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Biomedical subjects

H Bader

Publications and source records attributed to H Bader.

At least 19 recordsLinked to original sources
PubMed2006

[Risk factors in a young population with acute myocardial infarction: one year prospective study].

OBJECTIVE: The objective of this work is to give epidemiological data, established in a prospective way, on the myocardial infarction in young and its risk factors. METHODS: All patients admitted to the CHG of Pau for myocardial infarction, old, for the men of less than 45 years and for the women of less than 55 years, of November the 1st 2002 to October 31st, 2003, are included. RESULTS: Twenty-seven patients (11.2%) do a myocardial infarction including 44.4% women. The found traditional risk factors are: smoking (92.6%), absence of regular physical activity (81.5%), dyslipidaemia (66.7%), family history of cardiovascular disease (48.2%), hypertension (37.0%), obesity (18.5%), oral contraception (11.1%), diabetes (7.4%), personal thrombotic history (7.4%). The principal emergent risk factors highlighted are: stress (66.7%), inhibitor of the activation of the plasminogene (57.1%), C-reactive protein (50%), lipoprotein a (41.7%), fibrinogen (33.3%), elevated plasma homocysteine (25%), excessive alcohol use (22.2%). None patients does not have an absolute cardiovascular risk > 20%. The clinical characteristics, coronarographic data and the acute treatments were also listed. The prognosis is worse for the women with more risk factors, more complications, and risk of more significant ventricular replanning. CONCLUSION: The principal risk factors of the myocardial infarction in young can be modifiable. The prevention is of primary importance. The therapeutic education of the patients corresponds to the total assumption of responsibility required by this pathology.

Adult↗
PubMed2006

[Cardiac resynchronisation therapy in practical terms].

Cardiac resynchronisation therapy, associated with defibrillation therapy or not, has emerged as an effective treatment in heart failure patient. Cardiac resynchronisation technique can be difficult despite improvements in the implantation materials. Knowledge of the anatomy of the coronary venous network, especially the coronary sinus ostium and the distribution of the lateral branches could simplify device implantation. Coronarography with anterograde opacification of the coronary venous system could facilitate pre-selection of appropriate tools for coronary sinus and marginal vein catheterisation.

Coronary Angiography↗
PubMed2002

[Study of variations in preload on the new echocardiography parameters of diastolic function in health subjects].

The standard Doppler indices of transmitral filling are changed by variations in preload, relaxation and left ventricular compliance. Recent work in the literature suggests that the new parameters of diastolic function [mitral flux propagation speed in colour TM. (Vp) and tissue Doppler mitral ring velocities (Ea)] are independent of loading conditions. The objective of this work was to study the effect of modifications in the preload on Vp and Ea in normal subjects. Therefore, we have studied various Doppler echocardiographic measurements performed at rest, during a Trendelenberg manoeuvre at 60 degrees, and after sublingual administration of trinitrate in 25 healthy young (2 +/- 8 years) male volunteers. The end diastolic volume increased from 126 +/- 25 ml in the resting state to 145 +/- 24 ml during the Trendelenberg (p = 0.009) then decreased after trinitrate to 121 +/- 28 ml. The peak of the E wave increased from 88 +/- 12 cm/s in the resting state to 90 +/- 15 cm/s during the Trendelenberg and decreased to 70 +/- 11 cm/s after trinitrate (p < 0.0001). The peak Ea annular velocities of the septal and lateral walls were 22 +/- 4 cm/s and 15 +/- 1.6 cm/s in the resting state, without variation during the Trendelenberg (22 +/- 5 cm/s and 15 +/- 2 cm/s) but with a significant reduction after trinitrate to 19 +/- 5 cm/s and 13 +/- 2 cm/s (p = 0.02 and p = 0.002). In contrast, no significant variation was noted in Vp (60 +/- 14 cm/s in the resting state, 62 +/- 12 cm/s during the Trendelenberg and 59 +/- 14 cm/s after trinitrate). We conclude that Vp is not significantly affected by preload whereas Ea is not independent of the loading conditions.

Adult↗
PubMed2001

Sperm-cell volumetric measurements as parameters in bull semen function evaluation: correlation with nonreturn rate.

Sperm-cell volume, measured electronically by cell counter, is a parameter providing information about the state and integrity of the plasma membrane by determining cell osmotic reactivity (swelling level). Electronic volume measurement is a modification of the hypo-osmotic swelling test, based on the increase in sperm volume in response to hypo-osmotic stress. In this study the volumetric method was applied to bull ejaculates, and the relationships of volumetric parameters, osmolality of seminal plasma, and concentration of sodium and potassium ions in seminal plasma, with the nonreturn rate (NRR) were examined. Significant correlations were found between volumetric parameters, conventional spermatological parameters, and NRR. The relative volume shift of the mean volume correlated significantly with motility before and after thawing (P < 0.05). NRR correlated significantly with iso-osmotic cell volume (- 0.49; P < 0.05) and with the relative volume shift (0.51, P < 0.05). The prediction level of regression models was improved when volumetric parameters (iso-osmotic cell volume) were included in the multiple regression model. Therefore, using electronic volume measurement as a component for fast, correct and valid (up to 50,000 cells), recording sperm-cell population may help to evaluate ejaculate quality more precisely.

Animals↗
PubMed2000

Analogues of the potent nonpolyglutamatable antifolate N(alpha)-(4-amino-4-deoxypteroyl)-N(delta)-hemiphthaloyl-L-ornithine (PT523) with modifications in the side chain, p-aminobenzoyl moiety, or 9,10-bridge: synthesis and in vitro antitumor activity.

Seven N(alpha)-(4-amino-4-deoxypteroyl)-N(delta)-hemiphthaloyl-L-o rnithine (2, PT523) analogues were synthesized by modifications of the literature synthesis of the corresponding AMT (1) analogues and were tested as inhibitors of tumor cell growth. In growth assays against cultured CCRF-CEM human leukemic cells exposed to drug for 72 h, the IC(50) values of analogues in which N(10) was replaced by CH(2) and CHMe were found to be 0.55 +/- 0.07 and 0.63 +/- 0.08 nM, and thus these analogues are more potent than 1 (IC(50) = 4.4 +/- 1.0 nM) or 2 (IC(50) = 1.5 +/- 0.39 nM). The 10-ethyl-10-deaza analogue of 2 (IC(50) = 1.2 +/- 0.25 nM) was not statistically different from 2 but was more potent than edatrexate, the 10-ethyl-10-deaza analogue of 1, which had an IC(50) of 3.3 +/- 0.36 nM. In contrast, the analogue of 2 with both an ethyl and a CO(2)Me group at the 10-position had an IC(50) of 54 +/- 4.9 nM, showing this modification to be unfavorable. The 4-amino-1-naphthoic acid analogue of 2 had an IC(50) of 1.2 +/- 0.22 nM, indicating that replacement of the p-aminobenzoic acid (pABA) moiety does not diminish cytotoxicity. The analogues in which the (CH(2))(3) side chain was replaced by slightly longer CH(2)SCH(2) and (CH(2))(2)SCH(2) groups gave IC(50) values of 4.4 +/- 1.1 and 5.0 +/- 0.56 nM and thus were somewhat less potent than the parent molecule. However the analogues in which the aromatic COOH group was at the meta and para positions of the phthaloyl ring had IC(50) values of 7.5 +/- 0.47 and 55 +/- 0.07 nM, confirming the low potency we had previously observed with these compounds against other cell lines. Overall, the results in this study support the conclusion that, while the position of the phthaloyl COOH group and the length of the amino acid side chain in 2 are important determinants of cytotoxic potency, changes in the pABA region and 9, 10-bridge are well-tolerated and can even increase potency.

Antineoplastic Agents↗
PubMed1999

[Effect of the administration of PGF2 alpha synchronously with insemination on the pregnancy rate in mares in an insemination program].

Investigations in different species including the horse have demonstrated that prostaglandin F2 alpha (PGF2 alpha) is involved in initiating uterine contractions occurring during mating and artificial insemination (A.I.). Uterine contractions play an important role with respect to the sperm transport within the female genital tract. The objective of the present investigation was to evaluate whether the administration of PGF2 alpha (Dinoprost) synchronously to A.I. could have a positive effect on the pregnancy rate in mares. A field study including 346 warmblood-mares (age two to 20 years) belonging to a private studfarm was conducted during the breeding season 1996. The mares were assigned to two groups, group A: mares with spontaneous ovulation, group B: mares in which the ovulation was induced by a GnRH-analog-implant (Deslorelin). PGF2 alpha (Dinoprost) was administered either intramusculary (i.m., 5.0 mg) or intrauterine (i.ut., 0.5 mg diluted in 1.9 ml isotonic NaCl-solution and added to the semen dosis). The study was carried out in a double-blind fashion using isotonic NaCl-solution as a placebo. The mares of each group were randomly assigned to one of the two treatments (i.m. vs. i.ut.). The following first cycle pregnancy rates (day 18) were obtained in mares treated and inseminated once per oestrus: group A1 (PGF2 alpha, i.m.): 54.5% (n = 33); group A2 (placebo, i.m.): 69.7% (n = 33); group A3 (PGF2 alpha, i.ut.): 65.4% (n = 26); group A4 (placebo, i.ut.): 69.8% (n = 32); group B1 (PGF2 alpha, i.m.): 56.5% (n = 46); group B2 (placebo, i.m.): 29.6% (n = 27); group B3 (PGF2 alpha, i.ut.): 66.7% (n = 45); group B4 (placebo, i.ut.): 60.0% (n = 30). The pregnancy rates did not differ between the different groups with the exception of group B2 (p < 0.05). In mares treated repeatedly during the oestrus period (group A, n = 88; group B, n = 23), the pregnancy rates did not differ significantly between treatment and control groups. From the results obtained it is concluded that the PGF2 alpha-application did not show an effect on the pregnancy rate. Further factors influencing the results to a small degree were the stallions, semen age and quality and frequency of insemination per oestrus.

Animals↗
PubMed1999

[Diagnosis, therapy and endocrinologic parameters of persistent follicles in mares in comparison with preovulatory follicles].

During the 1997 breeding season persistent follicles were diagnosed in 17 mares. In 16 of these mares a total of 17 follicles were transabdominally punctured and the steroids oestradiol, progesterone and testosterone were measured in the follicular fluid and in blood serum. In ten mares serving as a control group preovulatory follicles were punctured. The follicular fluid of the persistent follicles revealed a very high variability of the steroid concentrations. Depending on the steroid ratio within the follicles, eight follicles were rated as being intact, three follicles were undergoing atresia and five follicles were luteinized. Because of the high oestradiol levels of the follicular fluid within the control group, all of these follicles were considered to be intact. In both groups, no correlation of the steroid concentration between serum and follicular fluid was detectable. This fact argues against a passive diffusion of the steroids through the follicular wall. By puncturing the persistent follicles it was possible to bring the affected mares back into a physiological oestrus cycle within a normal dioestrus period.

Animals↗
PubMed1998

Synthesis and potent antifolate activity and cytotoxicity of B-ring deaza analogues of the nonpolyglutamatable dihydrofolate reductase inhibitor Nalpha-(4-amino-4-deoxypteroyl)-Ndelta-hemiphthaloyl- L-ornithine (PT523).

Six new B-ring analogues of the nonpolyglutamatable antifolate Nalpha-(4-amino-4-deoxypteroyl)-Ndelta-hemiphthaloy l-L-ornithine (PT523, 3) were synthesized with a view to determining the effect of modifications at the 5- and/or 8-position on dihydrofolate reductase (DHFR) binding and tumor cell growth inhibition. The 5- and 8-deaza analogues were prepared from methyl 2-L-amino-5-phthalimidopentanoate and 4-amino-4-deoxy-N10-formyl-5-deaza- and -8-deazapteroic acid, respectively. The 5,8-dideaza analogues were prepared from methyl 2-L-[(4-aminobenzoyl)amino]-5-phthalimidopentanoate and 2, 4-diaminoquinazoline-6-carbonitriles. The Ki for inhibition of human DHFR by the 5-deaza and 5-methyl-5-deaza analogues was about the same as that of 3 (0.35 pM), 11-fold lower than that of aminopterin (AMT, 1), and 15-fold lower than that of methotrexate (MTX, 2). However the Ki of the 8-deaza analogue was 27-fold lower than that of 1, and that of the 5,8-dideaza, 5-methyl-5,8-dideaza, and 5-chloro-5,8-dideaza analogues was approximately 50-fold lower. This trend was consistent with the published literature on the corresponding DHFR inhibitors with a glutamate side chain. In colony formation assays against the human head and neck squamous carcinoma cell line SCC25 after 72 h of treatment, the 5- and 8-deaza analogues were approximately as potent as 3, whereas the 5,8-dideaza analogue was 3 times more potent. 5-Methyl and 5-chloro substitution was also favorable, with the 5-methyl-5-deaza analogue being 2. 5-fold more potent than the 5-deaza analogue. However the effect of 5-methyl substitution was less pronounced in the 5,8-dideaza analogues than in the 5-deaza analogues. The 5-chloro-5,8-dideaza analogue of 3 was the most active member of the series, with an IC50 = 0.33 nM versus 1.8 nM for 3 and 15 nM for MTX. The 5-methyl-5-deaza analogue of 3 was also tested at the National Cancer Institute against a panel of 50 human tumor cell lines in culture and was consistently more potent than 3, with IC50 values in the low-nanomolar to subnanomolar range against most of the tumors. Leukemia and colorectal carcinoma cell lines were generally most sensitive, though good activity was also observed against CNS tumors and carcinomas of the breast and prostate. The results of this study demonstrate that B-ring analogues of 3 inhibit DHFR activity and tumor cell colony formation as well as, or better than, the parent compound. In view of the fact that 3 and its B-ring analogues cannot form polyglutamates, their high cytotoxicity relative to the corresponding B-ring analogues of AMT is noteworthy.

Antineoplastic Agents↗
PubMed1998

Perceiving topological structure of 2-D patterns.

Four experiments investigated observers' sensitivity to the topological structure of visual stimuli. Three factors were taken to capture the topological structure of 2-D patterns: The number of disconnected components, the number of holes (connections), and inclusion relationships. If studied in isolation, any given topological property is typically confounded with the presence of particular features such as line terminations and contour length, or with Gestalt principles of perceptual organization. We went beyond existing studies and attempted to systematically remove potential confounds from the stimulus displays. Results showed that processing speeds for two-dimensional patterns are a function of their topological properties. The more patterns differ in their topological structure the easier they can be discriminated. Not only do all three topological factors contribute to pattern discriminability, they also can be combined to provide an overall measure of structural complexity. Forced choice comparison techniques agreed well with similarity judgments. Topological structure thus contributed to discriminability above and beyond many confounding variables. Claims suggesting a general topological analyzer in visual processing are discussed.

Adult↗
PubMed1997

Analogues of N alpha-(4-amino-4-deoxypteroyl)-N delta-hemiphthaloyl-L-ornithine (PT523) modified in the side chain: synthesis and biological evaluation.

Four heretofore undescribed side chain analogues of N alpha-(4-amino-4-deoxypteroyl)-N delta-hemiphthaloyl-L-ornithine (PT523, 4) were synthesized via straightforward methods of antifolate chemistry, and their properties were compared with those of PT523 and two related compounds with the aim of defining the contribution of the hemiphthaloyl-L-ornithine moiety to the exceptional in vitro antitumor activity of this novel non-polyglutamatable aminopterin analogue. The IC50 values of N alpha-(4-amino-4-deoxypteroyl)-N beta-hemiphthaloyl-L-2,3-diaminopropanoic acid (10) and N alpha-(4-amino-4-deoxypteroyl)-N gamma-hemiphthaloyl-L-2,4- diaminobutanoic acid (9) against A549 human non-small-cell lung carcinoma cells in culture were 23 and 22 nM, whereas those of PT523 and N alpha-(4-amino-4-deoxypteroyl)-N epsilon-hemiphthaloyl-L-lysine (8) were 1.3 and 5.2 nM. A decrease in the in vitro activities of 8 and 9 relative to PT523 was also observed against the panel of cell lines used by the National Cancer Institute to screen new drugs. However the potency of 8 and 9 remained several times greater than that of the historical control methotrexate against many of the cell lines in the screening panel. In an in vivo tumor model, SCC-VII murine squamous cell carcinoma, 9 and methotrexate were well tolerated as 5-day continuous infusions at doses of 0.52 and 0.75 mg/kg/day, whereas the highest tolerated dose of PT523 on this schedule was 0.19 mg/kg/day, in agreement with its lower IC50 in culture. To assess the importance of the hemiphthaloyl group in PT523, N alpha-(4-amino-4-deoxypteroyl)-N delta-isophthaloyl-L-ornithine (11), N alpha-(4-amino-4-deoxypteroyl)-N delta-terephthaloyl-L-ornithine (12), and N alpha-(4-amino-4-deoxypteroyl)-N delta-(4,5-dichlorohemiphthaloyl)-L-ornithine (13) were also synthesized. The IC50 values of 11 and 12 against A549 cells were 45 and 3300 nM, as compared with 1.3 nM for PT523 and 23 nM for methotrexate. In a clonogenic assay against SCC25 human squamous cell carcinoma cells, the IC50 values of 11 and 12 were 2.9 and 72 nM, as compared with 0.3 nM for PT523 and 27 nM for methotrexate. Thus, activity was decreased by moving the aromatic carboxyl group in PT523 to the meta position and was further diminished by moving it to the para position. The IC50 of the halogenated analogue 13 against SCC25 human head and neck squamous carcinoma cells was 18 nM, suggesting lack of tolerance for this 4,5-disubstitution in the phthaloyl moiety. Our results suggest that the combination of a hemiphthaloyl group and three CH2 groups in the side chain are critical determinants of the potent in vitro activity of PT523.

Animals↗
PubMed1997

Clinical and laboratory evaluation of powered electric toothbrushes: comparative efficacy of two powered brushing instruments in furcations and interproximal areas.

The purpose of this study was to compare the efficacy of two powered brushing instruments (Rota-dent, Pro-Dentec Inc. and Interplak, Bausch and Lomb Inc.) for control of plaque and gingivitis in interproximal spaces and furcations. Thirty-five patients, randomly selected from a pool of post-active therapy, periodontal surgical cases, completed this study. A split-mouth design was utilized in this twelve-week trial with each patient acting as his/her own control. Subjects alternately brushed one-half of their mouths with each of the instruments: a crossover in the brushing pattern occurred at six weeks. Single-blind clinical assessments were made by a calibrated investigator at baseline, six and twelve weeks. Gingival Index (GI), Plaque Index (PI) and Papillary Bleeding Index (PBI) were determined in interproximal and furcation areas. Mean percent reductions from baseline for GI, PI and PBI at the end of twelve weeks were 72%, 61% and 70%, respectively for the Rota-dent, and 46%, 43% and 27%, respectively for the Interplak. One-way analyses of variance (ANOVA) and co-variance (ANCOVA) indicate that the Rota-dent was significantly more effective (p < 0.001) than the Interplak in controlling plaque and gingivitis in furcation and interproximal areas with clinically relevant differences in all indices measured.

Adult↗
PubMed1997

[Separation techniques ro achieve vital and reproduction competent equine spermatozoa populations--a survey].

Equine ejaculates are significantly characterized by widely varying parameters especially in those of practical relevance for equine Al. Therefore it is of interest for practical purposes to get subpopulations of concentrated, vital, and competent spermatozoa from the origin ejaculates. Special preparation of the donor stallions will stabilize sperm output. Fractionated semen collection from stallions supplies sperm enriched seminal fractions very useful to work with further in semen preservation. Most important to achieve a concentrated sperm subpopulation are semen manipulations post ejaculation represented conventionally in semen centrifugation. In the last decade alternative measurements have been introduced. Above all semen filtration using glasswool-sephadex and more recently membrane techniques gave good results indicating that these new techniques may replace semen centrifugation in the future. This article gives a survey of the different starting points and methods for separation of vital and concentrated sperm subpopulations of equine semen.

Animals↗
PubMed1995

Increased expression of the multidrug resistance-associated protein gene in relapsed acute leukemia.

Quantitative reverse transcriptase polymerase chain reaction (RT-PCR) was used to determine relative levels of transcripts for MDR1 and the recently described multidrug resistance-associated protein (MRP) in normal lymphohematopoietic cells and in 62 bone marrow aspirates of newly diagnosed and recurrent acute leukemia. Levels of MRP expression in newly diagnosed AML samples were similar to those observed in normal bone marrow cells (CD34-negative and CD34-positive) and in unselected HL60 human promyelocytic leukemia cells, which were used as an internal control throughout this study. In contrast, samples of AML obtained at the time of relapse contained approximately twofold higher levels of MRP RNA (P < .01). Analysis of paired samples, the first obtained at diagnosis and the second at relapse, from 13 acute myelogenous leukemia (AML) and four acute lymphocytic leukemia (ALL) patients showed that MRP expression was increased at the time of relapse in greater than 80% of patients. In contrast, no consistent changes of MDR1 expression at relapse were observed. These results raise the possibility that increased MRP expression might contribute to leukemic relapse.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Synthesis and biological activity of N omega-hemiphthaloyl-alpha,omega- diaminoalkanoic acid analogues of aminopterin and 3',5-dichloroaminopterin.

Analogues of N alpha-(4-amino-4-deoxypteroyl)-N delta-(hemiphthaloyl)-L-ornithine (PT523) with 3',5'-dichloro substitution in the p-aminobenzoyl moiety or with one less or one more CH2 group in the amino acid moiety were synthesized and tested as inhibitors of dihydrofolate reductase (DHFR) activity and cell growth. Replacement of L-ornithine in PT523 by L-2,4-diaminobutanoic acid or L-lysine did not decrease binding to human recombinant DHFR but resulted in some loss of activity against SCC25 human and SCC VII murine squamous cell carcinoma and against MCF-7 human breast carcinoma in culture. PT523 was several times more potent than methotrexate (MTX), aminopterin (AMT), or trimetrexate (TMQ). 3',5'-Dichloro substitution did not decrease either DHFR binding or cytotoxicity. A new synthetic route to PT523 from 2,4-diamino-6-(hydroxymethyl)pteridine and methyl N alpha-(4-aminobenzoyl)-N delta-phthaloyl-L-ornithinate was investigated but was not found superior to previously described methods. In comparative experiments on the ability of PT523 and MTX to competitively inhibit the influx of (6R)-5,10-dideazatetra-hydrofolate (DDATHF, lometrexol), used here as a surrogate for MTX and reduced folates, the Ki of PT523 was lower than that of MTX in both wild-type CCRF-CEM human leukemic lymphoblasts and the transport- and polyglutamylation-defective subline CEM/MTX. The CCRF-CEM cells were 10-fold more sensitive to PT523 than to MTX, whereas the CEM/MTX cells were 240-fold more sensitive. However, in contrast to other MTX-resistant cells where collateral sensitivity to PT523 has been seen. CEM/MTX cells still showed substantial cross resistance to PT523 which may reflect an unusual heightened ability to utilize exogenous folic acid. The good correlation observed with both cell lines between the cytotoxicity of PT523 and MTX and the ability to inhibit DDATHF influx supported the view that PT523 and MTX share, at least in part, a common protein carrier for membrane transport.

Aminopterin↗