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Biomedical subjects

M Hill

Publications and source records attributed to M Hill.

At least 145 records · Page 8Linked to original sources
PubMed2000

[Results from the Registry of Complications in Users of Hormonal Contraception in 1998].

OBJECTIVE: To collect data on the use of hormonal contraception in the Czech Republic in 1998. SETTING: Department of Gynaecology and Obstetrics, Charles University School of Medicine and General University Hospital Prague. METHODS: A total of 2,134 questionnaires were sent to Czech gynaecologists in spring 1999. A total of 418 answers were processed. RESULTS: The estimated number of users presenting in gynaecologist's offices participating in our project was 237,099 women. The most often prescribed contraceptives were monophasic products (54.38%) containing 30-35 micrograms of ethinyl-estradiol (55.21%) with new progestins (53.8%) (norgestimate, gestoden, desogestrel). Regular follow-up of hormonal contraceptive users included the following examinations/tests: blood count in 8.5% offices, ultrasound examination in 8.0% offices, lipid spectrum in 49.8% offices, blood pressure in 74% offices, colposcopy in 97.6% offices, oncological cytology in 98.4% offices and liver tests in 77.1% gynecologist's offices. Only 10.85% of the gynaecologists did not perform lipid tests, almost 20% gynaecologists measured blood pressure only selectively in some users. 80 cases of cardiovascular disease were diagnosed, a figure consistent with an 0.0325% incidence of users. The most frequent complication was deep venous thrombosis (58 cases). The subgroup of women experiencing a cardiovascular event was not characterized by older age, higher body weight, more frequent smoking, or use of products with a higher oestrogen contents. CONCLUSION: There were major differences among gynaecologists in the follow-up of hormonal contraception users. The pattern of the products used varied markedly by regions. The number of diagnosed cardiovascular diseases was very low. Users with a previous a cardiovascular event were only exceptionally carriers of a risk factor.

Cardiovascular Diseases↗
PubMed2000

[Hormonal profile in men with premature androgenic alopecia].

Androgenetic alopecia especially that with premature onset can be a cause of serious psychic trauma. As far as the treatment with antiandrogens, inhibitors of 5 alpha-reductase or hair transplantation represents a heavy economic burden for the patient, we tried to exclude other hormonal causes or to find a criterion for the apt candidates for the treatment in 15 young men with premature androgenetic alopecia. Hormonal analysis discovered a significantly lower plasma level of sexual binding globulin (SHBG) and FSH and nearly significantly higher concentration of 17 alpha-hydroxyprogesterone. These data resemble those in the hormonal pattern of women suffering from the syndrome of polycystic ovaries (PCOS). The finding of premature balding as the possible male phenotype hormonal equivalent of polycystic ovaries is in concordance with several pedigree studies in kindreds with PCOS, which have suggested a genetic basis of this syndrome in some families in which balding and pilosity was frequent in male members.

17-alpha-Hydroxyprogesterone↗
PubMed2000

7-Hydroxydehydroepiandrosterone--a natural antiglucocorticoid and a candidate for steroid replacement therapy?

7-Hydroxylated metabolites of dehydroepiandrosterone (DHEA) are believed to be responsible for at least some immunomodulatory and antiglucocorticoid effects of DHEA and hence are considered candidates for hormone replacement therapy. Our experiments in vitro brought the evidence that 3beta, 7beta-dihydroxy-5-androsten-3-one (7beta-OH-DHEA), but not DHEA and its 7alpha-hydroxyisomer, could counteract the immunosuppressive effect of dexamethasone on the formation of plaques in culture of murine spleen lymphocytes. In another experiment, DHEA and after a 3-weeks pause 3beta-hydroxy-5-androstene-7,17-dione (7-oxo-DHEA) were applied transdermally to 6 male volunteers on 5 consecutive days. Blood levels of DHEA, its 7-hydroxylated metabolites, and in the first case also dehydroepiandrosterone sulphate (DHEAS), were measured before, during and one day after the end of treatment. Application of DHEA increased significantly not only DHEA and DHEAS, but also its both 7-hydroxyisomers. Application of 7-oxo-DHEA also led to a significant increase of both 7-hydroxyisomers of DHEA, with 7beta-OH-DHEA being the preferred metabolite the concentration of which was increased more than three times.

Administration, Cutaneous↗
PubMed2000

Analysis of relations between serum levels of epitestosterone, estradiol, testosterone, IGF-1 and prostatic specific antigen in men with benign prostatic hyperplasia and carcinoma of the prostate.

Epitestosterone competes with testosterone for androgen receptors and inhibits several enzymes of steroidogenesis. Insulin-like growth factors (IGFs) stimulate the growth of prostate cells and directly activate androgen receptors in prostatic tumor cell lines. The prostate-specific antigen (PSA) decreases the affinity of IGF-binding protein-3. The samples were collected from 71 patients suffering from various diseases of the prostate (56 patients without prostate cancer but with benign prostatic hyperplasia and 15 patients with prostate cancer). Correlations between age and IGF-1 (r = -0.281, p<0.05), age and serum epitestosterone (r = -0.261, p<0.05), estradiol and testosterone (r = 0.367, p<0.01), and between estradiol and epitestosterone (r = -0.414, p<0.001) were found. After age adjustment, IGF-I correlated with epitestosterone (r = -0.277, p<0.05). The age correlated positively with PSA (r = 0.286, p<0.05) and negatively with IGF-1 (r = -0.377, p<0.01) in partial correlations. PSA levels were higher in patients with prostate cancer (p<0.00001). Epitestosterone, which is negatively correlating with estradiol and IGF-1, may modulate the development of prostate diseases.

Age Factors↗
PubMed2000

Lack of melatonin response to acute administration of nifedipine and diltiazem in healthy men.

Calcium antagonists have been shown to influence some endocrinological processes in mammals. The use of calcium channel blockers in clinical practice is well documented. The current study monitored nocturnal melatonin, prolactin, and cortisol levels in 19 healthy volunteers before and after administration of calcium channel blockers. The effect of nifedipine was tested in 9 subjects, while diltiazem was administered in 10 men. The nocturnal profile of the given parameters was studied between 23:00 and 05:00 h. At midnight (zero time), the participants were given placebo, nifedipine (in a sublingual dose of 20 mg) or diltiazem (in a single dose of 90 mg). The hypothesis that calcium channel blockers decrease nocturnal melatonin secretion has not been confirmed. The mean nocturnal levels of melatonin between 01:00 and 05:00 h were: 78.1+/-8.8 (control study) vs. 82.4+/-10.2 ng/l (nifedipine study) and 73.0+/-5.3 ng/l (control study) vs. 75.1+/-5.1 ng/l (diltiazem study). In conclusion, the calcium channel blockers used in this study do not alter the nocturnal melatonin secretory process in healthy men.

Adult↗
PubMed2000

UFT/leucovorin plus irinotecan in advanced or metastatic colorectal cancer.

UFT (with leucovorin) and irinotecan both have single-agent activity in colorectal cancer, with non-cross-resistant mechanisms of action. Combining these drugs would be anticipated to increase response rates while maintaining the advantages of a regimen based on an orally administered fluoropyrimidine. This trial aims to determine the maximum tolerated dose, side-effect profile, dose-limiting toxicity, and response rate for the combination of UFT plus leucovorin, and irinotecan. The design is for an initial phase I study investigating escalating doses of UFT (250 to 350 mg/m2/d) and irinotecan (200 to 300 mg/m2) with fixed doses of leucovorin at 90 mg/d, in up to five cohorts of six patients each. UFT and leucovorin are given orally on days 1 to 14 of a 21-day cycle and irinotecan is given intravenously on day 1. The maximum tolerated dose is defined as the dose at which three of six patients in a cohort have a dose-limiting toxicity in the first cycle of treatment. In the second part of the study, the cohort below that experiencing maximum tolerated dose will be expanded up to a total of 20 patients in order to assess further the toxicity and response rate (phase II). To date, 17 assessable patients have been recruited, with a median age of 64 years (range: 35-80 years). At the first dose level (UFT 250 mg/m2/d and irinotecan 200 mg/m2), no dose-limiting toxicities were seen, and in cohort 2 (UFT 250 mg/m2/d and irinotecan 250 mg/m2), there was one grade 3 diarrhea. In cohort 3 (UFT 250 mg/m2/d and irinotecan 300 mg/m2), currently there have been two grade 3/4 toxicities (both neutropenic fever). Thus, the maximum tolerated dose has not yet been reached. Response has been assessed in the first six patients, with three having partial response, two having stable disease, and one having progressive disease (response rate 50%). We conclude that this regimen appears feasible with acceptable toxicity at these dose levels. There is also evidence of significant antitumor activity similar to that seen with other fluoropyrimidine-based combination regimens but without the requirement for indwelling catheters or inpatient admission.

Administration, Oral↗
PubMed2000

Effects of transdermal application of DHEA on the levels of steroids, gonadotropins and lipids in men.

In order to ascertain the kinetics of absorption and metabolism of transdermally administered dehydroepiandrosterone (DHEA), 10 men 29-72 years old (mean 52.4+/-14.5) received 50 mg DHEA/day in a gel applied onto the skin of the abdomen for 5 consecutive days. The objective was to establish the extent to which DHEA influences the levels of gonadotropins, sex hormone-binding globulin and lipids. It was found that DHEA is well absorbed and rapidly metabolized to its sulfate (DHEAS), androstenedione, and consequently to testosterone and estradiol. The DHEA levels that markedly increased after the first doses gradually declined already during the application, and this decline proceeded even after it was discontinued, reaching levels significantly lower than the original ones. On the other hand, the levels of DHEA metabolites (with the exception of DHEAS) rose during the application and reached values significantly higher than the basal ones within 5 weeks. This effect was accompanied by significantly decreased levels of LH. The serum levels of lipids, namely of cholesterol (both HDL and LDL cholesterol), triglycerides, apolipoproteins A-I and B and lipoprotein(a) after DHEA application were not changed significantly, and the atherogenic index (AI) remained unaltered. However, some correlations between hormones and lipids were found. Negative correlations concerned the following indices: DHEA/Lp(a); DHEAS/cholesterol; DHEA, DHEAS, testosterone/TG; testosterone/AI. On the other hand, LH, FSH/cholesterol, FSH, SHBG/LDL cholesterol, FSH/Apo B, Lp(a) correlated positively. It can be concluded that transdermal short-time application of DHEA results in a decrease of endogenous DHEA after finishing the treatment, with a parallel marked increase in the levels of sex hormones. Using this application protocol, exogenous DHEA neither altered the lipid spectrum, nor did it influence the atherogenic index.

Administration, Cutaneous↗
PubMed1999

Immunoassay of 7-hydroxysteroids: 2. Radioimmunoassay of 7alpha-hydroxy-dehydroepiandrosterone.

High sensitivity radioimmunoassay of 3beta, 7alpha-dihydroxy-5-androsten-17-one (7alpha-OH-DHEA) has been developed and evaluated. The method is based on polyclonal rabbit antisera raised against 19-O-(carboxymethyl)oxime bovine serum albumin conjugate and bridge- and position homologous [(125)I]iodotyrosine methyl ester as a tracer. Sensitivity of the assay amounted to 3.12 fmol (0.95 pg)/tube, precision as a mean intra- and interassay coefficient of variation was 7.1 and 10.6%, respectively, and the average recovery of the analyte added to steroid-free serum was 110%. Out of the steroids occurring in human serum which may interfere with the assay, the only important cross-reactants were dehydroepiandrosterone and 3beta, 7beta-dihydroxy-5-androsten-17-one (7beta-OH-DHEA) with cross-reactivities of 1.95 and 1.16%, respectively. The levels of free (unconjugated) 7alpha-OH-DHEA have been determined in 29 sera from healthy volunteers (23 females and 6 males), and from 48 patients (43 females and 5 males) in which dehydroepiandrosterone and its sulfate (DHEA/S) had been measured for various endocrinopathies. The levels in healthy subjects ranged from 0.21 to 6.57 (mean 2.33+/-1.50) nM, while those of the patients from 0 to 5. 99 (mean 1.46+/-1.52) nM. The levels of 7alpha-OH-DHEA in patients significantly correlated with those of DHEA and its sulfate.

Animals↗
PubMed1999

[Prevalence of genetic variants of luteinizing hormone in the Czech Republic].

BACKGROUND: The relatively common genetic variant of LH beta-subunit, resulting in changes of the pituitary-gonadal axis, displays different prevalence in various ethnic populations. METHODS AND RESULTS: Frequency of occurrence of the variant allele in our country has been determined by analysis of LH in a randomly selected population group from the Cheb region, comprising of 257 subjects (82 men and 175 women) in the age from 14 to 72 years. The LH variant was determined by a novel immunofluorescence method, based on two assays, of which the first detected the wild type of the hormone and its variant, while the second was specific for the wild type of LH only. The frequency of carriers of the variant allele for LH-beta-subunit amounted to 17.5%, i.e. 12.2% in males and 20.6% in females. CONCLUSIONS: The prevalence of the variant allele for LH-beta-subunit in the investigated region of West Bohemia was close to that of other Antral European and North European populations.

Adolescent↗
PubMed1999

Differential requirements for CD4 in TCR-ligand interactions.

The coreceptor molecule, CD4, plays an integral part in T cell activation; it is involved in both extracellular Ag recognition and intracellular signaling. We wanted to examine the functional role of CD4 in the recognition of agonist and altered peptide ligands (APLs). We generated two CD4-deficient T cell lines expressing well-characterized TCRs specific for Hb(64-76)/I-Ek. Although the responsiveness of the T cell lines to the agonist peptide was differently affected by the loss of CD4 expression, the recognition of APLs was in both cases dramatically reduced. Nearly full responsiveness to the agonist peptide was achieved by expression of a CD4 variant that did not associate with p56lck; however, the stimulation by APLs was only partially restored. Importantly, the expression of a CD4 variant in which domains interacting with MHC class II molecules have been mutated failed to restore the reactivity to all ligands. CD4-deficient T cells were able to be antagonized by APLs, indicating that CD4 was not required for antagonism. Overall, these findings support the concepts that CD4 is an integral part of the initial formation of the immunological synapse, and that the requirement for different CD4 functions in T cell activation varies depending upon the potency of the ligand.

Animals↗
PubMed1999

T cell responses to D-penicillamine in drug-induced myasthenia gravis: recognition of modified DR1:peptide complexes.

The anti-rheumatoid drug D-penicillamine (D-pen) has a reactive sulfhydryl group capable of modifying self antigens, and can provoke typical autoantibody-mediated myasthenia gravis (MG), especially in DR1+ individuals. We have selected T cell clones from one such patient that were highly specific for D-pen but not its L-isomer or D-cysteine. Moreover, they were restricted to HLA-DR1, had a Th1 phenotype and used TCR V alpha4.1, V beta6.1. They responded well to blood mononuclear cells prepulsed with D-pen either in the absence of serum or after chloroquine treatment, but not to autologous D-pen-pulsed B cell lines. Thus, D-pen may directly couple to distinctive peptides resident in surface DR1 molecules on circulating macrophages or dendritic cells.

Aged↗
PubMed1999

Electrophysiology and endocardial mapping of induced atrial fibrillation in patients with spontaneous atrial fibrillation.

We analyzed the patterns of atrial activation and characterized the electrophysiologic properties of regional atrial sites in the, right atrium and left atrium at the onset of atrial fibrillation (AF) induced with programmed right atrial (RA) stimulation. Intraatrial conduction, atrial electrogram return cycle lengths for the first AF cycle, RA and left atrial (LA) activation maps during AF, and the stability and reproducibility of atrial activation sequences at AF onset and maintenance were analyzed in 23 patients with AF. Correlation of intracardiac electrograms with surface electrocardiographic morphology was attempted. Maximum intraatrial conduction delay for high RA premature beats was observed at the coronary sinus ostium (n = 15), His bundle region (n = 13) or interatrial septum (n = 15). The return cycle lengths for the first AF cycle showed increasing conduction delay with increasing prematurity of the last extrastimulus in most patients. Suprisingly, discrete atrial electrograms with regular or irregular cycle lengths were present at the onset of electrocardiographic documented coarse AF in 13 of 15 patients (87%). Fragmented or chaotic atrial activity were present in 2 of 15 patients (13%) in coarse AF but observed at > or = 1 atrial sites in 7 of 8 patients (88%) with fine AF (p = 0.001). The atrial activation sequence at the onset of the induced AF elicited by high RA extrastimuli usually showed the earliest activation site at the crista terminalis (9 patients) or interatrial septum (9 patients). In contrast, induced AF elicited from other RA sites usually showed earliest atrial activation at the septum (3 patients) or coronary sinus ostium (3 patients). Atrial activation sequences for the first induced AF cycle were usually reproducible in most patients. Atrial activation patterns during the first 10 cycles for AF were stable in RA and LA regions in 6 of 23 patients (260%) but demonstrated significant change(s) at > or = 1 region in 17 of 23 patients (74%) (p <0.05). We conclude that pacing induced AF elicited by RA premature beats commences as a regular or irregular rapid atrial tachycardia consistent with a transitional, but often organized, arrhythmia. The activation sequence and electrophysiologic behavior of the first induced AF cycle is consistent with intraatrial reentry and reproducible in most patients. More than 1 atrial activation sequence can sometimes be observed, emphasizing the dynamic nature of the initial RA reentrant circuits.

Aged↗