Association between osteoarthritis-related serum biochemical markers over 11 years and knee MRI-based imaging biomarkers in middle-aged adults.

OBJECTIVE: To describe the associations between osteoarthritis (OA)-related biochemical markers (COMP, MMP-3, HA) and MRI-based imaging biomarkers in middle-aged adults over 10-13 years. METHODS: Blood serum samples collected during the Childhood Determinants of Adult Health (CDAH)-1 study (year:2004-06; n = 156) and 10-13 year follow-up at CDAH-3 (n = 167) were analysed for COMP, MMP-3, and HA using non-isotopic ELISA. Knee MRI scans obtained during the CDAH-knee study (year:2008-10; n = 313) were assessed for cartilage volume and thickness, subchondral bone area, cartilage defects, and BML. RESULTS: In a multivariable linear regression model describing the association of baseline biochemical markers with MRI-markers (assessed after 4-years), we found a significant negative association of standardised COMP with medial femorotibial compartment cartilage thickness (ß:-0.070; 95%CI:-0.138,-0.001), and standardised MMP-3 with patellar cartilage volume (ß:-141.548; 95%CI:-254.917,-28.179) and total bone area (ß:-0.729; 95%CI:-1.340,-0.118). In multivariable Tobit regression model, there was a significant association of MRI-markers with biochemical markers (assessed after 6-9 years); a significant negative association of patellar cartilage volume (ß:-0.001; 95%CI:-0.002,-0.00004), and total bone area (ß:-0.158; 95%CI-0.307,-0.010) with MMP-3, and total cartilage volume (ß:-0.001; 95%CI:-0.001,-0.0001) and total bone area (ß:-0.373; 95%CI:-0.636,-0.111) with COMP. No significant associations were observed between MRI-based imaging biomarkers and HA. CONCLUSION: COMP and MMP-3 levels were negatively associated with knee cartilage thickness and volume assessed 4-years later, respectively. Knee cartilage volume and bone area were negatively associated with COMP and MMP-3 levels assessed 6-9 years later. These results suggest that OA-related biochemical markers and MRI-markers are interrelated in early OA.

Antibacterial Activity and Conductivity Studies of CoS Nanoparticles Incorporated in PVA/PVP/NH4Br Electrolyte.

Solid polymer blend electrolytes are widely studied due to their extensive applications particularly in electrochemical devices. Blending polymer electrolytes make thermal stability and higher mechanical strength and enhance the ionic conductivity while incorporate inorganic salt. In these studies, 50% polyvinyl alcohol (PVA), 50% poly(N-vinyl pyrrolidone) (PVP) and 10% ammonium bromide (NH4Br) doped with different molecular weight percentage (M.Wt.%) of cobalt sulfide nanoparticles (CoS-NPs) as nano filler is synthesized using solution casting technique. The various M.Wt.% of CoS-NPs mixed blend polymer films are characterized by various analytical methods such as FT-IR, XRD, TG-DSC, SEM and Impedance spectroscopy. FT-IR, XRD and TG-DSC analysis are revealed the structural and thermal stability of the complex formation between CoS-NPs and PVA/PVP/NH4Br polymer matrix. The ionic conductivity and the dielectric properties of PVA/PVP/NH4Br/doped CoS-NPs polymer blend electrolyte films are examined using impedance analysis. The antibacterial studies are showed higher activity for high conductivity polymer blend film. The highest ionic conductivity is found to be 5.42×10-4 S cm-1 for the M.Wt.% of composition 50%PVA:50%PVP:10%NH4Br:1.5%CoS-NPs with low activation energy 0.3373 eV at ambient temperature.

Assimilation of NH4Br in Polyvinyl Alcohol/Poly(N-vinyl pyrrolidone) Polymer Blend-Based Electrolyte and Its Effect on Ionic Conductivity.

Biodegradable polymer blend electrolyte based on ammonium based salt in variation composition consisting of PVA:PVP were prepared by using solution casting technique. The obtained films have been analyzed by various technical methods like as XRD, FT-IR, TG-DSC, SEM analysis and impedance spectroscopy. The XRD and FT-IR analysis exposed the amorphous nature and structural properties of the complex formation between PVA/PVP/NH4Br. Impedance spectroscopy analysis revealed the ionic conductivity and the dielectric properties of PVA/PVP/NH4Br polymer blend electrolyte films. The maximum ionic conductivity was determined to be 6.14 × 10-5 Scm-1 for the composition of 50%PVA: 50%PVP: 10% NH4Br with low activation energy 0.3457 eV at room temperature. Solid state battery is fabricated using highest ionic conducting polymer blend as electrolyte with the configuration Zn/ZnSO4 · 7H2O (anode) ∥ 50%PVA: 50%PVP: 10% NH4Br ∥ Mn2O3 (cathode). The observed open circuit voltage is 1.2 V and its performance has been studied.

Not a simple fat-soluble vitamin: Changes in serum 25-(OH)D levels are predicted by adiposity and adipocytokines in older adults.

OBJECTIVE: To determine the associations between body adiposity and change in serum 25-(OH)D levels over 2.6 years, and if these associations are mediated by metabolic and inflammatory factors in older adults. METHODS: This is a longitudinal study of 859 randomly selected subjects (mean 62 years, range 51-80, 49% women). Serum 25-hydroxyvitamin D [25-(OH)D] was assessed by radioimmunoassay at baseline and 2.6 years later. Baseline serum level of leptin was assessed by radioimmunoassay and interleukin (IL)-6 by a chemiluminescent immunoassay in the first 183 subjects. RESULTS: In multivariable analyses, body mass index, trunk fat percentage and waist-to-hip ratio were significant predictors of increased incident vitamin D deficiency [a 25-(OH)D < 50 nmol L⁻¹ at follow-up when ≥50 nmol L⁻¹ at baseline] and decreased recovery of vitamin D deficiency [a 25-(OH)D ≥ 50 nmol L⁻¹ at follow-up when < 50 nmol L⁻¹ at baseline]. Change in 25-(OH)D levels per annum was also independently predicted by baseline leptin (ß: -0.09/unit, 95% CI: -0.17, -0.03), IL-6 (ß: -0.68/quartile, 95% CI: -1.35, -0.02) and total cholesterol/high-density lipoprotein (HDL) ratio (ß: -0.51, 95% CI: -0.88, -0.14). The associations between body adiposity measures and change in 25-(OH)D completely disappeared after adjustment for leptin, diminished after adjustment for IL-6, but remained unchanged after adjustment for total cholesterol/HDL ratio. All associations were independent of season and sun exposure. CONCLUSIONS: Body fat is not simply a passive reservoir for 25-(OH)D. In addition to season and sun exposure, 25-(OH)D levels appear to be determined by metabolic and, to a lesser extent, inflammatory factors, and these appear to mediate the effects of adiposity on change in 25-(OH)D.

Circulating levels of IL-6 and TNF-α are associated with knee radiographic osteoarthritis and knee cartilage loss in older adults.

OBJECTIVE: The role of inflammation in osteoarthritis (OA) pathogenesis is unclear, and the associations between inflammatory cytokines and cartilage loss have not been reported. We determined the associations between serum levels of interleukin (IL)-6 and tumor necrosis factor-α (TNF-α), knee radiographic OA (ROA) and cartilage loss over 2.9 years in older adults. METHODS: A total of 172 randomly selected subjects (mean 63 years, range 52-78, 47% female) were studied at baseline and approximately 3 (range 2.6-3.3) years later. IL-6 and TNF-α were assessed by radioimmunoassay. T1-weighted fat-suppressed magnetic resonance imaging of the right knee was performed at baseline and follow-up to determine knee cartilage volume. Knee ROA of both knees was assessed at baseline. RESULTS: At baseline, quartiles of IL-6 and TNF-α were associated with increased prevalence of medial tibiofemoral joint space narrowing (OARSI grade ≥ 1) in multivariate analyses [odds ratio (OR): 1.42 and 1.47 per quartile, respectively, both P<0.05]. Longitudinally, baseline IL-6 predicted loss of both medial and lateral tibial cartilage volume (ß: -1.19% and -1.35% per annum per quartile, P<0.05 and P<0.01, respectively), independently of TNF-α. Change in IL-6 was associated with increased loss of medial and lateral tibial cartilage volume (ß: -1.18% and -1.06% per annum per quartile, both P<0.05) and change in TNF-α was also negatively associated with change in medial cartilage volume (ß: -1.27% per annum per quartile, P<0.05). CONCLUSIONS: Serum levels of IL-6 and TNF-α are associated with knee cartilage loss in older people suggesting low level inflammation plays a role in the pathogenesis of knee OA.

Potential use of chitosan nanoparticles for oral delivery of DNA vaccine in Asian sea bass (Lates calcarifer) to protect from Vibrio (Listonella) anguillarum.

In recent years, attention has been focused on the possibility of utilizing DNA vaccines in fish aquaculture. A successful regime for intramuscular injection of naked DNA into fish has been developed and novel methods to deliver this DNA to fish are under investigation. The potential of chitosan as a polycationic gene carrier for oral administration has been explored since 1990s. The present study examines the potential efficacy of DNA vaccine against Vibrio anguillarum through oral route using chitosan nanoparticles encapsulation. The porin gene of V. anguillarum was used to construct DNA vaccine using pcDNA 3.1, a eukaryotic expression vector and the construct was named as pVAOMP38. The chitosan nanoparticles were used to deliver the constructed plasmid. In vitro and in vivo expression of porin gene was observed in sea bass kidney cell line (SISK) and in fish, respectively by fluorescent microscopy. The cytotoxicity of chitosan encapsulated DNA vaccine construct was analyzed by MTT assay and it was found that the cytotoxicity of pVAOMP38/chitosan was quite low. Distribution of gene in different tissues was studied in fish fed with the DNA (pVAOMP38) encapsulated in chitosan by using immunohistochemistry. The results indicate that DNA vaccine can be easily delivered into fish by feeding with chitosan nanoparticles. After oral vaccination Asian sea bass were challenged with Vibrio anguillarum by intramuscular injection. A relative percent survival (RPS) rate of 46% was recorded. The results indicate that Sea bass (Lates calcarifer) orally vaccinated with chitosan-DNA (pVAOMP38) complex showed moderate protection against experimental V. anguillarum infection.

Association between leptin, body composition, sex and knee cartilage morphology in older adults: the Tasmanian older adult cohort (TASOAC) study.

OBJECTIVE: To describe the associations between leptin, body composition, sex and knee cartilage volume/defects in older adults. METHODS: A cross-sectional sample of 190 randomly selected subjects (mean 63 years, range 52-78, 48% female) were studied. Knee cartilage volume and defects were determined using T1-weighted fat saturation MRI. Serum leptin levels were measured by radioimmunoassay. Fat and lean mass were measured by dual energy x ray absorptiometry (DXA). Body mass index (BMI) was calculated. RESULTS: In multivariable analysis, serum levels of leptin were negatively associated with total cartilage volume (beta: -541 mm3/log transformed unit, 95% CI -861 to -221) but not with prevalent knee cartilage defects. BMI was negatively associated with cartilage volume after adjustment for total lean mass and positively with prevalent knee cartilage defects. However, the association between BMI and cartilage volume disappeared after adjustment for leptin while the association between BMI and cartilage defects remained unchanged. Lastly, sex differences in total cartilage volume decreased substantially after adjustment for leptin (R2 from 51% to 30%). CONCLUSIONS: This cross-sectional study suggests cartilage volume loss with obesity and female sex is related to leptin and, thus, is hormonally mediated in older adults. By contrast, obesity related knee focal cartilage defects may be more related to non-hormonal factors.

Development of a pluripotent ES-like cell line from Asian sea bass (Lates calcarifer)--an oviparous stem cell line mimicking viviparous ES cells.

We report a pluripotent embryonic stem cell-like cell line designated as SBES from blastula stage embryos of Asian sea bass (Lates calcarifer), which is an economically important cultivable and edible marine fish species in India. The SBES cells were cultured at 28 degrees C in Leibovitz L-15 medium supplemented with 20% fetal bovine serum without a feeder layer. The ES-like cells were round or polygonal and grew exponentially in culture. The SBES cells exhibited an intense alkaline phosphatase activity and expression of transcription factor Oct 4. The undifferentiated state of these cells was maintained at low seeding densities and the cells formed embryoid bodies when seeded in bacteriological plates. On treatment with all-trans retinoic acid, these cells differentiated into neuron-like cells, muscle cells, and beating cardiomyocytes, indicating their pluripotency. This embryonic ES-like cell line derived from an oviparous fish blastula conserved several peculiar features of viviparous mammalian embryonic stem cell lines. The present study highlights the importance and potential of piscine ES-like cell line for stem cell research without evoking ethical issues and invasive interventions sparing mammalian embryos.

In vitro replication of Macrobrachium rosenbergii nodavirus and extra small virus in C6/36 mosquito cell line.

White tail disease (WTD) is a serious problem in hatcheries and nursery ponds of Macrobrachium rosenbergii in India and many parts of the world. The pathogenic agents have been identified as M. rosenbergii nodavirus (MrNV) associated with extra small virus (XSV), which is 27nm and 15nm in diameter, respectively. Replication of MrNV and XSV was investigated in apparently healthy C6/36 subclone of Aedes albopictus cell line. The results revealed that C6/36 cells were susceptible to these viruses. The replication of these viruses in C6/36 cells was confirmed by RT-PCR, acridine orange staining, infectivity study and electron microscopy. Cytoplasmic ribonucleic acid (RNA) stained by acridine orange increased by 48h, and by 72h larger proportion of cells which indicated alterations in quantity and localization of RNA in the infected cells. Post-larvae, challenged by immersion method using inoculum prepared from infected cells, exhibited lethargy, anorexia and opaqueness of abdominal muscle and 100% mortality was observed at 6 days post-infection. Experimentally infected C6/36 cells and post-larvae showed positive by RT-PCR, whereas control cells and healthy post-larvae showed negative. This is the first study to report the multiplication of MrNV and XSV in C6/36 cell line.

Protective efficiency of DNA vaccination in Asian seabass (Lates calcarifer) against Vibrio anguillarum.

Vibriosis is one of the most prevalent fish diseases caused by bacteria belonging to the genus Vibrio. Vibriosis caused by Vibrio anguillarum produces a 38-kDa major outer membrane porin protein (OMP) for biofilm formation and bile resistant activity. The gene encoding the porin was used to construct DNA vaccine. The protective efficiency of such vaccine against V. anguillarum causing acute vibrio haemorrhagic septicaemia was evaluated in Asian seabass (Lates calcarifer Bloch), a common species of the Indian coast and a potential resource for the aquaculture industry. In vitro protein expression of porin gene was determined by fluorescent microscopy after transfection of seabass kidney cell line (SISK). Fish immunized with a single intramuscular injection of 20 microg of the OMP38 DNA vaccine showed significant serum antibody levels in 5th and 7th weeks after vaccination, compared to fish vaccinated with the control eukaryotic expression vector pcDNA3.1. Asian seabass vaccinated with the OMP38 DNA vaccine was challenged with pathogenic V. anguillarum by intramuscular injection. A relative percent survival (RPS) rate of 55.6% was recorded. Bacterial agglutination and serum complement activity was analysed by using DNA vaccinated seabass serum above 80% of analysed strain was killed at the highest agglutination titre. Histopathological signs of V. anguillarum challenged fish were observed in around 45% of pVAOMP38, 90% of PBS and 87% of pcDNA3.1-vaccinated control fish. The results indicate that L. calcarifer vaccinated with a single dose of DNA plasmid encoding the major outer membrane protein shows moderate protection against acute haemorrhagic septicaemia and mortality by V. anguillarum experimental infection.

Development and characterization of two new cell lines from milkfish (Chanos chanos) and grouper (Epinephelus coioides) for virus isolation.

Two new cell lines, SIMH and SIGE, were derived from the heart of milkfish (Chanos chanos), a euryhaline teleost, and from the eye of grouper (Epinephelus coioides), respectively. These cell lines were maintained in Leibovitz's L-15 supplemented with 20% fetal bovine serum (FBS). The SIMH cell line was subcultured more than 50 times over a period of 210 days and SIGE cell line has been subcultured 100 times over a period of 1 1/2 years. The SIMH cell line consists predominantly of fibroblastic-like cells. The SIGE cell line consists predominantly of epithelial cells. Both the cell lines were able to grow at temperatures between 25 and 32 degrees C with an optimum temperature of 28 degrees C. The growth rate of these cells increased as the proportion of FBS increased from 2% to 20% at 28 degrees C with optimum growth at the concentrations of 15% or 20% FBS. Seven marine fish viruses were tested to determine the susceptibility of these cell lines. The SIGE cell line was found to be susceptible to nodavirus, MABV NC-1 and Y6, and the infection was confirmed by cytopathic effect (CPE) and reverse transcriptase-polymerase chain reaction. When these cells were transfected with pEGFP-N1 vector DNA, significant fluorescent signals were observed, suggesting that these cell lines can be a useful tool for transgenic and genetic manipulation studies. Further, these cell lines are characterized by immunocytochemistry using confocal laser scanning microscopy (CFLSM).

Establishment of embryonic cell line from sea bass (Lates calcarifer) for virus isolation.

A continuous cell line was established from blastula stage embryos of sea bass (Lates calcarifer). The sea bass embryonic cells were maintained in Leibovitz's L-15 supplemented with 15% fetal bovine serum. The embryonic cell line was sub-cultured more than 70 passages over a period of 1.5 years and is designated as Sahul Indian sea bass embryonic (SISE) cell line. The cells were able to grow at temperatures between 25 and 32 degrees C with an optimum temperature of 28 degrees C. The growth rate of sea bass embryonic cells increased as the FBS proportion increased from 2 to 20% at 28 degrees C with optimum growth at the concentration of 15 or 20%. Polymerase chain reaction products were obtained from embryonic cells and blastula of sea bass with primer sets of microsatellite markers of sea bass. Four fish viruses were tested on this cell line to determine its susceptibility to these viruses and this cell line was found to be susceptible to IPNV VR-299 and nodavirus, and the infection was confirmed by cytopathic effect (CPE) and RT-PCR. Further, this cell line was characterized by immunocytochemistry using confocal-laser-scanning microscopy (CFLSM), transfection with pEGFP-N1, proliferate marker (BrdU).

A randomized controlled trial of phytoestrogen supplementation, growth and bone turnover in adolescent males.

OBJECTIVE: To assess the effect of phytoestrogens on bone turnover and growth in adolescent boys. DESIGN: Randomized double-blind placebo-controlled trial. SETTING: Single school in northwest Tasmania. PARTICIPANTS: Adolescent boys (treatment n=69, placebo n=59, mean age 16.8 y). INTERVENTIONS: Six weeks of isoflavone supplementation (Novasoy, 50 mg daily of isoflavone equivalents). Bone turnover markers (bone specific alkaline phosphatase (BAP) and pyridinoline creatinine ratio (PYR)) were measured at baseline and follow-up. RESULTS: Despite marked increases in urinary genistein and daidzein in the treatment arm (both P<0.001), there were no significant differences in BAP, PYR or short-term height or weight change. This applied to both intention-to-treat and per protocol analysis. Neither was there a significant correlation between urinary genistein and daidzein levels and BAP or PYR. CONCLUSIONS: Phytoestrogen supplementation to the level of usual Japanese dietary intake has no measurable effect on bone turnover in adolescent boys. Longer-term studies of bone density may be desirable but it is unlikely that there will be a large effect in either girls or boys given the lower endogenous oestrogen levels in boys.

Recurrent iodine deficiency in Tasmania, Australia: a salutary lesson in sustainable iodine prophylaxis and its monitoring.

Even mild iodine deficiency during early childhood and pregnancy has the potential to impair neurological development. Often considered a problem of developing nations, a number of industrialized countries are at risk of deficiency. Despite past success with intentional and unintentional iodine fortification, recurrence of deficiency is an ever-present risk. Tasmania, an island state of the Commonwealth of Australia, has a history of endemic iodine deficiency, which was successfully eliminated by iodine prophylaxis initiated in 1950. In this report we describe a formal assessment of iodine nutrition in the Tasmanian population, 50 yr after initiation of the prophylaxis program. The requirements and obstacles to achieving sustainable iodine prophylaxis in an otherwise affluent community are considered. A cross-sectional study was undertaken during the yr 2000. Urinary iodine excretion (UIE) and thyroid ultrasonography were assessed in a representative statewide sample of school-age children. Children (n = 225) aged 4 to 17 yr from throughout Tasmania were studied. The sample comprised 99 girls and 126 boys. The median UIE was 84 microg/liter (87 microg/liter for males and 81 microg/liter for females), with UIE 50 microg/liter or less in 20%. Based on age-specific World Health Organization/International Council for the Control of Iodine Deficiency Disorders normative data for thyroid volume, the prevalence of elevated thyroid volume was 5.3% for boys and 3.5% for girls. However, after correcting the World Health Organization/International Council for the Control of Iodine Deficiency Disorders reference data, the prevalence increased to 24.6% for boys and 20.7% for girls. No significant difference in the thyroid volumes was found between males and females in this study. These data confirm the recurrence of mild iodine deficiency in Tasmania. The failure of sustained iodine prophylaxis highlights the universal importance of persistent surveillance, use of sustainable measures, public awareness, and a specific legislative framework for managing ongoing iodine prophylaxis. Our findings also emphasize the importance of accurate reference data for assessment thyroid volume.

Phenotype and phenocopy: the relationship between genotype and clinical phenotype in a single large family with multiple endocrine neoplasia type 1 (MEN 1).

BACKGROUND: The majority of reports describing the natural history and prognosis of multiple endocrine neoplasia type 1 (MEN 1) utilize phenotypic rather than molecular genetic criteria to establish a diagnosis of MEN 1. OBJECTIVES AND PATIENTS: We sought to determine the spectrum of endocrine abnormality amongst 152 members (64 gene carriers and 88 noncarriers) of a large MEN 1 family in whom a determination of MEN 1 status had previously been made by phenotype screening. The predictive utility of both clinical and molecular screening techniques are described. RESULTS: A novel IVS2-3 (C-G) MEN1 mutation was identified in affected members of this family. Seven (10%) of 71 individuals satisfying clinical diagnostic criteria for MEN 1 were found to be genetically negative (excluded by mutation analysis and haplotyping) for MEN 1. These cases of MEN 1 phenocopy comprised four cases of primary hyperparathyroidism, two 'nonsecretory' pituitary adenoma and one case of coincident prolactinoma and hyperparathyroidism. Three of the patients with hyperparathyroidism had previously required parathyroidectomy and each had achieved normocalcaemia following parathyroid resection. Predictive genetic testing prospectively identified three children with the MEN 1 genotype. Serum calcium was normal at the time of their initial molecular genetic diagnosis. In each case hyperparathyroidism subsequently developed during adolescence. CONCLUSION: Multiple endocrine neoplasia type 1 phenocopy is an important differential diagnosis in patients exhibiting an multiple endocrine neoplasia type 1 phenotype. This is a relevant consideration, particularly when the diagnosis of multiple endocrine neoplasia type 1 is made using sensitive, but nonspecific, criteria such as mild hyperparathyroidism, pituitary micoadenoma, and hyperprolactinaemia. Confirmatory genetic testing should be undertaken to confirm clinical diagnoses of multiple endocrine neoplasia type 1.

Vitamin D deficiency and secondary hyperparathyroidism: clinical and biochemical associations in older non-institutionalised Southern Tasmanians.

AIM: To determine the prevalence and associations of vitamin D (25-OHD) deficiency in a sample of older Tasmanian subjects. METHODS: A cross-sectional survey of: 109 patients with a mean age of 79 years (range 60-101 years) consecutively admitted to a short stay geriatric rehabilitation ward; 52 community dwelling subjects with a mean age of 75 years (range 64-88 years). Subjects answered a questionnaire, had anthropometric measurements and underwent venepuncture. RESULTS: The main outcome measure was 25 hydroxy vitamin D (25-OHD) level with deficiency defined as <28 nmol/L. Vitamin D deficiency was found in 67% and secondary hyperparathyroidism in 49% of the hospitalised group. Vitamin D deficiency was also found in 17% of the community group, in particular one in three residents of Independent Living Units was deficient. Subjects who were deficient were older (80 years vs 76 years [p<0.001]), had lower body mass index (23.7 kg/m2 vs 25.9 kg/m2 [p<0.001]) and had a lower serum albumin (35 gm/L vs 39 gm/L [p<0.001]). Deficient subjects had poorer physical functional status (p=0.02) and lower activity levels (p<0.001) and reported less habitual sun exposure (p<0.001). Biochemical measures such as parathyroid hormone, alkaline phosphatase and calcium were weakly predictive of vitamin D levels. By stepwise multiple regression analysis, the only significant predictors of vitamin D levels were the Frenchay Activity Index, albumin and calcium. CONCLUSION: Vitamin D deficiency and secondary hyperparathyroidism is common in community living older people who are hospitalised in Southern Tasmania and is associated with increasing age, poor physical function and activity and low reported sun exposure.

Octreotide improves biochemical, radiologic, and symptomatic indices of gastroenteropancreatic neoplasia in patients with multiple endocrine neoplasia type 1 (MEN-1). Implications for an integrated model of MEN-1 tumorigenesis.

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN-1) is an autosomal dominant tumor syndrome associated with parathyroid, gastroenteropancreatic (GEP), and pituitary neoplasia. Gastrinoma and GEP malignancy are common life-threatening endocrine complications of MEN-1. An effective management strategy for these disorders remains to be determined. The authors attempted to determine the role of the somatostatin analogue, octreotide, in ameliorating features of hypergastrinemic GEP neoplasia associated with MEN-1. METHODS: Five MEN-1 patients with hypergastrinemia and either symptoms of GEP neoplasia or hepatic metastases received a trial of octreotide, 100 microg subcutaneously, three times daily for 3 months. RESULTS: Treatment with octreotide was associated with a rapid symptomatic and biochemical response. In all patients serum gastrin fell to < 25% of the pretreatment value. The serum glycoprotein-alphasubunit (a marker of enterochromaffin-like [ECL] cell hyperplasia, gastric carcinoidosis, and disseminated enteropancreatic malignancy) was elevated at baseline in three patients. In each case the serum glycoprotein-alphasubunit normalized after treatment with octreotide. Hepatic metastases were present in two patients at baseline. The size of the metastases diminished by up to 15% during the period of octreotide treatment. Four patients reported symptoms prior to treatment: lethargy, easy fatigability, and generalized musculoskeletal discomfort. A marked symptomatic improvement occurred in each case. No patient experienced side effects related to octreotide therapy and all elected to remain on treatment after completion of the trial. CONCLUSIONS: Octreotide is a safe and effective adjunct to surgical strategies for the management of GEP neoplasia in hypergastrinemic MEN-1 patients.

Vitamin D levels in prepubertal children in Southern Tasmania: prevalence and determinants.

OBJECTIVE: To describe the prevalence and determinants of 25-hydroxy D3(25(OH)D) in children. DESIGN: Cross-sectional study. SETTING: Southern Tasmania between June and November 1997. SUBJECTS: Two hundred and one 8-y old male and female children taking part in a cohort study whose principal endpoints were blood pressure and high-density lipoprotein (HDL) cholesterol. RESULTS: The mean 25(OH)D level was 79 nmol/l (s.d. 29.5, median 73, range 12-222). Boys had higher levels than girls (82.1 vs 72.8 nmol/l, P=0.02). 25(OH)D was associated with sunlight exposure in winter school holidays (r=0.20, P=0.005) and winter weekends (r=0.16, P=0.02), the month after school holidays (87.5 vs 69.5 nmol, P<0.0001) and body mass index (r=-0.23, P=0.001). Dietary intake of vitamin D was low (mean 40 IU/day, range 5.2-384) and was not associated with 25(OH)D levels (r=0.01, P=0.91). Variation in skin melanin density was weakly associated with 25(OH)D (r=0.09, P=0.19). CONCLUSIONS: Sunlight is the major determinant of vitamin D stores in our population. Neither variation in skin type within Caucasians nor diet modified this association to any significant extent. Extrapolation of these findings to sunlight bone mass associations in a very similar population suggests that a minimum level of around 50 nmol/l in the population is required for optimal bone development in prepubertal children but this needs to be confirmed with further controlled trials of vitamin D supplementation and bone mass. SPONSORSHIP: Arthritis Foundation of Australia, Roche Pharmaceuticals.