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Biomedical subjects

M Ford

Publications and source records attributed to M Ford.

At least 19 recordsLinked to original sources

The time course of visual word recognition as revealed by linear regression analysis of ERP data.

EEG correlates of a range of psycholinguistic word properties were used to investigate the time course of access to psycholinguistic information during visual word recognition. Neurophysiological responses recorded in a visual lexical decision task were submitted to linear regression analysis. First, 10 psycholinguistic features of each of 300 stimulus words were submitted to a principal component analysis, which yielded four orthogonal variables likely to reflect separable processes in visual word recognition: Word length, Letter n-gram frequency, Lexical frequency and Semantic coherence of a word's morphological family. Since the lexical decision task required subjects to distinguish between words and pseudowords, the binary variable Lexicality was also investigated using a factorial design. Word-pseudoword differences in the event-related potential first appeared at 160 ms after word onset. However, regression analysis of EEG data documented a much earlier effect of both Word length and Letter n-gram frequency around 90 ms. Lexical frequency showed its earliest effect slightly later, at 110 ms, and Semantic coherence significantly correlated with neurophysiological measures around 160 ms, simultaneously with the lexicality effect. Source estimates indicated parieto-temporo-occipital generators for the factors Length, Letter n-gram frequency and Word frequency, but widespread activation with foci in left anterior temporal lobe and inferior frontal cortex related to Semantic coherence. At later stages (>200 ms), all variables exhibited simultaneous EEG correlates. These results indicate that information about surface form and meaning of a lexical item is first accessed at different times in different brain systems and then processed simultaneously, thus supporting cascaded interactive processing models.

Adult↗

Placentation in the African elephant, Loxodonta africana. IV. Growth and function of the fetal gonads.

The gonads, both ovaries and testes, of 44 elephant fetuses weighing 0.09-112 kg (6.1-21.3 months gestation) were examined grossly and histologically. As in equids, elephant fetal gonads undergo a phase of marked growth and enlargement during the second half of gestation, which is more pronounced in ovaries than testes due to growth and antrum formation of numerous follicles in the former. Stromal cells undergo hypertrophy and transformation to form zones of interstitial cells that are associated with the enlarged follicles in the ovaries and in which the primitive seminiferous tubules are embedded in the testes. The interstitial cells have the capacity to synthesize 5alpha-dihydroprogesterone and other 5alpha-reduced progestagens from cholesterol and pregnenelone and the hypothesis is raised that these fetal gonadal progestagens may supplement significantly the progestagens secreted by the multiple large corpora lutea of pregnancy in the elephant.

Animals↗

Gastroduodenal tolerability of lumiracoxib vs placebo and naproxen: a pilot endoscopic study in healthy male subjects.

BACKGROUND: Lumiracoxib (Prexige) is a cyclooxygenase-2 (COX-2) selective inhibitor. AIM: To compare the gastroduodenal tolerability of lumiracoxib with placebo and naproxen in a randomized, parallel-group, double-blind study. METHODS: : Sixty-five healthy male subjects were randomized to receive 8 days' dosing with lumiracoxib 200 mg twice daily (b.d.) (n = 21), placebo (n = 22) or naproxen 500 mg b.d. (n = 22). Endoscopic evaluations of gastric and duodenal mucosae were conducted at baseline and after 8 days' dosing. Serum was assayed for ex-vivo concentrations of thromboxane B2 (TxB2) to determine cyclooxygenase-1 (COX-1) inhibitory activity. RESULTS: Sixty subjects (20 per group) completed the study. No gastroduodenal erosions were observed in subjects receiving lumiracoxib. Thirteen subjects receiving naproxen developed duodenal erosions. At the gastric site, one subject in each of the naproxen and placebo groups had erosions; one subject receiving naproxen also developed a small asymptomatic gastric ulcer. Gastrointestinal adverse events accounted for 42.3% of all adverse events, occurring in 3/21, 4/22 and 6/22 of the lumiracoxib, placebo and naproxen groups, respectively. TxB2 levels were similar for patients receiving placebo or lumiracoxib, but were reduced by > 95% in patients receiving naproxen, compared with placebo. CONCLUSIONS: Multiple doses of lumiracoxib resulted in gastroduodenal tolerability similar to placebo and superior to naproxen.

Adolescent↗

Association of British Clinical Diabetologists (ABCD): survey of specialist diabetes care services in the UK, 2000. 2. Workforce issues, roles and responsibilities of diabetes specialist nurses.

AIM: To examine the provision and role of diabetes specialist nurses (DSNs), and the content of patient education programmes in the UK. METHOD: A postal survey of secondary care providers of diabetes services in the UK in 2000. RESULTS: Following two reminders, a 77% response rate demonstrated 2.5 (median) whole time equivalent DSNs per 250 000 population, with only 13% of centres meeting the recommended staffing level of four per 250 000 population. The vast majority carried out work both in hospital and in the community, the proportion a reflection of who employed and managed staff. There was a wide variation in the qualifications required and the nursing gradings of DSNs, and regional variation in the number of grade I nurses, with the greatest proportion based in the South-east of England. The vast majority (96%) provided patient education, and where it existed (in 60% of responses), were the major providers of a patient help line (90%). Although key providers of patient education, there had been no specific education for this task in over 20% of responses. There was broad consistency in the topics covered at educational sessions, although advice on footwear (76%) and home urine glucose monitoring (73%) were least frequently documented. The issuing of literature and cards for patient use was also very variable. Over 25% of bids for diabetes service improvement were for additional DSNs, but only 48% of these were successful. CONCLUSIONS: There has been an improvement in staffing levels of DSNs over the last 10 years but the numbers are many fewer than recommended in national strategy documents, with evidence that despite expansion being given a high profile, such efforts are often unsuccessful. There was also evidence of considerable variation in the qualifications and gradings of DSNs throughout the UK and indeed in their day-to-day roles, and the content of patient education programmes. This suggests the need for a nationally co-ordinated approach to training and recruitment.

Diabetes Mellitus↗

A novel selective medium for the detection of methicillin-resistant Staphylococcus aureus enabling result reporting in under 24 h.

A simple selective broth was devised to indicate the presence of methicillin resistant Staphylococcus aureus (MRSA) in clinical samples. The broth comprised nutrient broth supplemented with sodium chloride, ciprofloxacin, colistin and aztreonam as selective agents and also mannitol, trehalose and phenol red as an indicator system. In a preliminary study using 228 clinical samples this selective mannitol broth (SMB) proved to be more sensitive than other selective agars for detection of MRSA within 24 h. In an extended study of a further 1124 clinical samples from 470 randomly selected patients, SMB detected 85.1% of MRSA strains present with a specificity of 43.6%. We conclude that SMB offers a convenient, inexpensive and sensitive method for high-throughput screening for MRSA.

Bacterial Typing Techniques↗

MAGE-F1, a novel ubiquitously expressed member of the MAGE superfamily.

Most known members of the MAGE superfamily are expressed in tumors, testis and fetal tissues, which has been described as a cancer/testis or "CT" expression pattern. We have identified a novel member of this superfamily, MAGE-F1, which is expressed in all adult and fetal tissues tested. In addition to normal tissues, MAGE-F1 is expressed in many tumor types including ovarian, breast, cervical, melanoma and leukemia. MAGE-F1 is encoded on chromosome 3, identifying a sixth chromosomal location for a MAGE superfamily gene. The coding region of MAGE-F1 is contained within a single exon and includes a microsatellite repeat. Sequence analysis and expression profiles define a new class of ubiquitously expressed MAGE superfamily genes that includes MAGE-F1, MAGE-D1, MAGE-D2/JCL-1 and NDN. The finding that several MAGE genes are ubiquitously expressed suggests a role for MAGE encoded proteins in normal cell physiology. Furthermore, potential cross-reactivity to these ubiquitously expressed MAGE gene products should be considered in the design of MAGE-targeted immunotherapies for cancer.

Adult↗

Cervical spondylosis: the role of anterior instrumentation after decompression and fusion.

The role of plate stabilization after anterior decompression and fusion of the cervical spine for cervical spondylosis remains controversial. This study aimed to justify the use of instrumentation to stabilize anterior cervical fusion for cervical spondylosis through a risk-benefit analysis and comparison of the results with those reported in the literature on the outcome of fusion without instrumentation. The authors retrospectively reviewed the charts and radiographs of 47 patients with symptoms secondary to cervical spondylosis who underwent anterior cervical decompression and instrumented fusion. After operation, patients were mobilized early, and neither neurologic injury nor infection developed in any patient. At an average 3.4 years after surgery, the rate of graft complications, including nonunion (4.26%), was low, whereas the rate of hardware-related morbidity was minimal (6%). An average 0.4 degrees loss of the intraoperative correction of cervical lordosis was observed at the last follow-up examination. Accelerated degenerative changes at levels adjacent to the fusion were seen in 17% of patients, but only two patients required repeat operation for persistent symptoms. The use of instrumentation to stabilize the cervical spine in patients with cervical spondylosis after anterior decompression and fusion is relatively safe. It permits early pain-free mobilization, successfully maintains sagittal cervical spine alignment, and promotes consistent and reliable spinal fusion.

Adult↗

Reliability of DMSA for the diagnosis of renal parenchymal abnormality in children.

The objective of this study was to evaluate the variability of technetium-99m dimercaptosuccinic acid (DMSA) scintigraphy interpretation by four nuclear medicine physicians for the diagnosis of renal parenchymal abnormality in children, and to compare variability among three different DMSA methods in clinical use: planar alone, single-photon emission tomography (SPET) alone, and planar with SPET. One hundred consecutive DMSA studies were independently interpreted 3 times by four participating nuclear medicine specialists from different departments and in random order. All scans were classified by the presence or absence of renal parenchymal abnormality using the modified four-level grading system of Goldraich. Indices of agreement were the percentage of agreement and the kappa statistic. Disagreement was analysed using children, kidneys and kidney zones (three zones per kidney). Using patients as the unit of analysis, agreement for planar and planar with SPET methods was 87%-88% (kappa 0.74) for the normal-abnormal scan classification. The corresponding agreement value for the SPET alone method was 78% (kappa 0.56). Similarly, substantial disagreement (disagreement > or = 2 categories) occurred in 2.5% and 1.3% of comparisons between observers for planar alone and planar with SPET, respectively, but in 5.2% of comparisons for SPET alone. These results did not vary appreciably whether interpretation of patients, kidneys or kidney zones was compared. It is concluded that the four experienced nuclear medicine physicians showed substantial agreement in the interpretation of planar alone and planar with SPET DMSA scintigraphic images. Interpretation of SPET DMSA images, without planar images, was significantly more variable than interpretation using the two other methods, disagreement occurring in more than 20% of comparisons. SPET DMSA scintigraphy, when used without planar images, does not provide a firm basis for clinical decision making in the care of children who may have renal damage. There is no apparent benefit of reduced variability from the extra provision of SPET data to nuclear medicine physicians who already have planar images.

Child↗

Regulation of renin gene expression in kidneys of eNOS- and nNOS-deficient mice.

Our study aimed to assess the roles of nitric oxide derived from endothelium NO-synthase (eNOS) and macula densa neuronal NO-synthase (nNOS) in the regulation of renal renin expression. For this purpose renin mRNA levels and renin content were determined in kidneys of wild-type (wt), nNOS-deficient (nNOS-/-), and eNOS-deficient (eNOS-/-) mice, in which the renin system was suppressed by feeding a high-salt diet (NaCl 4%), or was stimulated by feeding a low-salt (NaCl 0.02%) diet together with the converting-enzyme inhibitor ramipril (10 mg kg(-1) day(-1)). In all mouse strains, renin mRNA levels were inversely related to the rate of sodium intake. In eNOS-/- mice renin mRNA levels and renal renin content were 50% lower than in wt mice at each level of salt intake, whilst in nNOS-/- mice renin expression was not different from wt controls. Administration of the general NO-synthase inhibitor nitro-L-arginine methyl ester (L-NAME, 50 mg kg(-1) day(-1)) to mice kept on the low-salt/ramipril regimen caused a decrease of renal renin mRNA levels in wt and nNOS-/- mice, but not in eNOS-/- mice. These observations suggest that neither eNOS nor nNOS is essential for up- or downregulation of renin expression. eNOS-derived NO appears to enhance renin expression, whereas nNOS-derived NO does not.

Animals↗

The nitroreductase/CB1954 combination in Epstein-Barr virus-positive B-cell lines: induction of bystander killing in vitro and in vivo.

Epstein-Barr virus (EBV)-based gene delivery vectors that preferentially express toxic genes in EBV-infected cells could be used to target EBV-positive tumors for destruction. We have shown previously that the cytosine deaminase (CD) enzyme, which converts the prodrug 5-fluorocytosine (5-FC) into the toxic compound 5-fluorouracil efficiently kills EBV-positive cells in the presence of 5-FC, with a substantial bystander killing effect in vitro and in vivo. To identify the optimal enzyme/prodrug combination for treating EBV-positive lymphomas, we have compared the effectiveness of the CD/5-FC combination with the nitroreductase (NTR)/CB1954 combination for killing EBV-positive B-cell lines. NTR metabolizes CB1954 into an alkylating agent that cross-links DNA. When the CD gene or the NTR gene were transfected into two different EBV-positive B-cell lines in vitro, approximately 90% of cells were killed in a prodrug-dependent manner, although the transfection efficiency was <5%. However, severe combined immunodeficient mouse tumors containing either 30% or 100% of NTR-expressing Burkitt lymphoma (Jijoye) cells were growth inhibited, but not cured, by treatment with intraperitoneal CB1954 (20 mg/kg/day) for 10 days. These results suggest that the NTR/CB1954 combination induces efficient bystander killing of EBV-positive B-cell lines in vitro but may not be as effective as the CD/5-FC combination for treating B-cell lymphomas in vivo.

Animals↗

Heat disinfection of clinical waste: microbiological assessment and monitoring of effectiveness.

Simple, rapid and reproducible protocols are described for the microbiological assessment of clinical waste treatment processes, using Bacillus subtilis spore tests and end-product sampling. The use of these protocols to commission a new heat disinfection system (HDS), based on a hot oil-filled auger, and to monitor it over the first 21 months of operation is described. It is suggested that these protocols are suitable for assessment of other non-burn heat-treatment technologies.

Bacillus subtilis↗

Family 10 and 11 xylanase genes from Caldicellulosiruptor sp. strain Rt69B.1.

Three family 10 xylanase genes (xynA, xynB, and xynC) and a single family 11 xylanase gene (xynD) were identified from the extreme thermophile Caldicellulosiruptor strain Rt69B.1 through the use of consensus PCR in conjunction with sequencing and polyacrylamide gel electrophoresis. These genes appear to comprise the complete endoxylanase system of Rt69B.1. The xynA gene was found to be homologous to the xynA gene of the closely related Caldicellulosiruptor strain Rt8B.4, and primers designed previously to amplify the Rt8B.4 xynA gene could amplify homologous full-length xynA gene fragments from Rt69B.1. The complete nucleotide sequences of the Rt69B.1 xynB, xynC, and xynD genes were obtained using genomic walking PCR. The full-length xynB and xynC genes are more than 5 kb in length and encode highly modular enzymes that are the largest xylanases reported to date. XynB has an architecture similar to the family 10 xylanases from Thermoanaerobacterium saccharolyticum (XynA) and Clostridium thermocellum (XynX) and may be cell wall associated, while XynC is a bifunctional enzyme with an architecture similar to the bifunctional beta-glycanases from Caldicellulosiroptor saccharolyticus. The xynD gene encodes a two-domain family 11 xylanase that is identical in architecture to the XynB family 11 xylanase from the unrelated extreme thermophile Dictyoglomus thermophilum strain Rt46B.1. The sequence similarities between the Rt69B.1 xylanases with respect to their evolution are discussed.

Bacteria, Anaerobic↗

Evaluation of tube coagulase and a fluorogenic substrate for rapid detection of methicillin-resistant Staphylococcus aureus from selective enrichment broth in an outbreak of EMRSA 15.

We investigated the use of tube coagulase and a fluorescent substrate, N-t-BOC-val-pro-arg-7-amido-4-methylcoumarin for the rapid detection of MRSA in selective broth enrichment cultures during an outbreak. These methods were compared with direct plating of swabs and plating a selective broth enrichment culture using 200 screening swabs collected from forty patients during the investigation of an outbreak of E-MRSA 15. Overall 66 swabs were positive for MRSA following subculture of broth enrichment culture. Direct plating detected 25 (38%) positives, tube coagulase 37 (56%), and fluorescent substrate 49 (74%) respectively, although nine of the 49 turned out to be false reactions. When detection from individual patients was analyzed, selective broth subculture identified 28 patients colonized with MRSA. Direct plating detected only 12 (43%) of these patients. The tube coagulase and fluorescence methods detected MRSA in 17 (60%) and 19 (68%) patients respectively. The tube coagulase method was found to be 100% specific for MRSA suggesting its use as a rapid method for the detection of MRSA from selective enrichment broth.

Bacteriological Techniques↗

Placebo-controlled comparison of candoxatril, an orally active neutral endopeptidase inhibitor, and captopril in patients with chronic heart failure.

AIMS: To compare the effects on exercise capacity of the neutral endopeptidase inhibitor candoxatril, and the angiotensin converting enzyme inhibitor captopril, in patients with mild to moderate heart failure. METHODS: In this multi-centre double-blind placebo controlled study, 60 patients with NYHA Class I-III heart failure were randomised to candoxatril 200 mg b.d. (n = 22), captopril 25-50 mg b.d. (n = 23) or placebo (n = 15). Treadmill exercise tests were carried out weekly during a 5-week single-blind placebo run-in phase until a stable baseline was achieved, and repeated at 4 weekly intervals during the 12-week double-blind treatment phase. RESULTS: Nine patients withdrew from the study--four candoxatril and five captopril. The placebo-adjusted increase in exercise duration after 12 weeks was 56 s (95% CI, -26 to +137 s; P = 0.12) with candoxatril and 37 s (-43 to + 117 s; P = 0.29) with captopril. CONCLUSIONS: Both candoxatril and captopril were well tolerated and treadmill exercise duration appeared to increase during 12 weeks of therapy but this did not achieve statistical significance. This study tentatively suggests that in patients with heart failure, neutral endopeptidase inhibition may provide similar symptomatic benefits to angiotensin converting enzyme inhibition.

Angiotensin-Converting Enzyme Inhibitors↗