Left atrial extension of lung malignancy with ECG changes resembling STEMI

Lung malignancy extending into left atrium is seen very infrequently. We had a patient with a fast growing symptomatic lung mass and electrocardiogram showing persistent coving ST elevation without any biomarker change. Transthoracic echocardiography showed a large left atrial mass which was fixed to the free walls and extended into the appendage. There was also a large lung mass that was compressing the heart from its lateral aspect. CT-scan of chest corroborated the lung mass & CT-guided FNAC showed small cell carcinoma.     

Antiplasmodial activity of [(aryl)arylsulfanylmethyl]Pyridine

A series of [(aryl)arylsufanylmethyl]pyridines (AASMP) have been synthesized. These compounds inhibited hemozoin formation, formed complexes (K(D) = 12 to 20 muM) with free heme (ferriprotoporphyrin IX) at a pH close to the pH of the parasite food vacuole, and exhibited antimalarial activity in vitro. The inhibition of hemozoin formation may develop oxidative stress in Plasmodium falciparum due to the accumulation of free heme. Interestingly, AASMP developed oxidative stress in the parasite, as evident from the decreased level of glutathione and increased formation of lipid peroxide, H(2)O(2), and hydroxyl radical (.OH) in P. falciparum. AASMP also caused mitochondrial dysfunction by decreasing mitochondrial potential (DeltaPsim) in malaria parasite, as measured by both flow cytometry and fluorescence microscopy. Furthermore, the generation of .OH may be mainly responsible for the antimalarial effect of AASMP since .OH scavengers such as mannitol, as well as spin trap alpha-phenyl-n-tertbutylnitrone, significantly protected P. falciparum from AASMP-mediated growth inhibition. Cytotoxicity testing of the active compounds showed selective activity against malaria parasite with selectivity indices greater than 100. AASMP also exhibited profound antimalarial activity in vivo against chloroquine resistant P. yoelii. Thus, AASMP represents a novel class of antimalarial.     

Association of ApoE genetic variants with obstructive sleep apnea in children

BACKGROUND AND PURPOSE: Although several studies have reported an association between obstructive sleep apnea (OSA) and the chromosomal region containing the Apolipoprotein E (ApoE) gene, findings about the exact location in the ApoE gene have been inconsistent. The objective of our study was thus to determine the allele, genotype, and haplotype frequencies at several single nucleotide polymorphisms (SNPs) in the region of ApoE and test their association with OSA status in children. PATIENTS AND METHODS: Caucasian children, ranging in age from 2 to 21 years, with polysomnographic evidence of OSA (>1 obstructive apnea or obstructive hypopnea episodes per hour of sleep) were recruited in the case group. Our race- and gender-matched control group was recruited from a population-based cohort of children enrolled in the Princeton School District Study. RESULTS: Comparison of allele and genotype frequencies between cases (n=92) and controls (n=92) revealed significant differences for SNPs rs405509 and rs7412. Multivariate logistic regression analysis with age and body mass index (BMI) as covariates revealed a significant association between OSA status and SNPs rs157580, rs405509, rs769455 and rs7412. The sliding window haplotype trend regression test revealed that SNP rs405509 was included in all haplotypes that are significantly associated with OSA status. CONCLUSIONS: We conclude that polymorphisms involving more than one locus in the ApoE gene and its regulatory region are associated with OSA in children. Further studies replicating these findings in different populations are needed as are studies involving fine mapping of this region.     

Bone morphogenetic protein regulation of enteric neuronal phenotypic diversity: relationship to timing of cell cycle exit

The effects of bone morphogenetic protein (BMP) signaling on enteric neuron development were examined in transgenic mice overexpressing either the BMP inhibitor, noggin, or BMP4 under control of the neuron specific enolase (NSE) promoter. Noggin antagonism of BMP signaling increased total numbers of enteric neurons and those of subpopulations derived from precursors that exit the cell cycle early in neurogenesis (serotonin, calretinin, calbindin). In contrast, noggin overexpression decreased numbers of neurons derived from precursors that exit the cell cycle late (gamma-aminobutyric acid, tyrosine hydroxylase [TH], dopamine transporter, calcitonin gene-related peptide, TrkC). The numbers of TH- and TrkC-expressing neurons were increased by overexpression of BMP4. These observations are consistent with the idea that phenotypic expression in the enteric nervous system (ENS) is determined, in part, by the number of proliferative divisions neuronal precursors undergo before their terminal mitosis. BMP signaling may thus regulate enteric neuronal phenotypic diversity by promoting the exit of precursors from the cell cycle. BMP2 increased the numbers of TH- and TrkC-expressing neurons developing in vitro from immunoselected enteric crest-derived precursors; BMP signaling may thus also specify or promote the development of dopaminergic TrkC/NT-3-dependent neurons. The developmental defects in the ENS of noggin-overexpressing mice caused a relatively mild disturbance of motility (irregular rapid transit and increased stool frequency, weight, and water content). Although the function of the gut thus displays a remarkable tolerance for ENS defects, subtle functional abnormalities in motility or secretion may arise when ENS defects short of aganglionosis occur during development.     

Fractionated stereotactic radiotherapy for acoustic neuroma: single-institution experience at The Princess Margaret Hospital

BACKGROUND: The clinical outcome and toxicity of fractionated stereotactic radiotherapy (FSRT) was assessed for acoustic neuroma in 60 patients treated in a single institution. METHODS: Between October 1996 and February 2005, 60 patients received FSRT for acoustic neuroma (AN). The mean total dose applied was 50 Gy in single daily 2-Gy fractions over 5 weeks. The median irradiated tumor volume was 4.9 cm(3) (range, 0.3-49.0 cm(3)). The median follow-up period was 31.9 months. RESULTS: FSRT was well tolerated in all patients. The 5-year actuarial local control rate was 96.2% (95% CI: 91.1%-100.0%). Five-year actuarial progression-free survival was 92.8% (95% CI: 84.8%-100.0%). The overall hearing preservation rate was 77.3%. Five of 6 patients with initial cranial nerve V (CNV) numbness remained stable post-FSRT. Two of 3 patients with baseline trigeminal neuralgia improved with the remaining patient stable. All 3 patients with nonsurgically related facial nerve weakness either improved or achieved stability in function. There were no cases of new cranial nerve toxicity post-FSRT. CONCLUSIONS: FSRT for the treatment of AN is safe, effective, and well tolerated. FSRT should thus be considered as an effective alternative treatment modality when compared with microsurgical resection or single fraction stereotactic radiosurgery.     

Radiation induced peripheral nerve tumors: <Emphasis Type="Italic">case series and review of the literature</Emphasis>

Purpose Radiation induced peripheral nerve tumors (PNT) are a rare but known complication of radiotherapy. The clinical and pathologic features of six cases of post-radiation PNT’s are reported here, more than doubling the number of known cases reported in the literature. Methods We reviewed six cases of radiation induced PNT and performed a review of the current literature on radiation induced neurofibromas. Results Patient’s ranged in age from 18 months to 49 years at the time of their original diagnosis, with radiation doses to the primary tumor ranging from 24 to 40 Gy with post radiation intervals from 10 to 50 years. The majority of PNT’s identified were neurofibromas (3) and schwannomas (3). Nuclear atypia, S100 positive staining and mild—moderate cellularity were common pathologic findings. Conclusions There are only a handful of neurofibromas in the 60 cases of PNT’s thus far reported. This case series broadens the post-radiation neurofibroma literature. While the pathology of PNT induced transformation is still poorly understood, experiments and pathology are congruent on the possibility of malignant transformation, especially for the “atypical neurofibroma”. On the clinical level, this case series lends its support to some, but not all, of the risk factors thought to predispose to the formation of radiation induced neurofibromas. Though rare, the complication of radiation-induced neurofibroma cannot be ignored, especially with the increasing use of focused radiosurgical techniques.     

Heart Failure Epidemiology: European Perspective

Heart failure poses an increasing problem for global healthcare systems. The epidemiological data which has been accrued over the last thirty years has predominantly been accumulated from experience within North America and Europe. Initial large cohort, prospective longitudinal studies produced the first publications; however latterly the focus has shifted onto epidemiological data governing hospitalisation and mortality. The emphasis behind this shift has been the resource implications with regards to repetitive, costly and prolonged hospitalisation. The European experience in heart failure, though similar to North America has recently demonstrated differences in hospitalisation which may underlie the differences between healthcare system configuration. Heart failure however remains an increasing global problem and the endpoint of a variety of cardiovascular diseases. Allied with the fact of increasingly elderly populations and prior data demonstrating a steep rise in prevalent cases within more elderly populations, it is likely that the increasing burden of disease will continue to pose challenges for modern healthcare. Despite the predicted increase in the number of patients affected by heart failure, over the last thirty years, a clear management algorithm has evolved for the use of pharmacotherapies (neuro-hormonal antagonists), device based therapies (Implantable Cardioverting Defibrillator (ICD) and Cardiac Resynchronisation Therapy (CRT)) and mechanical therapies including left ventricular assist devices and cardiac transplantation. Though the management of such patients has been clearly delineated in national and international guidelines, the underuse of all available and appropriate therapies remains a significant problem. When comparing various epidemiological studies from different settings and timepoints, it should be remembered that rates of prevalence and incidence may vary depending upon the definition used, methods of accumulating information (with the possibility of bias) and the chosen cut point of defining left ventricular systolic dysfunction (LVSD).     

Arsenic and liver disease.

The hepatotoxic action of arsenic, when used as a therapeutic agent, has long been recognised. Data on liver involvement following chronic exposure to arsenic-contaminated water are scanty. The nature and degree of liver involvement are reported on the basis of hospital based studies in patients who consumed arsenic contaminated drinking water for one to 15 years. Two hundred forty-eight patients with evidence of chronic arsenic toxicity underwent clinical and laboratory examination including liver function tests and hepatitis B surface antigen (HBsAg) status. Liver biopsy was done in 69 cases; in 29 patients, liver arsenic content was estimated by neutron activation analysis. Hepatomegaly was present in 190 of 248 patients (76.6%). Non-cirrhotic portal fibrosis was the predominant lesion (91.3%) in liver histology. The maximum arsenic content in liver was 6 mg/kg (mean 1.46 [0.42], control value 0.16 [0.04]; p <0.001); it was undetected in 6 of 29 samples studied. The largest number of patients with liver disease due to chronic arsenicosis from drinking arsenic contaminated water are reported. Non-cirrhotic portal fibrosis is the predominant lesion in this population. Hepatic fibrosis has also been demonstrated due to long term arsenic toxicity in an animal model. Initial biochemical evidence of hepatic membrane damage, probably due to reduction of glutathione and antioxidant enzymes, may be seen by 6 months. Continued arsenic feeding resulted in fatty liver with serum aminotransferases elevated at 12 months and hepatic fibrosis at 15 months.