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Biomedical subjects

D Martin

Publications and source records attributed to D Martin.

At least 37 records · Page 2Linked to original sources

Zinc protects renal function during cadmium intoxication in the rat.

This study investigates the effect in the rat of chronic CdCl2 intoxication (500 microg Cd2+/kg, daily i.p. injection for 5 days) on renal function and the changes in tight junction proteins claudin-2, claudin-3, and claudin-5 present in rat kidney. We also studied the effect of coadministration of ZnCl2 (500 microg Zn2+/kg) during chronic CdCl2 intoxication. Our results indicate that 1) most of the filtered Cd2+ is reabsorbed within the kidney; 2) chronic Cd2+ intoxication can induce a change in renal handling of ions without altering glomerular filtration rate; 3) a delayed nephropathy, showing Fanconi-like features, appears more than 5 days after the end of CdCl2 exposure; 4) epithelial integrity is altered by chronic Cd2+ intoxication affecting the expression and localization of claudin tight junction proteins; and 5) cotreatment with Zn2+ protects against the renal toxic effects of Cd2+, preventing altered claudin expression and inhibiting apoptosis. In conclusion, these results show that Cd2+ toxicity and cellular toxic mechanisms are complex, probably affecting both membrane transporters and tight junction proteins. Finally, Zn2+ supplementation may provide a basis for future treatments.

Animals↗

[First case in the world of autoreplantation of a limb associated with oral administration of an immunosupressant agent (FK 506-Tacrolimus)].

This is the case of the replantation of the upper limb of a sixty year old woman. The nature of the traumatism is an avulsion of the upper limb, at the junction of the middle third and the lower third of the humerus, which has a very bad prognosis. The originality of this report is the administration of Tacrolimus (immunosuppressive molecule) in an autotransplant. Tracolimus stimulates the nerve growing back, as already demonstrated in the animal and the fetus. In this preliminary report, the use of Tacrolimus over one year showed exceptional results. Indeed, the autors noticed clinical signs of intrinsic reinervation of the hand in the territory of the ulnar and median nerve. This has been confirmed with the use of electromyography. This is, as far as we know, the first observation of such results with adults and when the level of amputation is located so high. The authors think that the use of Tacrolimus should be tested in numerous cases of nerve lesions with bad prognosis such as high ulnar nerve lesions, serious plexus suffering or even in spinal cord trauma.

Administration, Oral↗

New Zealand's epidemic of meningococcal disease described using molecular analysis: implications for vaccine delivery.

New Zealand's epidemic of meningococcal disease began in mid 1991. Surveillance of meningococcal disease in New Zealand is based on a combination of disease notification and organism characterisation. Case numbers and population rates rose from 53 (1.5 per 100,000 population) in 1990 to a high of 650 (17.4 per 100,000 population) in 2001. The highest rates of disease occur in Pacific peoples under 20 years but the highest percentages of cases occur in Maori and European New Zealanders. The epidemic has been driven by a strain identified as B:4:P1.7b,4, ST-41/44 complex/Lineage III. The stability of the P1.7b,4 Por A protein has been demonstrated suggesting that the epidemic may be controlled by a strain-specific OMV vaccine.

Adolescent↗

Validation of the serum bactericidal assay for measurement of functional antibodies against group B meningococci associated with vaccine trials.

Provisional licensure of the trial vaccine, MeNZB, required demonstration of immune responses in vaccines, as measured by a validated Serum Bactericidal Assay (SBA). Reported are the investigations undertaken to define test parameters, lower limits of quantitation and measurement of SBA reproducibility. Results helped to formulate the operating procedure for the measurement of serum bactericidal antibodies during six age-group MeNZB vaccine trials. The lower limit of quantitation was determined as a titre of 4. A four-fold rise in antibody (sero-conversion) from a pre-vaccination titre of 2 (<4) required a minimum post-vaccination titre of 8, a more stringent measurement than has been used in other published studies.

Antibodies, Bacterial↗

Sequential loss of myelin proteins during Wallerian degeneration in the human spinal cord.

Axons undergo Wallerian degeneration (WD) distal to a point of injury. In the lesioned PNS, WD may be followed by successful axonal regeneration and functional recovery. However, in the lesioned mammalian CNS, there is no significant axonal regeneration. Myelin-associated proteins (MAPs) have been shown to play significant roles in preventing axonal regeneration in the CNS. Since relatively little is known about such events in human CNS pathologies, we performed an immunohistochemical investigation on the temporal changes of four MAPs during WD in post-mortem spinal cords of 22 patients who died 2 days to 30 years after either cerebral infarction or traumatic spinal cord injury. In contrast to experimental studies in rats, the loss of myelin sheaths is greatly delayed in humans and continues slowly over a number of years. However, in agreement with animal data, a sequential loss of myelin proteins was found which was dependent on their location within the myelin sheath. Myelin proteins situated on the peri-axonal membrane were the first to be lost, the time course correlating with the loss of axonal markers. Proteins located within compact myelin or on the outer myelin membrane were still detectable 3 years after injury in degenerating fibre tracts, long after the disappearance of the corresponding axons. The persistence of axon growth-inhibitory proteins such as NOGO-A in degenerating nerve fibre tracts may contribute to the maintenance of an environment that is hostile to axon regeneration, long after the initial injury. The present data highlight the importance of correlating the well documented, lesion-induced changes that take place in controlled laboratory investigations with those that take place in the clinical domain.

Adolescent↗

Candida species distribution in bloodstream cultures in Lyon, France, 1998-2001.

In order to determine the types of Candida spp. isolated from bloodstream cultures in Lyon, France, a retrospective study of isolates collected at five different bacteriology laboratories from 1998 to 2001 was conducted. During this period Candida spp. were isolated from 190 patients hospitalized in the internal medicine (32%), hematology (23%) and surgery (23%) wards, and in intensive care units (22%). C. albicans was the leading cause of Candida infection (49.5%), followed by C. glabrata (12.6%) and C. parapsilosis (12.1%). Among the onco-hematology patients, the major cause of candidemia was C. krusei (34%), followed by C. albicans (19%), while these two species were identified in 4% and 59% of patients in the other wards, respectively. In the single onco-hematology ward that was specialized in treating acute myeloid leukemia, 14 C. krusei isolates were identified in this study, which contrasts with the single C. krusei isolate recorded between 1992 and 1996. Since C. krusei has inherent resistance to the antifungal agent fluconazole, prophylactic use of fluconazole in these patients was investigated, but no relationship between these two parameters was found.

Aged↗

[Contribution of French surgeons to reconstructive microsurgery].

The authors report the contribution of French surgeons and particularly the plastic surgeons to the reconstructive microsurgery since 1972. Different domains are reviewed: animal experimentation, anatomical studies, reimplantations, free tissular transfer, free bone transfer, strategic original concept of transfer, free toes transfer, microsurgical reconstruction of malformative hand, free lymphatic transfer, nervous microsurgery, flap prefabrication, allotransplantations and the future of microsurgery. Three societies have the place of honour: the French Society of Plastic Reconstructive and Aesthetic Surgery, the Group for Advancement of Microsurgery and the World Society for Reconstructive Microsurgery.

Adult↗

[<< Reverse >> latissimus dorsi musculocutaneous flap: anatomic study of the secondary pedicles].

PURPOSE: The latissimus dorsi flap based on the secondary segmental vessels, wich is termed << reverse >> or << distally based >> latissimus dorsi flap, has been used to repair major thoraco-lumbar defects, to close myelomeningoceles and to reconstruct congenital diaphragmatic absences. The arc of flap rotation is markedly restricted because the blood supply is segmental. It is the most important factor that limits the flap mobility and so restricts its use. The authors report an anatomic study of these secondary pedicles in order to improve the flap dissection and to extend the arc of flap rotation. MATERIAL AND METHOD: The precise location of the secondary pedicles of the flap was determined by 24 anatomic dissections. RESULTS: The latissimus dorsi has 3, 4 or 5 secondary pedicles respectively in 50%, 25% and 25% of cases in the study. These pedicles take origin from the dorsal branches of the posterior intercostal arteries of the 7th, 8th, 9th, 10th and 11th intercostal spaces. CONCLUSION: The number of secondary pedicles is not constant. The entire flap can be safely based on 2 secondary pedicles when the latissimus dorsi muscle has 3 secondary pedicles. When this muscle has 4 or 5 secondary pedicles, the entire flap should be at least based on 3 secondary pedicles, particularly if the skin island is very far from the origin of these vessels.

Back↗

Cystatin C as a marker of renal function in kidney transplant patients.

INTRODUCTION: Serum creatinine (sCr) is the most commonly used biochemical parameter for gauging kidney function, but, due to its limitations, it is not the ideal marker for glomerular filtration rate (GFR). Cystatin C (sCyC) appears to be an endogenous marker of GFR. AIM: To assess the use of sCyC as a marker of renal function in kidney transplant patients, we compared it with sCr and with creatinine clearance either in a 24-hour urine or calculated using the Cockroft-Gault formula. METHODS: Among 78 patients (62.8% men, 37.2% women) undergoing kidney transplantation (average age 44.87 +/- 13.37 years) we determined at 2, 5, 7, 15, and 30 days, and 6, 12 and 18 months after kidney transplantation: sCr (using the Jaffé colorimetric method), sCyC (immunonephelometry), creatinine clearance with a 24-hour urine, creatinine clearance using the Cockroft-Gault formula. RESULTS: During the first 30 days following transplantation, there was a progressive decline in sCr levels. sCyC increased up to the fifth day, coinciding with the highest doses of steroids, and then decreased. At 6, 12, and 18 months, there was a correlation between sCyC and sCr, creatinine clearance in a 24-hour urine or calculated with the Cockroft-Gault formula (R = 0.859; R = -0.713, and R = -0.684, respectively, P < .001.) CONCLUSIONS: sCyC is an endogenous marker of GFR. Its limitations relate to its being affected by the high doses of steroids in the first days following transplantation. In the 18-month posttransplant period, it correlated with creatinine clearance in a 24-hour urine or calculated by the Cockroft-Gault formula.

Adult↗

Rituximab mediates in vitro antileukemic activity in pediatric patients after allogeneic transplantation.

Relapse is a major problem after allogeneic transplantation in children with acute B-lineage lymphoblastic leukemias (ALL) and lymphomas and additional therapeutic strategies are needed to increase graft versus leukemia effects without inducing graft versus host disease (GvHD). Several studies have shown the efficacy of a humanized CD20 antibody (rituximab) for treatment of CD20+ malignancies together with conventional chemotherapy but less is known about its post transplant usefulness. We studied the ability of rituximab to mediate antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) with effector cells and complement from patients who were transplanted with T-cell-depleted grafts from unrelated or mismatched related donors. Highest lytic activity (ADCC) was observed against leukemia-derived MHH4 cells and Burkitt's lymphoma-derived Raji cells in the first months after transplantation, corresponding to the high percentage of regenerating CD56+ CD16+ cells. Moreover, primary cryopreserved ALL-blasts from a pediatric patient were also efficiently lysed. Increased lysis was obtained after stimulation with interleukin-2. Combination of ADCC and CDC had additive effects. These findings encourage clinical trials on the use of rituximab for improving minimal residual disease control and relapse prevention after allogeneic high-risk transplantation in the small group of pediatric patients with CD20+ leukemias/lymphomas.

Animals↗

The effects of acute relaxation on indices of anxiety during pregnancy.

OBJECTIVES: Antenatal maternal anxiety has adverse effects on the fetus and the child. In this study we determined whether a short period of directed or of passive relaxation reduced maternal self-rated anxiety, heart rate, plasma catecholamines, cortisol and uterine artery resistance index, in pregnant women. METHODS: Fifty-eight women (28-32 wks gestation) were assigned randomly to a session of directed active or passive (sitting quietly) relaxation. Spielberger self-rating anxiety questionnaires were completed, and a venous blood sample taken, before and after a Doppler scan. RESULTS: Both active and passive relaxation significantly reduced State Anxiety and maternal heart rate, but the effect was significantly greater with the active relaxation. In contrast, the passive relaxation significantly reduced noradrenaline levels whereas active did not. Adrenaline levels were not changed significantly with either type of relaxation. Both methods significantly reduced cortisol, with a trend for the passive to have a greater effect. The active relaxation had no effect on uterine artery blood flow, whereas there was a statistically significant, but clinically negligible, increase in mean resistance index after passive relaxation. CONCLUSION: Both methods reduced maternal State Anxiety and heart rate, the active method more so. However there was a striking lack of correlation with the other biological indices studied. In order to reduce specific biological effects of anxiety during pregnancy, different methods may be needed from those which are most effective at reducing subjective anxiety.

Adult↗

Barriers to HIV/AIDS knowledge and prevention among deaf and hard of hearing people.

This study investigated knowledge about HIV/AIDS and barriers to HIV/AIDS education and prevention among deaf and hard of hearing people. Focus groups and individual interviews were used to elicit information from various groups of people with a hearing loss in different regions of New York State. Themes elicited in the interviews suggested that deaf sign language users are less knowledgeable about HIV/AIDS than oral deaf and hard of hearing participants, and that deaf adolescents have more knowledge than deaf adults. These findings likely reflect differences in levels of education and English proficiency. In addition, participants living in urban areas and in sizeable deaf communities are more exposed to information about HIV/AIDS than other participants. All participants reported difficulties in communication with medical providers, limiting their access to health information and proper medical care. Recommendations for the design and dissemination of educational materials and greater access to services for deaf and hard of hearing people are provided.

Acquired Immunodeficiency Syndrome↗

An initial investigation of spinal mechanisms underlying pain enhancement induced by fractalkine, a neuronally released chemokine.

Fractalkine is a chemokine that is tethered to the extracellular surface of neurons. Fractalkine can be released, forming a diffusible signal. Spinal fractalkine (CX3CL1) is expressed by sensory afferents and intrinsic neurons, whereas its receptor (CX3CR1) is predominantly expressed by microglia. Pain enhancement occurs in response both to intrathecally administered fractalkine and to spinal fractalkine endogenously released by peripheral neuropathy. The present experiments examine whether fractalkine-induced pain enhancement is altered by a microglial inhibitor (minocycline) and/or by antagonists/inhibitors of three putative glial products implicated in pain enhancement: interleukin-1 (IL1), interleukin-6 (IL6) and nitric oxide (NO). In addition, it extends a prior study that demonstrated that intrathecal fractalkine-induced mechanical allodynia is blocked by a neutralizing antibody to the rat fractalkine receptor, CX3CR1. Here, intrathecal anti-CX3CR1 also blocked fractalkine-induced thermal hyperalgesia. Furthermore, blockade of microglial activation with minocycline prevented both fractalkine-induced mechanical allodynia (von Frey test) and thermal hyperalgesia (Hargreaves test). Microglial activation appears to lead to the release of IL1, given that pretreatment with IL1 receptor antagonist blocked both fractalkine-induced mechanical allodynia and thermal hyperalgesia. IL1 is not the only proinflammatory cytokine implicated, as a neutralizing antibody to rat IL6 also blocked fractalkine-induced pain facilitation. Lastly, NO appears to be importantly involved, as l-NAME, a broad-spectrum NO synthase inhibitor, also blocked fractalkine-induced effects. Taken together, these data support that neuronally released fractalkine enhances pain via activation of spinal cord glia. Thus, fractalkine may be a neuron-to-glia signal triggering pain facilitation.

Animals↗

High light field confinement for fluorescent correlation spectroscopy using a solid immersion lens.

In this paper we present recent single molecule detection experiment using a solid immersion lens (SIL) for fluorescent correlation spectroscopy measurements. We compared the performance of the SIL in combination with an air objective (40x, numerical aperture (NA)=1.15) with a water immersion objective (40x, NA=0.6) in a confocal microscope system (ConfoCorr 1). Important parameters for single molecule experiments such as collection efficiency and excitation field confinement were investigated. Although the two set-ups have similar numerical aperture the measurements demonstrated higher field confinement and better collection efficiency for the SIL system in comparison to the conventional confocal set-up. Adding spherical aberrations shifts the sample volume up to 4 microm away from the plane surface of the SIL and conserves a diffraction limited focal volume. In this case the FCS autocorrelation demonstrates a free 3D diffusion of dye molecules in a highly confined light field.

Equipment Design↗

Introduction to the DAPPLE Air Pollution Project.

The Dispersion of Air Pollution and its Penetration into the Local Environment (DAPPLE) project brings together a multidisciplinary research group that is undertaking field measurements, wind tunnel modelling and computer simulations in order to provide better understanding of the physical processes affecting street and neighbourhood-scale flow of air, traffic and people, and their corresponding interactions with the dispersion of pollutants at street canyon intersections. The street canyon intersection is of interest as it provides the basic case study to demonstrate most of the factors that will apply in a wide range of urban situations. The aims of this paper are to introduce the background of the DAPPLE project, the study design and methodology for data collection, some preliminary results from the first field campaign in central London (28 April-24 May 2003) and the future for this work. Updated information and contact details are available on the web site at http://www.dapple.org.uk.

Air Pollution↗

Cu, Zn- and Mn-superoxide dismutase levels in brains of patients with schizophrenic psychosis.

Impaired oxidative stress defense has been reported in blood of both drug-naïve and antipsychotic-treated patients suffering from schizophrenic psychosis, indicating the involvement of free radical metabolism in the pathogenetic processes of schizophrenia. In this study, the concentrations of two isoenzymes of superoxide dismutase (SOD), Cu, Zn- and MnSOD, were determined with ELISA in various cortical (frontal, parietal, temporal and occipital cortex) and subcortical areas (putamen, caudate nucleus, thalamus, and substantia innominata) of post-mortem brain tissue from patients diagnosed with a schizophrenia spectrum disorder and compared with those of controls. Post-mortem brain tissue from individuals without neuropsychiatric disorders served for control. Cu, Zn- and MnSOD levels were significantly increased in frontal cortex and substantia innominata of the index group, respectively. In all other areas both types of SOD remained virtually unchanged. Detection of SOD changes in the brain supports previous reports of alterations of antioxidant indices in blood cells of patients with schizophrenia and suggests a specific neuroanatomical distribution pattern of oxidative stress processes possibly related to the pathophysiology of schizophrenia.

Adult↗