Pathological and molecular progression of astrocytomas in a GFAP:12 V-Ha-Ras mouse astrocytoma model

We previously characterized a genetically engineered mouse astrocytoma model with embryonic astrocyte-specific, activated ¹²V-Ha-RAS (GFAP-RAS) transgenesis. The GFAP-RAS line Ras-B8 appears normal at birth, but 50% of mice die by 4 months from low- and high-grade astrocytomas. We examined the development and progression of astrocytomas in the Ras-B8 genetically engineered mouse. At embryonic day 16.5 (E16.5), there were no pathological differences compared to control littermates, aside from transgene expression. Diffuse astroglial hyperplasia was the first distinguishing feature in the 1-week-old Ras-B8 mice; however, these astrocytes were not transformed in vitro or in vivo. From 3 to 8 weeks the incidence of low-grade astrocytomas progressively increased with 85% of 12-week-old mice harboring low- or high-grade astrocytomas, the latter characterized by increased proliferation, nuclear atypia, and angiogenesis. Tp53 mutations were detected in both astrocytoma grades, with high-grade astrocytomas expressing elevated levels of epidermal growth factor receptor and vascular endothelial growth factor, plus decreased levels of PTEN and p16, similar to human astrocytomas. We postulate that expression of ¹²V-Ha-RAS in astroglial precursors induces astroglial hyperplasia, but transformation and subsequent progression requires additional molecular alterations resulting from aberrant activated p21-RAS. Of interest, many of these acquired alterations occur in human astrocytomas, further validating GFAP-RAS as a useful model for studying astrocytoma development and progression.     

Effectiveness of anemia and chronic kidney disease as predictors for presence and severity of coronary artery disease in patients undergoing stress myocardial perfusion study

Chronic kidney disease (CKD) and anemia portend a higher risk of cardiac events and mortality. We sought to ascertain whether coronary artery disease (CAD) by myocardial perfusion single-photon emission computed tomography is more common in patients with CKD (glomerular filtration rate < or =60 ml/min/1.73 kg/m(2)) and/or anemia (hemoglobin level < or =13 g/L) and the impact of different degrees of CKD. One thousand five hundred eighty patients (mean age 65 +/- 10 years) underwent gated myocardial perfusion single-photon emission computed tomography and clinical evaluation. Patients were divided into 4 groups (group 1, no anemia/no CKD, n = 800; group 2, anemia/no CKD, n = 195; group 3, CKD/no anemia, n = 332; group 4, anemia/CKD, n = 253). Multivariate logistic regression analysis was undertaken to examine the association of these diagnoses with abnormal myocardial perfusion single-photon emission computed tomogram. Compared with patients with neither diagnosis, an abnormal scan was more common in those with anemia or CKD. Patients with anemia and CKD exhibited more severe CAD (mean summed stress score 6.8 vs 4.7, p <0.01). Established high-risk findings were more prevalent in patients with anemia and/or CKD, including a summed stress score > or =8, transient ischemic dilation, or a left ventricular ejection fraction < or =40% (group 1 28%, group 2 38%, group 3 38%, group 4 48%, all p values <0.01). Patients with moderate CKD demonstrated an increased risk of an abnormal scan (odds ratio 2.66, p <0.0001). After adjustment in multivariate analysis, anemia and CKD each remained predictors for an abnormal scan. The association was stronger in those with the 2 conditions (odds ratio for high-risk scan 1.89, p = 0.0002). In conclusion, in patients with suspected CAD, anemia and CKD are predictors of myocardial perfusion single-photon emission computed tomographic markers for worsened outcomes. The relation was independent of other risk factors, supporting the inclusion of anemia and CKD in global risk assessment for patients with suspected CAD.     

Cystic Hydatidosis of the Rib–Case Report and Review of the Literature

The hydatid disease is a zoonosis endemic to rural countries, such as those in the Mediterranean region, South America, North Africa, Central Asia and China. Hydatid cysts commonly affect liver and lungs, but less than 100 cases of costal hydatidosis have been reported in the literature. While diagnosis of the disease in commonly affected organs is relatively easy, uncommon locations can prove to be challenging as is the case with costal hydatidosis. Imaging techniques can suggest the diagnosis, but sometimes it remains uncertain until surgery. The treatment is surgical, assisted by long-time Albendazole chemotherapy. We present a rare case of costal hydatidosis, the first one to be reported in Romania according to our review of the literature.     

Predictors of Unsuccessful Laparoscopic Resection of Gastric Submucosal Neoplasms

Background

While laparoscopy has become integral to the performance of foregut surgery, its optimal use in resection of gastric submucosal neoplasms, including gastrointestinal stromal tumors (GISTs), remains uncertain. Concern exists for technical feasibility related to tumor size and location, as well as oncologic outcome.

Methods

From 2002 to 2012, 106 patients underwent resection for gastric submucosal neoplasms, comprising 79 laparoscopic and 27 open resections. Median follow-up was 15 months.

Results

Patients were 62?±?14 years and 56 % male. Mean tumor size was 5.5?±?4.3 cm, with 76 % being GISTs. A total of 8 (10 %) conversions occurred in the laparoscopic cohort. On multivariate analysis, conversion was predicted by size greater than 8 cm, while recurrence was predicted by mitotic index (p?<?0.05). Laparoscopic resection resulted in better perioperative outcomes, with less morbidity, operative time, blood loss, and length of stay (p?<?0.05). No significant difference was seen in survival, with 90 % and 81 % alive 3 years after laparoscopic and open resection, respectively (HR 0.4; 95 % CI 0.1–1.3; p?=?0.13).

Conclusions

Laparoscopic resection is feasible and effective in the management of gastric submucosal neoplasms, including GISTs. Caution should be reserved for tumors greater than 8 cm. Oncologic outcome appears to be predicted by tumor biology as opposed to surgical approach.     

Expression analysis of microRNA-155 in type 2 diabetes in Kashmiri population

International Journal of Diabetes in Developing Countries - The present study aimed to evaluate the expression of microRNA-155 (miR-155) in type 2 diabetes mellitus (T2DM) and assess its...     

C. Hypertension and Systemic Disease

Literature Survey

C. Hypertension and Systemic Disease     

When the worst headache becomes the worst heartache!

BACKGROUND AND PURPOSE: Although a great deal of literature has been generated regarding left ventricular wall abnormalities, ECG changes and cardiac enzyme leaks associated with subarachnoid hemorrhage (SAH), there have been only a few reports of true transient left ventricular apical ballooning syndrome in patients with SAH. Several pathophysiological mechanisms have been proposed to explain the unusual features of this syndrome, such as multivessel coronary vasospasm, abnormalities in coronary microvascular function, and catecholamine-mediated cardiotoxicity. Summary of Case- A previously healthy 64-year-old woman with no history of vascular disease was found unresponsive at home. She was taken to the emergency room where a CT head revealed an SAH due to a ruptured aneurysm of the posterior communicating artery. On admission, an ECG showed deeply inverted T-waves and QT prolongation, typical of SAH. Cardiac troponin was measured at 1.2 ng/mL, and later increased to 3.7 ng/mL. A transthoracic echocardiogram on the next day revealed a large left ventricular wall abnormality, characteristic of apical ballooning with an ejection fraction of 25% to 30%. The patient remained hemodynamically stable and was started on low dose beta-blocker and angiotensin-converting enzyme inhibitor. She had an uneventful cardiac recovery within 5 days at which time a repeat transthoracic echocardiogram revealed a normal ejection fraction with no wall motion abnormality. CONCLUSIONS: This report adds to the growing list of "stressors" for Takotsubo cardiomyopathy. Clinicians should be aware of the existence and the typical clinical manifestations of this syndrome, which is increasingly recognized in various populations. In particular, neurologists should consider this syndrome in the differential diagnosis of ECG changes and apical wall motion abnormalities in patients with SAH. Prognosis is generally very good with full recovery in most patients; however, there may be increased morbidity associated in patients with SAH.