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Biomedical subjects

J C Huber

Publications and source records attributed to J C Huber.

At least 19 recordsLinked to original sources
PubMed2005

Evaluation of the Texas 0.08 BAC law.

AIMS: The purpose of the present study was to assess the effects on alcohol-involved traffic crashes and fatalities of the 0.08 blood alcohol concentration (BAC) per se law introduced in the state of Texas in 1999. METHOD: Data pertaining to alcohol-involved traffic crashes and fatalities were extracted from two datasets: the Fatality Analysis Reporting System (FARS) compiled by the National Highway Traffic Safety Administration (for the period January 1995-September 2002), and the Texas Department of Public Safety (DPS) reports of Alcohol Related Motor Vehicle Traffic Accidents and Casualties (for the period January 1995-December 2000). The data were analysed using time-series methods (ARIMA routines). The effects of the law on all drivers were assessed, along with the effects among gender, racial, and age subgroups and crash location (urban vs rural). RESULTS: Separate time-series analyses were conducted with all alcohol-involved and fatal alcohol-involved crashes from the DPS dataset and fatal alcohol-involved crashes from the FARS dataset as the outcome variables. None of the effects for either the total sample or any of the subgroups analysed was statistically significant (this was true of both the FARS and DPS datasets). CONCLUSIONS: While there is a growing body of evidence that indicates that 0.08 BAC laws can be effective in reducing alcohol-involved traffic accidents and fatalities, the present study shows that this was not the case in Texas. Future research should move beyond the simple question of whether or not 0.08 BAC laws 'work' and instead explore in more detail the conditions, such as publicity and enforcement, under which the law does or does not contribute to a decline in alcohol-involved accidents and fatalities.

Accidents, Traffic↗
PubMed2005

Estrogen-metabolizing gene polymorphisms and age at natural menopause in Caucasian women.

BACKGROUND: Lifestyle parameters, personal history and genetic factors are thought to affect the timing of natural menopause in humans. Based on their biological function, estrogen-metabolizing gene polymorphisms have been regarded as candidate genes for early menopause. METHODS: In the present cross-sectional, multi-centre study, we analysed nine single nucleotide polymorphisms of six estrogen-metabolizing genes [three estrogen-synthesizing genes, i.e. 17-beta-hydroxysteroid dehydrogenase type 1 (17-beta HSD), cytochrome P-450 (CYP) 17 and CYP19; and three estrogen-inactivating genes, i.e. catechol-O-methyltransferase (COMT), CYP1A1 and CYP1B1] by sequencing-on-chip-technology in 1360 Caucasian women with natural menopause. Women's lifestyle parameters, reproductive and personal histories were ascertained. RESULTS: Carriage of at least one mutant allele of the CYP1B1-4 Asn453Ser A--> G polymorphism (P = 0.004) and the number of full-term pregnancies (P < 0.001) were found to be independently associated with age at natural menopause. Women with at least one polymorphic allele of CYP1B1-4 experienced natural menopause earlier than non-carriers of the polymorphism [mean (SD) 48.6 (5.0) versus 49.4 (4.3) years]. Women with no, one, two and three or more full-term pregnancies experienced natural menopause at 48.5 (5.0), 48.8 (4.8), 49.5 (4.2) and 49.6 (4.6) years, respectively. CONCLUSION: We present the most comprehensive data on estrogen-metabolizing gene polymorphisms and timing of natural menopause to date. The number of full-term pregnancies and the CYP1B1-4 polymorphism are significant predictors of timing of natural menopause in Caucasian women.

Adult↗
PubMed2005

A predictive model for endometriosis.

BACKGROUND: Aromatase is the key enzyme in the process of estrogen biosynthesis from the precursor androgen. Recently, aromatase has been found to be aberrantly expressed in eutopic endometrium of patients suffering from endometriosis. This finding has prompted speculation about the contribution of this enzyme to the prediction of this disease. METHODS: We prospectively aimed to evaluate whether endometrial biopsy, prior to laparoscopy in symptomatic women to screen for the presence of aromatase by real-time RT-PCR and immunohistochemistry, combined with select patients' characteristics, is of value to predict endometriosis. RESULTS: Of 48 consecutive symptomatic and eligible patients, 25 (52.1%) exhibited endometriosis and 23 (47.9%) were disease-free. A multiple logistic regression model revealed that 95.5% of patients whose eutopic endometrium was found to be positive for aromatase mRNA as well as immunohistochemically detected protein and who were additionally suffering from moderate to severe dysmenorrhoea (visual analogue scale score >4/10) exhibited endometriosis at laparoscopy. CONCLUSIONS: These findings provide direct evidence that screening for eutopic endometrial aromatase in combination with clinical data could be of discriminative value in the prediction of disease.

Adult↗
PubMed2005

Propolis solution for the treatment of chronic vaginitis.

OBJECTIVE: To evaluate the efficacy of 5% propolis solution in recurrent vaginitis. METHOD: Fifty-four patients with recurrent vaginal infections having undergone at least one cycle of antibiotic treatment were instructed to apply a 5% aqueous propolis solution as a vaginal douche for seven days. Vaginal smears and specific symptoms were evaluated at baseline and 14 days after treatment. Long-term well-being was assessed by telephone interview six months after follow-up. RESULT: At the follow-up, the vaginal smears of 41 patients (75.9%) had improved. Forty-seven patients (87%) reported reliefs concerning at least one complaint. Associated improvement of smear and well-being was observed in 36 women (66.7%). After 6 months, 33 patients (61.1%) were satisfied with their condition without having undergone further treatment. CONCLUSION: Propolis may have a role as an alternative treatment for chronic vaginal infection.

Anti-Infective Agents↗
PubMed2003

Influence of the catechol-O-methyltransferase (COMT) codon 158 polymorphism on estrogen levels in women.

BACKGROUND: Catechol-O-methyltransferase (COMT) is the principal enzyme in the conjugation pathway for hydroxylated estrogens. We hypothesize that blood 17beta-estradiol (E(2)) and estrone (E(1)) levels in postmenopausal women receiving an oral E(2) preparation are dependent on the enzyme activity of COMT. METHODS: To determine the influence of this enzyme on E(2) serum levels three groups of 12 selected from 159 healthy normotensive postmenopausal women were selected according to their codon 158 COMT genotype (COMT(HH), COMT(HL), COMT(LL)) which is known to be associated with enzyme activity. All selected women received one 2 mg tablet estradiol valerate and blood samples were taken before treatment and after 1, 3 and 48 h. RESULTS: After 3 h the serum levels of E(2) were significantly higher in women with the COMT(LL) genotype (median 69 pg/ml, range 58-91) and the COMT(HL) genotype (median 69 pg/ml, range 43-84) compared with women with the COMT(HH) genotype (median 45 pg/ml, range 15-68, P < 0.005). In a univariate analysis of variance, considering age, body weight, and COMT genotype, body weight (P = 0.034) and COMT genotype (P < 0.001) were independently related to the increase of serum E(2) levels, whereas age was not. CONCLUSIONS: Our data demonstrate that serum E(2) levels significantly correlate with the COMT genotype. Differences in COMT genotype might be involved in causing variable effects of estrogens on diseases such as hormone-dependent cancers, coronary heart disease and on efficacy of hormone replacement therapy.

Aged↗
PubMed2003

A polymorphism of the interleukin-6 gene promoter and idiopathic recurrent miscarriage.

BACKGROUND: Cytokines have been described to play a major role in the pathogenesis of idiopathic recurrent miscarriage (IRM). We investigated the association between IRM and a polymorphism of the interleukin-6 (IL-6) gene and IL-6 serum levels. METHODS: In a prospective case-control study, we studied 161 women with IRM and 124 healthy controls. Peripheral venous puncture, DNA extraction and PCR were employed to genotype women for the presence of a polymorphism at position -174 in the promoter region of IL-6. Serum IL-6 levels were assessed by a commercially available ELISA. RESULTS: Allele frequencies among women with IRM and controls were 63.4 and 58.1% respectively for allele G (wild type), and 36.6 and 41.9% respectively for allele C (mutant). No association between allele C and the occurrence of IRM was found (odds ratio 0.8; 95% confidence interval = 0.57-1.12; P = NS). IL-6 serum levels were not significantly different between genotypes and between the study and control groups. CONCLUSIONS: This is the first report on an IL-6 polymorphism in IRM. Although known to alter IL-6 expression, the IL-6 polymorphism investigated was not associated with IRM and alterations in IL-6 serum levels in a Middle-European Caucasian population.

Abortion, Habitual↗
PubMed2002

Genetic modelling of the estrogen metabolism as a risk factor of hormone-dependent disorders.

Estradiol is a pleiotropic hormone, involved in the etiology of a wide variety of diseases. Over the last decade individual genetic variability of the estradiol metabolism has been described as a significant contributor to disease susceptibility with variations depending on ethnic background. Among others, genetic variations of genes encoding cytochrome P450 (CYP) enzymes play an important role in this regard. Mutant alleles of the CYP 1A1 gene are major modulators of lung cancer risk among smokers, mediate gender differences in lung cancer susceptibility, and have been associated with an elevated risk for developing breast, prostate, colorectal, and oral squamous cell cancer. Variants of the CYP 1B1 gene modulate the risk for developing prostate, ovarian, lung, and breast cancer. Also, mutations in the CYP 1B1 gene are the major genetic determinant of congenital glaucoma. Mutant CYP 17 alleles are associated with serum and plasma levels of steroid hormones, use of hormone replacement therapy, and the development of endometrial, prostate, and breast cancer. Available data indicate that the protective effect against breast cancer of a later age at menarche is limited to wild-type CYP 17 allele carriers. Among women with the polycystic ovary syndrome, carriage of mutant CYP 17 alleles is sufficient to aggravate the clinical presentation of the disease. Molecular variants of the CYP 19 gene are associated with an increased risk for developing breast cancer, advanced breast cancer stages, and tumor aromatase production. Carriage of a mutant catechol-O-methyltransferase allele is associated with breast cancer, neurologic disorders such as Parkinson's disease, and modulates behavior among patients with schizophrenia, alcoholics and the general population. In summary, the available evidence points to genes that encode estrogen-metabolizing enzymes as strong hereditary determinants of the susceptibility to benign as well as malignant conditions.

Aryl Hydrocarbon Hydroxylases↗
PubMed2002

Genetic modeling of estrogen metabolism as a risk factor of hormone-dependent disorders.

Estradiol is a pleiotropic hormone, involved in the etiology of a wide variety of diseases. Over the last decade individual genetic variability of the estradiol metabolism has been described as a significant contributor to disease susceptibility with variations depending on ethnic background. Among others, genetic variations of genes encoding cytochrome P450 (CYP) enzymes play an important role in this regard. Mutant alleles of the CYP 1A1 gene are major modulators of lung cancer risk among smokers, mediate gender differences in lung cancer susceptibility, and have been associated with an elevated risk for breast, prostate, colorectal, and oral squamous cell cancer. Variants of the CYP 1B1 gene modulate the risk for prostate, ovarian, lung, and breast cancer. Also, mutations in the CYP 1B1 gene are the major genetic determinant of congenital glaucoma. Mutant CYP 17 alleles are associated with serum and plasma levels of steroid hormones, use of hormone replacement therapy, and endometrial, prostate, and breast cancer. Available data indicate that the protective effect of a later age at menarche is limited to mutant CYP 17 allele carriers. Among women with the Polycystic Ovary (PCO) syndrome, mutant CYP 17 alleles are sufficient to aggravate the clinical presentation of the disease. Molecular variants of the CYP 19 gene are associated with an increased risk for breast cancer, advanced disease stage, and tumor aromatase production. Carriage of a mutant catechol-O-methyltransferase (COMT) allele is associated with breast cancer, neurologic disorders such as Parkinson's disease, and modulates behavior among patients with schizophrenia, alcoholics and the general population. In summary, the available evidence points to estrogen metabolising genes as strong hereditary determinants of the susceptibility to benign and malignant conditions.

Breast Neoplasms↗
PubMed2002

[Ethical problems in genetics and reproduction medicine].

Novel knowledge in the fields of molecular biology, genetics and reproductive medicine will revolutionize medicine in the near future. Among many new therapeutical aspects arise a number ethical questions that include preimplantation diagnostics, embryonic stem cell research and gene therapy. Believing in scientific progress is often criticized but today it is primarily ignorance as well as fundamentalism that block sensible discussions. In the future it shall be of importance to differentiate between "to be alive" and "to have a life", hence yielding a new definition of the term "life". Also important is to keep in mind the difference between individual moral claims and general ethics. Without doubt, the current developments in medicine will bring about interesting consequences but the inherent dangers are recognizable as well. However, only a positive attitude will result in beneficial developments. More flexibility on all sides will be needed in the concurrent discussion process.

Ethics, Clinical↗
PubMed2002

Endometrial nuclear receptor co-factors SRC-1 and N-CoR are increased in human endometrium during menstruation.

Steroid hormone receptor co-factors are abundantly expressed in the uterus in order to modify steroid hormone receptor action, either leading to activation or repression of transcription in the endometrium. However, the role of co-factors in remodelling of the human endometrium has not been established. We therefore endeavoured to evaluate the presence of the co-activator SRC (steroid receptor co-activator)-1 and the co-repressors N-CoR (nuclear receptor co-repressor) and steroid co-repressor SMRT (silencing mediator of retinod and thyroid) receptors in the human endometrium during the different phases of the menstrual cycle. By using a real-time RT-PCR assay, we showed that SRC-1, N-CoR and SMRT mRNA are expressed in human endometrium during all phases of the menstrual cycle, as well as in inactive endometrium. Moreover, endometrial expression of SRC-1 and N-CoR mRNA increased during menstruation when compared with the other phases of the menstrual cycle (P < 0.001). Immunohistochemistry demonstrated that SRC-1 and N-CoR stain positive in the glandular epithelium and stroma in menstrual phase endometrium. The staining was weak in proliferative and secretory endometrium and absent in inactive endometrium. Our results suggest that differential expression of endometrial steroid receptor co-factors probably play a role in the regulation of human endometrium remodelling.

DNA-Binding Proteins↗
PubMed2002

Current concepts in aesthetic endocrinology.

The extragenital effects of ovarian steroids are relevant to the metabolism of skin and hair, the changes in body composition and the alterations of the subcutaneous fat distribution throughout life. When ovarian steroids become deficient or are produced in excess, different problems may arise in these tissues and some of these problems, i.e., obesity and cellulite, display gender-specific components. Therefore, a new field in endocrine research known as aesthetic endocrinology is gaining more interest. Because sex steroids are small molecules they can be transported into the skin by topical application when properly formulated. This possibility is used in aesthetic endocrinology in order to achieve local effects but to avoid systemic reactions. After reviewing the current data it collectively seems legitimate to recommend estrogens, either orally or topically, in order to counteract the aging of the skin after menopause. Although a reconstitution of juvenile skin cannot be achieved through this method, a slowing in the skin aging process seems a reasonable expectation. In contrast, the successful treatment of hair loss in women is only confirmed for the application of the non-hormonal compound minoxidil. Apart from the difficult problem of hirsutism, acne and changes in body composition offer promising therapeutical options for endocrinological methods.

Aging↗
PubMed2001

Calculated background elimination in quantifying nitric-oxide synthase enzyme activity.

Measuring nitric-oxide synthase (NOS) activity by monitoring the conversion of L-arginine to L-citrulline is currently the standard assay for NOS activity. We describe a simple method of quantifying low values of NOS activity by removing the background mathematically. When performing NOS activity studies in samples with low protein amount (< 25 microg/microl), we encountered the problem of sample values that can hardly be differentiated from blank values probably originating from radioactive-labeled arginine in the final eluate. Our method determines mathematically these background values and may be an improvement of the citrulline assay.

Arginine↗
PubMed2001

The influence of hormone replacement therapy on skin ageing: a pilot study.

OBJECTIVES: We studied the effect of hormonal treatment on skin ageing in menopausal women. METHODS: Twenty-four patients (45-68 years; mean age, 54.9 years) without hormone treatment for at least 6 months were included. Patients were assigned to three therapy groups: 1, oestrogen only (Estraderm TTS 50) (n=6); 2, transdermal oestrogen and progesterone (Estraderm TTS 50 and 0.4 mg progesterone vaginal suppository) (n=7); and 3, oral oestrogen and progesterone (2 mg Progynova and 0.4 mg progesterone vaginal suppository) (n=8). One group without therapy was included as a control group (n=3). Treatment was continued for 6 months. Three patients, one from group 2 and two from group 3, discontinued therapy before the study endpoint. The following skin parameters were measured at monthly intervals during treatment: skin surface lipids, epidermal skin hydration, skin elasticity and skin thickness. Concomitant clinical evaluation included a subjective clinical evaluation form, a patient questionnaire and laboratory tests for oestradiol, progesterone and follicle stimulating hormone. RESULTS: Mean levels of epidermal skin moisture, elasticity and skin thickness were improved at the end of treatment based on both subjective and objective evaluation in patients with hormone replacement therapy (HRT). Skin surface lipids were increased during combined HRT, which may reflect stimulatory effects of the progestagen component on sebaceous gland activity, while oestrogen alone has a sebum-suppressive action. In the HRT groups, the questionnaire for climacteric complaints demonstrated significant improvements, while laboratory tests showed increases in oestradiol and progesterone and decreases in FSH. CONCLUSIONS: HRT with the mentioned regimes significantly improved parameters of skin ageing.

Administration, Cutaneous↗
PubMed2001

Tissue specificity: the clinical importance of steroid metabolites in hormone replacement therapy.

Metabolic activations or inactivations of estrogens, progesterone and androgens are important steps towards the understanding of the physiological and the pathological effects of these hormones in the female organism. Analysis of the tissue specific metabolic pathways of sex steroids will result in a better understanding of successful hormone replacement therapy on the one hand and of the occurrence of steroid hormone related side effects on the other hand. In this contribution we analyse the different mechanisms involved in the synthesis of tissue specific metabolites and discuss the therapeutical importance of these metabolites in hormone replacement therapy.

Androgens↗
PubMed2001

Treatment of keratoconjunctivitis sicca with topical androgen.

OBJECTIVE: Androgens have been reported to influence lipid production of sebaceous glands and even many ocular tissues. The effect of topical androgen therapy on a 54-year-old patient with keratoconjunctivitis sicca (KCS) and decreased lipid phase of the tear film is reported. METHODS: For assessment of the lipid phase of the tear film, break up time (BUT) and lipid layer thickness (LLT) were monitored during 6 months before treatment as well as 3 months while using a daily topical androgen therapy. RESULTS: During the topical androgen therapy the pathological lipid phase of the tear film was completely restored indicated by the normalisation of the values of BUT and LLT. CONCLUSION: These findings are consistent with animal experiments indicating that topical administered androgen can restore the decreased lipid phase of the tear film. This may open up new therapeutic strategies for KCS.

Administration, Topical↗
PubMed2001

Interleukin 1 receptor antagonist polymorphism in women with idiopathic recurrent miscarriage.

OBJECTIVE: Proinflammatory cytokines have been described as etiologic factors in idiopathic recurrent miscarriage. We investigated the relation between idiopathic recurrent miscarriage and polymorphisms in the gene encoding for the interleukin 1 receptor antagonist, an indigenous modulator of proinflammatory immune response. DESIGN: Prospective case control study. SETTING: Academic research institution. PATIENT(S): One hundred five women with a history of three or more consecutive pregnancy losses before 20 weeks of gestation and 91 healthy, postmenopausal controls with at least two live births and no history of pregnancy loss. INTERVENTION(S): Peripheral venous puncture. MAIN OUTCOME MEASURE(S): Polymerase chain reaction was performed to identify the different alleles of the gene encoding for interleukin 1 receptor antagonist. RESULT(S): Allele frequencies among women with idiopathic recurrent miscarriage and controls were 0.34 and 0.11, respectively, for the polymorphic allele 2 (P=.002; odds ratio: 7.4, confidence interval: 2.9--10.8) and.05 and.05, respectively, for the polymorphic allele 3 (P=.6; odds ratio: 1.3, confidence interval: 0.8--2.3). Allele 2 was present in homozygous form in 9% of women with idiopathic recurrent miscarriage. In contrast, 1% of the control women were homozygous for this allele (P<.001; odds ratio: 13.5, confidence interval: 7.5--21.8). CONCLUSION(S): These data support a role for allele 2 of the gene encoding for interleukin 1 receptor antagonist as genetic determinant of idiopathic recurrent miscarriage.

Abortion, Habitual↗