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Biomedical subjects

J C Huber

Publications and source records attributed to J C Huber.

At least 73 records · Page 4Linked to original sources

Expression of endothelial (type III) nitric oxide synthase in cytotrophoblastic cell lines: regulation by hypoxia and inflammatory cytokines.

Expression of endothelial nitric oxide synthase (eNOS) has been localized to the villous syncytiotrophoblasts suggesting that NO release from these cells could prevent platelet adhesion and aggregation in the intervillous space. Hypoxia- or inflammation-dependent changes in the release of this vasoactive substance may result in thrombus formation and altered vascular resistance which occur in the placental bed of pre-eclamptic patients. To evaluate the influence of low-oxygen tension and inflammation on eNOS production in the trophoblast steady-state eNOS mRNA and protein levels were investigated in cytotrophoblastic BeWo and Jeg-3 cells cultured at 3.5 per cent oxygen and/or in the presence of the pro-inflammatory cytokines IL-1 and TNF-alpha. By RT-PCR and immunocytochemistry we demonstrate that BeWo cells produce eNOS mRNA and protein while eNOS polypeptide was undetectable in JEG-3 cells. In BeWo cells addition of both cytokines decreases eNOS mRNA and protein abundancies within 24 h of incubation while each substance alone had no effect. Compared to controls, the amount of eNOS transcripts was found to be elevated at low-oxygen tension, however, cNOS protein was downregulated after 24 h in the hypoxic environment, as shown by immunocytochemistry and Western blot analysis. Forskolin and methotrexate, which induce biochemical differentiation/ growth arrest in choriocarcinoma cells, stimulate eNOS mRNA and protein synthesis, but cannot overcome the decline of eNOS polypeptide levels during hypoxic incubation. It is speculated that acute hypoxia and inflammation impair eNOS/NO production of the trophoblast in vivo, which might contribute to pathological conditions of gestational diseases.

Adult↗

Induction of inducible nitric oxide synthase expression in human secretory endometrium.

The endometrial secretory phase is characterized by stromal oedema, a premenstrual increase in stromal macrophages and an increased cytokine production as menstruation approaches. Nitric oxide (NO) is a mediator of vasodilatation and cytotoxicity which is synthesized from L-arginine by NO synthases (NOS). These enzymes are either constitutively expressed or induced by lipopolysaccharides and/or cytokines. The presence and function of the inducible isoform of NOS (iNOS) in normal human endometrium has not been fully elucidated until recently. Frozen tissue sections taken from 22 women who underwent hysterectomy and adnexectomy for benign disease were immunostained with antibodies raised against the different NOS isoforms to investigate the presence of NOS in human endometrium. iNOS stained positive in the glandular epithelial cells of the secretory endometrium. Staining was either weak or absent in the proliferative and inactive endometrium, as well as in the oviduct and the glandular epithelium of the endocervix. The stroma remained uniformly negative. Immunoreactivity for endothelial constitutive NOS (eNOS) was confined exclusively to endothelial cells. Furthermore, epithelial cells from endometrium, oviduct and endocervix and all endothelial cells showed positive staining for reduced nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase, which is a histochemical marker for NOS activity. Reverse transcriptase polymerase chain reaction (RT-PCR) was performed in order to assess the presence of NOS mRNA. Abundant expression of iNOS mRNA was detected in the secretory phase endometrium only. The strong expression of inducible NO synthase in human secretory phase endometrium suggests that the increased production of NO, probably induced by cytokines, may be relevant to the process of menstruation.

Base Sequence↗

Treatment of menopausal keratoconjunctivitis sicca with topical oestradiol.

OBJECTIVE: To investigate the effect of 17 beta-oestradiol ophthalmic drops in comparison with a traditional tear substitute in postmenopausal women with keratoconjunctivitis sicca. DESIGN: Randomised prospective trial. SETTING: Menopause clinic. PARTICIPANTS: Eighty-four postmenopausal women suffering from keratoconjunctivitis sicca and necessitating a hormone replacement therapy (HRT) for general climacteric symptoms. METHODS: The women were randomised into two groups and were given 17 beta-oestradiol eye drops (n = 42, group 1) or a tear substitute (n = 42, group 2). Both groups received a systemic HRT. MAIN OUTCOME MEASURES: A Schirmer's test was performed immediately before the beginning of therapy and after four months. In addition, eye symptoms were assessed using a visual analogue scale. RESULTS: A comparison of visual analogue scores at four months in the women who received 17 beta-oestradiol eye drops versus those who received a tear substitute demonstrated a statistically significant difference in all observed ocular symptoms (P < 0.0001). The Schirmer's test revealed a significant difference of results before and after treatment in the oestradiol group (P < 0.0001) while in group 2 no significant difference was found. CONCLUSIONS: Our study demonstrates that topical oestrogen is successful in treating keratoconjunctivitis sicca while it seems that the blood-eye barrier prevents systemic oestrogens from acting on the conjunctivae.

Administration, Topical↗

[The role of nitric oxide in reproduction].

Nitrix oxide (NO) is a highly reactive and short-lived radical (half-life time: 10-12 s), which is derived from L-arginine by the NO synthases (NOS) in several organ systems. The release of NO by endothelial cells leads to rapid relaxation of vascular smooth muscle cells, whereas release by several neuronal cells causes neurotransmission. When NOS is actively induced in immune cells or certain epithelia it causes cytotoxicity and/or apoptosis of these cells. In the reproductive organs NO is now considered to be an important trigger molecule for several physiological mechanisms. Follicular synthesized NO is involved in rupture of the follicle during ovulation. Moreover, NO participates in the acrosome reaction of spermatozoa during capacitation. Apoptosis and collagenolysis of the functional endometrium may be involved in endometrial shedding during menstruation. Since NO induces both apoptosis and collagenolysis, the newly discovered production of NO in late secretory endometrium could act as a key mechanism in the process of menstrual disintegration of the endometrium. Additionally, NO is necessary to support and maintain the decidualization process and plays a pivotal role in implantation.

Female↗

Hormonal breast augmentation: prognostic relevance of insulin-like growth factor-I.

Many women would like to after their breasts but are deterred by the risks involved. Silicone breast implants have been linked to a variety of illnesses, the most controversial of which are connective-tissue diseases. These circumstances urged us to perform this pilot study using a non-invasive method that involved the application of 17 beta-estradiol as it is known that estradiol enhances expression of insulin-like growth factor-I (IGF-I) which can promote growth in breast tissue. Forty-five women were included in the study. Their breast volume, IGF-I, prolactin (PRL) and estradiol levels were measured before treatment and between each application of 80 mg estradiol polyphosphate. The women's satisfaction with the results obtained was also subsequently evaluated. In 21 women (46.7%), breast size increased from 824.3 +/- 13.7 mm to 898.5 +/- 12.5 mm after 6 months. In these women a significant increase in IGF-I values was noted after 4 weeks of treatment. The increase in IGF-I values was not statistically significant in the remaining women. In addition, treatment was not successful in these women. IGF-I concentration seems to be of prognostic value as far as the response of breast tissue to estrogen stimulation is concerned. If IGF-I levels do not increase within 1 month, treatment should be discontinued. If IGF-I values do increase, this indicates that treatment is likely to be successful and can therefore be continued.

Adult↗

[Thymopentin in alopecia areata].

Alopecia areata is a common cause of hair loss which leads to localized bald areas predominantly on the scalp. Etiological factors are not clear yet, but it is generally considered as a consequence of an autoimmune process. Histological findings revealed perifollicular infiltration of T-cells and antigen-presenting cells. Autoreactive T-cells are reported to amplify this abnormality by interacting with follicular epithelium. There is no effective treatment available at the moment. We report on a 53-year old climacteric woman who developed a bald lesion on her scalp spontaneously in november 1995. Alopecia areata was documented before and after therapy. Treatment with thymopentin 50 mg subcutaneously was offered successfully for 10 weeks, while continuing hormone replacement therapy. Other therapeutical strategies did not proof to be successful before.

Adjuvants, Immunologic↗

Worst headache and subarachnoid hemorrhage: prospective, modern computed tomography and spinal fluid analysis.

STUDY OBJECTIVE: This study investigated the hypothesis that modern computed tomographic (CT) imaging is sufficient to exclude subarachnoid hemorrhage (SAH) in patients with severe headache. METHODS: All 38,730 adult patients who presented to Hermann Hospital in Houston, Texas, during a 16-month period were prospectively screened to detect those with "the worst headache of my life." Two neuroradiologists blinded to the study hypothesis interpreted the CT scans. Patients with negative scans underwent comprehensive cerebrospinal fluid (CSF) analysis including cell count in first and last tubes, visual and spectrophotometric detection of xanthochromia, and CSF D-dimer assay. RESULTS: A chief complaint of headache was elicited in 455 patients, and 107 of these had "worst headache" and were enrolled in the study. CT-confirmed SAH was found in 18 of the 107 (17%). Only 2 patients (2.5%, 95% confidence interval, .3% to 8.8%) had SAH detected by CSF analysis among those with negative CT imaging result. CSF spectrophotometric detection was the most sensitive test for blood. Three patients with less than 6 red blood cells in tube 1 had positive spectrophotometric results, but in all 3, tube 4 was negative on spectrophotometric analysis, suggesting a high false-positive rate. CONCLUSION: Modern CT imaging is sufficient to exclude 97.5% of SAH in patients presenting to the ED with "worst headache" symptoms.

Adult↗

[The clinical value of 3 alpha-androstanediol-glucuronide in hirsute women].

Aim of this prospective diagnostic study was to determine the serum 3 alpha-androstanediol-glucuronide (AdiolG) level in hirsute women in order to assess the androgenic activity in peripheral tissue and to differentiate between hirsutism of peripheral origin and that of adrenal or ovarian origin. Diagnostic advantages might have been expected in patients with idiopathic hirsutism, in whom increased 5 alpha-reductase activity may be reflected by this parameter. Apart from serum AdiolG, we determined the established parameters testosterone, androstendione and dehydroepiandosterone sulfate in 63 hirsute premenopausal women and in 51 non-hirsute controls. AdiolG (P < 0.05), as well as the 3 established parameters (P < 0.001) were elevated in the hirsute women as compared with the controls; however, the subgroup of women with idiopathic hirsutism (n = 32) showed no elevation of serum AdiolG. Analysis of the combined hirsute and control groups showed that the correlation of AdiolG to the hirsutism score (r = 0.42) was markedly weaker than that of testosterone to the latter (r = 0.62). Moreover, no correlation was found between the body-mass index and AdiolG. Our data show that serum AdiolG is obviously not a specific marker for peripheral 5 alpha-reductase activity, but appears to reflect the adrenal and ovarian androgen precursors. Thus, determination of serum AdiolG is of no diagnostic benefit in the clinical assessment of hirsute women.

Adolescent↗

[6-sulfatoxymelatonin in women with secondary amenorrhea].

We evaluated the overnight urinary excretion of 6-sulfatoxymelatonin in a group of 347 women (range: 18-69 years). 26 women (range 20-29 years) with normogonadotrophic, hypoestrogenemic amenorrhoea (WHO II) were selected and compared with a group of 26 women menstruating normally (range: 19-30 years) with respect to urinary 6-sulfatoxymelatonin excretion, serum 17 beta-estradiol levels and response to the thyroid releasing hormone (TRH) test. Patients with hyperprolactinemia, hyperandrogenemia, thyroid dysfunction and weight problems were excluded. 6-sulfatoxymelatonin was found to be significantly higher in the amenorrhoeic women than in the controls (p < 0.000001). In the amenorrhoeic patients a statistically significant inverse correlation was found between serum 17 beta-estradiol levels and urinary 6-sulfatoxymelatonin excretion. A positive correlation was obtained between the thyroid stimulation hormone (TSH) value measured at 20 minutes after stimulation and 6-sulfatoxymelatonin excretion. Further clinical research in this field is required to evaluate its clinical impact, especially in patients with secondary amenorrhea.

Adolescent↗

Effect of hormone replacement therapy on growth hormone stimulation in women with premature ovarian failure.

OBJECTIVE: To assess the effect of oral hormone replacement therapy (HRT) on body weight, insulin-like growth factor I (IGF-I), and GH response to exogenous GHRH [corrected] in women with premature ovarian failure (POF) [corrected]. DESIGN: Controlled clinical study. SETTING: Outpatients studied in the department of endocrinology of the University Hospital in Vienna. PATIENT(S): Twenty-four women with POF (study group) and 24 volunteers with normal ovarian cycles (control group). INTERVENTION(S): Pituitary GHRH [corrected] stimulation was performed in all women at study entry and in patients with POF after 1, 6, and 12 months of standard oral HRT. Blood samples were collected from 15 minutes before to 120 minutes after GHRH administration [corrected]. Body weight also was evaluated. RESULT(S): No differences in baseline and stimulated serum GH were found either between POF women and controls or in POF women during HRT. Women with POF without HRT had significantly higher IGF-I levels; a reduction in circulating IGF-I levels occurred during HRT. Body weight remained stable. CONCLUSION(S): Our results show the following: [1] Women with POF have similar Gh secretion patterns as healthy age-matched women; [2] physiologic HRT has no impact on GHRH-induced [corrected] GH stimulation; and [3] HRT has no impact on body weight in women with POF.

Adult↗

Hormone replacement therapy and intraocular pressure.

OBJECTIVES: To evaluate the effect of hormone replacement therapy (HRT) on intraocular pressure (IOP) in menopausal women. METHODS: The IOP of 25 white menopausal women without an abnormal ophthalmologic history was measured before and during HRT regimen. IOP fluctations were recorded before and 1, 4, and 12 weeks after the beginning of HRT. These measurements were obtained according to a standardized time schedule (08:00, 12:00, 16:00, and 19:00 h). RESULTS: The mean IOP in the left eye decreased from 16.2 +/- 2.4 mmHg before therapy to 14.0 +/- 2.1 mmHg after 12 weeks of therapy (P < 0.001). In the right eye, whose IOP was at 15.3 +/- 2.3 mmHg before therapy there was a decrease to 14.0 +/- 1.9 mmHg after 12 weeks of therapy (P < 0.001). CONCLUSION: Hormone replacement therapy has a positive effect on IOP in menopausal women.

Estrogen Replacement Therapy↗

The mythology of hormone replacement therapy.

OBJECTIVE: To evaluate the literature on contraindications contained in pharmaceutical data sheets of five currently available oestrogen replacement preparations (HRT). These contraindications include cardiovascular disease, diabetes, liver diseases, otosclerosis, endometriosis, melanoma and hormone-dependent tumours. DESIGN: Systematic review. INTERVENTIONS: Oestrogen replacement regimens. RESULTS: The contraindications to the five HRT preparations have been taken uncritically from the data sheets of oral contraceptives. In some of these conditions not only is HRT not contraindicated, it is indicated. The data sheets for the HRT preparations all state that cardiovascular disease is a contraindication, but systematic review shows that ischaemic heart disease, hypertension and hyperlipidaemia are not contraindications, and in ischaemic heart disease HRT may actually be indicated. Similarly, systematic review shows that diabetes, chronic liver disease, endometriosis, some cases of treated cancer of the endometrium and breast, melanoma and otosclerosis are not contraindications to HRT. CONCLUSIONS: The information in the pharmaceutical data sheets of HRT regimens should be modified as more accurate information could influence how these preparations are prescribed by doctors as well as affect patient compliance.

Breast Neoplasms↗

[Second look laparoscopy after fallopian tube perforation with the tubal endoscope].

In recent years, falloposcopic, visualization of the tubal lumen has become a topic of great interest. The development of a linear everting catheter system (Imagyn Medical Inc., Laguna Niguel, Calif., USA) allows cannulation of the fallopian tubes without exerting shear forces upon the tubal epithelium. We report the findings of a second-look laparoscopy after accidental tubal perforation at falloposcopy. Second-look laparoscopy was performed in a patient 6 months after tubal perforation with the falloposcope and no adhesions or signs of inflammation could be detected. On chromopertubation, no tubal fistula was found to be present. Two months after treatment, the patient got pregnant spontaneously. Pregnancy and delivery were without any complications. We conclude that technique of falloposcopy provides a safe access to the endotubal lumen. Even a perforation created by the microendoscope does not appear to be associated with any long-term complications.

Adult↗

Androgen serum levels in women with premature ovarian failure compared to fertile and menopausal controls.

OBJECTIVE: The purpose of our study was to examine androgen serum levels and bone density in women with premature ovarian failure (POF) compared to healthy normal controls. STUDY DESIGN: Thirty-three women 19-35 years of age with idiopathic POF were compared to 33 well-matched women with normal ovarian function and 32 healthy postmenopausal (PMP) women concerning 17-hydroxyprogesterone (17-OHP), androstendione (A), testosterone (T), dehydroepiandrosterone-sulfate (DHEAS), insulin-like growth factor 1 (IGF-1), as well as bone density (BD). RESULTS: Women with POF showed statistically significantly lower concentrations of 17-OHP, A, T (p < 0.001) and a reduced bone density (p < 0.001) compared to fertile controls. No differences were found between POF and PMP women concerning estradiol (E2), T, A and 17-OHP. Regarding DHEAS, no statistically significant differences were found between women with POF and fertile controls whereas PMP women proved to have significantly lower DHEAS concentrations than fertile controls. Women with POF had the highest IGF-1 serum concentrations and PMP women the lowest. CONCLUSION: An important decrement of ovarian steroids and bone density was noticed in women with POF, while the time since menopause had no influence on androgen concentrations. The hormone concentrations in women with POF are similar to those observed in normal PMP women with the exception of DHEAS and IGF-1 levels.

Adult↗

Effects of estradiol valerate on growth hormone and prolactin response to growth hormone-releasing hormone stimulation in pre- and postmenopausal women.

We investigated the relationship between the growth hormone and prolactin response to stimulation of growth hormone-releasing hormone (GHRH) and changes in body weight in pre- and postmenopausal women before and after 4 and 20 weeks of oral hormone replacement therapy (HRT). Ten postmenopausal women (with levels of follicle-stimulating hormone (FSH) of > 30 mIU/ml) were compared to ten premenopausal women suffering from post-pill amenorrhea (FSH < 10 mIU/ml). Both patient groups reported anamnestic body weight increases in the course of the former use of sex hormones. Additionally, ten postmenopausal women without anamnestic weight changes were studied. A significant reduction in the growth hormone response to GHRH was observed during the first month of HRT in women gaining weight, which was restored to pre-therapeutic levels after 6 months of HRT. A small but statistically significant increase in insulin-like growth factor (IGF)-I levels occurred in the course of HRT in all patients studied. These changes in growth hormone stimulation testing and IGF-I levels were accompanied by distinct changes in body weight. No reduction in the GHRH response was observed in those patients who did not gain body weight. Although GHRH stimulation induces a significant rise of prolactin concentrations in all patients before therapy no influence on prolactin levels could be demonstrated during HRT.

Adolescent↗

[Progesterone and nitric oxide systems].

Sexual steroids play an established role in the mechanisms concerning reproduction, ovulation, menstruation and onset of labour. However, sexual steroids are also involved in extragenital mechanisms, which were described for both oestrogen, and progesterone. Progesterone and its mechanisms of signal transduction still remain to be fully understood. However, there is evidence, that nitric oxide (NO) seems to be an important mediator in these mechanisms. NO, the molecule, which was described to exist in acid rain, was elected the molecule of the year 1992 from the American Academy of Science. NO is a short-lived molecule, which is involved in many reactions as an modulating transmitter due to its high diffusibility and its polarity. NO regulates the immune response of mononuclear cells, contractility of smooth muscle cells and neuronal transmission of non-adrenergic and non-cholinergic nerves. Additionally it was found, that NO may be important in the regulation of menstruation, the maintenance of uterine quiescence as well as the initiation of labour and the maturation of the uterine cervix.

Animals↗