Exogenous Nitric Oxide Suppresses in Vivo X-ray-Induced Targeted and Non-Targeted Effects in Zebrafish Embryos.

The present paper studied the X-ray-induced targeted effect in irradiated zebrafish embryos (Danio rerio), as well as a non-targeted effect in bystander naïve embryos partnered with irradiated embryos, and examined the influence of exogenous nitric oxide (NO) on these targeted and non-targeted effects. The exogenous NO was generated using an NO donor, S-nitroso-N-acetylpenicillamine (SNAP). The targeted and non-targeted effects, as well as the toxicity of the SNAP, were assessed using the number of apoptotic events in the zebrafish embryos at 24 h post fertilization (hpf) revealed through acridine orange (AO) staining. SNAP with concentrations of 20 and 100 µM were first confirmed to have no significant toxicity on zebrafish embryos. The targeted effect was mitigated in zebrafish embryos if they were pretreated with 100 µM SNAP prior to irradiation with an X-ray dose of 75 mGy but was not alleviated in zebrafish embryos if they were pretreated with 20 µM SNAP. On the other hand, the non-targeted effect was eliminated in the bystander naïve zebrafish embryos if they were pretreated with 20 or 100 µM SNAP prior to partnering with zebrafish embryos having been subjected to irradiation with an X-ray dose of 75 mGy. These findings revealed the importance of NO in the protection against damages induced by ionizing radiations or by radiation-induced bystander signals, and could have important impacts on development of advanced cancer treatment strategies.

Characteristics and in vitro response of thin hydroxyapatite-titania films produced by plasma electrolytic oxidation of Ti alloys in electrolytes with particle additions.

The enhancement of the biological properties of Ti by surface doping with hydroxyapatite (HA) is of great significance, especially for orthodontic applications. This study addressed the effects of HA particle size in the electrolyte suspension on the characteristics and biological properties of thin titania-based coatings produced on Ti-6Al-4V alloy by plasma electrolytic oxidation (PEO). Detailed morphological investigation of the coatings formed by a single-stage PEO process with two-step control of the electrical parameters was performed using the Minkowski functionals approach. The surface chemistry was studied by glow discharge optical emission spectroscopy and Fourier transform infrared spectroscopy, whereas mechanical properties were evaluated using scratch tests. The biological assessment included in vitro evaluation of the coating bioactivity in simulated body fluid (SBF) as well as studies of spreading, proliferation and osteoblastic differentiation of MC3T3-E1 cells. The results demonstrated that both HA micro- and nanoparticles were successfully incorporated in the coatings but had different effects on their surface morphology and elemental distributions. The micro-particles formed an irregular surface morphology featuring interpenetrated networks of fine pores and coating material, whereas the nanoparticles penetrated deeper into the coating matrix which retained major morphological features of the porous TiO2 coating. All coatings suffered cohesive failure in scratch tests, but no adhesive failure was observed; moreover doping with HA increased the coating scratch resistance. In vitro tests in SBF revealed enhanced bioactivity of both HA-doped PEO coatings; furthermore, the cell proliferation/morphometric tests showed their good biocompatibility. Fluorescence microscopy revealed a well-organised actin cytoskeleton and focal adhesions in MC3T3-E1 cells cultivated on these substrates. The cell alkaline phosphatase activity in the presence of ascorbic acid and ß-glycerophosphate was significantly increased, especially in HA nanoparticle-doped coatings.

Long-term survival outcomes after definitive chemoradiation versus surgery in patients with resectable squamous carcinoma of the esophagus: results from a randomized controlled trial.

BACKGROUND: The aim of this study was to report on the 5-year survival outcomes of patients with resectable esophageal carcinoma who were treated by definitive chemoradiotherapy (CRT) or standard esophagectomy. PATIENTS AND METHODS: Between July 2000 and December 2004, 81 patients with resectable squamous cell carcinoma of the mid- or lower thoracic esophagus were randomized to receive esophagectomy or definitive CRT. The primary outcome was the overall survival and secondary outcomes included disease-free survival, morbidities and mortalities. RESULTS: Forty-five patients received esophagectomy and 36 patients were treated by definitive CRT. The overall 5-year survival favors CRT but the difference did not reach statistical significance (surgery 29.4% and CRT 50%, P=0.147). A trend to improved 5-year survival was observed for patients suffering from node-positive disease (P=0.061). The 5-year disease-free survival also showed a trend to significance favoring CRT (P=0.068), particularly for patients suffering from node-positive disease (P=0.017). Both the stage of the disease and albumin level were significant predictors to mortality and disease-free survival. CONCLUSIONS: Definitive CRT for squamous esophageal carcinoma resulted in comparable long-term survival to surgery. Further large-scale studies would be required to further investigate the role of CRT in node-positive patients. Clinicaltrials.gov identifier: NCT01032967.

A randomized study of aprepitant, ondansetron and dexamethasone for chemotherapy-induced nausea and vomiting in Chinese breast cancer patients receiving moderately emetogenic chemotherapy.

OBJECTIVES: This is a single center, randomized, double-blind placebo-controlled study to evaluate the NK(1)-receptor antagonist, aprepitant, in Chinese breast cancer patients. The primary objective was to compare the efficacy of aprepitant-based antiemetic regimen and standard antiemetic regimen for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients who received moderately emetogenic chemotherapy. The secondary objective was to compare the patient-reported quality of life in these two groups of patients. PATIENTS AND METHODS: Eligible breast cancer patients were chemotherapy-naive and treated with adjuvant AC chemotherapy (i.e. doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2)). Patients were randomly assigned to either an aprepitant-based regimen (day 1, aprepitant 125 mg, ondansetron 8 mg, and dexamethasone 12 mg before chemotherapy and ondansetron 8 mg 8 h later; days 2 through 3, aprepitant 80 qd) or a control arm which consisted of standard regimen (day 1, ondansetron 8 mg and dexamethasone 20 mg before chemotherapy and ondansetron 8 mg 8 h later; days 2 through 3, ondansetron 8 mg bid). Data on nausea, vomiting, and use of rescue medication were collected with a self-report diary, patients quality of life were assessed by self-administered Functional Living Index-Emesis (FLIE). RESULTS: Of 127 patients randomized, 124 were assessable. For CINV in Cycle 1 AC, there was no significant difference in the proportion of patients with reported complete response, complete protection, total control, 'no vomiting', 'no significant nausea' and 'no nausea'. The requirement of rescue medication appears to be lesser in patients treated with the aprepitant-based regimen compared to those with the standard regimen (11% vs. 20%; P = 0.06). Assessment of FLIE revealed that while there was no difference in the nausea domain and the total score between the two groups; however, patients receiving standard antiemetic regimen had significantly worse quality of life in the vomiting domain (mean score [SD] = 23.99 [30.79]) when compared with those who received the aprepitant-based regimen (mean score [SD] = 3.40 [13.18]) (P = 0.0002). Both treatments were generally well tolerated. Patients treated with the aprepitant-based regimen had a significantly lower incidence of neutropenia (53.2% vs. 35.5%, P = 0.0468), grade >or= 3 neutropenia (21.0% vs. 45.2, P = 0.0042) and delay in subsequent cycle of chemotherapy (8.1% vs. 27.4%, P = 0.0048). CONCLUSION: The aprepitant regimen appears to reduce the requirement of rescue medication when compared with the control regimen for prevention of CINV in patients receiving both an anthracycline and cyclophosphamide, and is associated with a better quality of life during adjuvant AC chemotherapy.

Clinicopathological features and prognostic factors of cutaneous melanoma among Hong Kong Chinese.

Cutaneous melanoma is rare among Chinese people. The clinicopathologic features and prognostic factors of 63 Hong Kong ethnic Chinese cases were analysed. We found that the mean age of onset was 65.5 years with a female : male ratio of 1 : 1.33. Forty-two (66.7%) patients had their tumours on their feet. More than 50% had the acral lentiginous histologic subtype. The mean tumour thickness was 5.73 mm with 92.1% (n = 58) having a Clark's level of III or more. Of the tumours, 57.1% were ulcerated. Stage I and II tumours comprised 73% (n = 46) while stage III and IV tumours made up of 26% (n = 17). The 1-, 3- and 5-year survival rates were 75%, 30% and 17%, respectively. Univariate analysis for overall survival showed that advanced clinical staging (stage III and IV), tumour ulceration and thicker tumour (>4 mm) had a significantly poorer prognosis. Multivariate analysis demonstrated that advanced clinical staging was the most decisive prognostic factor followed by tumour ulceration. Our study showed that cutaneous melanoma in Chinese people is a disease predominantly of an older age group with the acral lentiginous histologic type located mainly on the feet. The prognosis depends on clinical staging and ulceration status.

Evaluation of "point of care" devices in the measurement of low blood glucose in neonatal practice.

BACKGROUND: Low blood glucose in newborns is difficult to detect clinically. Hence a reliable "point of care" device (glucometer) for early detection and treatment of low glucose is needed. OBJECTIVE: To evaluate the performance of five readily available glucometers for the detection of low blood glucose in newborn infants. METHOD: Glucostix measurements were taken for newborns with risk factors using a Reflolux S (Boehringer) glucometer. If the initial reading was low (< 2.6 mmol/l), further measurements were taken with two other glucometers (phase I, Advantage and Glucotrend (Roche); phase II, Elite XL (Bayer) and Precision (Abbott)), and plasma glucose was measured in the laboratory (Aeroset; Abbott). RESULTS: Over 10 months, 101 specimens were collected from 71 newborns (57 in phase I; 44 in phase II). The Advantage glucometer usually overestimated blood glucose with a mean difference of 1.07 mmol/l (p < 0.01) at all low glucose ranges. The Glucotrend, Precision, and Elite XL glucometers performed better; the mean differences were not significantly different from the laboratory measured value (0.17 mmol/l (p = 0.37); -0.12 mmol/l (p = 0.13), and 0.24 mmol/l (p = 0.13) respectively). For detection of glucose concentrations < 2.6 mmol/l, the Precision glucometer had the highest sensitivity (96.4%) and negative predictive value (90%). For lower glucose concentrations (< 2.0 mmol/l), the Glucotrend glucometer performed even better (sensitivity 92.3%, negative predictive value 96.3%). CONCLUSION: Point of care devices should have good precision in the low glucose concentration range, sensitivity, and accuracy for early detection of neonatal hypoglycaemia. None of the five glucometers was satisfactory as the sole measuring device. The Glucotrend and Precision glucometers have the greatest sensitivity and negative predictive value. However, confirmation with laboratory measurements of plasma glucose and clinical assessment are still of the utmost importance.

Skin metastasis from nasopharyngeal carcinoma in four Chinese patients.

Nasopharyngeal carcinoma (NPC) is a common malignancy among southern Chinese. The tumours are mostly undifferentiated carcinomas and are associated with Epstein-Barr virus. Patients present with a blood-stained postnasal discharge, impaired hearing, tinnitus or cervical lymph node enlargement. Radiotherapy with or without chemotherapy is the standard treatment. Though metastatic lung, bone or liver disease is not uncommon on relapse, skin metastasis is rarely reported. The small number of reports in the literature are either brief or have only a few patients. In this report, we describe our series of four Hong Kong Chinese patients with NPC who had distant cutaneous metastases.

Extramammary Paget's disease: outcome of radiotherapy with curative intent.

Six patients with extramammary Paget's disease were treated with curative intent radiotherapy. Two of the patients had associated underlying adenocarcinoma. Radiotherapy was given as primary treatment (two patients), definitive treatment for postexcisional relapse (three patients) and adjuvant treatment (one patient). Radiotherapy techniques included high dose rate mould brachytherapy, electron beam, superficial X-ray and photon treatments. Follow-up durations after radiotherapy were 1.2-14.8 years. Complete response was obtained in five patients while one patient had a partial response. Marginal failure occurred in one complete-responder who was successfully salvaged by surgery. The two patients with underlying adenocarcinoma died of distant metastasis. Radiotherapy side effects were acute confluent wet desquamation and mild late skin atrophy. Our results confirmed the useful role of radiotherapy in the management of extramammary Paget's disease.

Epidemiology of diabetes mellitus in children in Hong Kong: the Hong Kong childhood diabetes register.

OBJECTIVES: To establish a registry for Chinese children with onset of type 1 (insulin dependent) diabetes mellitus before 15 years of age and to determine the incidence of childhood onset type 1 diabetes mellitus in Chinese children in Hong Kong. RESEARCH DESIGN AND METHODS: A registry was established in 1997 to collect childhood diabetes cases retrospectively from all districts in Hong Kong. The study included all newly diagnosed cases of diabetes with onset < 15 yr of age from 1st January 1984 to 31 December 1996. Primary ascertainment was based on review of medical records at all regional public hospitals in Hong Kong and survey of all the registered practitioners in Hong Kong. The secondary source of validation was made impractical, if not impossible, because of the recent implementation of the Personal Data Privacy Ordinance in Hong Kong. RESULTS: A total of 255 diabetic cases were identified, 227 type 1 diabetes mellitus (218 were Chinese), 18 type 2 diabetes mellitus and 11 secondary diabetes. 246 patients were Chinese and 9 non-Chinese. The age-standardized incidence of type 1 and type 2 diabetes mellitus in southern Chinese children in Hong Kong was 1.4/100,000/yr and 0.1/100,000/yr respectively for children < 15 yr of age during the study period. The incidence rates for type 1 diabetes were 0.9, 1.5 and 1.7 per 100,000/yr for 0-4 years, 5 to 9 years and 10 to 14 years age-groups respectively. The incidence for males was 1.2/100,000/yr and for females 1.7/100,000/yr. A significant increase in the incidence was demonstrated during the study period by simple linear regression (slope 0.14/100,000/year, r2 = 0.73, p = 0.0002) CONCLUSIONS: A diabetic registry is established in Hong Kong. This study documents a very low incidence rate of childhood type 1 diabetes mellitus in southern Chinese children in Hong Kong and we have seen an increasing incidence of the disease in the past 13 years.

Secular changes in standing height, sitting height and sexual maturation of Chinese--the Hong Kong Growth Study, 1993.

In 1993 a territory-wide cross-sectional growth survey on 25,000 Chinese children from birth to 18 years was performed in Hong Kong. Compared to the last growth survey in 1963, definite secular changes were observed. There was an increase of final adult standing height of 3.6 cm in boys and 2.7 cm in girls, in which 1.8 cm and 0.5 cm respectively for boys and girls was accounted for by the sitting height. Thus most of the height increase had occurred in the leg length in girls, but in boys only half of it. The height difference was more marked during the pubertal years because secular change had brought about an earlier sexual maturation, including an advancement of median menarcheal age by 0.5 year, coupled with an earlier growth spurt. This paper also provides the first growth standards for Chinese from birth to 18 years, with percentile charts on both standing height and sexual maturation in boys and girls.

Secular trend in the sexual maturation of southern Chinese boys.

A random sample of 3872 southern Chinese boys ranging from 7 to 21 years of age were selected from primary and secondary schools in Hong Kong for the assessment of sexual maturation. The median ages of onset of puberty and pubic hair development were 11.4 and 12.7 years, respectively. The advancement of sexual maturation coincides with the secular increase in height and weight for Chinese children in Hong Kong.

Active Ca2+ transport by vesicles reconstituted from Triton X-100-solubilized pigeon erythrocyte membrane.

Pigeon erythrocyte membrane was solubilized partially, but relatively unselectively by Triton X-100. Vesicles were reconstituted from mixtures of Triton-solubilized membrane and lipid (phosphatidylcholine plus phosphatidyl-ethanolamine plus cholesterol) by addition of bovine high-density lipoprotein. This efficiently removed the Triton X-100. Sodium dodecyl sulfate-polyacrylamide gel electropherograms of reconstituted vesicles showed band patterns resembling those of the original membrane. The reconstituted vesicles showed ATP-dependent active accumulation of 45Ca2+. ATP-dependent 45Ca2+ uptake by the reconstituted vesicles resembled the corresponding activity of the original membrane vesicles; in both preparations the Ca2+ uptake rate depended on the square of the Ca2+ concentration and had similar [Ca2+]1/2 values, 0.16 microM and 0.18 microM, respectively.