisms and haplotypes in breast cancer susceptibility and severity. We also studied the relationships of VEGF SNPs with circulating VEGF levels in healthy volunteers and protein expression in breast cancers. Single nucleotide polymorphisms (SNPs) in the regulatory regions of the VEGF gene were genotyped by high throughput methods in approximately 500 breast cancer cases and 500 appropriate controls. Haplotype frequencies were inferred using methods based on the Expectation Maximisation algorithm. The effect of VEGF genotypes on serum and plasma VEGF levels were studied in another cohort of healthy individuals. A semi-quantitative assessment of VEGF protein expression on tissue micro arrays (TMA) constructed from approximately 300 breast cancer samples was performed and compared with VEGF genotypes and with histopathological parameters and survival in breast cancer. The -460T/+405C/-7C/936C haplotype in the VEGF gene was found to be associated with decreased breast cancer risk (p = 0.029). The -7C>T polymorphism may influence overall breast cancer survival (p = 0.027). Individual polymorphisms however did not affect breast cancer susceptibility. There was no association between the individual polymorphisms and circulating VEGF levels in healthy volunteers and VEGF expression on the breast cancer micro array. VEGF expression in breast cancers was however associated with high grade (p = 0.002) and ER negative tumours (p = 0.03).     

Tube pedicle flap in the management of a Grade III C lower limb injury.

Salvage of a Grade III C lower limb injury is a challenging problem. Apart from microsurgical revascularisation, they frequently need soft tissue coverage procedures. Due to the magnitude of the injury, local flaps from adjacent tissues may not be available and microsurgical free flaps are the flaps of choice. We present an instance where the defect in the middle third of a revascularised leg was covered by a tube pedicle flap raised from the groin and transferred, with the wrist as the carrier. This was chosen because of the below knee amputation on the opposite side combined with long segment circumferential loss of skin in the affected extremity and paucity of vein graft sources. Thus the reconstruction of a limb which was saved by microsurgery was completed by tube pedicle flap. In exceptional circumstances 'old' techniques are still useful.     

Microsurgery in the urgent and emergent management of the hand

Appropriate use of microsurgical techniques in the emergency management of injured hands increases the salvage rate of complex upper limb injuries. Over time, the indications for replantation, both major and minor, have expanded and techniques refined to get better functional outcomes. The wide choice of free flaps available has made primary reconstruction possible to obtain a good functional and aesthetic outcome. The benefits microsurgery offers in the emergent management of the injured hand are now firmly established. The challenge is to create and maintain centers which can provide around-the-clock, high quality microsurgery services. The issues of adequate training opportunities, obtaining adequate work load to maintain high skill levels, attracting talent into the field are the challenges faced in maintaining high levels of service. In the developing countries, in addition to these issues, increasing the awareness of the potential of microsurgical services among the medical personal and the public has to be addressed.     

Right precordial and posterior electrocardiographic leads do not increase detection of ischemia in low-risk patients presenting with chest pain

BACKGROUND: A number of innovative approaches have been investigated for their value in the early detection of acute ischemia or infarction in patients presenting to the emergency department (ED) with chest pain suggestive of a cardiac origin. Prior investigations have demonstrated the utility of adding right precordial and posterior chest leads to the standard 12-lead electrocardiogram (ECG) for identifying right ventricular and posterior wall infarctions in the ED. HYPOTHESIS: To assess the utility of additional ECG leads in low-risk patients presenting to the ED with symptoms suggestive of acute coronary syndromes who are managed in a chest pain evaluation unit (CPEU). METHODS: We studied low-risk patients who presented to the ED with chest pain compatible with myocardial ischemia. Low-risk patients were identified by a normal 12-lead ECG, no arrhythmias or hemodynamic instability, and one negative serum cardiac troponin I. Patients were admitted to the CPEU where a 16-lead ECG was recorded by the addition of 2 right-sided precordial leads (V4R, V5R) and 2 posterior leads (V8, V9) to the standard 12-lead ECG. RESULTS: The 16-lead ECG system was applied to 316 consecutive patients. The study group was a middle-aged population with equal numbers of men and women and an average of 2 cardiac risk factors per patient. The 16-lead ECG demonstrated evidence of myocardial injury in only 1 patient and no evidence of ischemia in any of the 316 patients. CONCLUSION: In patients presenting to the ED with chest pain and evidence of low clinical risk by our criteria, the addition of both right-sided precordial and posterior chest leads to the standard 12-lead ECG did not provide additional information for risk stratification.     

Synovitis of the wrist joint caused by an intraarticular perforation of an osteoid osteoma of the scaphoid

Uncommon location and atypical presentation of the osteoid osteomas of the scaphoid can pose a diagnostic challenge. Because of its intraarticular location, scaphoid osteoid osteoma can present with synovitis which is the more commonly reported presentation for other intraarticular locations like in hip and elbow and only rarely reported at the wrist. We report a case of perforation of the osteoid osteoma into the wrist joint, resulting in exuberant synovitis. The clinical significance of this report is to reinforce that synovitis can be a presentation of osteoid osteoma and it should be considered in the differential diagnosis of monoarticular arthritis. Prolonged synovitis may cause damage to the other joint surfaces of the wrist and hence carpal osteoid osteoma should be considered for early surgical excision.     

Severe congenital hypoplasia of tongue and abnormal shape of soft palate and tonsillar pillars

Summary This paper describes an 8-year-old boy who presented with the very rare condition of congenital right-sided aglossia. The left side of tongue was hypoplastic and tethered to the floor of the mouth. The soft palate was short and almost absent on the right side with abnormal positioning of the right anterior and posterior tonsillar pillars; this situation resulted in significant velopharyngeal incompetence (VPI). The left mandible was slightly hypoplastic with anodontia posterior to the first premolar tooth. There has been no previous report of a similar defect. The possible differential diagnoses related to the abnormality are discussed. The correction of the VPI is presented to demonstrate the versatility of the sphincter pharyngoplasty.