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D Martin

Publications and source records attributed to D Martin.

At least 19 recordsLinked to original sources
PubMed2007

The calcimimetic R-568 increases vitamin D receptor expression in rat parathyroid glands.

We previously demonstrated that extracellular calcium regulates vitamin D receptor (VDR) expression by parathyroid cells. Since the calcimimetic R-568 potentiates the effects of calcium on the calcium-sensing receptor, it was hypothesized that administration of R-568 may result in increased VDR expression in parathyroid tissue. In vitro studies of the effect of R-568 on VDR mRNA and protein were conducted in cultures of whole rat parathyroid glands and human hyperplastic parathyroid glands. In vivo studies in Wistar rats examined the effect of R-568 and calcitriol alone and in combination. Incubation of rat parathyroid glands in vitro with R-568 (0.001-1 microM) resulted in a dose-dependent decrease in parathyroid hormone (PTH) secretion and an increase in VDR expression (mean +/- SE). Incubation in 1 mM calcium + 0.001 microM R-568 elicited an increase in VDR mRNA (306 +/- 46%) similar to the maximum increase detected with 1.5 mM calcium (330 +/- 42%). In vivo, VDR mRNA was increased after administration of R-568 (168 +/- 9%, P < 0.001 vs. control) or calcitriol (198 +/- 16%, P < 0.001 vs. control). Treatment with R-568 also increased VDR protein in normal rat parathyroid glands and in human parathyroid glands with diffuse, but not nodular, hyperplasia. In conclusion, the present study shows that the calcimimetic R-568 exerts a stimulatory effect on VDR expression in the parathyroid glands of study models and provides additional evidence for the use of calcimimetics in the treatment of secondary hyperparathyroidism.

Aniline Compounds↗
PubMed2007

Establishing a workplace antiretroviral therapy programme in South Africa.

Ways to expand access to antiretroviral treatment (ART) in low income settings are being sought. We describe an HIV care programme including ART in an industrial setting in South Africa. The programme uses guidelines derived from local and international best practice. The training component aims to build capacity among health care staff. Nurses and doctors are supported by experienced HIV clinicians through telephone consultation and site visits. Patients undergo a three-stage counselling procedure prior to starting ART. Drug regimens and monitoring are standardised and prophylaxis against opportunistic infections (isoniazid and cotrimoxazole) is offered routinely. Laboratory and pharmacy services, using named-patient dispensing, are centralized. The programme is designed to ensure that data on clinical and economic outcomes will be available for programme evaluation. Between November 2002-December 2004, ART delivery has been established at 70 ART workplace ART sites. The sites range from 200 to 12000 employees, and from small occupational health clinics and general practitioner rooms to larger hospital clinics. During this period, 2456 patients began ART. Of those on treatment for at least three months, 1728 (78%) have been retained on the programme and only 38 (1.7%) patients have failed the first-line ART regimen. This model for delivery of ART is feasible and successful in an industrial setting. The model may be generalizable to other employment health services in settings of high HIV prevalence, and as a model for implementing ART in other types of health-care settings.

Anti-HIV Agents↗
PubMed2006

Calcification inhibitors and Wnt signaling proteins are implicated in bovine artery smooth muscle cell calcification in the presence of phosphate and vitamin D sterols.

Administration of active vitamin D sterols to treat secondary hyperparathyroidism in patients with chronic kidney disease receiving dialysis has been associated with elevated serum calcium and phosphorus levels, which may lead to increased risk of vascular calcification. However, calcimimetics, by binding to the parathyroid gland calcium-sensing receptors, reduce serum parathyroid hormone, calcium, phosphorus, and the calcium-phosphorus product. Using cultured bovine aorta vascular smooth muscle cells (BASMCs), an in vitro model of vascular calcification, we compared calcification levels and gene expression profiles after exposure to the phosphate source ss-glycerolphosphate (BGP), the active vitamin D sterols calcitriol and paricalcitol, the calcimimetic R-568, or BGP with the active vitamin D sterols or R-568. Cells exposed to BGP (10 mM) alone or with calcitriol or paricalcitol showed dose-dependent BASMC calcification. No change in calcification was observed in cultures exposed to BGP with R-568, consistent with the observed lack of calcium-sensing receptor expression. Microarray analysis using total cellular RNA from cultures exposed to vehicle or BGP in the absence and presence of 10(-8) M calcitriol or paricalcitol for 7 days showed that cells exposed to BGP with calcitriol or BGP with paricalcitol had virtually identical gene expression profiles, which differed from those of cells treated with BGP or vehicle alone. Several osteoblast- and chondrocyte-associated genes were modulated by BGP and vitamin D exposure. In this study, exposure of BASMCs to phosphate and active vitamin D sterols induced calcification and changes in expression of genes associated with mineralized tissue.

Alkaline Phosphatase↗
PubMed2006

[Thyroiditis and gluten intolerance: extrapancreatic auto-immune diseases associated with type 1 diabetes].

OBJECTIVES: This study aimed at evaluating the screening of thyroïditis and coeliac disease, in a population of children and adolescents with type 1 diabetes, and at comparing the appearance of antibodies specific for these 2 diseases as a function of age. PATIENTS AND METHODS: The study included 370 children and adolescents, 179 girls and 191 boys, aged 13.8 +/- 4.4 yr and with diabetes for 7.1 +/- 3.8 yr. Auto-immune thyroïditis was screened using antimicrosomal and antithyroglobulin auto-antibodies, at a mean rhythm of 3 tests per patient (1 every 2 yr), associated with dosages of TSH and FT4. Coeliac disease was screened using antigliadin (+/- antiendomysium) auto-antibodies, at a mean rhythm of 2 tests per patient, and was confirmed by duodenojejunal biopsy. Antithyroïd auto-antibodies were correlated with age following the "censured data analysis" type approach. RESULTS: Antithyroïd autoantibodies were found in 42 patients (11.4%), of whom 9 were treated for hypothyroïdism and 1 for Basedow disease, and coeliac disease autoantibodies were found in 9 patients (3.2% of tested patients). The cumulated frequency of antithyroïd auto-antibodies increased regularly with age and was significantly higher in girls, reaching 28% in girls and 12% in boys around 18 yr of age. As a consequence of this evolution, antithyroïd auto-antibodies were frequently found at the time of diagnosis of diabetes when it declared after 10 yr of age, while they often became positive secondarily when diabetes occurred before 10 yr of age. Coeliac disease specific auto-antibodies appeared much earlier and were found at the time of diagnosis of diabetes or at the first screening test. CONCLUSION: Antithyroïd autoantibodies are increasingly frequent with age in children with type 1 diabetes, and become very elevated in girls. The rhythm for screening should be adapted to this evolution of autoantibodies with age, which is very different between thyroïditis and coeliac disease.

Adolescent↗
PubMed2006

[Filling of a lateral pre-malleolar soft tissue defect with the extensor digitorum brevis flap and the abductor digiti minimi flap].

The authors report the filling of a lateral pre-malleolar soft tissue defect after sub-talar arthrodesis. Four months after surgery the loss of substance measured 2,5 cm in depth, 3 cm diameter at the skin level and 5 cm diameter at the bone level. An autologous tricortical bone graft impacted in the sinus tarsi was also exposed. In this area of the body, soft tissue coverage is difficult because of the lake of local sub-cutaneus tissue and muscle. The authors used two locoregional pedicled flaps: the extensor digitorum brevis flap and the abductor digiti minimi flap. These transfers left a minimum of functional and aesthetic after-effects. The optimal coverage of the exposed structures allowed the patient to walk thirty days after surgery. The way to harvest these flaps, their advantages and disadvantages are detailed.

Adolescent↗
PubMed2006

Soft-tissue reconstruction of the distal lower leg and foot: are free flaps the only choice? Review of 215 cases.

Free flaps are the first choice procedure to manage soft-tissue defect of the lower limb for many authors, but loco-regional pedicled flaps are an alternative since they were described in the 1980s. We analysed the changes in our practice to reconstruct soft-tissue defects of the distal third of the leg. A retrospective chart review identified 215 cases of distal leg soft-tissue defect treated in the department during 15 years. The mean age was 43, and the sex ratio was 2.4. The aetiology, the size, the septic status and location of each wound were noted. The surgical procedures used and the complications have been analysed. The size and location of the wounds were comparable over the 15 years considered. Microsurgical tissue transfers were predominant in the 1980s and decreased in the 1990s, whereas the pedicled flap had an opposite evolution. In our experience, pedicled flaps are related to a non-significant lower rate of complication (18%) than free flaps (27%). Moreover, complications of local and regional flaps are less severe. Our practice has changed to make pedicled flaps our first choice to cover soft-tissue defects of the lower limb. However, we still use free flaps as a first choice for wide or composite defects, when pedicled flaps are not feasible or for cosmetic considerations to avoid additional scarring of the leg.

Adolescent↗
PubMed2006

Effect of isomalt consumption on faecal microflora and colonic metabolism in healthy volunteers.

Due to its low digestibility in the small intestine, a major fraction of the polyol isomalt reaches the colon. However, little is known about effects on the intestinal microflora. During two 4-week periods in a double-blind, placebo-controlled, cross-over design, nineteen healthy volunteers consumed a controlled basal diet enriched with either 30 g isomalt or 30 g sucrose daily. Stools were collected at the end of each test phase and various microbiological and luminal markers were analysed. Fermentation characteristics of isomalt were also investigated in vitro. Microbiological analyses of faecal samples indicated a shift of the gut flora towards an increase of bifidobacteria following consumption of the isomalt diet compared with the sucrose diet (P<0.05). During the isomalt phase, the activity of bacterial beta-glucosidase decreased (P<0.05) whereas beta-glucuronidase, sulfatase, nitroreductase and urease remained unchanged. Faecal polyamines were not different between test periods with the exception of cadaverine, which showed a trend towards a lower concentration following isomalt (P=0.055). Faecal SCFA, lactate, bile acids, neutral sterols, N, NH3, phenol and p-cresol were not affected by isomalt consumption. In vitro, isomalt was metabolized in several bifidobacteria strains and yielded high butyrate concentrations. Isomalt, which is used widely as a low-glycaemic and low-energy sweetener, has to be considered a prebiotic carbohydrate that might contribute to a healthy luminal environment of the colonic mucosa.

Adult↗
PubMed2006

Understanding the immune responses to the meningococcal strain-specific vaccine MeNZB measured in studies of infants.

Vaccine trials with infants enrolled between 6 and 10 weeks of age (young infants) and 6 and 8 months of age (older infants) provided an opportunity to evaluate immunoglobulin G (IgG) isotype distribution and avidity maturation as indicators of antibody function and immunologic memory. Following vaccination with a strain-specific outer membrane vaccine, MeNZB, pre- and postvaccination sera were used to determine IgG isotype responses and avidity indices (AI) in subsets of vaccinated subjects. Measurements of IgG isotypes involved 100 infants from each trial. AI were measured in 50 infants from the young infant trial who received a fourth vaccine dose and in 40 older infants from whom serum was collected 7 months after the primary vaccination course. IgG1 and IgG3 dominated the responses to the vaccine. A modest linear correlation (P < 0.001) occurred between serum bactericidal antibody (SBAb) titers and the total IgG or the IgG1 antibody units in older infants. The young infants showed a modest linear correlation between SBAb and total IgG (P = 0.005) and a weak linear correlation between SBAb and IgG1 (P = 0.003). Increased avidity with age was demonstrated in both groups. The AI in the young infants increased from 51.5% (95% confidence interval [CI], 47.7 to 54.7) postvaccination to 68.7% (95% CI, 65.5 to 71.9%) following the fourth dose of vaccine (P < 0.001). The mean avidity of the older infants increased significantly (P = 0.00012) from 42.4% (95% CI, 39.1 to 45.3%) postvaccination to 50.4% (95% CI, 47.2 to 53.6%) 4 months later. A fourth dose of MeNZB is now being given to young infants at 10 months of age.

Antibodies, Bacterial↗
PubMed2006

European multicenter evaluation of high-density DNA probe arrays for detection of hepatitis B virus resistance mutations and identification of genotypes.

Polymorphisms along the hepatitis B virus (HBV) genome have an impact on disease outcome, sensitivity to antiviral treatment, escape from vaccination, and laboratory diagnosis. We have designed a diagnostic tool based on duplex amplification of the whole HBV genome and a high-density DNA chip designed to detect 245 mutations, 20 deletions, and 2 insertions at 151 positions and to determine the genotype of the virus in serum. Assay performances were evaluated with 170 samples, characterized by determination of viral load and sequencing of the Pol, S, and precore genes and the basal core promoter. One hundred fifty-three samples (90%) could be amplified and analyzed by the chip. Only two samples with more than 10(3) genome copies/ml could not be analyzed. Genotype had no impact on analytical sensitivity. Reproducibility studies showed no difference between repeats for codon and genotype determination. Genotype determination by sequencing and the chip were concordant in 148 of 151 samples. Twelve thousand one hundred sixty-one codons were analyzed by both techniques. Only 89.4% could be determined by sequencing, and among the remaining 11,335 codons, 92.8% were identical by sequencing and the chip. Failures to identify an amino acid by the chip were mainly due to reduced hybridization efficiency attributed to unexpected polymorphisms. Optimization of the chip-based reagent for the analysis of the HBV genome is ongoing. This first evaluation showed that DNA chip technology can provide important information in relation to the clinical management of chronic hepatitis B.

DNA, Viral↗
PubMed2006

Wide clinical variability among 13 new Cockayne syndrome cases confirmed by biochemical assays.

Cockayne syndrome is a multi-systemic, autosomal recessive disease characterised by postnatal growth failure and progressive multi-organ dysfunction. The main clinical features are severe dwarfism (<-2 SD), microcephaly (<-3 SD), psychomotor delay, sensorial loss (cataracts, pigmentary retinopathy, and deafness), and cutaneous photosensitivity. Here, 13 new cases of Cockayne syndrome are reported, which have been clinically diagnosed and confirmed using a biochemical transcription assay. The wide clinical variability, ranging from prenatal features to normal psychomotor development, is emphasised. When cardinal features are lacking, the diagnosis of Cockayne syndrome should be considered when presented with growth retardation, microcephaly, and one of the suggesting features such as enophthalmia, limb ataxia, abnormal auditory evoked responses, or increased ventricular size on cerebral imaging.

Abnormalities, Multiple↗
PubMed2005

[Antebrachial flap based on distal perforators of the radial artery: anatomic study of 10 cases].

PURPOSE: The radial forearm flap based on distal perforators of the radial artery is a recent flap, derived from the so-called << chinese-flap >>. The interest of this flap resides in the preservation of the main arteries of the forearm. The aim of this study was to count the distal perforators of the radial artery and to study sub-cutaneous vascular system. MATERIALS AND METHOD: We performed 10 dissections on fresh cadavers, after selective injection of the radial artery with a solution of plasticized resin. The dissection was performed from the palmar flexor fold of the wrist up to 15 cm proximally, allowing to count all of the distal perforators. RESULTS: We determined three different intervals, among which the one located between 2 and 6 cm from the palmar flexor fold of the wrist was the most vascularized. This interval should be considered as the rotation point of the flap. CONCLUSION: This study allowed to make clear and more reliable the operative procedure to raise the flap. This procedure is easy to handle and intended to cover proximal defects of the dorsal aspect of the hand, while sparing the radial artery.

Arm↗
PubMed2005

Skin wound closure with a novel shape-memory alloy fixator.

BACKGROUND: Previously, we have described novel, thermally deployable tissue fixators based on the shape-memory properties of nickel titanium. The present study reports on the in vivo wound closure with these fixators as a preliminary to evaluating their use for bowel anastomoses. METHODS: Twenty adult Sprague-Dawley rats had 2.0-cm dorsal skin incisions approximated either with shape-memory alloy (SMA) fixators or conventional skin staples on a random basis. Electrical resistance heating was used to transform and deploy the SMA fixators into the wound. The rats were killed on day 14 or day 28 and wound specimens were harvested for force distraction studies and histologic examination. RESULTS: There was no incidence of wound dehiscence. 14- and 28-day wounds from both groups showed no significant difference in breaking force or energy. Histology revealed appropriate stages of wound healing for both SMA-closed and control wounds. CONCLUSIONS: The results confirm the efficacy and safety of tissue-edge approximation with SMA fixators.

Alloys↗
PubMed2005

The receptor activator of nuclear factor-kappaB ligand inhibitor osteoprotegerin is a bone-protective agent in a rat model of chronic renal insufficiency and hyperparathyroidism.

Osteoprotegerin (OPG) acts by neutralizing the receptor activator of nuclear factor-kappaB ligand (RANKL), the primary mediator of osteoclast differentiation, function, and survival. We examined whether OPG could affect the bone loss associated with chronic kidney disease (CKD) in a rodent model of CKD and secondary hyperparathyroidism (SHPT). SHPT was induced in rats by 5/6 nephrectomy (5/6 Nx) and a 1.2% P/0.6% Ca(2+) diet. Starting 1 week after 5/6 Nx, rats were treated with vehicle (veh) or OPG-Fc (3 mg/kg, intravenously) every 2 weeks for 9 weeks. At baseline, 3, 6, and 9 weeks, blood was taken and bone mineral density (BMD) and bone mineral content (BMC) were assessed by dual-energy X-ray absorptiometry. Serum parathyroid hormone (sPTH) levels reached 912 pg/ml in 5/6 Nx rats vs. 97 pg/ml in shams at 9 weeks. OPG-Fc had no effect on sPTH or Ca(2+) levels throughout the 9-week study, indicating that SHPT was a renal effect independent of bone changes. At 3 weeks, 5/6 Nx-veh rats had osteopenia compared with sham-veh rats and 5/6 Nx-OPG-Fc rats had significantly higher percent changes in whole-body BMC, leg BMD, and lumbar BMD versus 5/6 Nx-veh rats. By 6-9 weeks, elevated sPTH was associated with reversal of bone loss and osteitis fibrosa in the proximal tibial metaphysis. OPG-Fc decreased this sPTH-driven high bone turnover, resulting in augmented thickness of proximal tibial trabeculae in 5/6 Nx rats. Thus, RANKL inhibition with OPG-Fc can block the deleterious effects of continuously elevated sPTH on bone, suggesting that RANKL may be an important therapeutic target for protecting bone in patients with CKD and SHPT.

Absorptiometry, Photon↗
PubMed2005

Safety and immunogenicity of New Zealand strain meningococcal serogroup B OMV vaccine in healthy adults: beginning of epidemic control.

As the first step towards control of a strain specific epidemic of meningococcal disease in New Zealand (NZ), this study, an observer-blind, randomised controlled trial in 75 healthy adults, evaluated safety and immunogenicity of two different dosages of a meningococcal group B vaccine administered in a three dose regime. The "tailor-made" outer membrane vesicle (OMV) vaccine (candidate vaccine) developed using a New Zealand meningococcal group B strain (B:4:P1.7b,4) was well tolerated with no vaccine related serious adverse events. Similar local and systemic reactions were observed in those receiving the New Zealand candidate vaccine and the control parent Norwegian vaccine (MenBvac). A four-fold rise in serum bactericidal antibodies (SBAb) against the vaccine strain 4-6 weeks after the third vaccination was achieved in 100% of New Zealand candidate vaccine 2,519 microg participants and in 87% of 50 microg participants. The safety and immunogenicity profile observed in this study of healthy adults enabled studies in children to be initiated using 25 microg dosage.

Adolescent↗