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Biomedical subjects

A Martin

Publications and source records attributed to A Martin.

At least 271 records · Page 15Linked to original sources
PubMed1998

The influence of ondansetron and m-chlorophenylpiperazine on scopolamine-induced cognitive, behavioral, and physiological responses in young healthy controls.

BACKGROUND: There is evidence from animal and human experiments that learning and memory come under the separate influence of both cholinergic and serotonergic pathways. We were interested in learning whether serotonergic drugs could attenuate or exacerbate the memory-impairing effects of anticholinergic blockade in humans. METHODS: The selective serotonin 5-HT3 receptor antagonist ondansetron (0.15 mg/kg i.v.) and the serotonergic agent m-chlorophenylpiperazine (m-CPP; 0.08 mg/kg i.v.) were administered in combination with the anticholinergic agent scopolamine (0.4 mg PO) and compared to scopolamine alone in 10 young, healthy volunteers. Testing occurred on three separate days. RESULTS: As expected, i.v. administration of scopolamine induced significant impairments in episodic memory and processing speed; however, these scopolamine-induced cognitive deficits were not attenuated by pretreatment with i.v. ondansetron (0.15 mg/kg), nor were they exacerbated by administration of i.v. m-CPP (0.8 mg/kg) in addition to scopolamine; however, administration of i.v. m-CPP was followed by a significant increase of self-rated functional impairment, altered self-reality, and dysphoria ratings, and scopolamine's effect on pupil size was potentiated. CONCLUSIONS: Together, these results suggest that in young, healthy volunteers scopolamine-induced changes of cognitive performance are only minimally modulated by the serotonergic effects on ondansetron and m-CPP. Further studies with older controls are needed to test whether these findings may be influenced by age.

Adult↗
PubMed1998

Phosphorylcholine on the lipopolysaccharide of Haemophilus influenzae contributes to persistence in the respiratory tract and sensitivity to serum killing mediated by C-reactive protein.

Haemophilus influenzae undergoes phase variation in expression of the phosphorylcholine (ChoP) epitope, a structure present on several invasive pathogens residing in the human respiratory tract. In this study, structural analysis comparing organisms with and without this epitope confirmed that variants differ in the presence of ChoP on the cell surface-exposed outer core of the lipopolysaccharide. During nasopharyngeal carriage in infant rats, there was a gradual selection for H. influenzae variants that express ChoP. In addition, genotypic analysis of the molecular switch that controls phase variation predicted that the ChoP+ phenotype was predominant in H. influenzae in human respiratory tract secretions. However, ChoP+ variants of nontypable H. influenzae were more sensitive to the bactericidal activity of human serum unrelated to the presence of naturally acquired antibody to ChoP. Serum bactericidal activity required the binding of C-reactive protein (CRP) with subsequent activation of complement through the classical pathway. Results of this study suggested that the ability of H. influenzae to vary expression of this unusual bacterial structure may correlate with its ability both to persist on the mucosal surface (ChoP+ phenotype) and to cause invasive infection by evading innate immunity mediated by CRP (ChoP- phenotype).

Amino Acid Sequence↗
PubMed1998

Acute and chronic changes in swallowing and quality of life following intraarterial chemoradiation for organ preservation in patients with advanced head and neck cancer.

BACKGROUND: Health-related quality of life (QOL) provides a measure of the patient's perception of his life after treatment. This study was undertaken to assess changes in QOL and swallowing in patients undergoing concurrent chemoradiotherapy (CR) for head and neck cancer. The assessment tools consisted of the Head and Neck Radiotherapy Questionnaire (HNRQ) and a swallowing questionnaire (SQ). METHODS: The HNRQ and SQ were administered to a group of CR patients prior to treatment (n = 58), after the last week of treatment (n = 37), and 6 months after treatment (n = 27). Weight change was monitored in treatment subjects. RESULTS: The results indicate that QOL and swallowing function decrease acutely during CR (p < .05) but improvement begins shortly after the treatment-related decline. At 6 months after CR, mean QOL exceeds pretreatment level. The oropharynx patients have the poorest outcome when compared with laryngeal and hypopharyngeal patients. A stronger correlation exists between swallowing and QOL at 6 months post-CR than during treatment (R = .52 versus R = .30). CONCLUSIONS: Quality of life and swallowing are compromised in advanced head and neck cancer patients prior to treatment. There was a further decrease in QOL and swallow function during CR. Organ-preservation programs in head and neck cancer result in improved QOL and swallowing 6 months after treatment. The degree of improvement is site-specific.

Acute Disease↗
PubMed1998

[First experiences with computer-assisted frameless stereotactic interstitial brachytherapy (CASIB)].

PURPOSE: To reach an optimal treatment result and to avoid damage to critical structures a homogeneous dose distribution in the tumor volume with a rapid decreasing dose to the surrounding structures is necessary. Fractionated interstitial brachytherapy of tumors in the ENT region employing needles depends on exact localization of the target volume during all fractions. Therefore reproducibility of positioning of the needle(s) plays an important role. MATERIAL AND METHODS: We used the ISG Viewing Wand system in combination with the Vogele-Bale-Hohner (VBH) head holder and a new targeting device. Point of entrance, pathway, and target point of the needle were planned and insertion of the needle simulated in advance. To date we have treated 7 patients with inoperable tumors in the ENT region. The actual position of the needle in the control CT was compared to the planned position. RESULTS: The accuracy of positioning of the needle depended on the location of the tumor. In a patient with a recurrent retroorbital adenocarcinoma the mean accuracy was 1 mm. Due to soft tissue displacement in the neck region and the resulting necessity to readjust the targeting device the needle was placed with a mean deviation of 15 mm between the planned and the actual position. CONCLUSIONS: Computer-assisted frameless stereotactic interstitial brachytherapy allows for precise, reproducible and preplanned insertion of hollow needles into target structures closely adherent to the surrounding tissue, thus avoiding damage of neighbouring structures. This technique is of great advantage in treating deeply seated tumors which are fixed to bony structures, especially at the skull base. Inaccuracy in the neck region caused by soft tissue shift requires improvement of the immobilization in this region.

Brachytherapy↗
PubMed1998

Work of breathing, inspiratory flow response, and expiratory resistance during continuous positive airway pressure with the ventilators EVITA-2, EVITA-4 and SV 300.

OBJECTIVE: To analyze work of breathing (WOB) imposed by the respirators EVITA-2, EVITA-4 (Drägerwerk, Lübeck, Germany) and SV 300 (Siemens-Elema, Sweden) as well as inspiratory flow response and expiratory flow resistance during continuous positive airway pressure (CPAP). DESIGN: Five study conditions on a lung model (CPAP at 0, 5, and 10 mbar, CPAP 5 mbar plus pressure support 2 mbar with both EVITA models, and CPAP 5 mbar with decreasing levels of flow and pressure trigger sensitivity with the SV 300) and three randomized study conditions in nine patients recovering from open heart surgery (condition A: EVITA-2, CPAP 5 mbar; condition B: SV 300, CPAP 5 mbar, flow trigger; condition C: SV 300, pressure trigger-4 mbar). SETTING: University hospital intensive care unit and laboratory of pulmonary physiology. MEASUREMENTS AND RESULTS: At each study condition we measured WOB, pressure-time product (PTP), WOB and PTP imposed (WOBimposed and PTPimposed), tidal volume, minute ventilation, respiratory rate, inspiratory trigger time, trigger pressure, trigger PTP, duration of inspiration, mean and peak inspiratory flow, and the delay from the onset of inspiration to peak inspiratory flow. Since the SV 300 automatically generates an additional pressure support of 2 cm H2O PTP, WOB, WOBimposed, and PTPimposed were higher with the EVITA-2 and EVITA-4 regardless of the trigger sensitivity set on the SV 300. The difference was neutralized with both types of EVITA ventilator by adding 2 mbar of pressure support during CPAP in order to achieve comparable conditions. Inspiratory flow response was faster with both EVITA models, expiratory flow resistance was higher with the SV 300. Decrements of trigger sensitivity with the SV 300 accelerated the flow response. CONCLUSIONS: Under similar conditions, no difference in WOBimposed was observed, although inspiratory flow response and expiratory flow resistance differed substantially between the three ventilators tested. Trigger sensitivity plays a minor role in determining PTP and WOB but has major influence on flow.

Aged↗
PubMed1998

Ambulatory blood pressure monitoring in pregnancy: what is normal?

OBJECTIVE: Noninvasive 24-hour ambulatory blood pressure monitoring holds great promise as a useful tool in the management of hypertensive pregnancies and pregnancies considered "at risk" for development of preeclampsia. The purpose of this study was to define ambulatory blood pressure monitoring parameters throughout normal pregnancy, including women considered at risk for development of hypertension who continued to have a completely normal pregnancy. STUDY DESIGN: Two hundred seventy-six 24-hour ambulatory blood pressure monitoring studies were made cross-sectionally with use of a Spacelabs 90207 device (validated for use in pregnancy), at one or more of 9 to 17, 18 to 22, 26 to 30, and >30 weeks' gestation. Upper limits of normal were defined as the mean plus 2 SDs for awake and sleep ambulatory blood pressure monitoring results at each stage. RESULTS: Average awake upper limits of normal were 130/77, 132/79, 133/81, and 135/86 mm Hg at the four stages of pregnancy, respectively. Systolic blood pressure fell significantly by 12% to 14% (p < 0.0001) and diastolic blood pressure by 18% to 19% (p < 0.0001) during sleep at all stages of pregnancy. Awake ambulatory blood pressure monitoring systolic measurements were 11 to 12 mm Hg higher than "clinic" measurements (p < 0.001) and diastolic measurements were 5 to 11 mm Hg higher (p < 0.0001) throughout pregnancy. Maximum blood pressure variability ranged from 8 to 13 mm Hg. CONCLUSIONS: The upper limits of normal ambulatory blood pressure monitoring-derived measurements rise slightly as pregnancy progresses. Awake measurements are higher than "clinic" measurements recorded under relaxed conditions by a clinical researcher. The diurnal blood pressure fall and variabilities are similar during pregnancy to those seen in nonpregnant subjects. These data should provide valuable references for further studies of ambulatory blood pressure monitoring in high risk pregnancies.

Blood Pressure Monitoring, Ambulatory↗
PubMed1998

Analysis of infraspecific variation among five strains of Eimeria maxima from North America.

Two laboratory strains from the eastern shore of Maryland 15 years ago and from an Ontario broiler house 23 years ago and three recent field strains of Eimeria maxima (isolated in Maryland, North Carolina and Florida) were examined for phenotypic and genotypic variation using protein profiles, random amplified polymorphic DNA-PCR analysis and DNA sequences obtained from the internal transcribed spacer regions of the rRNA genes. Staining profiles obtained by one-dimensional SDS-PAGE of sporozoite proteins were identical in all five strains. Using random amplified polymorphic DNA-PCR analysis with high %G-C content decamers as primers, we were able to confirm that the five strains are all E. maxima, but were unable to discern any relationships among them because of the limited number of shared polymorphisms identified. In contrast, cloning and sequencing of the internal transcribed spacer-1, 5.8S rDNA and internal transcribed spacer-2 regions of the rRNA genes provided sufficient sequence information to infer phylogenetic relationships among the strains. Almost all of the infraspecific variation was located in the internal transcribed spacer regions. Only two base changes were identified within the 5.8S rRNA gene. Evolutionary relationships among the strains inferred using parsimony analysis of the aligned internal transcribed spacer sequences were well supported, but the hypothesised relationships did not correlate well with the demonstrated immunological cross-reactivities of these strains.

Animals↗
PubMed1998

Dietary specific sugars for serum protein enzymatic glycosylation in man.

All glycoprotein sugars can theoretically derive from glucose. However, dietary specific sugars could represent preferential substrates or have regulatory roles in enzymatic glycosylation. This hypothesis was tested in man using stable isotopes. Healthy subjects ingested different amounts (150, 300, or 550 mg) of artificially 13C-enriched sugar (galactose, mannose, or glucose) diluted in 200 mL water containing 50 g 13C-poor sucrose. 13C enrichment of expired CO2 was monitored for 8 hours during indirect calorimetry. Serum glycoproteins were precipitated and delipidated at various intervals. Glycoprotein neutral sugars were obtained by acidic hydrolysis, purified by ion-exchange chromatography, derivatized to alditol acetates, and analyzed by gas chromatography-isotope ratio mass spectrometry. The oxidation rate for galactose and mannose was slower than the rate for glucose. Total oxidation over the 8-hour period was less than 10% of the ingested amount of galactose or mannose. Galactose and mannose were readily incorporated into glycoprotein glycans, in the native form or after interconversion, despite ingestion of a large excess of sucrose: glycoprotein sugar 13C enrichment was strongly higher after 13C-galactose or 13C-mannose than after 13C-glucose. Thus, the metabolism of these three sugars appears to be different. Specific dietary sugars could represent a new class of non essential nutrients displaying interesting metabolic roles. This could have practical consequences especially in parenteral nutrition, where glucose is currently the only sugar available for metabolism.

Adult↗
PubMed1998

A one-year review of maxillofacial sports injuries treated at an accident and emergency department.

To assess the aetiology and demand for oral and maxillofacial surgery services associated with sports injuries, a prospective study was undertaken. Data were collected from consecutive patients (with maxillofacial injuries associated with sports) attending the accident and emergency department at the Cardiff Royal Infirmary in the UK during a 12-month period and analysed. Data relating to demography, aetiology, site and extent of injury, treatment and outcome were collected. There were 790 attendances (695M:85F) arising principally from injuries related to rugby (n = 206), cycling (n = 189) and football (n = 109) but few from recognized contact sports (n = 26). The principal causes of these injuries were direct bodily contact (n = 260) and falls (n = 219). The commonest injury was soft-tissue laceration (n = 604); 80 patients had dentoalveolar fractures and 64 patients had fractures of the facial skeleton. Injuries were located in the upper- (n = 257), middle- (n = 201) and lower third of the face (n = 124) with 188 lip/intraoral injuries. Repair of lacerations (n = 600) was the commonest treatment; only 46 fractures required interventive treatment. Follow-up was performed for most of these patients at the Department of Oral and Maxillofacial Surgery at the Dental Hospital (n = 404) and general medical/dental practitioners (n = 258). These data highlight the importance of oral and maxillofacial surgery staff in the management of sports injuries in accident and emergency departments. Moreover, they suggest the need for prioritization of rule and legislation changes and the continuing need to improve safety standards to prevent maxillofacial injuries.

Accidental Falls↗
PubMed1998

Availability of specific sugars for glycoconjugate biosynthesis: a need for further investigations in man.

We review the metabolism of specific sugars used for protein glycosylation, focusing on the fate of exogenously provided sugars. Theoretically, all glycoprotein sugars can derive from glucose, but previous studies show that other exogenous sugars can be incorporated into glycoproteins. From data obtained in congenital galactosemia, exogenous galactose may be important for correct glycosylation. Contrary to galactose, the metabolism of other sugars seems to depend on insulin regulation: stimulation of their endogenous production in diabetic subjects might participate in some diabetic complications, precluding the need for an exogenous supply. The metabolic fate of these sugars is different according to the administration route and exogenous supply may be important either in enteral nutrition or in some clinical situations as has been suggested for sialic acid in the newborn. Data in man are too sparse to reach firm conclusions, implying a need for further investigations. Our preliminary results in animals and man demonstrate that stable isotope methodology allows one to trace glycoprotein sugar metabolism in nutritionally relevant conditions with accuracy and sensitivity, using doses of specific sugars well below toxic levels.

Animals↗
PubMed1998

Properties and mechanisms of perceptual priming.

Recent evidence suggests that the behavioral phenomenon of perceptual priming and the physiological finding of decreased neural responses with item repetition have similar properties. Both the behavioral and neurophysiological effects show graded changes with multiple repetition, are resistant to manipulations of particular stimulus attributes (e.g. size and location), and occur independently of awareness. These and other recent findings (e.g. from functional brain imaging in humans) suggest that perceptual priming may be mediated by decreased neural responses associated with perceptual learning.

Brain Mapping↗
PubMed1998

Diacylglycerols and phosphatidates: which molecular species are intracellular messengers?

In eukaryotes, many receptor agonists use phospholipase-generated lipids as intracellular messengers. Receptor occupation stimulates the production of polyunsaturated 1,2-diacylglycerols by phosphatidylinositol-4,5-bisphosphate specific phospholipases C and/or of mono-unsaturated and saturated phosphatidates by phospholipase-D-catalysed phosphatidylcholine breakdown. The primary phospholipase products are rapidly metabolized: polyunsaturated 1,2-diacylglycerols are converted to polyunsaturated phosphatidates by diacylglycerol kinase; mono-unsaturated and saturated phosphatidates are dephosphorylated to give mono-unsaturated and saturated 1,2-diacylglycerols by phosphatidate phosphohydrolase. The phospholipase-generated polyunsaturated 1,2-diacylglycerols and mono-unsaturated and saturated phosphatidates appear to be intracellular messengers, whereas their immediate metabolites probably do not have signalling functions.

Animals↗
PubMed1998

The suppression of fibroblast growth factor 2/fibroblast growth factor 4-dependent tumour angiogenesis and growth by the anti-growth factor activity of dextran derivative (CMDB7).

Our previous studies showed that carboxymethyl benzylamide dextran (CMDB7) blocks basic fibroblast growth factor (FGF-2)-dependent cell proliferation of a human breast epithelial line (HBL100), suggesting its potential role as a potent antiangiogenic substance. The derived cell line (HH9), which was transformed with the hst/FGF4 gene, has been shown to be highly proliferative in vitro and to induce angiogenic tumours in nude mice. We show here that CMDB7 inhibits the mitogenic activities of the conditioned media from HBL 100 and HH9 cells in a dose-dependent manner. When HH9 cells were injected s.c. into nude mice, CMDB7 treatment (300 mg kg(-1) week(-1)) suppressed the tumour take and the tumour growth by about 50% and 80% respectively. Immunohistochemical analysis showed a highly significant decrease, by more than threefold, in the endothelial density of viable tumour regions, together with a significant increase in the necrosis area. This antiangiogenic activity of CMDB7 was further demonstrated by direct inhibition of calf pulmonary artery (CPAE) and human umbilical vein (HUVEC) endothelial cell proliferation and migration in vitro. In addition, we showed that CMDB7 inhibits specifically the mitogenic effects of the growth factors that bind to heparin such as FGF-2, FGF-4, platelet-derived growth factor (PDGF-BB) and transforming growth factor (TGF-beta1), but not those of epidermal growth factor (EGF) and insulin-like growth factor (IGF-1). These results demonstrate that CMDB7 inhibits FGF-2/FGF-4-dependent tumour growth and angiogenesis, most likely by disrupting the autocrine and paracrine effects of growth factors released from the tumour cells.

3T3 Cells↗
PubMed1998

The effect of heparin on trinitrobenzene sulphonic acid-induced colitis in the rat.

BACKGROUND: Reduced blood coagulability seems to protect against inflammatory bowel disease; pilot studies using heparin in patients with inflammatory bowel disease have reported positive results. AIM: To evaluate the effects of heparin treatment on microangiographic and on inflammatory parameters in experimental colitis, induced by trinitrobenzene sulphonic acid (TNBS)-ethanol. METHODS: Four groups of rats: (i) controls (saline enema), TNBS-induced colitis with (ii) sham treatment (saline, s.c.), (iii) dexamethasone (0.25 mg/kg/day s.c.) and (iv) heparin (500 U/kg t.d.s., s.c.). Microangiography was performed 2 and 4 days after colitis induction. Partial thromboplastin time, colonic wet weight, macroscopic damage score and mucosal myeloperoxidase (MPO) activity were determined at day 4. RESULTS: TNBS-induced colitis caused a reduction in visible bowel wall vessels, which was prevented by heparin (P < 0.05) but not by steroids. The macroscopic damage scores and colon wet weights were similar in all colitis groups. Compared to untreated colitis the MPO activity in heparin-treated animals was of borderline significance. CONCLUSIONS: Heparin treatment improved microangiographic features and reduced inflammation to a certain degree. Steroids delayed development of colon hypoperfusion, but were ineffective on MPO activity. It remains to be determined if the observed effects are due to the antithrombotic activity of heparin or to an anti-inflammatory action.

Animals↗
PubMed1998

Functional analysis of the p53 protein in AIDS-related non-Hodgkin's lymphomas and polymorphic lymphoproliferations.

Alteration of the tumour suppressor gene p53 is frequent in AIDS-related non-Hodgkin's lymphomas (AIDS-NHL), particularly in Burkitt's or Burkitt's-like lymphomas (BL/BLL). Since mechanisms of inactivation other than mutations have been advanced, the transcriptional activity of the p53 protein was studied in a functional assay in yeast in a series of AIDS-NHL lesions and compared with their morphology, immunohistochemistry (IHC) and single-strand conformation polymorphism (SSCP) analysis detection of other p53 abnormalities, Epstein-Barr virus (EBV) status, MDM-2 oncoprotein expression and c-MYC rearrangement. Polymorphic lymphoproliferations (PL), identified as precursors of NHL in HIV-patients, were also analysed in attempt to detect p53 modifications related to clonal progression. The functional assay detected p53 mutants in 40% (12/ 30) of the tumours: 50% (6/12) of BL/BLL, 40% (4/10) of diffuse large cell lymphomas (DLCL) and 25% (2/8) of PL. An oligoclonal or monoclonal population was identified in the two PL cases with mutant p53. An accumulation of the p53 protein was detected by IHC in 26% (8/30) of the tumours (five BL/BLL and three DLCL) and was associated with positive functional assay. In the 20 lesions tested by both of the screening methods for mutations, a p53 mutant pattern was detected in 55% of cases (11/20) and in 25% of cases (5/ 20) respectively with the functional assay and SSCP analysis of exons 5-8. There was no inverse correlation between the detection of EBV genome and the presence of p53 mutations and no overexpression of MDM-2 protein for the whole series. In conclusion, the functional assay was more sensitive than IHC and SSCP for the detection of p53 mutations in tumour samples. The mutations identified in AIDS-NHL lesions inactivate the p53 protein and in PL they could represent a selection of an aggressive clone.

Cell Division↗