Suprasellar germ cell tumours: specific problems and the evolution of optimal management with a combined chemoradiotherapy regimen

OBJECTIVE: Suprasellar germ cell tumours are rare, and there are few series of patients outlining the problems in diagnosis and management, and providing clear guidelines for optimal therapy. We have therefore reviewed our own series of 11 such patients who were managed in a joint endocrinology/clinical oncology setting. PATIENTS AND DESIGN: A retrospective case review assessment of all patients seen within a given time. Clinical, biochemical and radiological findings were reviewed, the types of therapy administered noted, and the responses to treatment analysed. RESULTS: In the years 1977-2001, 11 patients with suprasellar (SS) germ cell tumours (GCT) were seen (germinomatous : nongerminomatous = 8 : 3). SSGCT had an approximately equal sex incidence (M : F, 6 : 5), in contrast to pineal tumours, the commonest site of origin of intracranial GCT and which occur predominantly in men. The median age at presentation was 20 years (range 6-49 years) with a median duration of symptoms before diagnosis of 17 months (range 1-35 months). Polyuria was the commonest presenting symptom (10 patients). Diabetes insipidus occurred in all patients, as did partial or complete anterior pituitary failure. Visual failure was present in 55% of cases. Anorexia, weight loss and disturbed thirst sensation were also common. Positron emission tomography scanning was occasionally useful in the evaluation of suprasellar tumours/pituitary stalk lesions deemed too risky to biopsy. A "central nervous system-friendly" chemoradiotherapy regimen comprising vincristine, etoposide and carboplatin and differential daily dose irradiation, usually administered using a partial transmission block technique, produced a 5-year survival of 100% with low morbidity. Treatment did not correct previously abnormal endocrine function although it did improve vision in three of six patients. CONCLUSIONS: We therefore emphasize the use of techniques other than biopsy in the diagnosis of these patients, note the problems in the management of their fluid control, and highlight the favourable response to a combined chemotherapy-radiotherapy protocol.     

Glucose-6-phosphate dehydrogenase modulates cytosolic redox status and contractile phenotype in adult cardiomyocytes

Reactive oxygen species (ROS)-mediated cell injury contributes to the pathophysiology of cardiovascular disease and myocardial dysfunction. Protection against ROS requires maintenance of endogenous thiol pools, most importantly, reduced glutathione (GSH), by NADPH. In cardiomyocytes, GSH resides in two separate cellular compartments: the mitochondria and cytosol. Although mitochondrial GSH is maintained largely by transhydrogenase and isocitrate dehydrogenase, the mechanisms responsible for sustaining cytosolic GSH remain unclear. Glucose-6-phosphate dehydrogenase (G6PD) functions as the first and rate-limiting enzyme in the pentose phosphate pathway, responsible for the generation of NADPH in a reaction coupled to the de novo production of cellular ribose. We hypothesized that G6PD is required to maintain cytosolic GSH levels and protect against ROS injury in cardiomyocytes. We found that in adult cardiomyocytes, G6PD activity is rapidly increased in response to cellular oxidative stress, with translocation of G6PD to the cell membrane. Furthermore, inhibition of G6PD depletes cytosolic GSH levels and subsequently results in cardiomyocyte contractile dysfunction through dysregulation of calcium homeostasis. Cardiomyocyte dysfunction was reversed through treatment with either a thiol-repleting agent (L-2-oxothiazolidine-4-carboxylic acid) or antioxidant treatment (Eukarion-134), but not with exogenous ribose. Finally, in a murine model of G6PD deficiency, we demonstrate the development of in vivo adverse structural remodeling and impaired contractile function over time. We, therefore, conclude that G6PD is a critical cytosolic antioxidant enzyme, essential for maintenance of cytosolic redox status in adult cardiomyocytes. Deficiency of G6PD may contribute to cardiac dysfunction through increased susceptibility to free radical injury and impairment of intracellular calcium transport. The full text of this article is available online at http://www.circresaha.org.     

Optimal vortex formation time index in mitral valve stenosis

The International Journal of Cardiovascular Imaging - Left ventricular vortex formation time (VFT) is a novel dimensionless index of flow propagation during left ventricular diastole, which has...     

Incidence of and risk factors for difficult ventilation via a supraglottic airway device in a population of 14 480 patients from South‐East Asia

Difficult airway practice guidelines include the use of a supraglottic airway device as part of the armamentarium to provide and maintain ventilation and oxygenation. We retrospectively reviewed 14 480 patients aged ≥ 18 years who underwent general anaesthesia. We identified 74 (0.5%) patients whose lungs were identified as having been difficult to ventilate via a supraglottic airway device, and 29 (0.2%) patients in whom device placement failed. Multivariate analysis identified four risk factors for difficult ventilation via a supraglottic airway device: male sex (OR 1.75, 95% CI 1.07–2.86, p = 0.02); age > 45 years (OR 1.70, 95% CI 1.01–2.86, p = 0.04); short thyromental distance (OR 4.35, 95% CI 2.31–8.17, p < 0.001); and limited neck movement (OR 2.75, 95% CI 1.02–7.44, p = 0.04). Adverse respiratory events including oxygen desaturation, hypercapnoea, laryngospasm, and bronchospasm occurred in 17 patients (22%). The incidence of difficult ventilation via a supraglottic airway device was 0.5% in a large cohort of South‐East Asian patients.     

Myocardial infarction with normal coronary angiogram. Possible mechanism of smoking risk in coronary artery disease.

The coronary angiograms of 120 consecutive patients under 40 years of age were examined. Ten new cases of myocardial infarction with normal coronary arteriogram were identified (group 1) and compared with 30 cases of myocardial infarction and obstructive coronary disease (group 2). Heavy cigarette smoking was the sole major risk factor in group 1. Patients in group 2 smoked as well but most also had hypercholesterolaemia or hypertension. Pre- and postinfarction angina was rare among the patients with myocardial infarction and normal coronary arteriogram, and recanalisation after smoking-induced thrombotic occlusion is thought to be the most likely mechanism. Smoking-induced thrombosis is only likely to be recognised in special circumstances, when it develops in apparently normal coronary arteries, is followed by recanalisation, and is complicated by infarction as a permanent marker of previous obstruction to regional myocardial blood flow. Thrombotic occlusion of a "normal" coronary artery without recanalisation will only be recognised when infarction is fatal. If smoking can predispose to thrombosis in "normal" coronary arteries, it may be even more likely to accelerate thrombosis in atheromatous coronary arteries. The importance of recognising group 1 may well be in relation to the much commoner group 2.     

Semi-automated identification of cones in the human retina using circle Hough transform

A large number of human retinal diseases are characterized by a progressive loss of cones, the photoreceptors critical for visual acuity and color perception. Adaptive Optics (AO) imaging presents a potential method to study these cells in vivo. However, AO imaging in ophthalmology is a relatively new phenomenon and quantitative analysis of these images remains difficult and tedious using manual methods. This paper illustrates a novel semi-automated quantitative technique enabling registration of AO images to macular landmarks, cone counting and its radius quantification at specified distances from the foveal center. The new cone counting approach employs the circle Hough transform (cHT) and is compared to automated counting methods, as well as arbitrated manual cone identification. We explore the impact of varying the circle detection parameter on the validity of cHT cone counting and discuss the potential role of using this algorithm in detecting both cones and rods separately.OCIS codes: (100.0100) Image processing, (170.3880) Medical and biological imaging, (110.1080) Active or adaptive optics, (170.4470) Ophthalmology     

Renal Mechanisms of Association between Fibroblast Growth Factor 1 and Blood Pressure

The fibroblast growth factor 1 (FGF1) gene is expressed primarily in the kidney and may contribute to hypertension. However, the biologic mechanisms underlying the association between FGF1 and BP regulation remain unknown. We report that the major allele of FGF1 single nucleotide polymorphism rs152524 was associated in a dose-dependent manner with systolic BP (P=9.65×10⁻⁵) and diastolic BP (P=7.61×10⁻³) in a meta-analysis of 14,364 individuals and with renal expression of FGF1 mRNA in 126 human kidneys (P=9.0×10⁻³). Next-generation RNA sequencing revealed that upregulated renal expression of FGF1 or of each of the three FGF1 mRNA isoforms individually was associated with higher BP. FGF1-stratified coexpression analysis in two separate collections of human kidneys identified 126 FGF1 partner mRNAs, of which 71 and 63 showed at least nominal association with systolic and diastolic BP, respectively. Of those mRNAs, seven mRNAs in five genes (MME, PTPRO, REN, SLC12A3, and WNK1) had strong prior annotation to BP or hypertension. MME, which encodes an enzyme that degrades circulating natriuretic peptides, showed the strongest differential coexpression with FGF1 between hypertensive and normotensive kidneys. Furthermore, higher level of renal FGF1 expression was associated with lower circulating levels of atrial and brain natriuretic peptides. These findings indicate that FGF1 expression in the kidney is at least under partial genetic control and that renal expression of several FGF1 partner genes involved in the natriuretic peptide catabolism pathway, renin-angiotensin cascade, and sodium handling network may explain the association between FGF1 and BP.