Effects of primary granulocyte-colony stimulating factor prophylaxis on neutropenic toxicity and chemotherapy dose delivery in Chinese patients with breast cancer who received adjuvant docetaxel plus cyclophosphamide chemotherapy: a retrospective cohort study.

INTRODUCTION: This study was performed to examine the effects of primary granulocyte-colony stimulating factor (G-CSF) prophylaxis on neutropenic toxicity, chemotherapy delivery, and hospitalisation among Chinese patients with breast cancer in Hong Kong. METHODS: This retrospective study included patients with breast cancer who received adjuvant docetaxel plus cyclophosphamide chemotherapy from November 2007 to October 2013 at Princess Margaret Hospital. Data were collected regarding the usage of G-CSF prophylaxis; incidences of grade 3 or 4 neutropenia, febrile neutropenia, non-neutropenic fever, and infection; hospital admissions, and chemotherapy dose delivery. Patients who began to receive G-CSF prophylaxis during the first cycle of chemotherapy and continued such prophylaxis in subsequent cycles were regarded as the primary G-CSF prophylaxis group. RESULTS: In total, 231 female Chinese patients with breast cancer were included in the analysis. Overall, 193 (83.5%) patients received primary G-CSF prophylaxis. The demographics and tumour characteristics were comparable between patients with and without primary G-CSF prophylaxis. Primary G-CSF prophylaxis significantly reduced febrile neutropenia incidence from 31.6% to 14.5% (relative risk=0.45, 95% confidence interval=0.25-0.81). Primary G-CSF prophylaxis also significantly reduced the incidence of grade 3 or 4 neutropenia from 57.9% to 24.7% (relative risk=0.43, 95% confidence interval=0.30-0.62) and the incidence of febrile neutropenia-related hospital admission from 31.6% to 12.4% (P=0.025). Finally, it enabled more patients to receive adequate chemotherapy dose delivery. CONCLUSION: Primary G-CSF prophylaxis effectively reduced the incidences of grade 3 or 4 neutropenia and febrile neutropenia, while enabling adequate chemotherapy dose delivery and reducing hospital admissions among Chinese patients with breast cancer who received adjuvant docetaxel plus cyclophosphamide chemotherapy.

Fluctuation of BCR-ABL1 qPCRIS level beyond 0.1%IS after stopping tyrosine kinase inhibitor in chronic myeloid leukaemia patients with deep molecular response for at least two years.

Fluctuation of BCR-ABL1 real-time quantitative polymerase chain reaction in International Scale (qPCRIS) level below major molecular response (MMR) (0.1%IS) is a known phenomenon after stopping tyrosine kinase inhibitor (TKI) in chronic myeloid leukaemia (CML) patients who are attempting treatment free remission (TFR). We report here four cases of fluctuation beyond MMR during conduct of a Malaysia Stop TKI Trial (MSIT) to examine the validity of the commonly used relapse criterion - loss of MMR for one reading - aiming to provide evidence in setting relapse criteria for future CML patients who want to attempt TFR.

Correction to: Adipokines and the insulin resistance syndrome in familial partial lipodystrophy caused by a mutation in lamin A/C.

The authors regret that Alexandra Bargiota's name was spelt incorrectly in the author list. The details given in this correction are correct.

Spirometric reference standards for preschool children in Hong Kong.

1. Prediction equations and normograms are established using incentive spirometry in a community cohort of 770 Hong Kong Chinese children aged 2 to 6 years. 2. All spirometric parameters depend mainly on standing height. Boys have higher values than girls. 3. Forced expiratory volumes depend on birth weight, place of birth, history of wheezing, and environmental tobacco smoke (ETS) exposure. 4. High urinary cotinine level as a biomarker of ETS exposure is noted in about one tenth of the children. 5. Urinary cotinine level is inversely associated with all spirometric parameters. This supports implementation of the smoking cessation programme.

Biological properties of sodium alkyl methyl ester sulfonate/alkyltrimethylammonium bromide surfactant mixtures.

Quaternary ammonium compounds (QACs) are commonly used as disinfectant in medical care, food industry, detergents and glue industries. This is due to a small concentration of QACs is sufficient to inhibit the growth of various bacteria strains. In this work, the inhibitive power of cationic surfactants, alkyltrimethylammonium bromide (C(n)TAB) in the presence of anionic surfactants, sodium alkyl methyl ester α-sulfonate (C(n)MES) was studied. The growth inhibition test with gram-positive (Staphylococcus aureus) and gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacteria were used to determine the toxicity of single and mixed surfactants. Results from this work showed that certain mixed surfactants have lower minimum inhibition concentration (MIC) as compared to the single C(n)TAB surfactants. Besides that, it was also found that alkyl chain length and the mixing ratios of the surfactants play a significant role in determining the mixture inhibitive power.

Ghrelin does not orchestrate the metabolic changes seen in fasting but has significant effects on lipid mobilisation and substrate utilisation.

OBJECTIVE: Short-term fasting is associated with increased GH pulsatility and mobilisation of fats, but underlying mechanisms are unclear. We studied ghrelin's role during fasting and the effects of exogenous ghrelin on lipid mobilisation. DESIGN: Randomised placebo-controlled study. METHODS: In this study, ten controls (body mass index (BMI) 23.3±3.2), ten morbidly obese subjects (BMI 50.1±10.6) and six post-gastrectomy subjects (BMI 25.2±1.0) were fasted for 36  h undergoing regular blood sampling. On a separate occasion, subjects were infused with either i.v. ghrelin (5  pmol/kg per min) or saline over 270  min. RESULTS: Obese and post-gastrectomy subjects had lower ghrelin compared with controls (ANOVA, P=0.02) during the fast. Controls and gastrectomy subjects showed a similar increase in GH pulsatility, circulating non-esterified fatty acids (NEFA) and 3ß-hydroxybutyrate (3 HB). Obese subjects had an impaired GH response (P<0.001), reduced excursions of 3 HB (P=0.01) but no change in NEFA excursions (P=0.09) compared with controls. Ghrelin infusion increased GH, NEFA and ketone bodies (ANOVA, P<0.0001) in all the three groups, but GH response was impaired in the obese subjects (P=0.001). Ghrelin also induced a significant (ANOVA, P=0.004) biphasic NEFA response to meals in all the subjects. CONCLUSIONS: Despite low circulating ghrelin, gastrectomy subjects maintain a normal metabolic response to fasting, implying that ghrelin plays a minimal role. In contrast, infused ghrelin has significant effects on lipid mobilisation and induces a marked biphasic NEFA response to meals. Hence, ghrelin may play a significant role in meal-related substrate utilisation and metabolic flexibility.

Non-viral S/MAR vectors replicate episomally in vivo when provided with a selective advantage.

The ideal gene therapy vector should enable persistent expression without the limitations of safety and reproducibility. We previously reported that a prototype plasmid vector, containing a scaffold matrix attachment region (S/MAR) domain and the luciferase reporter gene, showed transgene expression for at least 6 months following a single administration to MF1 mice. Following partial hepatectomy of the animals, however, we found no detectable vector replication and subsequent propagation in vivo. To overcome this drawback, we have now developed an in vivo liver selection strategy by which liver cells transfected with an S/MAR plasmid are provided with a survival advantage over non-transfected cells. This allows an enrichment of vectors that are capable of replicating and establishing themselves as extra-chromosomal entities in the liver. Accordingly, a novel S/MAR plasmid encoding the Bcl-2 gene was constructed; Bcl-2 expression confers resistance against apoptosis-mediated challenges by the Fas-activating antibody Jo2. Following hydrodynamic delivery to the livers of mice and frequent Jo2 administrations, we demonstrate that this Bcl-luciferase S/MAR plasmid is indeed capable of providing sustained luciferase reporter gene expression for over 3 months and that this plasmid replicates as an episomal entity in vivo. These results provide proof-of-principle that S/MAR vectors are capable of preventing transgene silencing, are resistant to integration and are able to confer mitotic stability in vivo when provided with a selective advantage.

In humans the adiponectin receptor R2 is expressed predominantly in adipose tissue and linked to the adipose tissue expression of MMIF-1.

In this study, the regional adipose tissue-adiponectin (AT-ADN) and adiponectin receptor (R1 and R2) expression and their relation with metabolic parameters, circulating and AT-derived cytokine expressions were compared. Paired subcutaneous adipose tissue (SCAT) and visceral adipose tissue (VAT) were taken from 18 lean and 39 obese humans, AT-mRNA expression of adipokines analysed by RT-PCR and corresponding serum levels by enzyme-linked immunosorbent assay (ELISA). R1 and R2 adipocyte expression was compared with 17 other human tissues. ADN-gene expression was lower in VAT than SCAT [mean (SD) 1.54 (1.1) vs. 2.84 (0.87); p < 0.001], and lower in obese subjects (VAT : p = 0.01;SCAT : p < 0.001). SCAT-ADN correlated positively with serum ADN (r = 0.33;p = 0.036) but not VAT-ADN. AT expressions of ADN and macrophage migration inhibiting factor (MMIF), IL18 and cluster of differentiation factor 14 (CD14) in both depots showed inverse correlations. R1 and R2 were expressed ubiquitously and R2 highest in SCAT, and this is much higher (x100) than R1 (x100). R expression was similar in lean and obese subjects and unrelated to the metabolic syndrome, however, receptors correlated with VAT-MMIF (R 1: r = 0.4;p = 0.008;R 2: r = 0.35,p = 0.02) and SCAT-MMIF expression (R 2: r = 0.43;p = 0.004). Unlike ADN, its receptors are expressed in many human tissues. Human R2 expression is not highest in the liver but in AT where it is associated with MMIF expression. The adiponectin-dependent insulin-sensitizing action of thiazolidinediones is thus probably to differ amongst species with weaker effects on the human liver.

Successful treatment of leflunomide-induced acute pneumonitis with cholestyramine wash-out therapy.

Drug-induced acute pneumonitis is a rare but potentially fatal adverse drug reaction. A high index of suspicion is needed for early diagnosis as it mimics community acquired pneumonia and interstitial lung disease that can occur in rheumatoid arthritis. We report a 32-year-old Chinese lady who suffered from leflunomide-induced pneumonitis and improved dramatically after receiving cholestyramine wash-out therapy. This case illustrates the need for clinical alertness to this potentially fatal complication. When in doubt, discontinuation of leflunomide and empirical wash-out therapy should be administered without delay.

Container survey of mosquito breeding sites in a university campus in Kuala Lumpur, Malaysia.

A survey on container breeding sites of Aedes spp. and Culex spp. larvae was conducted in the campus of the University of Malaya, Kuala Lumpur. Sampling was carried out by dipping using pipette or dipper depending on container types. All breeding sources of mosquito larvae were grouped into eight different container types: plastic container, plastic pail, bottle, earthen plate, natural container, vase, can and concrete tank. A total of 262 containers were identified as potential breeding sites. However, only 65 containers (86.15% outdoors and 13.85% indoors) were found containing larvae. Among all types of containers, 50.00% of the total surveyed natural containers were positive with mosquito larvae, followed by plastic containers (32.77%), plastic pails (23.81%), concrete tanks (20.00%), vases (18.75%), bottles (14.71%), cans (13.33%) and earthen plates (11.90%). The collected mosquito larvae were those of Aedes albopictus (86.96%), Aedes niveus group (5.80%) and Culex quinquefasciatus (7.24%). No Aedes aegypti was found in any container in the study site. This study indicated that Ae. albopictus was capable of breeding in a wide range of container types. To control these mosquitoes, the elimination of artificial and natural containers or alteration of breeding sites in and around the campus areas should be taken into consideration. Towards this goal, the university management should practise Integrated Vector Management (IVM) in the campus.

Bioassays for estrogenic activity: development and validation of estrogen receptor (ERalpha/ERbeta) and breast cancer proliferation bioassays to measure serum estrogenic activity in clinical studies.

Standard estrogenic prodrugs such as estradiol valerate (E2V) and increasingly popular phytoestrogen formulations are commonly prescribed to improve menopausal health. These drugs are metabolized to numerous bioactive compounds, known or unknown, which may exert combinatorial estrogenic effects in vivo. The aim of this study is to develop and validate estrogen receptor (ER) alpha/ERbeta reporter gene and MCF-7 breast cancer cell proliferation bioassays to quantify serum estrogenic activities in a clinical trial setting. We measured changes in serum estrogenicity following ingestion of E2V and compared this to mass spectrometric measurements of its bioactive metabolites, estrone and 17beta-stradiol. ERalpha bioactivity of the 192 serum samples correlated well (R = 79%) with 17beta-estradiol levels, and adding estrone improved R to 0.83 (likelihood ratio test, P < 0.0001), suggesting that the ERalpha assay reflects summated activity of compounds in serum. ERbeta correlated moderately (R = 0.52) with estrone and 17beta-estradiol, with an estrone/17beta-estradiol coefficient ratio that was twice that of ERalpha, indicating estrone was more active on a molar basis in the ERbeta assay. Unlike the ERalpha and ERbeta bioassays, MCF-7 cell proliferation was driven by 17beta-estradiol, and addition of estrone did not increase the predictive value of the model, suggesting that the driver or drivers for breast cancer cell proliferation were not the same as for ERalpha and ERbeta transactivation. In contrast, a decoction of the traditional Chinese medicinal herb Epimedium pubescens did not induce significant changes in estrogenic bioactivity over baseline. These data indicate that ERalpha/ERbeta reporter gene and MCF-7 breast cancer cell proliferation bioassays reflect different aspects of estrogenic activity and that these assays suggest that the Epimedium formulation tested is unlikely to exert significant estrogenic effects in humans.

Ghrelin restores 'lean-type' hunger and energy expenditure profiles in morbidly obese subjects but has no effect on postgastrectomy subjects.

OBJECTIVE: To examine the effects of ghrelin on appetite and energy expenditure in lean, obese and postgastrectomy subjects. DESIGN: A randomized, double-blind, placebo-controlled study. PATIENTS: Nine lean subjects (mean body mass index (BMI) 23.5+/-3 kg/m(2)) and nine morbidly obese subjects (mean BMI 51.4+/-10 kg/m(2)) and eight postgastrectomy subjects (mean BMI 22.4+/-1.0 kg/m(2)). INTERVENTIONS: Subjects were infused with either intravenous ghrelin (5 pmol kg(-1) min(-1)) or saline over 270 min. They were given a fixed energy breakfast followed by a free buffet lunch towards the end of the infusion. MAIN OUTCOME MEASURES: Visual analogue scales were used to record hunger and energy expenditure was measured by indirect calorimetry. RESULTS: Ghrelin increased energy intake at the buffet lunch in lean subjects (a 41% increase, P<0.01) and obese subjects (35% increase, P=0.04) but not in postgastrectomy subjects. Lean subjects showed a characteristic preprandial rise and postprandial fall in hunger scores, which was exaggerated by ghrelin infusion. Obese subjects showed little variation in hunger scores, but a 'lean-type' pattern was restored when given exogenous ghrelin. Ghrelin had no effect on resting metabolic rate but did increase respiratory quotient (RQ) in obese subjects. Ghrelin also increased RQ variability over time in all three groups (ANOVA, P<0.001). CONCLUSIONS: Hunger scores are abnormal in the obese, perhaps because of impaired ghrelin secretion. The effect of ghrelin in restoring normal hunger profiles in the obese suggests causality, confirming an important role in eating behaviour. Ghrelin also increases RQ in obese humans and increased RQ variability in all groups. This suggests that ghrelin regulates substrate utilization and may promote metabolic flexibility.

Improving strategies for syphilis control in China: selective testing of sexually transmitted disease patients--too little, too late?

SUMMARY: Syphilis testing guidelines in China are usually based on symptomatic criteria, overlooking risk assessment and ultimately opportunities for disease detection and control. We used data from 10,695 sexually transmitted disease (STD) clinic patients in Guangxi, China, to assess the efficacy of a potential screening tool inquiring about behavioural and health risk factors in identifying the STD patients who should not be triaged for syphilis testing under current guidelines, but on the contrary receive such testing. Validity testing of the screening tool was performed and receiver-operating characteristic curves were plotted to determine an optimal total risk score cut-off for testing. About 40.9% of patients with positive toluidine red unheated serum test and Treponema pallidum particle agglutination test did not show hallmark signs of syphilis. The screening tool was more sensitive in detecting infection in non-triaged male versus female patients (highest sensitivity = 90% vs. 55%) and the cut-off score to warrant testing was lower in non-triaged female patients than in non-triaged male patients (cut-off = 1 vs. 2). Most of the cases were missed among female STD patients. In spite of selective testing based on behavioural and health indicators that improve case detection, cases were still missed. Our study supports universal testing for syphilis in the STD population.

Suppression and recovery of the hypothalamic function after high-dose corticosteroid treatment in preterm infants.

BACKGROUND: High-dose systemic dexamethasone is effective in facilitating extubation of ventilated infants with bronchopulmonary dysplasia. Although the suppression and recovery of pituitary-adrenal response had been assessed after corticosteroid treatment in very low birth weight infants, its effect on hypothalamic function has not been longitudinally monitored. AIMS: This study was designed to assess the longitudinal hypothalamic response before, during and 4 weeks after a 3-week dose-tapering course of systemic dexamethasone treatment. PATIENTS AND METHODS: Twenty very low birth weight infants had blood collected for corticotropin-releasing hormone, ACTH and cortisol measurements immediately before starting dexamethasone (week 0), after receiving the maximum dose of treatment (week 1), at the end of the 3-week course (week 3) and 4 weeks after stopping corticosteroids (week 7). RESULTS: All circulating hormone concentrations were significantly suppressed during the treatment period at week 1 and week 3 compared with pretreatment concentrations at week 0 (p < 0.001). The recovery of pituitary function started early soon after week 1, whereas that of hypothalamus and adrenal functions started after the end of the dexamethasone course. Plasma ACTH concentration at week 7 had returned to the pretreatment level, but plasma corticotropin-releasing hormone (p < 0.05) and serum cortisol (p < 0.001) concentrations remained significantly suppressed. Partial recovery of hypothalamic and adrenal function was observed at week 7 (62 vs. 36% of their pretreatment levels, respectively). CONCLUSION: Our findings suggest that the hypothalamic function is suppressed during systemic corticosteroid treatment but partial recovery occurs 4 weeks after stopping therapy. Even in preterm infants, the hypothalamic-pituitary-adrenal axis behaves in a similar manner as in adult subjects and the pituitary function recovers earlier than that of hypothalamus and adrenals.

Persistent episomal transgene expression in liver following delivery of a scaffold/matrix attachment region containing non-viral vector.

An ideal gene therapy vector should enable persistent transgene expression without limitations of safety and reproducibility. Here we report the development of a non-viral episomal plasmid DNA (pDNA) vector that appears to fulfil these criteria. This pDNA vector combines a scaffold/matrix attachment region (S/MAR) with a human liver-specific promoter (alpha1-antitrypsin (AAT)) in such a way that long-term expression is enabled in murine liver following hydrodynamic injection. Long-term expression is demonstrated by monitoring the longitudinal luciferase expression profile for up to 6 months by means of in situ bioluminescent imaging. All relevant control pDNA constructs expressing luciferase are unable to sustain significant transgene expression beyond 1 week post-administration. We establish that this shutdown of expression is due to promoter methylation. In contrast, the S/MAR element appears to inhibit methylation of the AAT promoter thereby preventing transgene silencing. Although this vector appears to be maintained as an episome throughout, we have no evidence for its establishment as a replicating entity. We conclude that the combination of a mammalian, tissue-specific promoter with the S/MAR element is sufficient to drive long-term episomal pDNA expression of genes in vivo.

Plasma obestatin levels are lower in obese and post-gastrectomy subjects, but do not change in response to a meal.

OBJECTIVE: To investigate a potential role for obestatin in humans by examining response to a fixed energy meal. CONTEXT: A new anorectic peptide hormone, obestatin has recently been isolated from rat stomach. The significance of this peptide in humans is unknown. STUDY DESIGN: Case-control study. SETTING: Hospital-based study. PATIENTS: Nine healthy controls, nine morbidly obese subjects and eight post-gastrectomy subjects. INTERVENTION: Subjects attended after an overnight fast and were given a fixed energy meal (1550 kJ). MAIN OUTCOME MEASURE: The response of obestatin to a meal in the different groups. RESULTS: Fasting obestatin was significantly lower in obese subjects as compared to lean subjects (27.8+/-4 vs 17.2+/-2 pg/ml, P=0.03). Obestatin was also decreased in gastrectomy subjects but this did not reach statistical significance (27.8+/-4 vs 21.9+/-3 pg/ml, P=0.3). Obestatin did not change significantly from baseline in response to the meal. Lean and obese subjects had a similar obestatin/ghrelin ratio (0.04+/-0.003 vs 0.05+/-0.009, P=0.32), but this was higher in the gastrectomy group (0.04+/-0.003 vs 0.1+/-0.01, P<0.001). CONCLUSIONS: Obestatin does not vary significantly with a fixed energy meal, but is significantly lower in morbidly obese subjects as compared to lean subjects supporting a possible role for obestatin in long-term body weight regulation. Obestatin tended to be lower in gastrectomy subjects and their obestatin/ghrelin ratio differed from healthy controls. Hence, the expression of obestatin is altered following gastrectomy, suggesting other sites outside the stomach may also secrete obestatin.

Standardization and evaluation of botanical mixtures: lessons from a traditional Chinese herb, Epimedium, with oestrogenic properties.

Botanical extracts differ from conventional supplements in that they are complicated mixtures of many bioactive compounds. Here we describe our experience with a traditional Chinese medicinal plant Epimedium sp. to illustrate the scientific challenges of firstly, obtaining a standardized product from a complex mixture and secondly, evaluating that product for preclinical and clinical efficacy. In contrast, to its colloquial name 'Horny goat weed' and Internet advertisements as a herbal 'Viagra' for men, extracts of Epimedium are strongly oestrogenic due to the presence of novel potent phytoestrogens of the prenyl-flavone family. Since Epimedium is not cultivated, it was necessary to source for taxonomically identified samples and to authenticate their species by phylogenetic, chemical and bioresponse profiling. The feasibility of using a panel of oestrogen-responsive cell-based bioassays to measure summated oestrogenic effects at close time points for pharmacokinetic/pharmacodynamic (PK/PD) modelling was evaluated. We document proportionate oestrogenic responses in sera of animals fed oestrogenic drugs and botanical extracts, indicating that these target molecule responsive cell-based bioassays may have utility to capture the global effects of the myriad bioactive compounds in botanical extracts, informing the design of rigorous clinical trials for safety and efficacy.

Lack of an acute effect of ghrelin on markers of bone turnover in healthy controls and post-gastrectomy subjects.

BACKGROUND: Ghrelin is a gut-brain peptide that powerfully stimulates appetite and growth hormone secretion and is also known to directly regulate osteoblast cell function in vitro and in animal models. Little is known about the effects of ghrelin on bone turnover in humans. As the stomach is the main site of ghrelin synthesis, gastrectomy patients are deficient in ghrelin; they are also prone to osteopenia and osteomalacia. HYPOTHESIS: Ghrelin may play a role in bone regulation in humans; ghrelin deficiency following gastrectomy is associated with the disrupted regulation of bone turnover seen in these subjects. SUBJECTS AND METHODS: In a randomised, double-blind, placebo-controlled study 8 healthy controls and 8 post-gastrectomy subjects were infused with intravenous ghrelin (5 pmol/kg/min) or saline over 240 min on different days. Subjects were given a fixed energy meal during the infusion. Ghrelin, GH, type-1 collagen beta C-telopeptide (betaCTX), a marker of bone resorption, and procollagen type-1 amino-terminal propeptide (P1NP), a marker of bone formation, were measured. RESULTS: Fasting ghrelin was significantly lower in the gastrectomy group during the saline infusion (226.1+/-62.0 vs. 762+/-71.1 ng/l p<0.001). Growth hormone was significantly higher at 90 min after the ghrelin infusion, compared to saline in both healthy controls (61.1+/-8.8 vs. 1.4+/-0.6 mIU/l p<0.001) and gastrectomy subjects (61.1+/-11.8 vs. 0.9+/-0.2 mIU/l p<0.001) confirming the ghrelin was bioactive. Gastrectomy subjects were significantly older and had significantly higher plasma betaCTX than healthy controls at all time points (ANOVA p=0.009). After adjustment for age and BMI ghrelin was found to be a significant predictor of baseline plasma betaCTX and was inversely correlated with baseline plasma betaCTX (beta=-0.54 p=0.03 R2=26%). However, there was no significant effect of the ghrelin infusion on plasma betaCTX or P1NP in either subject group. CONCLUSIONS: Ghrelin infusion has no acute effect on markers of bone turnover in healthy controls and post-gastrectomy subjects, but is inversely correlated with bone resorption.

Electron field emission properties of Co quantum dots in SiO2 matrix synthesised by ion implantation.

In this work, Co ions were implanted into thermally oxidised SiO2 layers on silicon substrates. The implantation energy was 50 keV and the doses were 1, 3, 5 and 7 x 10(16) Co+/cm2. The field emission (FE) properties of these layers were studied and correlated with results from atomic force microscopy and transmission electron microscopy measurements. Other than that for the lowest dose sample, crystallised Co nanoclusters, with sizes ranging from 1.8 to 5.7 nm, are observed in these Co-implanted layers. The higher dose samples exhibit excellent FE properties and give an emission current of 1 nA at electric fields as low as 5 V/microm, for a dose of 5 x 10(16) Co+/cm2, compared with 120 V/microm for the lowest dose samples. We attribute the excellent FE properties of these layers to the formation of Co nanoclusters, with the electrical inhomogeneity giving rise to local field enhancement. Finally, repeatable staircase-like current-field (I-F) characteristics are observed in FE measurements of these higher dose samples as compared to conventional Fowler-Nordheim-type I-F characteristics in the lower dose sample. We believe this data may be a result of Coulomb blockade effects arising from the isolated low-capacitance metal quantum dots formed by controlled ion implantation.

Adipokines and the insulin resistance syndrome in familial partial lipodystrophy caused by a mutation in lamin A/C.

AIMS/HYPOTHESIS: Familial partial lipodystrophy (FPLD) and obesity are both associated with increased risks of type 2 diabetes and cardiovascular disease. Although adipokines have been implicated, few data exist in subjects with FPLD; therefore we investigated a family with FPLD due to a lamin A/C mutation in order to determine how abnormalities of the plasma adipokine profile relate to insulin resistance and the metabolic syndrome. METHODS: Plasma levels of adiponectin, leptin, resistin, IL-1beta, IL-6 and TNF-alpha in 30 subjects (ten patients, 20 controls) were correlated with indices of metabolic syndrome. RESULTS: Compared with controls, FPLD patients had significantly lower plasma levels of adiponectin (3.7+/-1.0 in FDLP cases vs 7.1+/-0.72 mug/ml in controls, p=0.02), leptin (1.23+/-0.4 vs 9.0+/-1.3 ng/ml, p=0.002) and IL-6 (0.59+/-0.12 vs 1.04+/-0.17 pg/ml, p=0.047) and elevated TNF-alpha (34.8+/-8.1 vs 13.7+/-2.7 pg/ml, p=0.028), whereas IL-1beta and resistin were unchanged. In both groups, adiponectin levels were inversely correlated with body fat mass (controls, r=-0.44, p=0.036; FDLP, r=-0.67, p=0.025), insulin resistance (controls, r=-0.62, p=0.003; FDLP, r=-0.70, p=0.025) and other features of the metabolic syndrome. TNF-alpha concentrations were positively related to fat mass (controls, r=0.68, p=0.001; FDLP, r=0.64, p=0.048) and insulin resistance (controls, r=0.86, p=0.001; FDLP, r=0.75, p=0.013). IL-6, IL-1beta and resistin did not demonstrate any correlations with the metabolic syndrome in either group. CONCLUSIONS/INTERPRETATION: Low adiponectin and leptin and high TNF-alpha were identified as the major plasma adipokine abnormalities in FPLD, consistent with the hypothesis that low adiponectin and high TNF-alpha production may be mechanistically related, and perhaps responsible for the development of insulin resistance and cardiovascular disease in FPLD.