Isolated myxopapillary ependymoma of the fourth ventricle: case report and review of literature.

We report a case of isolated myxopapillary ependymoma (MPE) of the fourth ventricle. This is the thirteenth reported case of primary intracranial MPE and the fourth reported case of MPE originating from the fourth ventricle. We suggest that exhaustive clinical and radiological investigation of a spinal ependymoma must be undertaken in all cases of intracranial ependymoma.

Ultra-thin alumina and silicon nitride MEMS fabricated membranes for the electron multiplication.

In this paper we demonstrate the fabrication of large arrays of ultrathin freestanding membranes (tynodes) for application in a timed photon counter (TiPC), a novel photomultiplier for single electron detection. Low pressure chemical vapour deposited silicon nitride (Si x N y ) and atomic layer deposited alumina (Al2O3) with thicknesses down to only 5 nm are employed for the membrane fabrication. Detailed characterization of structural, mechanical and chemical properties of the utilized films is carried out for different process conditions and thicknesses. Furthermore, the performance of the tynodes is investigated in terms of secondary electron emission, a fundamental attribute that determines their applicability in TiPC. Studied features and presented fabrication methods may be of interest for other MEMS application of alumina and silicon nitride as well, in particular where strong ultra-thin membranes are required.

Sterilization of rotary NiTi instruments within endodontic sponges.

AIM: To determine whether the following can be sterilized by autoclaving - endodontic sponges, rotary nickel-titanium (NiTi) instruments within endodontic sponges, and rotary NiTi instruments with rubber stoppers. METHODOLOGY: Sixty-four samples of eight different endodontic sponges (n = 512) were placed into brain heart infusion broth (BHI) for 72 h. An aliquot of this was then spread onto horse blood agar and cultured aerobically and anaerobically to test sterility at purchase. Bacterial suspensions of Enterococcus faecalis, Porphyromonas gingivalis and Geobacillus stearothermophilus in BHI were used to contaminate sterile sponges and rotary NiTi instruments (with and without rubber stoppers) inserted into sponges. The various samples were autoclaved and then cultured aerobically and anaerobically. Success of sterilization was measured qualitatively as no growth. The experiment was repeated with clinically used rotary NiTi instruments (n = 512). All experiments were conducted in quadruplicate. RESULTS: No sponges on purchase had microbial growth when anaerobically cultured but some did when aerobically cultured. All autoclaved sponges and instruments (within or without sponges, and with or without rubber stoppers) were associated with no microbial growth. All nonautoclaved positive control samples showed microbial growth. CONCLUSIONS: Autoclaving was effective in the sterilization of sponges and endodontic instruments. Endodontic sponges should be autoclaved before clinical use. For clinical efficiency and cost-effectiveness, rotary NiTi instruments can be sterilized in endodontic sponges without removal of rubber stoppers.

The expression of the let-7 miRNAs and Lin28 signalling pathway in human term gestational tissues.

INTRODUCTION: Labour and delivery are processes associated with inflammation within intrauterine and cervical tissues. The mechanisms that induce labour-associated changes and, in particular, the role of microRNAs (miRNAs) remain to be elucidated. MiRNAs are small non-coding RNAs that repress gene expression via mRNA degradation and translational repression. Let-7 miRNAs are negatively regulated by RNA-binding protein, Lin28, and both function downstream of NF-κB signalling. In non-gestational tissues, let-7 and Lin28 reportedy function as negative and positive regulators of IL-6 expression. We hypothesised that labour-associated inflammation involves the downregulation of let-7 miRNAs and upregulation of Lin28 expression. AIM: To determine the expression of Lin28 protein and let-7 miRNA in human gestational tissue obtained before and after labour. METHOD: Gestational tissues were collected from women at term by Caesarean section with and without labour and following normal vaginal delivery (n = 6 per group). Protein and RNA was extracted and Lin28 and let-7 miRNA expression was measured by Western blotting and real-time PCR. RESULTS: The data obtained established that let-7 miRNA and Lin28 display tissue-specific expression: Lin28 was strongly expressed in the placenta and choriodecidua, but not measurable in amnion; and let-7b and -7c expression were significantly lower in choriodecidua compare to placenta and amnion, whereas the amnion expressed less let-7d and -7f than other tissues. CONCLUSION: While the expression of Lin28 protein and let-7 miRNA did not vary significantly with labour onset and delivery, changes in their bioactivity and impact on nuclear signalling pathways in human gestational tissues remain to be established.

IL-2/IL-15 activate the human clonally restricted KIR3DL1 reverse promoter.

Killer cell immunoglobulin-like receptors (KIRs) are expressed in a clonally restricted manner by human natural killer (NK) cells and allow detection of aberrant cells with low major histocompatibility complex class I levels. Clonally restricted KIR transcription is maintained by demethylation of the proximal promoter. Antisense transcripts also arise from this promoter and may enforce silencing of nonexpressed methylated KIR alleles in NK cells. Here we show that interleukin (IL)-2 and IL-15, cytokines critical for NK cell development and maintenance, greatly stimulated KIR3DL1 reverse promoter activity, but not forward promoter activity. Activated STAT5 was both necessary and sufficient for this effect and bound to the promoter in NK cells that expressed KIR3DL1 or were poised for expression. A systematic investigation of the KIR3DL1 reverse promoter showed significant differences from the forward promoter, with STAT and YY1 sites having relatively greater roles in regulating reverse proximal promoter activity. On the basis of our data, we propose a new role for antisense transcripts in the initiation of KIR gene expression during NK cell development.

A new class of drug for the management of type 2 diabetes: sodium glucose co-transporter inhibitors: 'glucuretics'.

BACKGROUND: Type 2 diabetes is a common, chronic disease with a prevalence that is increasing at epidemic proportions. Management involves advice on lifestyle changes, oral anti-hyperglycaemic agents and/or insulin. The kidneys play a major role in the regulation of glucose, re-absorbing 99% of the plasma glucose filtered through the renal glomeruli tubules. The glucose transporter, SGLT2, which is found primarily in the S1 segment of the proximal renal tubule accounts for 90% of glucose re-absorption. Competitive inhibition of SGLT2 induces glucosuria in a dose dependent manner and appears to have beneficial effects on glucose regulation in individuals with type 2 diabetes. O-glucoside phlorozin is the model substance for SGLT2 inhibitors: various O-, C-, N- and S-glucosides with varying affinity and specificity have been synthesised. AIMS: The aim of this review is to describe the background, the mechanism of action and the possible role for sodium glucose co-transporter inhibitors in the treatment of diabetes. MATERIALS AND METHODS: Databases, including MEDLINE, COCHRANE, EMBASE and EBM reviews were searched for literature relating to sodium glucose transport inhibitors and improvements in glycaemic control in patients with diabetes. RESULTS: The data suggest that sodium glucose transport inhibitors significantly improve glycaemic control by increasing glucosuria. Some studies described significant reductions in weight and improvement in blood pressure. The most common side effect was infection involving the urinary and genital tracts. CONCLUSIONS: Sodium glucose co-transport inhibitors appear to be an effective line of treatment, well tolerated and could be a further drug class in the armamentarium available for the management of type 2 diabetes.

Prevalence and associated comorbidities of moderate to severe chronic renal impairment in Chinese nursing home older adults.

OBJECTIVE: To investigate the prevalence and associated comorbidities of Stage 3 (GFR 30-59 mL/min/1.73m(2)) and Stages 4 and 5 (GFR <30 mL/min/1.73m(2)) chronic kidney disease (CKD) among Chinese nursing home older adults. DESIGN: Retrospective cross-sectional study. Glomerular filtration rate (GFR) was estimated by Modification of Diet in Renal Disease Study (Chinese-adjusted) equation and The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. SETTING: Nine nursing homes in Hong Kong PARTICIPANTS: Participants included 812 nursing home older adults (271 men and 571 women), mean age 86.0 ± 7.6. MEASUREMENTS: Prevalence of Stage 3 (GFR 30-59 mL/min/1.73m(2)) and Stages 4 and 5 (GFR <30 mL/min/1.73m(2)) CKD. The comorbidities associated with renal impairment were also assessed. RESULTS: There were 18.4% of nursing home older adults who had elevated serum creatinine levels above the normal limits. Using Modification of Diet in Renal Disease Study and CKD-EPI equations, 26.4% and 21.2% of them had Stage 3 CKD, whereas 6.8% and 4.4% had Stage 4-5 CKD, respectively. Diabetes mellitus, hypertension, congestive heart failure, and ischemic heart disease correlated significantly with moderate to severe renal impairment in Chinese nursing home older adults. CONCLUSION: Stages 3 to 5 CKD are prevalent in Chinese nursing home older adults. Early identification of these patients facilitates drug prescription, renal management, and advance care planning.

Identification of an immunodominant region of the major house dust mite allergen Der p 2 presented by common human leucocyte antigen alleles.

BACKGROUND: Better understanding of the relevance of the immune response to common environmental allergens, such as the major house dust mite (HDM) allergen Der p 2, requires characterization of constituent T-cell epitopes. AIM: To identify CD4(+) T-cell epitopes within Der p 2 recognized by commonly expressed human leucocyte antigen (HLA) alleles. METHODS: HLA-blocking antibodies, peptide pools and truncations were used in ELISpot assays to establish restricted T-cell epitopes. RESULTS: People with and without atopic dermatitis have detectable Der p 2-specific T cells in the peripheral blood, which can proliferate in response to Der p 2 peptides. Interleukin-4-specific responses, both ex vivo and cultured to Der p 2 peptides, had a significant positive correlation with HDM-specific serum IgE. Within one pool of Der p 2 peptides, the 20mer D11 was found to induce multiple responses restricted through several alleles, including HLA-DPB1*0401 and HLA-DRB1*01. CONCLUSIONS: We have identified an immunogenic region of Der p 2 presented by common HLA class II alleles, including the most commonly expressed HLA allele DPB1*0401. Identification of such epitopes may be of future value in peptide immunotherapeutic approaches.

Phenotypic analysis of perennial airborne allergen-specific CD4+ T cells in atopic and non-atopic individuals.

BACKGROUND: Accumulating evidence suggests that T cells play an important role in the pathogenesis of atopic dermatitis (AD); yet, little is known of the differentiation status of CD4+ T cells specific for common environmental allergens, such as the major cat allergen, Fel d 1. OBJECTIVE: To determine the frequency, differentiation phenotype and function of circulating Fel d 1-specific CD4+ T cells in adult individuals with severe persistent AD in comparison with healthy controls. METHODS: Using HLA class II tetrameric complexes based on a HLA-DPB1*0401-restricted Fel d 1 epitope, ex vivo and cultured T cell frequency and phenotype were analysed in individuals with AD and healthy controls. Cytokine secretion was measured by ex vivo and cultured IL-4 and IFN-γ ELISpots. RESULTS: Ex vivo Fel d 1-specific DPB1*0401-restricted CD4+ T cells in both atopics and non-atopics express high levels of CCR7, CD62L, CD27 and CD28, placing the cells largely within the central memory subgroup. However, the functional phenotype was distinct, with greater IL-4 production from the cells derived from atopics, which correlated with disease severity. CONCLUSIONS AND CLINICAL RELEVANCE: Circulating Fel d 1-specific DPB1*0401-restricted CD4+ T cells in both atopic and non-atopic donors maintain a central memory phenotype; however in atopics, the cells had greater Th2 effector function, compatible with a disease model of altered antigen delivery in atopic individuals.

Impact of delayed graft function on renal function and graft survival in deceased kidney transplantation.

OBJECTIVES: To define the risk factors for delayed graft function and study the impact of such delays on renal function and long-term allograft survival in renal transplant recipients. DESIGN: Single-centre retrospective study. SETTING: Regional hospital, Hong Kong. PATIENTS: Records of 118 Chinese renal transplant recipients from 1 July 1997 to 31 July 2005 were reviewed, and categorised into delayed and immediate graft function groups. RESULTS: Delayed graft function was observed in about 19% of patients, for which cold ischaemic time was an important independent predictor. For each additional hour of cold ischaemic time, the odds ratio increased for delayed function by 0.002 (95% confidence interval, 0.001-0.003; P=0.03). Multivariate analysis revealed that neither cold ischaemic time nor delayed graft function was associated with acute rejection. On the other hand, at 1 year both delayed graft function (odds ratio=18.5; 95% confidence interval, 2.6-130.5; P=0.003) and donor age (1.2; 1.1-1.3; P=0.003) were related to a glomerular filtration rate of less than 30 mL/min. When renal function between patients with and without delayed graft function during the first 3 years was compared, it was significantly better in those without delayed graft function. However, there was no significant difference in death-censored graft survival between delayed graft function and immediate graft function groups. CONCLUSIONS: Delayed graft function has a significant adverse effect on graft function at 1 year. Limiting cold ischaemic time is important as it is an independent predictor of delayed graft function.

Prevalence of metabolic syndrome in Chinese renal transplant recipients.

OBJECTIVE: To investigate the prevalence of metabolic syndrome in Chinese renal transplant recipients, using two different sets of diagnostic criteria. DESIGN: Cross-sectional study. SETTING: Regional hospital, Hong Kong. PATIENTS: All Chinese patients who received solitary living-related or cadaveric kidney transplantation from 1 July 1997 to 31 December 2005 in our hospital with follow-up of more than 6 months were recruited. The diagnosis of metabolic syndrome was made according to the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII) criteria and the International Diabetes Federation criteria. RESULTS: Using the modified (Asian) NCEP-ATPIII criteria, a total of 39 (32%) of 121 patients had metabolic syndrome, which included 20/69 (29%) of the males and 19/52 (37%) of the females. Using the International Diabetes Federation criteria, metabolic syndrome was diagnosed in 26% of the patients, 22% in males and 31% in females. In our patients, the most common component of metabolic syndrome was hypertension and the least common was low high-density-lipoprotein-cholesterol level. Low high-density-lipoprotein-cholesterol levels were significantly more common in female patients. CONCLUSION: This study shows that there is a high prevalence of metabolic syndrome in our Chinese renal transplant recipients.

Glutathione peroxidase and glutathione reductase activities are partially responsible for determining the susceptibility of cells to oxidative stress.

Different cell types response differently to toxic insult. In a previous study, it was demonstrated that the C6 glioma cell is more sensitive to Cd induced oxidative stress than the HepG2 cells. To explain the difference between the two cell lines in their response to oxidative stress, it was hypothesized that the activity of glutathione metabolizing enzymes may be different. The objective of this study is to determine the activities of glutathione peroxidase (GPx) and glutathione reductase (GR) in the two cell lines and to explain how these differences may affect the susceptibility of the two cells to oxidative stress. In the HepG2 cells, the activity of GPx was 2.24+/-0.18 micromol/mg protein/min and that for GR was 5.63+/-0.58 micromol/mg protein/min. For the C6 glioma cells, GPx and GR activities were 1.29+/-0.14 and 1.07+/-0.11 micromol/mg protein/min, respectively. Using the kinetic equilibrium: K(eq)=([GSSG]x[NADPH]x[H(+)])/([GSH](2)x[NADP(+)]), and the GSH/GSSG previously published (HepG2: 2.6 and C6 glioma: 3.6), resting NADPH/NADP(+) for the cell lines were calculated. The results showed that NADPH/NADP(+) for HepG2 cells (17.8) is higher than that in the C6 glioma cells (10.8). These data supported the notion that the reducing power (NADPH/NADP(+)) in the HepG2 cells is higher than that in the C6 glioma cell and thus, the later would be more susceptible to oxidative stress. The results also suggested that besides GSH/GSSG, the activities of GPx and GR are important in predicting tissue redox state. Applying this hypothesis to animal tissues, the ratio of the activities of the two enzymes in mouse liver, cerebral cortex, hippocampus and cerebellum were measured. It was demonstrated that the activities of GPx and GR were different in the different tissues studied. The possible correlation between enzymatic activities and the redox state in the different tissues were discussed.

Sodium ramping reduces hypotension and symptoms during haemodialysis.

OBJECTIVES: To evaluate the effectiveness of sodium ramping (profiling) in reducing hypotensive episodes and symptoms during haemodialysis. DESIGN: Prospective study. SETTING: Regional hospital, Hong Kong. PATIENTS: Thirteen patients who experienced frequent episodes of hypotension and/or symptoms such as cramps, dizziness, chest pain, nausea, vomiting, and headache during haemodialysis in the preceding 4 weeks. INTERVENTIONS: Each patient was switched from standard haemodialysis with a constant dialysate sodium concentration of 135 to 140 mmol/L to a ramped sodium haemodialysis for a period of 4 weeks. During this time the dialysate sodium concentration was ramped linearly downwards from 150 mmol/L at the beginning of dialysis to 140 mmol/L at the end of dialysis. MAIN OUTCOME MEASURES: Intradialytic hypotensive episodes, intradialytic symptoms, nursing interventions, systolic and diastolic blood pressures, and interdialytic weight gain. RESULTS: A total of 248 haemodialysis sessions undertaken by 13 patients were analysed. Switching from constant sodium haemodialysis to ramped sodium haemodialysis resulted in a significant reduction in the number of intradialytic hypotensive episodes from 5.8 (standard deviation, 6.4) to 2.2 (3.3) [P<0.05], the total number of intradialytic symptoms from 7.1 (3.4) to 0.9 (1.3) [P<0.01], and nursing interventions from 11.3 (6.3) to 1.7 (3.9) [P<0.01]. Post-dialysis systolic and diastolic blood pressures were higher during ramped sodium haemodialysis compared with constant sodium haemodialysis (systolic blood pressure, 139 [standard deviation, 23] vs 133 [22] mm Hg, P<0.001; diastolic blood pressure, 77 [11] vs 74 [13] mm Hg, P<0.01), and there was a trend towards a smaller drop in blood pressure after dialysis. The interdialytic weight gain with sodium ramping haemodialysis was greater compared with constant sodium haemodialysis (3.1 [standard deviation, 1.0] vs 2.7 [1.1] kg, P<0.001). CONCLUSION: Sodium ramping during haemodialysis effectively reduces hypotensive episodes and intradialytic symptoms. Post-dialysis blood pressure is better maintained. A side-effect of sodium ramping is a greater interdialytic weight gain.

Recurrent acute heart failure caused by sliding hiatus hernia.

The case is reported of a 75 year old woman who presented with recurrent nocturnal episodes of acute pulmonary oedema. The cause was uncertain as she had normal cardiothoracic ratio on chest radiography and normal left ventricular systolic and diastolic function by transthoracic echocardiogram. Another transthoracic echocardiogram was repeated when she was recumbent for an hour and had a full stomach. It showed a striking finding of severe left atrial compression by an external structure. Computed tomography of the thorax showed an intrathoracic mass behind the left atrium causing external compression of the left atrium suggestive of a sliding hiatus hernia. Cardiac catheterisation confirmed the diagnosis by showing a pronounced rise of pulmonary capillary wedge pressure in the recumbent position compared with the sitting up position.

Renal tubular acidosis and severe hypophosphataemia due to toluene inhalation.

A 21-year-old woman developed severe muscle paralysis after sniffing toluene-containing thinner solution for 2 weeks. Her serum chemistries revealed severe hypokalaemia and a normal anion gap hyperchloraemic metabolic acidosis secondary to renal tubular acidosis. Her initial presentation mimicked hypokalaemic periodic paralysis, but toxicology screening of her blood and urine revealed the correct diagnosis of toluene poisoning. Her electrolyte and acid-base status returned to normal 4 days after cessation of toluene sniffing. On another occasion, apart from renal tubular acidosis, the patient also developed severe hypophosphataemia with the phosphate level decreasing to 0.15 mmol/L. Hypophosphataemia with such a low phosphate level after toluene poisoning has been rarely reported in the literature. Toluene inhalation can result in multiple electrolyte and acid-base abnormalities, and should be considered in the diagnosis of any young patient who presents with unexplained hypokalaemia and normal anion gap metabolic acidosis.

Primary immunosuppression with tacrolimus and low-dose mycophenolate mofetil in renal transplant recipients.

Both tacrolimus and mycophenolate mofetil (MMF) are potent immunosuppressive agents used in combination for prevention of acute rejection in renal transplantation. We studied the efficacy and safety of tacrolimus/MMF-based primary immunosuppression as well as their pharmacokinetics (PK) in Chinese renal transplant recipients. Oral tacrolimus was initiated at about 0.2 mg/kg/d, dose which was adjusted to achieve target trough levels of 10 to 20 ng/mL at 3 months and 5 to 10 ng/mL thereafter. The patients also received MMF (0.5 g bid) and prednisolone. PK profiles were studied at 1 week, and 1, 3, and 6 months posttransplant. Blood samples were taken at 0 (predose), 20, 40, 60, 75, and 90 minutes and 2, 4, 6, 8, 10, and 12 hours postdose for each profile. Plasma MPA and whole blood tacrolimus levels were determined by HPLC and EMIT methods respectively. Eight patients were studied with mean follow-up of 16.1 +/- 2.4 months. One patient (12.5%) experienced a borderline acute rejection episode. Both 1-year graft and patient survival rates were 100%. Posttransplant diabetes, diarrhea, and hand tremor occurred in 12.5%, 12.5%, and 37.5%, respectively. No patient had an opportunistic infection. Tacrolimus trough concentrations showed a fair correlation with AUC(0-12h) (R(2) = 0.587). Mean MPA AUC values at 1, 3, and 6 months were 40.5 +/- 9.4, 44.4 +/- 17.3, and 57.2 +/- 20.7 mug*h/mL, respectively (P = .0486, n = 7). In conclusion, primary immunosuppression with tacrolimus, low-dose MMF (0.5 g bid), and prednisolone is effective and safe with adequate systemic MPA exposure in renal transplant recipients.

Hijacking epidermal growth factor receptors by angiotensin II: new possibilities for understanding and treating cardiac hypertrophy.

Activation of the type 1 angiotensin II receptor (AT(1)R) is associated with the aetiology of left ventricular hypertrophy, although the exact intracellular signalling mechanism(s) remain unclear. Transactivation of the epidermal growth factor receptor (EGFR) has emerged as a central mechanism by which the G protein-coupled AT(1)R, which lacks intrinsic tyrosine kinase activity, can stimulate the mitogen-activated protein kinase signalling pathways thought to mediate cardiac hypertrophy. Current studies support a model whereby AT(1)R-dependent transactivation of EGFRs on cardiomyocytes involves stimulation of membrane-bound metalloproteases, which in turn cleave EGFR ligands such as heparin-binding EGF from a plasma membrane-associated precursor. Numerous aspects of the 'triple membrane-passing signalling' paradigm of AT(1)R-induced EGFR transactivation remain to be characterised, including the identity of the specific metalloproteases involved, the intracellular mechanism for their activation and the exact EGFR subtypes required. Here we examine how 'hijacking' of the EGFR might explain the ability of the AT(1)R to elicit the temporally and qualitatively diverse responses characteristic of the hypertrophic phenotype, and discuss the ramifications of delineating these pathways for the development of new therapeutic strategies to combat cardiac hypertrophy.

Candidate genetic polymorphisms for asthma in Chinese schoolchildren from Hong Kong.

BACKGROUND: Polymorphisms in several genes have been associated with asthma, atopy and bronchial hyperresponsiveness in white and Japanese populations. In this study we tested for associations of 11 polymorphisms with wheeze and asthma in 10-year-old Chinese schoolchildren. METHODS: The subjects were 107 children who had wheeze in the last 12 months and 118 without wheeze in the last 12 months. They were randomly selected from 3110 children who took part in Phase II of the International Study of Asthma and Allergies in Childhood. These schoolchildren underwent questionnaire, spirometry and methacholine challenge testing. RESULTS: The A allele of the tumor necrosis factor-alpha (TNFA) G-308A polymorphism was significantly associated with wheeze in the last 12 months (odds ratio [OR] 2.1, P = 0.04) and current asthma (OR 2.6, P = 0.006). When stratified by gender, these associations were only seen in the female study participants. In girls, the OR for the TNFA-308A allele and wheeze in the last 12 months was 3.6 (P = 0.01) and for current asthma it was 6.0 (P = 0.0006). CONCLUSION: The A allele of the TNFA G-308A polymorphism was a risk factor for asthma-related phenotypes in girls but not boys.