The construction of a new evaluative GERD questionnaire--methods and state of the art

Gastroesophageal reflux disease (GERD) is one of the most prevalent diseases worldwide, and it is becoming increasingly important to monitor the effect of various interventions on GERD symptoms. There can be rapid temporal changes in the severity and frequency of patients' symptoms as well as their health status and well-being, all of which could, theoretically, be monitored using diaries or questionnaires. However, current GERD monitoring instruments are not appropriate because they do not assess symptoms daily, they are not sufficiently responsive to short-term changes in health status or they are not adequately validated. To address these problems, the conceptual and psychometric requirements for a GERD symptom assessment questionnaire were identified. A dimension-based scale was designed to reduce the number of symptoms monitored on a daily basis, and the validation process was defined to produce parallel long and short forms of a scale for patients' self-assessment of their GERD symptom response to therapy. These basic principles which underlie the successful development of a new, self-assessed symptomatic reflux questionnaire (ReQuest) are also applicable to the development of validated questionnaires for daily symptom self-assessment in other disease areas.     

Investigation of ethanol-induced impairment of spatial memory in γ2 heterozygous knockout mice

GABA_A receptors, the major inhibitory receptors in the mammalian central nervous system, are affected by a number of drug compounds, including ethanol. The pharmacological effects of certain drugs have been shown to be dependent upon specific GABA_A receptor subunits. Because benzodiazepines and ethanol have similar effect signatures, it has been hypothesized that these drugs share the γ2-containing GABA_A receptors as a mechanism of action. To probe the involvement of the γ2 subunit in ethanol's actions, spatial memory for the Morris water maze task was tested in γ2 heterozygous knockout mice and wild type littermate controls following ethanol administration at the following doses: 0.0, 1.25, 1.75, and 2.25 g/kg. While baseline learning and memory were unaffected by reduction of γ2 containing GABA_A receptors, ethanol dose-dependently impaired spatial memory equally in γ2 heterozygous knockouts and wild type littermate controls.     

Inhibition of thalamic excitability by 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridine-3-ol: a selective role for δ-GABAA receptors

The sedative and hypnotic agent 4,5,6,7‐tetrahydroisoxazolo[4,5‐c]pyridine‐3‐ol (THIP) is a GABA_A receptor (GABA_AR) agonist that preferentially activates δ‐subunit‐containing GABA_ARs (δ‐GABA_ARs). To clarify the role of δ‐GABA_ARs in mediating the sedative actions of THIP, we utilized mice lacking the α₁‐ or δ‐subunit in a combined electrophysiological and behavioural analysis. Whole‐cell patch‐clamp recordings were obtained from ventrobasal thalamic nucleus (VB) neurones at a holding potential of ?60 mV. Application of bicuculline to wild‐type (WT) VB neurones revealed a GABA_AR‐mediated tonic current of 92 ± 19 pA, which was greatly reduced (13 ± 5 pA) for VB neurones of δ^0/0 mice. Deletion of the δ‐ but not the α₁‐subunit dramatically reduced the THIP (1 μm )‐induced inward current in these neurones (WT, ?309 ± 23 pA; δ^0/0, ?18 ± 3 pA; α₁^0/0, ?377 ± 45 pA). Furthermore, THIP selectively decreased the excitability of WT and α₁^0/0 but not δ^0/0 VB neurones. THIP did not affect the properties of miniature inhibitory post‐synaptic currents in any of the genotypes. No differences in rotarod performance and locomotor activity were observed across the three genotypes. In WT mice, performance of these behaviours was impaired by THIP in a dose‐dependent manner. The effect of THIP on rotarod performance was blunted for δ^0/0 but not α₁^0/0 mice. We previously reported that deletion of the α₁‐subunit abolished synaptic GABA_A responses of VB neurones. Therefore, collectively, these findings suggest that extrasynaptic δ‐GABA_ARs vs. synaptic α₁‐subunit‐containing GABA_ARs of thalamocortical neurones represent an important molecular target underpinning the sedative actions of THIP.     

Role of HSP27 and reduced glutathione in modulating malathion-induced apoptosis of human peripheral blood mononuclear cells: Ameliorating effect of N-acetylcysteine and curcumin

Malathion exerts cholinergic effects at high doses. However, a consequence of low dose (non-cholinergic) exposure causes immunotoxicity and oxidative stress. Hence, this study was designed to find out (i) the cytotoxic and apoptotic effects of cholinergic and non-cholinergic doses of malathion using cultured peripheral blood mononuclear cells (PBMCs) and (ii) the role of GSH and HSP27 and (iii) protective effects of N-acetylcysteine (GSH inducer) and curcumin (HSP27 inducer). In low doses, malathion caused mild depletion of GSH, threefold increase in HSP27 level and a range bound cytotoxicity and apoptosis of PBMC. In contrast, cholinergic dose exposures caused severe GSH depletion and exhibited dose dependent cytotoxicity and necrosis without any significant effect on HSP27 levels. Curcumin increased the levels of HSP27 in PBMC only in presence of low doses and not at high doses of malathion. Both NAC and curcumin were able to prevent malathion-mediated apoptosis of PBMC effectively at non-cholinergic doses and at this concentration of malathion, HSP27 induction keeps apoptosis and GSH depletion under control. Also NAC and curcumin may act as potential therapeutic agents to prevent malathion-induced immunotoxicity.     

Cystothecostomy: a new technique to treat long segment spinal extradural arachnoid cyst

Pathogenesis and treatment of the spinal arachnoid cyst has not been well established. A novel method of treatment of a long segment spinal arachnoid cyst is being presented in a 9-year-old boy. He presented to us with a slowly progressive spastic paraparesis. MRI revealed dorsal epidural arachnoid cyst extending from T7 vertebral body to L1 body producing marked cord compression. In order to save the child from a long segment laminectomy or laminoplasty, a new minimally invasive technique was devised. In this technique L1 laminectomy was performed under local anaesthesia, and the cyst was communicated to thecal sac by making an interconnecting stoma. We named this procedure as cystothecostomy. There was gradual neurological recovery after the procedure.     

The morphology of coronary arterial dissection occurring subsequent to angioplasty and its influence on acute complications

We reviewed the records of 402 patients undergoing percutaneous transluminal coronary angioplasty to identify factors predicting an ischemic event with arterial disruption during an otherwise uncomplicated angioplasty. Major dissection of the coronary arteries without immediate occlusion was found in 25 patients, who exhibited 28 dissected lesions. Dissections were classified into 2 types: those producing a continuous extraluminal and parallel filling tract, and those with a continuous parallel filling tract extending into and compromising the lumen. Ischemic complications (defined as myocardial infarction, the need for repeat angioplasty, or coronary arterial bypass surgery) occurred in 6 patients (24%) within 24 hours of the completion of the procedure. The remaining 19 patients had an uncomplicated hospital course. Acute ischemic complications following dissection correlated with the percentage of luminal compromise 50 +/- 0% in those with complications as opposed to 17 +/- 21% in those without: P less than 0.001) and the development of dissection producing a filling tract which compromised at least half the lumen (100% in those with complications versus 9.1% in those without: P less than 0.001). There was a trend towards an increase in ischemic complications in patients with proximal and eccentric lesions. We conclude that patients who develop dissections which produce significant luminal compromise after an otherwise uncomplicated angioplasty are at a high risk of developing an acute ischemic complication within 24 hours of the procedure.     

Stereotactic radiosurgery for IDH wild type glioblastoma: an international,multicenter study

Journal of Neuro-Oncology - Isocitrate dehydrogenase (IDH) mutation status is recommended used for diagnosis and prognostication of glioblastoma patients. We studied efficacy and safety of...