Search PubMed⌕ Search

Biomedical subjects

D Martin

Publications and source records attributed to D Martin.

At least 271 records · Page 15Linked to original sources

Effects of macrophage transplantation in the injured adult rat spinal cord: a combined immunocytochemical and biochemical study.

Early and robust invasion by macrophages may be one of the reasons why axonal regeneration is more effective in the PNS than in the CNS. Therefore, we have grafted autologous peritoneal macrophages labeled with fluorescent latex microspheres into spinal cord compression lesions. At various survival times, we have studied their effect on the expression of neuronal (neurofilaments [NF], calcitonin gene-related peptide [CGRP], 5-hydroxytryptamine [5-HT]) and nonneuronal markers (myelin-associated glycoprotein [MAG], glial fibrillary acidic protein [GFAP], laminin) by using semiquantitative Western blot and immunohistochemical techniques. After 1 month, we observed a significant decrease of the expression of MAG as well as an important invasion of the lesion site by neurites, chiefly peptidergic axons of presumed dorsal root origin, in macrophage-grafted animals compared with controls. In addition, angiogenesis and Schwann cell infiltration were more pronounced after macrophage grafts, providing an increase in laminin, a favorable substrate for axonal regrowth. By using reverse transcription-polymerase chain reaction (RT-PCR), mRNAs for tumor necrosis factor-alpha (TNF-alpha) were detected in the transplanted cells, whereas results were negative for nerve growth factor (NGF), neurotrophin-3 (NT-3), brain-derived neurotrophic factor (BDNF), or acidic fibroblast growth factor (aFGF) and basic fibroblast growth factor (bFGF). Thus, macrophage grafts may represent an interesting strategy to promote axonal regeneration in the CNS. Our study suggests that they may exert their beneficial effects by degrading myelin products, which inhibit axonal regrowth, and by promoting a permissive extracellular matrix containing notably laminin. No evidence for a direct synthesis of neurotrophic factors by the transplanted macrophages was found in this study, but resident glial cells could secrete such factors as a result of stimulation by macrophage-released cytokines.

Animals↗

Leptin and ciliary neurotropic factor (CNTF) inhibit fasting-induced suppression of luteinizing hormone release in rats: role of neuropeptide Y.

Periods of chronic undernutrition and short periods of fasting suppress pituitary luteinizing hormone (LH) secretion and upregulate hypothalamic neuropeptide Y (NPY), the orexigenic peptide. The effect of suppression of NPY upregulation with ciliary neurotropic factor (CNTF), a cytokine, and leptin, an adipocyte hormone, on pituitary LH secretion was evaluated in fasted rats. In the first experiment, daily injection of CNTF (0.2 nmol) intracerebroventricularly (i.c.v.) for 4 days drastically reduced food intake and body weight gain similar to the weight loss seen in pair-fed rats. Food deprivation (FD) also decreased body weight. Despite drastic loss in body weight, plasma LH was reduced in FD and pair-fed rats, but not in CNTF-treated rats. In the second experiment, FD rats received either control vehicle, CNTF (0.2 nmol) or leptin (0.2 nmol) daily for 4 days. FD increased steady state levels of preproNPY mRNA in the hypothalamus over the control freely-fed rats. However, both CNTF and leptin suppressed hypothalamic gene expression and significantly attenuated LH suppression in response to FD. Taken together, these results support the hypothesis that the upregulation of hypothalamic NPY system may underlie diminution in pituitary gonadotropin secretion and that the NPYergic pathway may serve as a communication bridge between the neural processes that regulate reproduction and those that maintain energy balance.

Adipocytes↗

Pharmacokinetics of intravenously and orally administered eprosartan in healthy males: absolute bioavailability and effect of food.

Eighteen healthy males received a single 300 mg oral dose of eprosartan as the commercial wet granulation formulation under fasting conditions and following a high-fat breakfast and a single 20 mg intravenous (i.v.) dose. The pharmacokinetics of i.v. eprosartan (mean +/- S.D.) were characterized by a low systemic plasma clearance (131.8 +/- 36.2 mL min(-1)) and a small steady-state volume of distribution (12.6 +/- 2.6 L). Oral bioavailability averaged 13.1%, due to incomplete absorption. In vitro dynamic flow cell dissolution data showed that pH-dependent aqueous solubility of eprosartan is one factor which limits absorption. Eprosartan terminal half-life was shorter after i.v. (approximately 2 h) versus oral (approximately 5-7 h) administration, which may be due to detection of an additional elimination phase or absorption rate-limited elimination following oral administration. Oral administration of eprosartan following a high-fat meal compared with fasting conditions resulted in a similar extent of absorption (based on AUC), but a decreased absorption rate. Cmax was approximately 25% lower, and a median delay of 1.25 h in time to Cmax was observed when eprosartan was administered with food. These minor changes in exposure are unlikely to be of clinical consequence; therefore, eprosartan may be administered without regard to meal times.

Acrylates↗

Interleukin 6, but not ciliary neurotrophic factor or leukaemia inhibitory factor, is responsible for the acute phase response to turpentine-induced myositis.

The acute phase response to inflammation is mediated in part by the endogenous production of pro-inflammatory cytokines. Interleukin 6 (IL-6) and members of its superfamily, including ciliary neurotrophic factor (CNTF) and leukaemia inhibitory factor (LIF) have been implicated as primary mediators of the hepatic acute phase response. In the present report, mice suffering a turpentine-induced myositis were passively immunized with antibodies against either IL-6, CNTF or LIF. Passive immunization against IL-6 attenuated the anorexia and completely prevented the hypoalbuminaemia, and increases in the serum concentration of the acute phase reactants, amyloid P, amyloid A and seromucoid. In contrast, passive immunization against either CNTF or LIF failed to modulate the anorexia, weight loss or hepatic acute phase protein responses. The findings suggest that IL-6, but not other members of its superfamily, is primarily responsible for the hepatic acute phase response, and contributes to the anorexia, associated with turpentine-induced myositis.

Acute-Phase Reaction↗

LPS-induced TNF-alpha release from and apoptosis in rat cardiomyocytes: obligatory role for CD14 in mediating the LPS response.

The bacterial endotoxin lipopolysaccharide (LPS) contributes to the cardiovascular collapse and death observed in patients with sepsis. Because LPS has such profound effects on cardiac performance, we speculate that direct effects of LPS could be demonstrated on cardiomyocytes in culture, and that these direct effects are mediated by the LPS receptor, CD14. Accordingly, in this study, we provide evidence for CD14-dependent cardiotoxic effects of LPS including the LPS-stimulated secretion of tumor necrosis factor alpha (TNF-alpha) from cardiomyocytes. TNF-alpha is an inflammatory cytokine which is known for its negative inotropic effects on cardiac performance, but has not until recently been shown to be produced by cardiac cells. In this study, LPS was found to stimulate strongly in a dose-dependent manner the secretion of TNF-alpha from cultured adult rat cardiomyocytes. Further, LPS-induced TNF-alpha secretion was blocked by an inhibitor of TNF-alpha processing, metallomatrix protease inhibitor (TAPI). Molecular and immunological evidence demonstrated the presence of LPS receptors (CD14) on cardiomyocytes. Attenuated TNF-alpha secretion following PI-PLC treatment confirmed the functional importance of CD14 for LPS-mediated myocardial effects. Importantly, LPS also triggered apoptosis in cultured cardiomyocytes as quantified by single-cell gel electrophoresis of nuclei exhibiting DNA fragmentation patterns characteristic of apoptosis (i.e. cardiac comets). Apoptotic cell death was blocked by pre-incubation with the soluble TNF-alpha receptor fragment (TNFRII:Fc), suggesting that LPS-induced apoptosis was TNF-alpha-dependent and probably involved an autocrine function for the TNF-alpha whose secretion was under LPS control. The results of this study suggest that the cardiodepressant effects of LPS are dependent on CD14 signaling and may not only be due to acute negative inotropic effects of TNF-alpha but also may be complicated by TNF-alpha-induced apoptotic cell death which effectively reduces the number of working myocardial cells.

Animals↗

[Pancreas transplantation with bladder and intestinal drainage technique with systemic-venous and initial experiences with portal venous drainage. Which technique can be recommended today?].

The experience worldwide with pancreas transplantation includes more than 9000 cases. In the most popular patient group (simultaneous pancreas-kidney transplantation, SPK) the graft-function rate at 1 year now reaches more than 80%. More than 90% of all pancreas transplants were performed using the bladder-drainage technique (BD) with systemic venous anastomosis. Late problems with the BD require enteric conversion in 10-20% in the long term. In the present study we report the results of 40 SPK using the BD (n = 20) and enteric drainage (ED) techniques (n = 20). After 3 months, the patients pancreas and kidney survival rates in the BD group were 100, 95 and 100% and in the ED group 100, 100 and 100%, respectively. No anastomosis leakage occurred in either group. In two cases of the ED group the pancreas grafts were drained portal venously via the superior mesenteric vein without surgical complications. With growing experience, excellent SPK results can be reached with both the BD and ED techniques.

Adult↗

Comparative evaluation of cerebral aneurysms with selective arterially enhanced CT and DSA.

The purpose of our study was to compare selective arterially enhanced spiral computed tomographs (ACT) with digital subtraction angiographies (DSA) in the presurgical assessment of cerebral aneurysms. A total of 24 aneurysms in 18 patients were explored in a prospective study by ACT and DSA, using an interactive combined CT-angiography suite. Dimensions of the aneurysm, its relation to the parent vessel, and the aneurysmal index were defined on DSA and on surface-shaded display of 3D reformatted images obtained from ACT. Results were correlated with surgical findings. Three aneurysms suspected on DSA were not confirmed by ACT. One fusiform aneurysm suspected on DSA corresponded to a sacciform aneurysm on ACT. Surgical findings confirmed 20 sacciform aneurysms. The aneurysmal index could be measured in all 20 cases of sacciform aneurysms on ACT and could not be determined with confidence in 55 % of the cases on DSA. DSA and ACT gave identical results in 35 % of cases. In 10 %, the index measured by ACT was superior to that determined by DSA for aneurysms which had a diameter of less than 3 mm. In conclusion, the combination of DSA and ACT improved the results of DSA alone. ACT is a reliable method to measure the aneurysmal index in aneurysms with a diameter superior to 3 mm.

Angiography, Digital Subtraction↗

Cold effect on oxygen uptake, perceived exertion, and spasticity in patients with multiple sclerosis.

OBJECTIVE: To determine the effect of a cold bath (24 degrees C) on oxygen consumption and perceived exertion during ambulation and on spasticity in individuals with mild to moderate multiple sclerosis. DESIGN: A repeated-measures design with random assignment of experimental and control conditions. SETTING: Outpatient physical therapy department associated with an academic institution. PATIENTS: Fourteen individuals with clinically definite multiple sclerosis exhibiting spasticity and capable of ambulating at 0.7 m/sec on a motorized treadmill without handrail support. MEASUREMENT: Assessment of oxygen uptake, heart rate, and perceived exertion occurred during two 10-minute walks interspersed with a 30-minute rest on 2 separate days. Measurement of spasticity occurred three times during each session. RESULTS: Oxygen consumption and perceived exertion were unchanged. Spasticity was higher immediately (p < .05) after the cold bath. CONCLUSIONS: Increase in spasticity was statistically significant, but unlikely to be of any clinical importance. Contrary to our hypothesis, a cold bath (24 degrees C) for 20 minutes did not reduce oxygen consumption or rating of perceived exertion during ambulation.

Adult↗

Soft acrylic resin materials containing a polymerisable plasticiser I: mechanical properties.

Conventional soft acrylic resin materials depend on the use of plasticisers for their compliance. In aqueous environments the plasticisers leach out causing the material to harden. Use of a polymerisable plasticiser has been shown to solve this problem. One such material was developed but failed mechanically during clinical trial. The aim of this study was to reformulate to produce a material with improved strength. Three different methacrylate monomers were used with two different levels of plasticiser, each monomer mix was used with the same copolymer powder at three powder/liquid ratios. Tensile strength, tear energy and hardness were measured and results compared with 'Supersoft', a proprietary plasticised acrylic resin soft lining material. All the experimental materials had a higher tensile strength than the original Parker/Braden material. The 30% plasticiser materials with the higher powder/liquid level had strength, tear energy and hardness values in the same range as 'Supersoft'. Materials of improved strength have been produced.

Acrylic Resins↗

[Persistent hyperinsulinemic hypoglycemia in the newborn and infants].

Persistent hyperinsulinemic hypoglycaemia of infancy (PHHI) is the most frequent cause of hypoglycaemia in infancy. Clinical presentation is heterogeneous, with variable onset of hypoglycaemia and response to diazoxide, and presence of sporadic or familial forms. Underlying histopathological lesions can be focal or diffuse. Focal lesions are characterised by focal hyperplasia of pancreatic islet-like cells, whereas diffuse lesions implicate the whole pancreas. The distinction between the two forms is important because surgical treatment and genetic counselling are radically different. Focal lesions correspond to somatic defects which are totally cured by limited pancreatic resection, whereas diffuse lesions require a subtotal pancreatectomy exposing to high risk of diabetes mellitus. Diffuse lesions are due to functional abnormalities involving several genes and different transmission forms. Recessively inherited PHHI have been attributed to homozygote mutations for the beta-cell sulfonylurea receptor (SUR1) or the inward-rectifying potassium-channel (Kir6.2) genes. Dominantly inherited PHHI can implicate the glucokinase gene, particularly when PHHI is associated with diabetes, the glutamate dehydrogenase gene when hyperammonaemia is associated, or another locus.

Diazoxide↗

Quantitative health research in an emerging information economy.

This paper is concerned with the changing information environment in the U.K. National Health Service and its implications for the quantitative analysis of health and health care. The traditionally available data series are contrasted with those sources that are being created or enhanced as a result of the post-1991 market-orientation of the health care system. The likely research implications of the commodification of health data are assessed and illustrated with reference to the specific example of the geography of asthma. The paper warns against a future in which large-scale quantitative health research is only possible in relation to projects which may yield direct financial or market benefits to the data providers.

Asthma↗

Altitude training at 2690m does not increase total haemoglobin mass or sea level VO2max in world champion track cyclists.

Haemoglobin mass (Hb mass), maximum oxygen consumption (VO2max), simulated 4000 m individual pursuit cycling performance (IP4000), and haematological markers of red blood cell (RBC) turnover were measured in 8 male cyclists before and after (A) 31 d of altitude training at 2690 m. The dependent variables were measured serially after altitude on d A3-4, A8-9 and A20-21. There was no significant change in Hb mass over the course of the study and VO2max at d A9 was significantly lower than the baseline value (79.3 +/- 0.7 versus 81.4 +/- 0.6 ml x kg(-1) x min(-1), respectively). No increase in Hb mass or VO2max was probably due to initial values being close to the natural physiological limit with little scope for further change. When the IP4000 was analysed as a function of the best score on any of the three test days after altitude training there was a 4% improvement that was not reflected in a corresponding change in VO2max or Hb mass. RBC creatine concentration was significantly reduced after altitude training, suggesting a decrease in the average age of the RBC population. However, measurement of reticulocyte number and serum concentrations of erythropoietin, haptoglobin and bilirubin before and after altitude provided no evidence of increased RBC turnover. The data suggest that for these elite cyclists any benefit of altitude training was not from changes in VO2max or Hb mass, although this does not exclude the possibility of improved anaerobic capacity.

Adult↗

Using videotaped benchmarks to improve the self-assessment ability of family practice residents.

PURPOSE: To address methodologic and statistical problems of previous studies of self-assessment by exposing participants to relevant standards, anchoring rating scales, and providing practice in the use of the assessment tool. METHOD: Fifty first- and second-year family practice residents performed a ten-minute patient interview with a difficult communication problem. Following each interview, the resident and two experts independently evaluated the resident's communication skills. The resident was then shown a videotape of four performances (ranging in quality from poor to good) of the same scenario. The resident evaluated the communication skills displayed in each performance and then reevaluated his or her own performance. RESULTS: The correlation between experts' evaluations and residents' self-evaluations was moderate immediately after the interview (r = 0.38) but increased significantly after the residents viewed the videotape (r = 0.52). This effect was more pronounced for first-year residents (0.22 to 0.45) than for second-year residents (0.53 to 0.65), although the difference was not significant. Post-hoc analysis revealed that neither initial nor post-benchmark self-assessment ability was related to the ability to accurately evaluate the benchmarks in a manner consistent with the experts. CONCLUSIONS: The ability to self-assess does not seem strongly tied to the ability to assess the performances of others on the same task. Nonetheless, providing a set of benchmarks against which trainees can compare their own performances improves their ability to self-evaluate even if the qualities of the benchmarks are not explicitly identified.

Adult↗