Familial neonatal atrial tachycardia.

A father and his two sons each presented with atrial tachycardia in the newborn period. The father went on to develop dilated cardiomyopathy. The first son (who also had transposition of the great arteries) died from the arrhythmia after surgery. The second son is currently successfully managed pharmacologically.     

The management of arteriovenous malformations in children

Between January 1941 and June 1989, 46 children below the age of 18 with an arteriovenous malformation (AVM) were managed. There were 7 patients with AVM diagnosed before the age of 2; 10 patients were diagnosed between the ages of 3 and 10; and 29 patients were diagnosed between 11 and 18. There were equal numbers of male and female patients. Twenty-five of the AVMs were large (>5 cm longest diameter). All 7 AVMs diagnosed before the age of 2 were large. The usual clinical presentation was congestive heart failure, bruit and an enlarging head. Three patients underwent excision with 2 deaths and 1 excellent result. In 11 patients (aged 3–18) with AVM without history of hemorrhage, 3 had excision with 2 excellent and 1 fair result. Four remained stable. Four developed progressive deficits or hemorrhage. In 10 patients (aged 3–18) with AVM and hemorrhage who were treated medically, 7 (70%) had an episode of re-hemorrhage. Three patients had excision of AVM after re-hemorrhage, but before the age of 18 with an excellent result. Eighteen patients (aged 3–18) with AVM and a single episode of hemorrhage underwent excision with 17 excellent or good results and 1 fair result. The overall mortality was 7%. Eighty-five percent of the children with excision of AVM had an excellent or good result. The best treatment for AVM in children is surgical excision.Presented at the XVII Annual Meeting of the International Society for Pediatric Neurosurgery, Bombay 1989     

Characterization of a 10- to 14-kilodalton protease-sensitive Mycobacterium tuberculosis H37Ra antigen that stimulates human gamma delta T cells.

gamma delta T-cell receptor-bearing T cells (gamma delta T cells) are readily activated by intracellular bacterial pathogens such as Mycobacterium tuberculosis. The bacterial antigens responsible for gamma delta T-cell activation remain poorly characterized. We have found that heat treatment of live M. tuberculosis bacilli released into the supernatant an antigen which stimulated human gamma delta T cells. gamma delta T-cell activation was measured by determining the increase in percentage of gamma delta T cells by flow cytometry in peripheral blood mononuclear cells stimulated with antigen and by proliferation of gamma delta T-cell lines with monocytes as antigen-presenting cells. Supernatant from heat-treated M. tuberculosis was fractionated by fast-performance liquid chromatography (FPLC) on a Superose 12 column. Maximal gamma delta T-cell activation was measured for a fraction of 10 to 14 kDa. Separation of the supernatant by preparative isoelectric focusing demonstrated peak activity at a pI of < 4.0. On two-dimensional gel electrophoresis, the 10- to 14-kDa FPLC fraction contained at least seven distinct molecules, of which two had a pI of < 4.5. Protease treatment reduced the bioactivity of the 10- to 14-kDa FPLC fraction for both resting and activated gamma delta T cells. Murine antibodies raised to the 10- to 14-kDa fraction reacted by enzyme-linked immunosorbent assay with antigens of 10 to 14 kDa in lysate of M. tuberculosis. In addition, gamma delta T cells proliferated in response to an antigen of 10 to 14 kDa present in M. tuberculosis lysate. gamma delta T-cell-stimulating antigen was not found in culture filtrate of M. tuberculosis but was associated with the bacterial pellet and lysate of M. tuberculosis. These results provide a preliminary characterization of a 10- to 14-kDa, cell-associated, heat-stable, low-pI protein antigen of M. tuberculosis which is a major stimulus for human gamma delta T cells.     

Platelet glycoprotein VI-dependent thrombus stabilization is essential for the intraportal engraftment of pancreatic islets

Platelet activation and thrombus formation have been implicated to be detrimental for intraportal pancreatic islet transplants. The platelet-specific collagen receptor glycoprotein VI (GPVI) plays a key role in thrombosis through cellular activation and the subsequent release of secondary mediators. In aggregometry and in a microfluidic dynamic assay system modeling flow in the portal vein, pancreatic islets promoted platelet aggregation and triggered thrombus formation, respectively. While platelet GPVI deficiency did not affect the initiation of these events, it was found to destabilize platelet aggregates and thrombi in this process. Interestingly, while no major difference was detected in early thrombus formation after intraportal islet transplantation, genetic GPVI deficiency or acute anti-GPVI treatment led to an inferior graft survival and function in both syngeneic mouse islet transplantation and xenogeneic human islet transplantation models. These results demonstrate that platelet GPVI signaling is indispensable in stable thrombus formation induced by pancreatic islets. GPVI deficiency resulted in thrombus destabilization and inferior islet engraftment indicating that thrombus formation is necessary for a successful intraportal islet transplantation in which platelets are active modulators.     

A single‐blinded case controlled study on effects of cardiopulmonary circulation on hearing during coronary artery bypass grafting

Objectives: To evaluate the effect of extra‐corporeal (cardiopulmonary) bypass on hearing during coronary artery bypass grafting. Design: Prospective (single‐blinded) controlled study. Setting: District General Hospital. Participants: Fifty‐two patients undergoing coronary artery bypass grafting completed this study. Comparison was made between 14 control patients undergoing off‐pump coronary artery bypass grafting and 38 study patients undergoing on‐pump coronary artery bypass grafting. The age range of patients was 48–81 years, with 50% between 64 and 66 years. Main outcome measures: Pure tone audiograms were performed in all patients before and after coronary artery bypass grafting. Data were analysed for any significant difference between pre‐ and post‐operative pure tone audiograms. Results: Mann–Whitney U‐test demonstrated no difference between the area generated between mean pre‐ and post‐operative audiograms (P = 0.754). No significant difference between off versus on pump was demonstrated for average differences at 250–500 Hz, 4 kHz, 4–8 kHz and 8 kHz. Wilcoxon matched‐pairs signed‐rank test demonstrated no difference between right and left ears for each individual frequency. Spearman's test to analyse the effect on vessel number or minutes on bypass pump revealed no significant difference at 4–8 kHz (P = 0.550 for number of vessels and P = 0.276 for minutes on pump.) Conclusion: In this study, it was not possible to demonstrate any statistically significant deleterious effect of extra‐corporeal (cardiopulmonary) bypass on hearing during coronary artery bypass grafting.     

Targeting choline phospholipid metabolism: GDPD5 and GDPD6 silencing decrease breast cancer cell proliferation,migration, and invasion

Abnormal choline phospholipid metabolism is associated with oncogenesis and tumor progression. We have investigated the effects of targeting choline phospholipid metabolism by silencing two glycerophosphodiesterase genes, GDPD5 and GDPD6, using small interfering RNA (siRNA) in two breast cancer cell lines, MCF‐7 and MDA‐MB‐231. Treatment with GDPD5 and GDPD6 siRNA resulted in significant increases in glycerophosphocholine (GPC) levels, and no change in the levels of phosphocholine or free choline, which further supports their role as GPC‐specific regulators in breast cancer. The GPC levels were increased more than twofold during GDPD6 silencing, and marginally increased during GDPD5 silencing. DNA laddering was negative in both cell lines treated with GDPD5 and GDPD6 siRNA, indicating absence of apoptosis. Treatment with GDPD5 siRNA caused a decrease in cell viability in MCF‐7 cells, while GDPD6 siRNA treatment had no effect on cell viability in either cell line. Decreased cell migration and invasion were observed in MDA‐MB‐231 cells treated with GDPD5 or GDPD6 siRNA, where a more pronounced reduction in cell migration and invasion was observed under GDPD5 siRNA treatment as compared with GDPD6 siRNA treatment. In conclusion, GDPD6 silencing increased the GPC levels in breast cancer cells more profoundly than GDPD5 silencing, while the effects of GDPD5 silencing on cell viability/proliferation, migration, and invasion were more severe than those of GDPD6 silencing. Our results suggest that silencing GDPD5 and GDPD6 alone or in combination may have potential as a new molecular targeting strategy for breast cancer treatment. Copyright © 2016 John Wiley & Sons, Ltd.     

Impact of oral potentially malignant disorders on quality of life

Background

Oral potentially malignant disorders (OPMDs) could have a significant psychological impact on patients, principally because of the unknown risk of malignant transformation, while the physical and functional impairments could differ. This study aimed to assess the impact of three different OPMDs and their disease stages on the quality of life (QoL) of affected patients.

Methods

Oral leukoplakia (OL), oral lichen planus (OLP) and oral submucous fibrosis (OSF) patients who were undergoing treatment at an oral medicine clinic of a dental teaching hospital in India were the study population. All subjects completed the recently developed OPMDQoL questionnaire and a short form 12 item (version 2) health survey questionnaire (SF‐12v2). OPMDQoL questionnaire consists of 20 items over four dimensions. A higher score denotes poor OHRQoL. SF‐12v2 has two components, a Physical Component Summary (PCS) and Mental Component Summary (MCS).

Results

A total of 150 subjects (50 each of OL, OLP and OSF) participated. OL patients (37.7 ± 7.9) reported significantly better OPMDQoL scores than OLP (47.3 ± 5.8) and OSF (45.4 ± 9.2) patients. OLP patients reported significant problems in obtaining a clear diagnosis for their condition, more so than the other OPMDs. OL patients reported fewer problems for the dimension, “physical impairment and functional limitations” than the OLP and OSF patients. A significant trend was observed with the overall OPMDQoL and MCS, deteriorating as the disease stage increased.

Conclusions

OLP and OSF have a significant impact on the QoL of affected individuals: OL less so. Increasing stage of the disease is associated with worsening QoL.