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Biomedical subjects

J Martin

Publications and source records attributed to J Martin.

At least 91 records · Page 5Linked to original sources
PubMed2003

Spinal epidural abscess: a diagnostic challenge.

The objective of the study was to highlight the diagnostic challenge of this elusive rare disease. A retrospective study of non-tuberculous spinal epidural abscesses (SEA) was carried out in Southern General Hospital, Glasgow, University Hospital of Wales, Cardiff, and Morriston Hospital, Swansea, from 1990 to 2000. Thirty-nine patients, consisting of 20 females and 19 males, with an age range from 20 to 85 years (mean: 61.1) were identified. Thirty-eight had localized back/neck pain. Eighteen were apyrexial. Twenty-nine demonstrated neurological deficit. All patients had raised inflammatory markers and gadolinium-enhanced magnetic resonance imaging (MRI) was diagnostic in 34. The most commonly identified organism was Staphylococcus aureus. All underwent surgical decompression, of which 13 required stabilization. Three died, seven lacked sphincter control and nine had motor deficit at the end of 1 year. It was concluded that fever is not mandatory for the diagnosis of SEA. Patients with localized back/neck pain and raised inflammatory markers need urgent MRI.

Adult↗
PubMed2003

Thrombotic microangiopathy and digital necrosis: two unrecognized toxicities of gemcitabine.

We report one new case of hemolytic-uremic syndrome (HUS) and one case of digital necrosis after treatment with gemcitabine (Gemzar). Case 1, a 34-year-old man, was given first-line metastatic treatment with gemcitabine for a adenocarcinoma of the pancreas. After a cumulative dose of 10 000 mg/m2 gemcitabine, the onset of subacute renal failure associated with hemolytic anemia of mechanical origin was observed. A diagnosis of probable gemcitabine-induced thrombotic microangiopathy was arrived at. Symptoms resolved after stopping the chemotherapy, in spite of the progression of the disease. Case 2, a 61-year-old man, was administered a combination of gemcitabine and a platinum salt as first-line metastatic treatment for carcinoma of the bladder urothelium. Following a cumulative dose of 10 000 mg/m2 of gemcitabine, the patient suffered from bilateral peripheral vascular disease of somewhat acute onset with hemorrhagic lesions of the finger pads that became necrotic. The work-up was negative and a causal relationship was attributed to gemcitabine. The patient made good progress when given an i.v. infusion of Ilomedine (iloprost trometamol) and chemotherapy was withdrawn. We conclude that gemcitabine must be added to the list of drugs that cause HUS and necrotizing vasculitis.

Adenocarcinoma↗
PubMed2003

Cluster analysis of symptoms and health seeking behaviour differentiates subgroups of patients with severe irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is a heterogeneous condition which is diagnosed according to specific bowel symptom clusters. The aim of the present study was to identify subgroups of IBS subjects using measures of rectal sensitivity and psychological symptoms, in addition to bowel symptoms. Such groupings, which cross conventional diagnostic approaches, may provide greater understanding of the pathogenesis of the condition and its treatment. METHOD: A K means cluster analysis was used to group 107 clinic patients with IBS according to physiological, physical, and psychological parameters. All patients had severe IBS and had failed to respond to usual medical treatment. Twenty nine patients had diarrhoea predominant IBS, 26 constipation predominant, and 52 had an alternating bowel habit. RESULTS: The clusters were most clearly delineated by two variables: "rectal perceptual threshold (volume)" and "number of doctor visits". Three subgroups were formed. Group I comprised patients with low distension thresholds and high rates of psychiatric morbidity, doctor consultations, interpersonal problems, and sexual abuse. Group II also had low distension thresholds but low rates of childhood abuse and moderate levels of psychiatric disorders. Group III had high distension thresholds, constipation or alternating IBS, and low rates of medical consultations and sexual abuse. CONCLUSION: The marked differences across the three groups suggest that each may have a different pathogenesis and respond to different treatment approaches. Inclusion of psychosocial factors in the analysis enabled more clinically meaningful groups to be identified than those traditionally determined by bowel symptoms alone or rectal threshold.

Adult↗
PubMed2003

Demystified. Human endogenous retroviruses.

Human endogenous retroviruses (HERVs) are a family of viruses within our genome with similarities to present day exogenous retroviruses. HERVs have been inherited by successive generations and it is possible that some have conferred biological benefits. However, several HERVs have been implicated in certain cancers and autoimmune diseases. This article demystifies these retroviruses by providing an insight into HERVs, their means of classification, and a synopsis of HERVs implicated in cancer and autoimmunity. Furthermore, the biological roles of HERVs are explored.

Antibodies, Viral↗
PubMed2002

A phase I trial of antibody directed enzyme prodrug therapy (ADEPT) in patients with advanced colorectal carcinoma or other CEA producing tumours.

Antibody-directed enzyme prodrug therapy is a targeted therapy in which a prodrug is activated selectively at the tumour site by an enzyme, which has been targeted to the tumour by an antibody (antibody-enzyme conjugate). Previous clinical trials have shown evidence of tumour response, however, the activated drug had a long half-life, which resulted in dose-limiting myelosuppression. Also, the targeting system, although giving high tumour to blood ratios of antibody-enzyme conjugate (10 000 : 1) required administration of a clearing antibody in addition to the antibody-enzyme conjugate. The purpose of this current study therefore was to attempt tumour targeting of the antibody-enzyme conjugate without the clearing antibody, and to investigate a new prodrug (bis-iodo phenol mustard, ZD2767P) whose activated form is highly potent and has a short half-life. Twenty-seven patients were treated with antibody-directed enzyme prodrug therapy using A5CP antibody-enzyme conjugate and ZD2767P prodrug, in a dose-escalating phase I trial. The maximum tolerated dose of ZD2767P was reached at 15.5 mg m(-2)x three administrations with a serum carboxypeptidase G2 level of 0.05 U ml(-1). Myelosuppression limited dose escalation. Other toxicities were mild. Patients' quality of life was not adversely affected during the trial as assessed by the measures used. There were no clinical or radiological responses seen in the study, but three patients had stable disease at day 56. Human anti-mouse antibody and human anti-carboxypeptidase G2 antibody were produced in response to the antibody enzyme conjugate (A5CP). The antibody-enzyme conjugate localisation data (carboxypeptidase G2 enzyme levels by HPLC on tumour and normal tissue samples, and gamma camera analysis of I-131 radiolabelled conjugate) are consistent with inadequate tumour localisation (median tumour: normal tissue ratios of antibody-enzyme conjugate of less than 1). A clearance system is therefore desirable with this antibody-enzyme conjugate or a more efficient targeting system is required. ZD2767P was shown to clear rapidly from the circulation and activated drug was not measurable in the blood. ZD2767P has potential for use in future antibody-directed enzyme prodrug therapy systems.

Adult↗
PubMed2002

Buoyancy-driven instability of an autocatalytic reaction front in a Hele-Shaw cell.

An autocatalytic reaction-diffusion front between two reacting species may propagate as a solitary wave, namely, at constant velocity and with a stationary concentration profile. Recent experiments on such reactions have been reported to be buoyancy unstable, under certain conditions. We calculate the linear dispersion relation of the resulting instability, by applying our recent analysis of the Rayleigh-Taylor instability of two miscible fluids in a Hele-Shaw cell. The computed dispersion relation as well as our three-dimensional lattice Bhatnagar-Gross-Krook (BGK) simulations fit reasonably well experimental growth rates reported previously.

Journal Article↗
PubMed2002

Nocardia asteroides isolated from three patients with cystic fibrosis.

Over a 7-year period, three patients with cystic fibrosis had multiple sputum specimens that were smear- and culture-positive for Nocardia asteroides. Two of the patients had received long-term, low-dose inhalational corticosteroid therapy. Although all three patients were treated with cotrimoxazole, resulting in eradication of the organism from the sputum, there was no change in their clinical state, radiological findings, or pulmonary function. The isolation of Nocardia asteroides from the respiratory tract of cystic fibrosis patients is an unusual finding. Its presence does not necessarily imply disease, and in these three cases, it most likely represented colonisation. The clinical significance of Nocardia spp. isolated from the respiratory tract of cystic fibrosis patients needs to be considered in the context of the individual clinical picture.

Adolescent↗
PubMed2002

Statistical study of the relationship between free chlorine levels and bacteriological checks on systems in the Paris area.

The majority of French cities are supplied with treated surface water. The primary factor in determining the quality of this water concerns disinfection to ensure that the system is not contaminated with parasites, coliforms and streptococci; some of these organisms, especially coliforms, are capable of multiplying within the system. The presence of bacteria indicative of faecal contamination in water samples, which contains a significant amount of free chlorine, has revealed a possible link between the two. Based upon sampling points of the Parisian system (and in the suburbs for purposes of comparison), we show the existence of a linear relationship between the results of analyses for coliforms on a given day, D, and the content of free chlorine in the water on days D-2 and D-3. Subsequent ground tests confirm the explanations proposed regarding these phenomena.

Animals↗
PubMed2002

Increased expression of activation markers in renal cell carcinoma infiltrating lymphocytes.

PURPOSE: As manifested by the presence of immune competent cells, failure to control the progression of renal cell carcinoma by a local immune response attests to impaired local cell mediated immunity. To test this hypothesis we compared the expression of T-cell activation markers in renal cell carcinoma infiltrating lymphocytes with the expression of activation markers of peripheral blood lymphocytes in the same patients. MATERIALS AND METHODS: Tumor infiltrating lymphocytes were harvested from a patient with renal cell carcinoma undergoing radical nephrectomy. Peripheral blood was obtained before surgery. Tumor infiltrating and peripheral blood lymphocytes were incubated with monoclonal antibodies defining specific differentiation and activation markers on the cell surface, and analyzed by flow cytometry. Cell subsets are expressed as a fraction of the total number of mononuclear cells. RESULTS: The T-cell subset level was significantly higher in peripheral blood than in renal cell carcinoma tissue of the same patient. However, the level of activated T-cell subset expressing HLA-DR was significantly higher in renal cell carcinoma tissue than in peripheral blood. The levels of interleukin-2 receptor and transferrin receptors expressing T-cell subsets were also significantly higher in carcinoma tissue than in peripheral blood. Natural killer cells were found in significantly higher proportions in renal cell carcinoma than in peripheral blood. CONCLUSIONS: These results point to significant activation of T, B and natural killer tumor infiltrating lymphocytes. The inability of tumor infiltrating lymphocytes to mount an effective immune response to renal cell carcinoma may be secondary to the presence of suppressive factors in the tumor that prevent tumor infiltrating lymphocytes from transforming into effector cells. These factors may be particularly valuable for the further study of renal cell carcinoma-host interactivity.

Aged↗
PubMed2002

Population variability in Chironomus (Camptochironomus) species (Diptera, Nematocera) with a Holarctic distribution: evidence of mitochondrial gene flow.

Phylogenetic analysis of DNA sequences from mitochondrial (mt) genes (Cytochrome b and Cytochrome oxidase I) and one nuclear gene (globin 2b) was used for the investigation of Nearctic and Palearctic populations representing four Chironomus species of the subgenus Camptochironomus, namely C. biwaprimus, C. pallidivittatus, C. tentans sensu stricto and C. dilutus (the last two species constitute Holarctic C. tentans sensu lato). Phenograms constructed on the basis of mt sequences were not congruent with trees based on nuclear genes, or with morphological and cytological data. The mt tree divided the populations by continental region, rather than by the species groupings recognized by the other data sets. The incongruence is explained by mt gene flow resulting from hybridization between the sympatric species on each continent. Calculation of divergence times, based on the sequence data, suggest that C. tentans (s.l.) and C. pallidivittatus have both been in North America for about 2.5 My.

Animals↗
PubMed2002

Comparison of genotypic and phenotypic techniques for assessing the variability of the fungus Epicoccum nigrum.

AIMS: The diversity within a collection of worldwide isolates of Epicoccum nigrum has been studied using several phenotypic approaches. In addition, the abilities of phenotypic and genotypic techniques for the differentiation of a set of isolates are compared. METHODS AND RESULTS: The methodology used include the study of isozymes (acetyl esterase and alkaline phosphatase), HPLC profile of metabolites and antibiotic activities against a panel of bacteria, yeasts and filamentous fungi, and cytotoxicity against three mammalian cell lines. Two procedures for assessing the relationships within a collection of isolates, using a combination of the techniques, were evaluated, comparing the advantages and disadvantages of each method. CONCLUSIONS: The results showed that each individual technique allows differentiation of the isolates studied to some degree and that the information provided by each technique could be considered as complementary. Genotypic techniques were more powerful than the phenotypic ones to discriminate among the strains. SIGNIFICANCE AND IMPACT OF THE STUDY: This work evaluates the predictive value of several phenotypic techniques on a collection of fungal isolates, and compares the results obtained with genotypic techniques performed on the same strains.

Acetylesterase↗
PubMed2002

Significance of the caspase family in Helicobacter pylori induced gastric epithelial apoptosis.

BACKGROUND AND AIMS: H. pylori infection results in an increased epithelial apoptosis in gastritis and duodenal ulcer patients. We investigated the role and type of activation of caspases in H. pylori-induced apoptosis in gastric epithelial cells. METHODS: Differentiated human gastric cancer cells (AGS) and human gastric mucous cell primary cultures were incubated with H. pylori for 0.5-24 hours in RPMI 1640 medium, and the effects on cell viability, epithelial apoptosis, and activity of caspases were monitored. Apoptosis was analyzed by detection of DNA-fragments by Hoechst stain(R), DNA-laddering, and Histone-ELISA. Activities of caspases were determined in fluorogenic assays and by Western blotting. Cleavage of BID and release of cytochrome c were analyzed by Western blot. Significance of caspase activation was investigated by preincubation of gastric epithelial cells with cell permeable specific caspase inhibitors. RESULTS: Incubation of gastric epithelial cells with H. pylori caused a time and concentration dependent induction of DNA fragmentation (3-fold increase), cleavage of BID, release of cytochrome c and a concomittant sequential activation of caspase-9 (4-fold), caspase-8 (2-fold), caspase-6 (2-fold), and caspase-3 (6-fold). No effects on caspase-1 and -7 were observed. Activation of caspases preceded the induction of DNA fragmentation. Apoptosis could be inhibited by prior incubation with the inhibitors of caspase-3, -8, and -9, but not with that of caspase-1. CONCLUSIONS: Activation of certain caspases and activation of the mitochondrial apoptotic pathway are essential for H. pylori induced apoptosis in gastric epithelial cells.

Apoptosis↗
PubMed2002

[CompuRecord--A perioperative information management-system for anesthesia].

Since 1977 procedures for automatic documentation of anesthesias have repeatedly been described. Because of a limited arrangement of the desk top and because of its focussing on intraoperative documentation only a widespread introduction could not be established so far. Todays systems are offered with graphically orientated desktops which can be operated by intuition. The CompuRecord(R)-System (Philips Healthcare) is a perioperative management system for anaesthesia. It is constructed with modular components, recording the complete anaesthesiological care of a patient from preanaesthesiological assessment to the recovery room. Additional modules allow an economical check, provide for quality management and exportation of a core data base. Except for the original software all other components of the system including the net work components are IT standard products allowing reduced costs for supplementation, expansion and support. The advantage of an automatical documentation system of anaesthesia is frequent and detailed recording of anaesthesiological data as well as the possibility of a meticulous calculation of cost for each patient. The anaesthesiologist's time used for documentation is reduced remarkably with a limited and reasonable amount of data to be recorded. This leaves more time of attention for the patient himself. Time necessary for training is kept low with the touch screens of the CompuRecord(R) - System, which can be operated intuitively. Primary to purchase an exact analysis of process and of subsequent costs should be done. Standardized documentation allows to establish Standard Operating Procedures in a department of Anaesthesia. Using the given systems an implementation is possible already today despite restricted resources of man power.

Anesthesia↗
PubMed2002

Effectiveness of the Ultraflex Diamond stent for the palliation of malignant biliary obstruction.

BACKGROUND AND STUDY AIMS: Endoscopically placed metallic biliary stents provide durable drainage for malignant biliary obstruction. The best-studied metal stent is the Wallstent, which has a greater duration of patency than polyethylene stents. Recently, the Ultraflex Diamond stent has been introduced, with reports from Europe which suggest efficacy similar to that of the Wallstent. We report our experience with this new metal stent and compare it with a historical cohort of Wallstent-treated patients. PATIENTS AND METHODS: Between July 1997 and July 1998 all metal stents placed for malignant biliary obstruction were Diamond stents (10 mm diameter, 6 or 8 cm length). Prospective follow-up details with regard to patient death or stent occlusion were obtained. In total, 32 patients underwent stenting, but 11 patients were excluded because of the following: death from pre-existing cholangitis (2); placement of bilateral hilar stents (2); placement of stent through occluded metal stents (3); failure to palliate jaundice due to complex hilar stricture (2) or concomitant liver failure (1); or inability to obtain follow-up (1), leaving 21 patients for analysis. Occlusion rates and stent patency were also determined retrospectively for 19 patients with malignant biliary obstruction who had Wallstents (10 mm diameter, 6.8 cm length) placed during the preceding year and for whom accurate and complete follow-up details were available. RESULTS: In the Diamond stent group there were 14 men and seven women, mean age 73. In the Wallstent group there were 11 men and eight women, mean age 66. The types of cancer, level of stricture and percentage with prior polyethylene stenting were similar in both groups. Stent occlusion occurred in 9/21 (43%), Diamond stents at a mean of 74 +/- 43 days compared with 8/19 (42%) Wallstents at a mean of 178 +/- 138 days (P < 0.04). Mean time of stent patency was 110 +/- 89 days for Diamond stents and 253 +/- 218 days for Wallstents (P < 0.01). Analysis of occlusion-free survival using a Kaplan-Meier plot showed a trend favoring the Wallstent (P = 0.12; Wilcoxon test). CONCLUSIONS: The occlusion rate and patency of Diamond stents for malignant biliary obstruction appear to be inferior to those of Wallstents and similar to reported values for polyethylene stents. Prospective randomized comparisons of Wallstents and newer self-expanding metal stents are warranted.

Aged↗
PubMed2002

An endoscopic curved Kerrison rongeur for spinal stenosis surgery.

OBJECTIVE: Adequate neural decompression with minimal structural alteration is the goal of lumbar stenosis surgery. Often because of limited visualization significant parts of the facet joints are removed enhancing the potential for developing instability. To overcome this problem we have developed a small curved Kerrison rongeur that contains a 10 000-pixel endoscope. This instrument allows one to visualize and decompress structures within the lateral recess that may have required more extensive removal of portions of the facet joints. METHODS: Ten patients with symptomatic lumbar spinal stenosis were decompressed using the endoscopic rongeur. RESULTS: Compression of the lateral dura and nerve root by the facet and ligamentum could easily be identified. In all cases the ligament could be easily removed and the facet joint was undercut only enough to decompress the nerve. CONCLUSION: This instrument has the potential for less invasive decompression of spinal stenosis and further study of its utility is planned.

Endoscopes↗
PubMed2002

HLA haplotypes and susceptibility to rheumatoid arthritis. More than class II genes.

Our aim was to examine, using microsatellite (ms) markers, the contribution of the telomeric part of the HLA region to rheumatoid arthritis (RA) predisposition in the Spanish population. We have looked at the distribution of DQB1, DRBI and five ms loci (D6S1014, D6S273, D6STNFa, MIB and C1-2-5) within the HLA region in 147 Spanish RA patients and 202 control subjects. A total of 19 conserved ms configurations were observed, twelve of them in linkage disequilibrium with particular DQB1-DRB1 haplotypes. Interestingly, haplotype c1 (DQB1*0201-DRB1*0301-D6S1014*143-D6S273*139-D6STNFa*99-MIB*350-C1-2-5*196) was significantly associated with RA predisposition. As part of this haplotype, the MIB*350 allele was found to be a risk factor independently of the RA-predisposing haplotypes. The present results along with data from others prove the existence of a second predisposing locus located inside the MHC region, and suggest that might be located within the TNFa-HLA-B region.

Arthritis, Rheumatoid↗