Strain patterns in primary mitral regurgitation due to rheumatic heart disease and mitral valve prolapse

ObjectiveLeft atrial (LA) and left ventricular (LV) remodelling are the adaptive changes that occur in primary mitral regurgitation (MR) and are related to its clinical outcomes. Despite the pathophysiological differences in MR in rheumatic heart disease (RHD) and mitral valve prolapse (MVP), whether the pattern of LV and LA remodelling is different between the two conditions remains unknown. Hence, we compared the LA and LV strain pattern in MR due to RHD, the predominant etiology in developing countries topatients with MVP and age and sex-matched controls.MethodsA total of 50 patients of severe MR which included 30 MVP MR and 20 RHD MR were assessed by strain imaging by speckle tracking echocardiography (STE) and were compared with age and sex-matched controls. 2D STE was used for LA and 3D STE was used for LV strain analysis. LA and LV strain parameters were compared between MVP MR and RHD MR groups.Results30 patients with MVP and 20 with RHD were studied. 60% (n = 30) were symptomatic. Mean GLS was ?17.2 ± 4.4% compared to ?20 ± 3.2% among controls and mean LA strain was 17.35 ± 10.3% compared to 51.34 ± 11.5% among controls which were significantly lower (both p < 0.01). No significant difference in LA strain and GLS was found between MVP and RHD subgroups (LA strain 20.45 ± 11.9% and 14.63 ± 8.85%; p = 0.08; GLS - 18.25 ± 4.3% and-16.2 ± 4.6%; p = 0.12). PALS in the RHD group was lower compared to MVP(p = 0.08) which showed a trend towards significance. LV strain parameters showed no significant difference among the MVP and RHD groups.ConclusionLA and LV strain parameters showed no significant difference in MR due to either RHD or MVP. There was a trend towards lower LA strain in RHD which needs validation with large multicentric studies. The current strain parameters from MVP with the prognostic value may be applied to MR of RHD etiology, pending confirmation of our results by other groups.     

Annual Review of Advances in Lung Cancer Clinical Research: A Report for the Year 2009

The use of positron emission tomography compared with conventional staging increases the detection of extrathoracic metastases and reduces the number futile thoracotomies in patients being evaluated for surgical resection. Long-term follow-up of one of the two adjuvant chemotherapy trials revealed a continued overall survival (OS) benefit to adjuvant chemotherapy. In locally advanced non-small cell lung cancer, a phase III trial of chemoradiotherapy alone and with surgical resection revealed no statistically significant difference in OS between the treatment arms. In advanced stage non-small cell lung cancer, a phase III trial compared gefitinib with carboplatin and paclitaxel in a clinically enriched patient population for epidermal growth factor receptor (EGFR) tyrosine kinase (TK) mutations; among patients with an EGFR TK mutation, patients in gefitinib arm compared with carboplatin and paclitaxel arm experienced a statistically significant superior response rate and progression-free survival, and among patients without EGFR TK mutation patients in the gefitinib arm compared with carboplatin and paclitaxel experienced a statistically significant inferior response rate and progression-free survival. A phase III trial of platinum-based therapy with and without cetuximab in the first-line setting revealed improved OS in the cetuximab arm. A phase III trial of maintenance pemetrexed compared with placebo in patients who had not progressed after initial platinum-based therapy revealed an improvement in OS of patients in the pemetrexed arm with nonsquamous histology. In limited-stage small cell lung cancer, a phase III trial compared standard and high-dose prophylactic cranial irradiation and revealed no significant difference in the rate of brain metastases between the two treatment arms.     

Rapid as well as delayed inhibitory effects of glucocorticoid hormones on pituitary adrenocorticotropic hormone release are mediated by type II glucocorticoid receptors and require newly synthesized messenger ribonucleic acid as well as protein

Glucocorticoid hormones suppress the release of ACTH by the anterior pituitary gland: rapid feedback inhibits hormone secretion within 30 min of steroid application, delayed feedback is most effective at 1-2 h, and slow feedback becomes manifest in several hours. The aim of the present study was to determine the type of glucocorticoid receptor that mediates the rapid and delayed feedback actions of glucocorticoids and whether genomic activation occurs during the rapid and delayed time domains. Rat anterior pituitary cell columns were perfused with Dulbecco's minimum essential medium, 41-residue CRF (10(-9) M) was used as the secretagogue, which stimulated ACTH secretion to a peak of about 8- to 10-fold of basal release. The amount of ACTH released upon repeated 5 or 10 min stimulation with CRF was constant. Treatment with 10(-7) M corticosterone for 20 min immediately before and for 10 min during stimulation with CRF reduced ACTH release by about 50% (rapid feedback), while at 1 h and 2 h after the initial exposure to corticosterone the secretory response was 33% and 15% of control, respectively. The effect of corticosterone was prevented by the type II glucocorticoid/progesterone antagonist RU 38486 (10(-6) M). The selective type II receptor agonist RU 28362 (10(-7) M) was even more potent than corticosterone in inhibiting ACTH release; the time course of action was similar. When actinomycin D (10(-4) M) was applied in conjunction with RU28362 or corticosterone, no inhibitory effects appeared up to 2 h after the exposure to steroid. Puromycin (10(-4) M), given during and for 1 h after the administration of the steroid prevented the rapid as well as the delayed (1 h) inhibitory action of RU28362. When puromycin was removed from the system, a 75% inhibition of stimulated ACTH release developed at 2 h after the application of the steroid, indicating that translatable messenger RNA (mRNA) was still present in the cells. Cycloheximide (10(-4) M) was only partially effective at inhibiting rapid or delayed feedback, and increasing its concentration impaired the ACTH response to CRF-41. In summary, at the pituitary level the rapid as well as the delayed feedback inhibition of ACTH secretion by adrenal corticoids is exerted via type II glucocorticoid receptors. Furthermore, both rapid and delayed feedback require the synthesis of new mRNA and protein.     

Primary myxopapillary ependymoma of the fourth ventricle with cartilaginous metaplasia: a case report and review of the literature

Myxopapillary ependymoma (MPE), which is a benign histological subtype of ependymoma, is found predominantly in the cauda equina region. It occurs rarely in the brain and mostly as a metastatic deposit from a spinal lesion. The occurrence of primary intracranial MPE is exceptional, with only 11 cases reported to date. We report an additional case of intracranial MPE, which is the third reported case in the fourth ventricle. The tumor manifested in a 50-year-old lady, who presented with features of raised intracranial pressure. A gross total resection of the tumor was achieved. Histologically, the tumor had characteristic features of MPE with focal metaplastic cartilaginous deposit. On further evaluation, there was no evidence of a primary tumor in the spinal cord. Intracranial MPE needs further evaluation by craniospinal MRI to exclude an unrecognized primary in the spinal region, which could warrant surgical attention.     

Diffusion tensor analysis of temporal and extra-temporal lobe tracts in temporal lobe epilepsy

OBJECTIVE: To determine whether the major temporal lobe white matter tracts in patients with temporal lobe epilepsy manifest abnormal water diffusion properties. METHODS: Diffusion tensor MRI measurements were obtained from tractography for uncinate, arcuate, inferior longitudinal fasciculi and corticospinal tract in 13 children with left temporal lobe epilepsy and normal conventional MRI, and the data were compared to measurements in 12 age-matched normal volunteers. The relationship between tensor parameters and duration of epilepsy was also determined. RESULTS: All four tracts in the affected left hemisphere showed lower mean anisotropy, planar and linear indices, but higher spherical index in patients versus controls. Diffusion changes in the left uncinate and arcuate fasciculus correlated significantly with duration of epilepsy. Arcuate fasciculus showed a reversal of the normal left-right asymmetry. Various diffusion abnormalities were also seen in the four tracts studied in the right hemisphere. CONCLUSION: Our findings indicate abnormal water diffusion in temporal lobe and extra-temporal lobe tracts with robust changes in the direction perpendicular to the axons. Diffusion abnormalities associated with duration of epilepsy suggest progressive changes in ipsilateral uncinate and arcuate fasciculus due to chronic seizure activity. Finally, our results in arcuate fasciculus are consistent with language reorganization to the contralateral right hemisphere.     

Physiological studies of stress responses in the hypothalamus of vasopressin-enhanced green fluorescent protein transgenic rat

Arginine vasopressin (AVP) plays an important role in stress-induced activation of the hypothalamic-pituitary adrenal axis. In the present study, AVP-enhanced green fluorescent protein (eGFP) transgenic rats were used to investigate changes in AVP-eGFP expression in the hypothalamic paraventricular nucleus (PVN) and the median eminence (ME) upon exposure to stress conditions. The eGFP fluorescence in the parvocellular division of the PVN (pPVN) was markedly increased 5 days after bilateral adrenalectomy (ADX) and it was colocalised with corticotrophin-releasing hormone-like immunoreactivity in the pPVN. Peripheral administration of dexamethasone completely suppressed the increase of eGFP fluorescence in the pPVN and the external layer of the ME (eME) after bilateral ADX. Significant increases of eGFP fluorescence were observed in the pPVN 6, 12, 24 and 48 h after intraperitoneal (i.p.) administration of lipopolysaccharide (LPS). In the eME, eGFP fluorescence was significantly increased 48 h after i.p. administration of LPS. By contrast, eGFP fluorescence changed neither in the magnocellular division of the PVN, nor the internal layer of the ME after i.p. administration of LPS. Our results indicate that AVP-eGFP transgenic rats are useful animal model to study dynamic changes of AVP expression in the hypothalamus under stressful conditions.     

PTEN and phosphorylated AKT expression and prognosis in early- and late-stage non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is the commonest cause of cancer mortality worldwide. Growth factor receptor signalling pathways constitute an important mediator for tumor growth and proliferation. PTEN and pAKT play important roles in regulating signal transduction along this pathway. Separate cohorts of stage I (n=25) and stage IV (n=34) NSCLC were examined by immunohistochemistry for PTEN and pAKT expression. There was no correlation between PTEN expression and pAKT expression and neither were associated with age, sex or smoking status. Patients with stage IV disease who overexpressed pAKT (at least 2+) or were PTEN-null had poorer overall survival and progression-free survival. This suggests that PTEN-null or pAKT-positive tumors constitute more aggressive tumors whose clinical course is not altered by therapy. There was no difference in the clinical outcome for stage I disease by PTEN or pAKT expression. A greater proportion of the stage IV patients had PTEN-null disease compared to the stage I cohort, suggesting that loss of PTEN is important in the tumor biology of advanced disease. Loss of PTEN or overexpression of pAKT predicts for an aggressive subset of lung tumors that have a poor prognosis. This will allow identification of a poor prognosis subset that can be targeted with novel treatments that either restore PTEN function or target activated AKT, mTOR and other downstream signal transduction molecules.