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Biomedical subjects

A Mueller

Publications and source records attributed to A Mueller.

At least 19 recordsLinked to original sources

Role of estrogen and progesterone in the regulation of uterine peristalsis: results from perfused non-pregnant swine uteri.

BACKGROUND: Adequate uterine contractility and peristalsis are involved in the transport of semen and gametes and in successful embryo implantation. Estrogen and progesterone fluctuate characteristically during the menstrual cycle. It has been suggested that both hormones influence uterine peristalsis in characteristic ways. METHODS: An extracorporeal perfusion model of the swine uterus was used that keeps the uterus in a functional condition and is suitable for the study of physiological questions. The effects of estrogen and progesterone on oxytocin-induced uterine peristalsis were assessed using an intrauterine double-chip microcatheter. RESULTS: Estrogen perfusion was associated with an increase in intrauterine pressure (IUP) in a dose-dependent manner. There was a significant difference between the IUP increase measured in the isthmus uteri and that in the corpus uteri, resulting in a cervico-fundal pressure gradient. Estrogen perfusion resulted in a significantly higher rate of peristaltic waves starting in the isthmus uteri and directed towards the corpus uteri. Progesterone was able to antagonize the estrogen effect in general. CONCLUSIONS: This study demonstrates that estrogen and progesterone have differential effects in the regulation of uterine peristalsis. The present observation shows that estrogen stimulates uterine peristalsis and is able to generate a cervico-fundal direction of peristalsis, whereas progesterone inhibits directed uterine peristalsis.

Animals↗

Is it necessary to measure free testosterone to assess hyperandrogenemia in women? The role of calculated free and bioavailable testosterone.

Hirsutism in women is defined as excessive facial and/or body terminal hairs showing a masculine distribution; the condition affects approximately 7% of women of reproductive age, and chronic anovulation is a common problem for infertile couples, with a rate of 20-25%. There is a general consensus that these women should be evaluated endocrinologically, as many are found to have an androgen excess (AE) disorder. Free testosterone (FT) is the most prevalent marker in women with androgen excess, but the reference measurement procedures for FT are time-consuming and complex manual procedures that are not routinely practicable in large laboratories. Recently, models have been developed for calculating FT from total testosterone (TT), sex hormone binding globulin (SHBG), and albumin. These calculated values have been found to correlate closely with values estimated using the reference measurement procedures. This study compared measured endocrinological parameters--TT, free testosterone (aFT) by analogue ligand immunoassay method, dihydrotestosterone (DHT), dehydroepiandrosterone sulfate (DHEAS), (SHBG), And calculated parameters--calculated free testosterone (cFT), calculated bioavailable testosterone (cBT), and the free androgen index (FAI) in hirsute women and women with polycystic ovary syndrome (PCOS)--with the values in control individuals. A modified Ferriman-Gallwey score was use to describe the hirsutism pattern. No differences were observed when the measured hormone parameters were compared, while the calculated parameters were significantly increased in women in the hirsutism and PCOS groups in comparison with the values in the control group. Calculate parameters mat be more appropriate markers for assessing hyperandrogenemia in women in comparison with measured values of simple enzyme immuno-assays. These calculated values may be capable of replacing the values estimated using reference measurement procedures, so that time-consuming and complex manual procedures for measuring free testosterone with the reference methods may be dispensable in clinical practice.

Adult↗

Successful uterus cryopreservation in an animal model.

Cryopreservation of whole organs would not only be advantageous for experimental biology but also for transplantation surgery. The objective of this study was to evaluate the feasibility of cryopreserving swine uterus as an experimental model of cryopreservation affecting a whole visceral muscle organ. Organs were frozen slowly (0.2 degrees C/min) after arterial perfusion with 10% dimethyl sulfoxide solution for 10 min and equilibration in this solution for 30 min. Viability of the organs was tested by biochemical parameters, LIVE/DEAD fluorescent staining and capability for contraction in a perfusion system. Ten fresh and ten cryopreserved uteri showed living cells in the LIVE/DEAD assay, and were viable for at least 7 h as shown by their ability to produce rhythmic contractions after oxytocin administration. This is the first report known to us on successful cryopreservation of a whole swine uterus to demonstrate that perfusion with a cryoprotectant and slow freezing provides a promising method for cryopreserving whole organs, and may encourage further studies with other cryoprotective agents and freezing protocols as well as other organs.

Animals↗

Effects on the male endocrine system of long-term treatment with gonadotropin-releasing hormone agonists and estrogens in male-to-female transsexuals.

We studied hormonal changes resulting from long-term treatment with gonadotropin-releasing hormone agonist and 17beta estradiol valerate in 40 healthy middle-aged male-to-female transsexuals over a period of two years. All of the participants received injections of 3.8 mg goserelin acetate every four weeks in combination with 6 mg oral 17beta estradiol valerate per day for cross-sex hormone treatment for male-to-female transsexuals. There was a significant reduction in the levels of serum luteinizing hormone and follicle-stimulating hormone to the hypogonadal stage. Mean testosterone levels decreased by 97% to 0.52 and 0.59 nmol/l after 12 months and 24 months, respectively. There was a significant reduction in dehydroepiandrosterone sulfate by 37% after 12 months and 43% after 24 months, and androstendione by 29% after 12 months and 27% after 24 months, respectively. Cortisol levels were reduced by 43% and 50%, respectively. Estrogen levels were significantly increased from 77.51 to 677 after 12 months and 661 pmol/l after 24 months. Sex hormone-binding globulin and corticoid-binding globulin levels were significantly increased after 12 and 24 months. There was a significant decrease in all measured androgen fractions and cortisol during long-term treatment with gonadotropin-releasing hormone agonist and 17beta estradiol valerate. Apart from suppression of testicular hormone production, one possible interpretation is that treatment with long-term gonadotropin-releasing hormone agonist and 17beta estradiol valerate influences adrenal hormone levels in healthy middle-aged male-to-female transsexuals. Cortisol serum levels may be decreased due to estrogen-induced increase in corticoid-binding globulin.

Adolescent↗

Ultrasonically implanted PLA suture anchors are stable in osteopenic bone.

We compared the in vitro pullout strengths of a metallic screw-type suture anchor (5-mm Corkscrew) and a new ultrasonically implanted absorbable pin from cadaveric humeral heads with different bone densities. They were assessed quantitatively using microcomputed tomography. Pullout tests were done at four standardized sites and then correlated with the local bone density. The mean pullout strengths for the 5-mm Corkscrew and the 3.5-mm polylactic pin were similar in weak bone (76 +/- 24 N versus 104 +/- 46 N), intermediate quality bone (194 +/- 81 N versus 218 +/- 76 N), and strong bone (349 +/- 127 N versus 325 +/- 100 N). Pullout strength correlated with bone density for both implants (r = 0.76 and r = 0.86 for the Corkscrew and polylactic pin, respectively). The ultrasonically implanted absorbable 3.5-mm polylactic pin achieved equal pullout strength in weak bone as the larger 5-mm titanium Corkscrew. Bone density is highly variable in humeral heads and influenced the pullout strength of both implants.

Absorbable Implants↗

The role of oestradiol in the uterine peristalsis in the perfused swine uterus.

This study was designed to examine the effects of oestradiol (E2) on sperm transport in the swine uterus. The bicornuate swine uterus is optimal for the study of the uterine transport and peristalsis because the influence of various factors can be examined on each uterine horn independently. Forty swine uteri (with or without ovarectomy) were perfused for a period of up to 7 h. Two different E2 concentrations (3 or 30 pg/ml) in the perfusion medium were administered for 30 min unilaterally. Through an intracervical catheter 1 ml of a high concentrated dextran blue solution was administered directly in the upper part of the cervix. After bilateral perfusion of the swine uterus with a bolus of 0.3 IU oxytocin the distribution of coloured particles was assessed macroscopically before and after incision of the uterine horns. Coloration was evaluated by two observers blinded to the site-specific administration of E2. In the 10 ovarectomized uteri with the 3 pg/ml E2 concentration a unilateral distribution towards the side of oestradiol administration was observed in six uteri, in four it was a bilateral distribution. In the 10 non-ovarectomized uteri with the 3 pg/ml E2 concentration a uni- and ipsilateral coloration was observed in five uteri, in five it was a bilateral distribution. In the 20 uteri with 30 pg/ml E2, a unilateral coloration of the uterus horns was observed in all uteri. Oestradiol is one of the main factors, which influences the direction of the sperm transport in a dose-dependent manner, in the perfused swine uterus.

Animals↗

B lymphocyte maturation in Wegener's granulomatosis: a comparative analysis of VH genes from endonasal lesions.

BACKGROUND: Anti-neutrophil cytoplasmic antibodies (ANCA) directed against proteinase 3 (PR3) are highly specific for Wegener's granulomatosis (WG). Evidence for a pivotal role of PR3-ANCA in the induction of vasculitis has been demonstrated. B cell clusters have been observed within endonasal biopsy specimens. OBJECTIVES: To determine whether B cell selection and maturation take place in granulomatous lesions of WG. METHODS: Granulomatous lesions and the immunoglobulin (VH) gene repertoire from nasal tissue of six WG patients-two active and two smouldering localised WG (ANCA negative, restricted to respiratory tract), plus one active and one smouldering PR3-ANCA positive generalised WG-were characterised by immunohistochemistry, polymerase chain reaction, cloning, DNA sequencing and database comparison. RESULTS: B lymphocyte-rich, follicle-like areas were observed proximal to PR3 positive cells and plasma cells in granulomatous lesions; 184 VH genes from these granulomatous lesions were compared with 84 VH genes from peripheral blood of a healthy donor. The mutational pattern of VH genes from active WG resembled memory B cells. Structural homologies of VH genes from granulomatous lesions to PR3-ANCA encoding genes were detected. Significantly more genes (55%, 45%, and 53%, respectively) from active WG compared with the healthy repertoire carried mutations to negatively charged amino acids within the binding site coding regions, favouring affinity to the positively charged PR3. CONCLUSIONS: Selection and affinity maturation of potentially PR3-ANCA producing autoreactive B cells may start in granulomatous lesions, thereby contributing to disease progression from ANCA negative localised to PR3-ANCA positive generalised WG.

Aged↗

Olfactory bulb volumes in patients with idiopathic Parkinson's disease a pilot study.

Olfactory loss is among early signs of idiopathic Parkinson's disease (IPD). The present pilot study aimed to investigate whether this loss would be reflected in a decreased volume of the olfactory bulb (OB) established through magnetic resonance imaging. Eleven consecutive IPD patients were compared to 9 healthy, age-matched controls. Results indicated that there is little or no difference between IPD patients and healthy controls in terms of OB volume. Based upon the relation between loss of olfactory input to the olfactory bulb and consecutive decrease in volume, these data support the idea that olfactory loss in IPD is not a primary consequence of damage to the olfactory epithelium but rather results from central-nervous changes.

Adult↗

Endocrine treatment of male-to-female transsexuals using gonadotropin-releasing hormone agonist.

In transsexual people, cross-sex hormone therapy is an important component of medical treatment. In male-to-female transsexuals, feminizing effects should be achieved before irreversible sex reassignment surgery (SRS) is considered. The most common treatment regimen in male-to-female transsexuals is a combination of ethinyl oestradiol and cyproterone acetate, with the exception of transdermal oestradiol-17beta in individuals over the age of 40. The mortality and morbidity rates with this treatment regimen have been reported in more than 800 patients. Typical side effects include venous thrombosis, elevated liver enzymes, symptomatic gallstones, hyperprolactinaemia and depression. Sixty male-to-female transsexuals were treated with monthly injections of gonadotropin-releasing hormone agonist (GnRHa) and oral oestradiol-17beta valerate for 2 years to achieve feminisation until SRS. There was a significant decline in gonadotropins, total testosterone and calculated free testosterone. In general, the treatment regimen was well accepted. An equal increase in breast size was achieved compared to common hormone therapy. Two side effects were documented. One, venous thrombosis, occurred in a patient with a homozygous MTHFR mutation. One patient was found to be suffering from symptomatic preexisting gallstones. No other complications were documented. Liver enzymes, lipids, and prolactin levels were unchanged. Significantly increased oestradiol and SHBG serum levels were detectable. In addition, an increase in bone mass density, in the femoral neck and lumbar spine, was recorded. We conclude that cross-sex hormone treatment of male-to-female transsexuals using GnRHa and oestradiol-17beta valerate is effective, and side effects and complication rates can be reduced using the treatment regimen presented here.

Adult↗

Comparison of tiotropium once daily, formoterol twice daily and both combined once daily in patients with COPD.

This study compared the bronchodilator effects of tiotropium, formoterol and both combined in chronic obstructive pulmonary disease (COPD). A total of 71 COPD patients (mean forced expiratory volume in one second (FEV1) 37% predicted) participated in a randomised, double-blind, three-way, crossover study and received tiotropium 18 microg q.d., formoterol 12 microg b.i.d. or both combined q.d. for three 6-week periods. The end-points were 24-h spirometry (FEV1, forced vital capacity (FVC)) at the end of each treatment, rescue salbutamol and safety. Compared with baseline (FEV1 prior to the first dose in the first period), tiotropium produced a significantly greater improvement in average daytime FEV1 (0-12 h) than formoterol (127 versus 86 mL), while average night-time FEV1 (12-24 h) was not different (tiotropium 43 mL, formoterol 38 mL). The most pronounced effects were provided by combination therapy (daytime 234 mL, night-time 86 mL); both differed significantly from single-agent therapies. Changes in FVC mirrored the FEV1 results. Compared with both single agents, daytime salbutamol use was significantly lower during combination therapy (tiotropium plus formoterol 1.81 puffs.day(-1), tiotropium 2.41 puffs x day(-1), formoterol 2.37 puffs x day(-1)). All treatments were well tolerated. In conclusion, in chronic obstructive pulmonary disease patients, tiotropium q.d. achieved a greater improvement in daytime and comparable improvement in night-time lung function compared with formoterol b.i.d. A combination of both drugs q.d. was most effective and provided an additive effect throughout the 24-h dosing interval.

Administration, Inhalation↗

Predictive value of impaired uterine transport function assessed by negative hysterosalpingoscintigraphy (HSSG).

BACKGROUND: Hysterosalpingoscintigraphy (HSSG) has given insight into the dynamics of rapid sperm transport inside the female genital tract. RESULTS: While there is an increase of an ipsilateral transport on the side bearing the dominant follicle in 70% of the subjects in the periovulatory phase, 15% of the patients do not demonstrate transport to the fallopian tubes (negative HSSG). In these patients the pregnancy rate achieved spontaneously or by intrauterine insemination is significantly reduced compared to the patients who showed an intact transport mechanism confirmed by positive HSSG. On the other hand, by means of assisted reproductive techniques (ART), pregnancy rates were higher in the group of patients showing negative HSSG (P < 0.0005). CONCLUSIONS: Our data clearly indicate that HSSG is a helpful method to evaluate the integrity of the utero-tubal transport mechanism. As pregnancy rates remain low in patients with negative HSSG, this result should be considered as an indication for IVF-treatment even in patients with patent fallopian tubes and normozoospermia of the partner.

Fallopian Tube Patency Tests↗

[Uterine adenomyosis in infertile patients: MR imaging findings and clinical conclusions].

PURPOSE: To evaluate the clinical value of magnetic resonance imaging (MRI) of the uterus and the pelvis in infertile female with symptomatic endometriosis for the assessment of uterine morphology and function. MATERIALS AND METHODS: Forty-one infertile women (mean age: 33.2 years) with symptomatic endometriosis documented by laparoscopy were evaluated with high-field MRI (Sonata, Siemens) using T2- and T1-weighted sequences. In addition, the patients underwent hysterosalpingoscintigraphy (HSSG) for evaluation of the uterotubal transport capacity. Pathologic findings of the uterine junction zone were correlated with the laparoscopic results, clinical symptoms and uterotubal transport capacity. RESULTS: Adenomyosis was diagnosed on T2-weigthed MR-images in 35 (85.4 %) patients (focal adenomatosis in 26 patients and diffuse adenomatosis in 9). Patients showing signs of adenomyosis tended to be older than patients without adenomyosis (mean age 34.1 years vs. 30.1 years) and showed a longer history of symptomatic endometriosis. A positive transport capacity in HSSG was observed in 73.1 % (19/26) of the patients with focal adenomyosis and in only 22.2 % (2/9) of patients with diffuse adenomyosis. In 83.3 % (5/6) of the patients without signs of adenomyosis, a positive uterotubal transport was documented. CONCLUSION: MRI of the uterus is a helpful diagnostic tool for the diagnosis of adenomyosis and for planning further therapies. Patients with the diagnosis of adenomyosis showed a reduced uterotubal transport capacity that depended on the severity of adenomyotic changes and might be a possible cause of infertility.

Adult↗

Intranasal vaccination with streptococcal fibronectin binding protein Sfb1 fails to prevent growth and dissemination of Streptococcus pyogenes in a murine skin infection model.

Fibronectin binding protein F1 (Sfb1) of Streptococcus pyogenes (group A streptococcus [GAS]) is a well-characterized adhesin that has been shown to induce protection in mice against a lethal intranasal GAS challenge after intranasal immunization with cholera toxin B subunit (CTB) as adjuvant. With a murine skin infection model, we have shown that Sfb1/CTB vaccination neither elicits opsonizing antibodies nor prevents systemic bacterial growth and dissemination to internal organs after a subcutaneous GAS challenge. These results indicate that an Sfb1-based vaccine should be complemented with additional protective antigens in order to be used in areas such as the tropical north of Australia, where the skin is the primary route of entry for invasive streptococcal diseases.

Adhesins, Bacterial↗

Hydroxypyridinium collagen crosslinks in serum, urine, synovial fluid and synovial tissue in patients with rheumatoid arthritis compared with osteoarthritis.

OBJECTIVE: To investigate the relationship between inflammation markers and content of pyridinium crosslinks in hydrolysates of synovial tissue and to specify the significance of urinary excreted pyridinoline, released primarily from collagen I and II of bone and cartilage, and deoxypyridinoline released especially from collagen I of bone and dentin, dependent on disease activity in rheumatoid arthritis (RA). METHODS: Synovial tissue and fluid from knee endoprosthesis surgery, as well as simultaneously obtained serum and urine, were collected from 12 patients with inactive RA or RA with low disease activity [iRA: C-reactive protein (CRP) <28 mg/l], 10 with active RA (aRA: CRP > or =28 mg/l) and 21 with OA. After preparation of the synovial tissue, including hydrolysis, completely released synovial pyridinoline and deoxypyridinoline crosslinks as well as those from synovial fluid, serum and urine were investigated using a gradient ion-paired reversed-phase HPLC method. Crosslink levels in synovial tissue are expressed as mol/mol collagen, assuming 300 residues of hydroxyproline per collagen molecule, also measured by HPLC. RESULTS: In the synovial tissue of aRA patients we found significantly elevated total pyridinoline concentrations and pyridinoline/deoxypyridinoline (Pyr/Dpyr) quotients compared with the iRA and OA controls, indicating an elevated crosslinking density of mature synovial tissue collagen with increased activity of RA. Pyridinoline levels and the Pyr/Dpyr ratio were correlated with those of urine and with acute-phase reactants in RA patients. Compared with serum crosslink levels, which were unrelated to disease activity, the urinary concentration of pyridinoline was increased by a factor of 2 and showed a simultaneous increase with increasing synovitis. CONCLUSION: Both crosslinking density and degradation of mature collagen from synovial tissue depend on the disease activity in RA. Urinary excretion of associated crosslinks, expressed as the Pyr/Dpyr ratio, correlates with those in synovial tissue and may be confirmed as a marker of synovial tissue collagen degradation. We suggest that increased crosslinking of mature collagen in the synovial tissue of RA is related to an inflammation-dependent regulation of collagen synthesis in activated synovial fibroblasts, in which lysyl oxidase represents the final enzymatic step for crosslinking.

Adult↗

Imbalanced secretion of IL-1beta and IL-1RA in Chlamydia pneumoniae-infected mononuclear cells from COPD patients.

Balanced secretion of pro- and anti-inflammatory cytokines is essential in limiting pulmonary inflammation in respiratory infections. It was hypothesised that, in acute infection with Chlamydia pneumoniae, mononuclear cells from chronic obstructive pulmonary disease (COPD) patients lack the opportunity to compensate for the inflammatory immune response by secreting adequate amounts of anti-inflammatory cytokines. Alveolar macrophages (AMs) and peripheral blood mononuclear cells (PBMCs) from eight COPD patients and eight healthy controls were infected with C. pneumoniae in order to determine interleukin (IL)-1beta, IL-1 receptor antagonist (IL-1RA) and IL-8 expression and messenger ribonucleic acid levels. Secretion of IL-1beta was significantly enhanced in AMs (six-fold) and PBMCs (four-fold) from COPD patients after infection with C. pneumoniae. Compared to the control group, release of its anti-inflammatory counterpart IL-1RA was diminished in COPD patients, resulting in a significantly higher IL-1beta/IL-1RA ratio in C. pneumoniae-infected AMs and PBMCs from COPD patients. Mononuclear cells from chronic obstructive pulmonary disease patients have less capacity for balancing the pro-inflammatory immune response caused by Chlamydia pneumoniae infection than those from healthy controls. These findings suggest that, during acute exacerbation with intracellular pathogens, chronic obstructive pulmonary disease patients are predisposed to inflammatory changes in the lungs.

Adult↗