Prognostic gene expression signature for high-grade serous ovarian cancer.

BACKGROUND: Median overall survival (OS) for women with high-grade serous ovarian cancer (HGSOC) is ∼4 years, yet survival varies widely between patients. There are no well-established, gene expression signatures associated with prognosis. The aim of this study was to develop a robust prognostic signature for OS in patients with HGSOC. PATIENTS AND METHODS: Expression of 513 genes, selected from a meta-analysis of 1455 tumours and other candidates, was measured using NanoString technology from formalin-fixed paraffin-embedded tumour tissue collected from 3769 women with HGSOC from multiple studies. Elastic net regularization for survival analysis was applied to develop a prognostic model for 5-year OS, trained on 2702 tumours from 15 studies and evaluated on an independent set of 1067 tumours from six studies. RESULTS: Expression levels of 276 genes were associated with OS (false discovery rate < 0.05) in covariate-adjusted single-gene analyses. The top five genes were TAP1, ZFHX4, CXCL9, FBN1 and PTGER3 (P < 0.001). The best performing prognostic signature included 101 genes enriched in pathways with treatment implications. Each gain of one standard deviation in the gene expression score conferred a greater than twofold increase in risk of death [hazard ratio (HR) 2.35, 95% confidence interval (CI) 2.02-2.71; P < 0.001]. Median survival [HR (95% CI)] by gene expression score quintile was 9.5 (8.3 to -), 5.4 (4.6-7.0), 3.8 (3.3-4.6), 3.2 (2.9-3.7) and 2.3 (2.1-2.6) years. CONCLUSION: The OTTA-SPOT (Ovarian Tumor Tissue Analysis consortium - Stratified Prognosis of Ovarian Tumours) gene expression signature may improve risk stratification in clinical trials by identifying patients who are least likely to achieve 5-year survival. The identified novel genes associated with the outcome may also yield opportunities for the development of targeted therapeutic approaches.

Isokinetic Fatigue Ratio of Shoulder Rotators in Elite Softball Players With and Without Rotator Cuff Tendinopathy, and its Association With the Subacromial Space.

CONTEXT: Fatigue of the shoulder rotators may cause reduction of the subacromial space (SAS) and contribute to rotator cuff tendinopathy. OBJECTIVES: To compare the isokinetic peak torques and fatigue ratios of shoulder external rotators (ER) and internal rotators (IR) between elite softball athletes with and without rotator cuff tendinopathy and to investigate their associations with the SAS. DESIGN: Cross-sectional study. SETTING: University laboratory. PARTICIPANTS: Twenty-five elite softball players and 31 asymptomatic sedentary controls participated in this study. MAIN OUTCOME MEASURES: Isokinetic concentric IR and ER peak torque and fatigue ratio were measured at 60°/s and at 180°/s, respectively; and ultrasound measurement of the SAS was measured during 0° and 60° of shoulder abduction. RESULTS: Athletes with rotator cuff tendinopathy demonstrated lower peak torque in shoulder concentric ER when compared with their healthy counterparts (37.8 [5.8%] vs 43.6 [8.5%]). No significant difference was found in the fatigue ratios of ER, IR, and ER/IR when compared between elite softball athletes with and without rotator cuff tendinopathy (all P > .24). In asymptomatic athletes, greater IR peak torque (r = .583, P = .03), lower ER/IR strength ratio (r = -.605, P = .02), and greater ER/IR fatigue ratio (r = .575, P = .03) were moderately associated with more reduction of the SAS during 0° and 60° of shoulder abduction. CONCLUSIONS: Decreased strength ratio and fatigue ratio of ER/IR were related to reduction of the SAS.

Joint recommendations on management of anaemia in patients with gastrointestinal bleeding in Hong Kong.

The demand for blood products continues to grow in an unsustainable manner in Hong Kong. While anaemia associated with gastrointestinal bleeding (GIB) is the leading indication for transfusion, there is no local recommendation regarding best practices for transfusion. We aimed to provide evidence-based recommendations regarding management of anaemia in patients with acute and chronic GIB. We reviewed all original papers, meta-analyses, systematic reviews, or guidelines that were available in PubMed. For acute GIB, a restrictive transfusion strategy, targeting a haemoglobin threshold of 7 to 8 g/dL, should be adopted because overtransfusion is associated with significantly higher all-cause mortality and re-bleeding. A liberal transfusion strategy should only be considered in patients with co-existing symptomatic coronary artery disease, targeting a haemoglobin threshold of 9 to 10 g/dL. When acute GIB settles, patients should be prescribed iron supplements if iron deficiency is present. For chronic GIB, iron stores should be replenished aggressively via iron supplementation before consideration of blood transfusion, except in patients with symptoms of severe anaemia. Oral iron replacement is the preferred first-line therapy, while intravenous iron is indicated for patients with inflammatory bowel disease, poor response or poor tolerability to oral iron, and in whom a rapid correction of iron deficit is preferred. Intravenous iron is underutilised and the risk of anaphylactic reaction to current preparations is extremely low. These recommendations are provided to local clinicians to facilitate judicious and appropriate use of red cell products and iron replacement therapy in patients with GIB.

In-situ medical simulation for pre-implementation testing of clinical service in a regional hospital in Hong Kong.

The implementation of a new clinical service is associated with anxiety and challenges that may prevent smooth and safe execution of the service. Unexpected issues may not be apparent until the actual clinical service commences. We present a novel approach to test the new clinical setting before actual implementation of our endovascular aortic repair service. In-situ simulation at the new clinical location would enable identification of potential process and system issues prior to implementation of the service. After preliminary planning, a simulation test utilising a case scenario with actual simulation of the entire care process was carried out to identify any logistic, equipment, settings or clinical workflow issues, and to trial a contingency plan for a surgical complication. All patient care including anaesthetic, surgical, and nursing procedures and processes were simulated and tested. Overall, 17 vital process and system issues were identified during the simulation as potential clinical concerns. They included difficult patient positioning, draping pattern, unsatisfactory equipment setup, inadequate critical surgical instruments, blood products logistics, and inadequate nursing support during crisis. In-situ simulation provides an innovative method to identify critical deficiencies and unexpected issues before implementation of a new clinical service. Life-threatening and serious practical issues can be identified and corrected before formal service commences. This article describes our experience with the use of simulation in pre-implementation testing of a clinical process or service. We found the method useful and would recommend it to others.

Intravenous lignocaine infusion facilitates acute rehabilitation after laparoscopic colectomy in the Chinese patients.

INTRODUCTION: Intravenous infusion of lignocaine has emerged in recent years as a feasible, cost-effective, and safe method to provide postoperative analgesia. There is, however, no literature about this perioperative pain control modality in Chinese patients. This study aimed to determine whether perioperative intravenous lignocaine safely reduces postoperative pain, shortens postoperative ileus, and reduces the length of hospital stay in laparoscopic colorectal surgery. METHODS: Between September 2012 and May 2015, 16 patients who underwent elective laparoscopic resection of colorectal cancer and received a 1% lignocaine infusion for 24 hours postoperatively were studied. After surgery, categorical pain scores were obtained immediately, followed by hourly pain scores at rest. Pain scores at rest and with mobilisation, and patient satisfaction score were documented on postoperative day 1. Return of bowel function was measured by time of first flatus and bowel opening. The patient's rehabilitation was assessed by time taken to tolerate diet, full mobilisation, and length of hospital stay. RESULTS: The median (interquartile range) self-reported pain scores at 2 hours and 6 hours after surgery were 1.5 (0-4) and 2 (0-3), respectively. The median pain scores at rest and mobilisation on postoperative day 1 were 1 (0-2.5) and 2 (2.5-5), respectively, with a median satisfaction score of 7.5 (7-9). The median times to first flatus and first bowel opening were 21 (18-35) hours and 3 (1-3) days, respectively. No patient had postoperative ileus. The median times to tolerating diet and mobilisation were 1 (1-1) day and 2 (2-3) days, respectively. The median postoperative stay was 6 (5-8) days. CONCLUSIONS: Intravenous lignocaine is a safe and effective postoperative analgesic in a Chinese population. It enhances the rehabilitation process for patients following laparoscopic resection of colorectal cancer.

Colorectal endoscopic submucosal dissection at a low-volume centre: tips and tricks, and learning curve in a district hospital in Hong Kong.

INTRODUCTION: Colorectal endoscopic submucosal dissection is not a widely adopted procedure due to its technical difficulties. This study aimed to share the experience in setting up this novel procedure and to report the learning curve for such a procedure at a low-volume district hospital in Hong Kong. METHODS: This case series comprised 71 colorectal endoscopic submucosal dissections that were performed by a single endoscopist without experience in gastric or colorectal endoscopic submucosal dissection. Lesion characteristics, procedure time per unit area of tumour, en-bloc resection rate, R0 resection rate, complications, and length of stay were recorded prospectively. Results were compared for two consecutive periods to study the learning curve. RESULTS: Overall, 41 (57.7%) tumours were located in the right colon, 21 (29.6%) in the left colon, and nine (12.7%) in the rectum. The median tumour area was 4 cm(2) (range, 0.25-16 cm(2)). The median operating time was 105 (range, 47-342) minutes. The median procedure time per unit area of tumour was 24.9 min/cm(2). There was one instance of intra-operative bleeding that required conversion to laparoscopic colectomy. There was no postoperative haemorrhage. The overall perforation rate was 15.5%, in which one required conversion to laparoscopic colectomy. The overall morbidity rate was 16.9% and there was no mortality. The median hospital stay was 1 day (range, 0-11 days). The overall en-bloc resection rate and R0 resection rate was 81.2% and 58.0%, respectively. Comparison of the two study periods revealed that procedure time per unit area of tumour decreased significantly from 31.5 min/cm(2) to 21.5 min/cm(2) (P=0.032). The en-bloc resection rate improved from 78.8% to 83.3% (P=0.15). The R0 resection rate improved significantly from 39.4% to 75.0% (P<0.01). CONCLUSION: Untutored colorectal endoscopic submucosal dissection is feasible with acceptable clinical outcomes at a low-volume district hospital in Hong Kong.

Preparation of alpha-bisabolol and phenylethyl resorcinol/TiO2 hybrid composites for potential applications in cosmetics.

OBJECTIVE: Bifunctional alpha-bisabolol and phenylethyl resorcinol/TiO2 hybrids were prepared to apply in cosmetic fields, particularly in anti-ageing and hyperpigmentation treatment. The synergistic effect of combined antioxidant and UV filtering properties was achieved through functionalization of TiO2 particles with skin-lightening materials such as alpha-bisabolol and phenylethyl resorcinol. METHODS: TiO2 microspheres with a diameter of about 1 µm were synthesized through surfactant-assisted sol-gel method for use as supporting materials in the formation of hybrid composites. Carboxylation treatment was performed for surface modification of the TiO2 surface with carboxyl groups as chemical binders. Esterification reaction between carboxyl groups of carboxylated TiO2 and hydroxyl groups of alpha-bisabolol or phenylethyl resorcinol was performed. The hybrids were characterized using various techniques such as FE-SEM, DLS, EDS, ATR-FTIR, XPS and TGA. For application of prepared TiO2 composites in the field of cosmetics, the anti-radicular antioxidant abilities were evaluated using ABTS and DPPH colorimetric antioxidant assay. RESULTS: Organic/inorganic hybrid composites were successfully formed using esterification reaction between the carboxyl groups at TiO2 surface and the hydroxyl groups of the skin-lightening materials. The results demonstrate that both functionalized microspheres show scavenging ability towards the ABTS(•) and DPPH(•) radicals. Specifically, the phenylethyl resorcinol/TiO2 composites exhibited the highest antioxidant ability among the prepared samples owing to the presence of phenolic groups to scavenge free radicals. CONCLUSION: Using this strategy, it could be possible to prepare not only inorganic UV filter but also hybrid organic/inorganic materials with multifunctions and advantages which would be in a great demand for cosmetic applications.

Whole exome sequencing is an efficient, sensitive and specific method for determining the genetic cause of short-rib thoracic dystrophies.

Short-rib thoracic dystrophies (SRTDs) are congenital disorders due to defects in primary cilium function. SRTDs are recessively inherited with mutations identified in 14 genes to date (comprising 398 exons). Conventional mutation detection (usually by iterative Sanger sequencing) is inefficient and expensive, and often not undertaken. Whole exome massive parallel sequencing has been used to identify new genes for SRTD (WDR34, WDR60 and IFT172); however, the clinical utility of whole exome sequencing (WES) has not been established. WES was performed in 11 individuals with SRTDs. Compound heterozygous or homozygous mutations were identified in six confirmed SRTD genes in 10 individuals (IFT172, DYNC2H1, TTC21B, WDR60, WDR34 and NEK1), giving overall sensitivity of 90.9%. WES data from 993 unaffected individuals sequenced using similar technology showed two individuals with rare (minor allele frequency <0.005) compound heterozygous variants of unknown significance in SRTD genes (specificity >99%). Costs for consumables, laboratory processing and bioinformatic analysis were

Plasmacytoid dendritic cell dichotomy: identification of IFN-α producing cells as a phenotypically and functionally distinct subset.

Plasmacytoid dendritic cells (pDC) produce large amounts of type I IFN in response to invading pathogens, but can also suppress immune responses and promote tolerance. In this study, we show that in mice, these functions are attributable to two distinct pDC subsets, one of which gives rise to the other. CD9(pos)Siglec-H(low) pDC secrete IFN-α when stimulated with TLR agonists, induce CTLs, and promote protective antitumor immunity. By contrast, CD9(neg)Siglec-H(high) pDC secrete negligible amounts of IFN-α, induce Foxp3(+) CD4(+) T cells, and fail to promote antitumor immunity. Although newly formed pDC in the bone marrow are CD9(pos) and are capable of producing IFN-α, after these cells traffic to peripheral tissues, they lose CD9 expression and the ability to produce IFN-α. We propose that newly generated pDC mobilized from the bone marrow, rather than tissue-resident pDC, are the major source of IFN-α in infected hosts.

A metabolomic study of low estimated GFR in non-proteinuric type 2 diabetes mellitus.

AIMS/HYPOTHESIS: We carried out a urinary metabolomic study to gain insight into low estimated GFR (eGFR) in patients with non-proteinuric type 2 diabetes. METHODS: Patients were identified as being non-proteinuric using multiple urinalyses. Cases (n = 44) with low eGFR and controls (n = 46) had eGFR values <60 and ≥60 ml min(-1) 1.73 m(-2), respectively, as calculated using the Modification of Diet in Renal Disease formula. Urine samples were analysed by liquid chromatography/mass spectrometry (LC/MS) and GC/MS. False discovery rates were used to adjust for multiple hypotheses testing, and selection of metabolites that best predicted low eGFR status was achieved using least absolute shrinkage and selection operator logistic regression. RESULTS: Eleven GC/MS metabolites were strongly associated with low eGFR after correction for multiple hypotheses testing (smallest adjusted p value = 2.62 × 10(-14), largest adjusted p value = 3.84 × 10(-2)). In regression analysis, octanol, oxalic acid, phosphoric acid, benzamide, creatinine, 3,5-dimethoxymandelic amide and N-acetylglutamine were selected as the best subset for prediction and allowed excellent classification of low eGFR (AUC = 0.996). In LC/MS, 19 metabolites remained significant after multiple hypotheses testing had been taken into account (smallest adjusted p value = 2.04 × 10(-4), largest adjusted p value = 4.48 × 10(-2)), and several metabolites showed stronger evidence of association relative to the uraemic toxin, indoxyl sulphate (adjusted p value = 3.03 × 10(-2)). The potential effect of confounding on the association between metabolites was excluded. CONCLUSIONS/INTERPRETATION: Our study has yielded substantial new insight into low eGFR and provided a collection of potential urinary biomarkers for its detection.

Exon-array profiling unlocks clinically and biologically relevant gene signatures from formalin-fixed paraffin-embedded tumour samples.

BACKGROUND: Degradation and chemical modification of RNA in formalin-fixed paraffin-embedded (FFPE) samples hamper their use in expression profiling studies. This study aimed to show that useful information can be obtained by Exon-array profiling archival FFPE tumour samples. METHODS: Nineteen cervical squamous cell carcinoma (SCC) and 9 adenocarcinoma (AC) FFPE samples (10-16-year-old) were profiled using Affymetrix Exon arrays. The gene signature derived was tested on a fresh-frozen non-small cell lung cancer (NSCLC) series. Exploration of biological networks involved gene set enrichment analysis (GSEA). Differential gene expression was confirmed using Quantigene, a multiplex bead-based alternative to qRT-PCR. RESULTS: In all, 1062 genes were higher in SCC vs AC, and 155 genes higher in AC. The 1217-gene signature correctly separated 58 NSCLC into SCC and AC. A gene network centered on hepatic nuclear factor and GATA6 was identified in AC, suggesting a role in glandular cell differentiation of the cervix. Quantigene analysis of the top 26 differentially expressed genes correctly partitioned cervix samples as SCC or AC. CONCLUSION: FFPE samples can be profiled using Exon arrays to derive gene expression signatures that are sufficiently robust to be applied to independent data sets, identify novel biology and design assays for independent platform validation.

Vitamins B-12 and C Supplementation Improves Arterial Reactivity and Structure in Passive Smokers: Implication in Prevention of Smoking-Related Atherosclerosis.

BACKGROUND: Atherosclerosis is an important medical problem of modern society. High environmental tobacco smoke in casino is associated with an accelerated atherogenic process. We have previously shown vitamin B12 and C supplementation improves vascular reactivity and may be beneficial in vascular protection. OBJECTIVE: To evaluate the impact of vitamin supplementation on atherosclerosis (brachial artery reactivity FMD and carotid intima-media thickness IMT) in subjects exposed to high environmental tobacco smoke. DESIGN: Double-blind 2x2 factorial design fashion. SETTING: Computer randomization in 4 treatment groups: placebo (n=24), vitamin B12 (n=21), vitamin C (n=23) and vitamin B12+C (n=23) groups. PARTICIPANTS: 91 passive-smoking casino employees (19.2% male, mean age 45.0±8.2 years). INTERVENTION: Subjects were randomized to receive vitamin B12 (500µg daily), vitamin C (200mg daily), vitamin B12+C or image-matched placebo capsules for 1 year. MEASUREMENT: Brachial FMD and carotid IMT (surrogate atherosclerotic markers) were measured by ultrasound at baseline and on completion at 12 months. METHODS: 91 passive smoking casino employees (19.2% male, mean age 45.0±8.2 years) were randomized to receive vitamin B12 (500µg daily), vitamin C (200mg daily), vitamin B12+C or image-matched placebo capsules in double-blind 2 x 2 factorial design fashion for 1 year. Brachial FMD and carotid IMT (surrogate atherosclerotic markers) were measured by ultrasound at baseline and 12 months. RESULTS: Of the 78 (85.7%) passive-smoking employees completed the study, 11.5% had hypertension, 5.1% diabetes mellitus and 15.4% hypercholesterolemia. There were no significant changes in their blood pressures, lipid profiles, glucose and body mass index after supplementation for 1 year, but mild decrease in DBP (p<0.001) and blood creatinine (p<0.01) after combined vitamin B12 and C, and significant increase in blood B12 after vitamin B12 (p<0.01) and vitamin B12+C supplementations (p<0.001). Brachial FMD and cartotid IMT improved after the 3 vitamin supplementations (p<0.001), but not after placebo, being more significant after combined vitamin supplementations (p<0.0001). No adverse effects were reported. CONCLUSION: Vitamin B12 or C supplementation in passive smokers improved vascular reactivity and structures at 1 year, with implication in long term atherosclerosis prevention.

Barriers to implementing a national health screening program for men in Malaysia: An online survey of healthcare providers.

INTRODUCTION: This study aimed to determine the views and practices of healthcare providers and barriers they encountered when implementing the national health screening program for men in a public primary care setting in Malaysia. METHODS: An online survey was conducted among healthcare providers across public health clinics in Malaysia. All family medicine specialists, medical officers, nurses and assistant medical officers involved in the screening program for adult men were invited to answer a 51-item questionnaire via email or WhatsApp. The questionnaire comprised five sections: participants' socio-demographic information, current screening practices, barriers and facilitators to using the screening tool, and views on the content and format of the screening tool. RESULTS: A total of 231 healthcare providers from 129 health clinics participated in this survey. Among them, 37.44% perceived the implementation of the screening program as a "top-down decision." Although 37.44% found the screening tool for adult men "useful," some felt that it was "time consuming" to fill out (38.2%) and "lengthy" (28.3%). In addition, 'adult men refuse to answer' (24.1%) was cited as the most common patient-related barrier. CONCLUSIONS: This study provided useful insights into the challenges encountered by the public healthcare providers when implementing a national screening program for men. The screening tool for adult men should be revised to make it more user-friendly. Further studies should explore the reasons why men were reluctant to participate in health screenings, thus enhancing the implementation of screening programs in primary care.

Nurse-administered propofol-alfentanil sedation using a patient-controlled analgesia pump compared with opioid-benzodiazepine sedation for outpatient colonoscopy.

BACKGROUND AND STUDY AIM: Nurse-administered propofol sedation (NAPS) and patient-controlled sedation using patient-controlled analgesia (PCA) pumps are gaining increasing popularity for gastrointestinal endoscopy. We compared the safety and efficacy of NAPS using PCA pumps with diazemuls-pethidine sedation (DPS) for outpatient colonoscopy. PATIENTS AND METHODS: In a prospective randomized controlled trial patients underwent outpatient colonoscopy with sedation by either NAPS or DPS. For NAPS, following intravenous loading of 0.8 mg/kg propofol, mixtures of 14.3 mg propofol and 35 microgram alfentanil were titrated by nurses using a PCA pump. For DPS, 0.1 mg/kg diazemuls and 0.5 mg/kg pethidine were given as intravenous bolus; further titration was administered as half doses at the endoscopist's discretion. Adequacy of sedation was measured by the Observer's Scale for Sedation and Alertness (OSSA) score (range 1-5). RESULTS: Between July 2005 and June 2006, 88 patients were randomly allocated to NAPS and 90 to DPS. The groups were comparable for baseline characteristics and procedure time. With NAPS, levels of sedation both during colonoscopic intubation and at reaching the cecum were significantly deeper than with DPS (OSSA 3 vs. 5, P < 0.0001). There were no significant differences in cardiopulmonary complication rates, pain scores, satisfaction scores, and patients' willingness to repeat colonoscopy with the same sedation. Drugs cost for NAPS was higher than for DPS (Hong Kong dollars [HKD] 98.34 vs. 5.01). CONCLUSION: Despite higher costs, nurse-administered propofol-alfentanil sedation using a PCA pump can provide deeper conscious sedation, comparable satisfaction, and similar complication risks compared with conventional opioid-benzodiazepine sedation.

Vimentin autoantibodies induce platelet activation and formation of platelet-leukocyte conjugates via platelet-activating factor.

Anti-vimentin antibodies (AVA) are associated with autoimmunity and solid organ transplantation, conditions associated with vascular disease, but their contribution to disease pathogenesis is unknown. Here, we have examined interactions between AVA (mAb and serum from patients) and various leukocyte populations using whole blood and flow cytometry. Normal blood treated with patient sera containing high AVA-IgM titers or with a vimentin-specific monoclonal IgM led to activation of platelets and other leukocytes, as demonstrated by induced expression of P-selectin, fibrinogen, tissue factor, and formation of platelet:leukocyte (P:L) conjugates and a reduction in platelet counts. This activity was antigen (vimentin)-specific and was not mediated by irrelevant IgM antibodies. Flow cytometry demonstrated that AVA do not bind directly to resting platelets in whole blood, but they bind to approximately 10% of leukocytes. Supernatant, derived from AVA-treated leukocytes, induced platelet activation, as measured by the generation of platelet microparticles, when added to platelet-rich plasma. When AVA were added to whole blood in the presence of CV-6209, a platelet-activating factor (PAF) receptor inhibitor, platelet depletion was inhibited. This suggests that PAF is one of the mediators released from AVA-activated leukocytes that leads to P:L conjugation formation and platelet activation. In summary, AVA bind to leukocytes, resulting in release of a PAF and prothrombotic factor that exert a paracrine-activating effect on platelets. Overall, this proposed mechanism may explain the pathogenesis of thrombotic events in autoimmune diseases associated with AVA.

Scan-directed unilateral neck exploration for primary hyperparathyroidism: eight-year results from a regional hospital.

OBJECTIVE: To determine the results of scan-directed unilateral neck exploration for primary hyperparathyroidism. DESIGN: Retrospective study. SETTING: Regional hospital, Hong Kong. PATIENTS: Patients who underwent parathyroid surgery for primary hyperparathyroidism between January 2000 and December 2007 were included. MAIN OUTCOME MEASURES: The demographic, imaging, biochemical, and pathological data, as well as surgical outcomes were analysed according to the treatment received. RESULTS: A total of 78 patients were included in this study; 65 underwent unilateral neck exploration with image guidance by ultrasonography or technetium Tc99m sestamibi scan. The scan sensitivity for localising the side of the lesion was 66% for ultrasound scans, 71% for technetium Tc99m sestamibi scans, and 85% for both scans used in combination. Pathological analysis showed that 95% (74/78) of the patients had a single parathyroid adenoma, two had hyperplasia of four glands, one had a double adenoma, and one a parathyroid carcinoma. Among the patients undergoing scan-directed unilateral neck exploration, one defaulted follow-up, while the remaining 64 patients achieved normal calcium levels at a median follow-up of 6 months. CONCLUSION: Scan-directed unilateral neck exploration is a safe alternative form of treatment for patients with primary hyperparathyroidism, with a cure rate similar to conventional therapy.

Effects of putative stressors in public aquaria on locomotor activity, metabolic rate and cortisol levels in the Mozambique tilapia Oreochromis mossambicus.

Mozambique tilapia Oreochromis mossambicus were housed individually during 7 days in a continuous flow-trough respirometry system and daily exposed to one of three treatments: (1) a series of knocks on the side of the aquarium, (2) a series of photo-flashes and (3) control group. Exposure to photo-flashes did not change locomotor activity but decreased both night-time and daytime oxygen consumption throughout the experiment. Knocking induced a short-lived increase in locomotor activity and tended to increase oxygen consumption, but this latter effect was not significant. Night-time oxygen consumption was not affected by knocking exposure. Cortisol levels assayed from fish-holding water collected at the end of the experiment were significantly lower in subjects exposed to photo-flashes than in subjects exposed to knocks or controls. Males did not respond differently than females to the treatments in any of the measurements taken. In summary, the data reported here suggest that exposure to repetitive photo-flashes, but not knocking, suppressed normal energy metabolism and cortisol levels. These effects were present hours to a half day after exposure to the flashes.

Reduced GFR and albuminuria in Chinese type 2 diabetes mellitus patients are both independently associated with activation of the TNF-alpha system.

AIMS/HYPOTHESIS: The involvement of chronic inflammation in albuminuria and renal function was investigated in a cross-sectional study of 320 type 2 diabetic Chinese patients from the Singapore Diabetes Cohort Study. METHODS: Plasma levels of TNF-alpha and its two cellular receptors and of IL-6 and C-reactive protein (CRP) were measured. A composite TNF-alpha score was extracted using principal component analysis. Multiple linear regression analysis was implemented to evaluate the relationship between log( e ) (ln) albumin:creatinine ratio (ACR) and estimated GFR (eGFR) with the inflammatory variables and other clinical covariates. A Bonferroni correction was applied based on the total number of variables entered into regression analyses. RESULTS: ln ACR was significantly associated with TNF-alpha score independently of eGFR even after a Bonferroni correction. TNF-alpha score was also significantly associated with eGFR independently of ln ACR even after correction for multiple testing. These findings were similar when the individual molecules of the TNF-alpha system were analysed separately instead of using the composite TNF-alpha score. No association was observed for IL-6 and CRP with either renal trait. Diabetes duration was a significant predictor for ln ACR but not eGFR. Conversely, age was significantly associated with eGFR but not ln ACR. CONCLUSIONS/INTERPRETATION: Activation of the TNF-alpha system may potentially exert independent effects on ln ACR and eGFR in type 2 diabetes. Because of the study design, one may also consider the possibility that changes in these renal traits may conversely be responsible for such an inflammatory response.