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Biomedical subjects

P J Keller

Publications and source records attributed to P J Keller.

At least 19 recordsLinked to original sources
PubMed2001

Nonpalpable ultrasonographically not detectable Implanon rods can be localized by magnetic resonance imaging.

Recently, the contraceptive implant Implanon has been introduced in several European countries. In comparison to the six-capsule preparation Norplant, the removal of this single-rod system should be associated with less complications. However, the removal of nonpalpable Implanon rods can be difficult because the implant is not always visible with ultrasound. The aim of this study was to find a radiologic method for the localization of Implanon implants that are nonpalpable and can not be detected by ultrasound. X-ray, ultrasound, computed tomography, and magnetic resonance imaging (MRI) were investigated as methods to localize Implanon in a pig chest preparation and in a woman with a nonpalpable implant. The implant in the woman could be localized unequivocally only by MRI. We conclude that MRI is the best method for the unequivocal localization of nonpalpable, ultrasonographically not detectable Implanon rods. To avoid unnecessary scar tissue formation, it may be appropriate to defer surgery for the removal until definitive localization.

Animals↗
PubMed2001

Increased incidence of numerical chromosome abnormalities in spermatozoa injected into human oocytes by ICSI.

The potential risk of transmitting chromosomally abnormal spermatozoa from infertile males into oocytes through intracytoplasmic sperm injection (ICSI) has prompted us to investigate the male pronuclei of tripronuclear zygotes (3PN) obtained after ICSI. To specify the type of anomalies, we used triple colour fluorescent in-situ hybridization (FISH) with three specific probes for chromosomes X, Y and 18. From a total of 163 paternal complements of ICSI-3PN zygotes, 90 (55.2%) had Y-chromosome signals. Eighty-three of these were normal, four had the disomy XY and three were diploid. In the remaining 73 ICSI-3PN zygotes without Y-chromosome signals, the origin of paternal pronuclei was extrapolated through chromosome constitution of the first polar body. Five anomalies were found in this group of zygotes, giving a total rate of numerical chromosome aberrations for fertilizing spermatozoa of 7.4%. In contrast to ICSI, only two disomies (1.5%) were found in the control group of IVF-3PN zygotes. Compared with the incidence of chromosome anomalies between paternal-derived pronuclei of ICSI- and IVF-3PN zygotes, the difference was statistically significant (P < 0.025). This study provides the first direct evidence of a higher incidence of numerical chromosome anomalies in sperm-fertilized human oocytes after ICSI.

Chromosome Aberrations↗
PubMed2001

Estradiol metabolites inhibit endothelin synthesis by an estrogen receptor-independent mechanism.

Estradiol inhibits endothelin-1 synthesis, an effect that may contribute to the cardiovascular protective effects of estradiol. Recent findings that estradiol inhibits neointima formation in mice lacking estrogen receptors suggests that the cardiovascular protective effects of estradiol may be mediated by means of an estrogen receptor-independent mechanism. Because 2-hydroxyestradiol and 2-methoxyestradiol, metabolites of estradiol with little/no affinity for estrogen receptors, are more potent than estradiol in inhibiting vascular smooth muscle cell growth, we investigated whether these metabolites also inhibit endothelin-1 synthesis by means of an receptor-independent mechanism. Treatment of porcine coronary artery endothelial cells for 4 to 24 hours with 0.001 to 1 micromol/L of estradiol, 2-hydroxyestradiol, or 2-methoxyestradiol concentration-dependently inhibited basal as well as serum-induced (2.5%), TNFalpha-induced (10 ng/mL), angiotensin II-induced (100 nmol/L), and thrombin-induced (4 U/mL) endothelin-1 synthesis. Estradiol, 2-hydroxyestradiol, and 2-methoxyestradiol also inhibited serum-induced mitogen-activated protein kinase activity. As compared with estradiol, its metabolites were more potent in inhibiting endothelin-1 secretion and mitogen activated protein kinase activity. The inhibitory effects of 2-hydroxyestradiol and 2-methoxyestradiol on endothelin-1 release and mitogen-activated protein kinase activity were not blocked by ICI182780 (50 micromol/L), an estrogen receptor antagonist. Our findings indicate that the estradiol metabolites 2-hydroxyestradiol and 2-methoxyestradiol potently inhibit endothelin-1 synthesis by means of an estrogen receptor-independent mechanism. This effect of estradiol metabolites may be mediated by inhibition of mitogen activated protein kinase activity and may contribute to the cardioprotective effects of estradiol.

2-Methoxyestradiol↗
PubMed2000

The incidence of actinomyces-like organisms in Papanicolaou-stained smears of copper- and levonorgestrel-releasing intrauterine devices.

Actinomyces-like organisms (ALOs) are a common finding in Papanicolaou-stained cervico-vaginal smears (PAP smears) of women using an intrauterine device (IUD). The incidence of ALOs positive PAP smears depends on the type of IUD. Pelvic actinomycosis is a severe disease that may require hysterectomy and salpingo-oophorectomy. In a retrospective study we compared the incidence of ALOs positive PAP smears in users of the new levonorgestrel-releasing intrauterine device (LNG-IUD) (n = 52) with the incidence in Multiload Copper IUD (ML375) users (n = 104). All IUDs had been inserted from 1996-1998. Women with a follow-up period of more than 9 months were included into the final analysis (LNG-IUD: n = 34; ML375: n = 65). The incidence of ALOs in LNG-IUD users (2.9%) was significantly lower than in ML375 users (20%). Clinical consequences of ALOs positive PAP smears are discussed controversially. The low incidence in the LNG-IUD users probably leads to less IUD-removals, reinsertions and less pelvic-inflammatory-diseases.

Actinomyces↗
PubMed2000

The effect of the menstrual cycle and of ethinylestradiol on nitric oxide, endothelin-1 and homocysteine plasma levels.

The use of the estrogen ethinylestradiol is associated with an increased cardiovascular risk. It is not known whether this might be caused by an influence of ethinylestradiol on endothelium-derived factors or on the cardiovascular risk factor homocysteine. Our aim was to evaluate whether a short-term treatment with ethinylestradiol results in changes of nitric oxide (NO), endothelin-1 and homocysteine. Participants were ten healthy women with regular menstrual cycles. NO, homocysteine, endothelin-1, estradiol and progesterone were measured during one cycle and before and after treatment with ethinylestradiol at 50 microg/day. Homocysteine and NO did not change significantly during the menstrual cycle or after treatment. However, endothelin-1 levels decreased during the cycle (from 3.89 ng/l to 2.93 ng/l p < 0.05) and after ethinylestradiol (from 2.94 ng/l to 2.26 ng/l p<0.03). Analysis of the pretreatment data showed a positive correlation between homocysteine and NO and between NO and endothelin-1. Treatment with ethinylestradiol caused a shift in the balance between NO and endothelin-1 in the direction of vasodilatation. This finding is one factor concerning the effects of ethinylestradiol on the vascular system but does not explain the cardiovascular risk of this substance.

Adult↗
PubMed2000

A prospective study on the effects of depot medroxyprogesterone acetate on trabecular and cortical bone after attainment of peak bone mass.

OBJECTIVE: To study the annual change of bone mass in women aged 30-45 years being treated with depot medroxyprogesterone acetate (DMPA) in order to evaluate whether the bone mass depends on the duration of DMPA use or the oestradiol level. DESIGN: Prospective longitudinal study over an interval of 12 months. SETTING: A family planning centre of a university hospital. PATIENTS: Thirty-six current users of DMPA. INTERVENTIONS: Injection of 150 mg DMPA every 12 weeks. MEASUREMENTS: Bone mass was measured at the distal radius by peripheral quantitative computed tomography (reproducibility 0.3%). RESULTS: Mean annual changes (SD) in trabecular and cortical bone mass were 0.06 (1.6%) [P = 0.8] and -0.26% (0.6) [P < 0.04]. The decrease in cortical bone mass was not significant because the changes were within the precision error of the method used for the measurements. Duration of DMPA use and oestradiol levels were not associated to the bone parameters. CONCLUSION: We did not find a negative impact of DMPA on the bone mass of premenopausal women aged 30-45 years.

Adult↗
PubMed2000

Clinically used estrogens differentially inhibit human aortic smooth muscle cell growth and mitogen-activated protein kinase activity.

Some estrogenic compounds modify vascular smooth muscle cell (SMC) biology; however, whether such effects are mediated in part by estrogen receptors is unknown. The purpose of this study was to evaluate whether the actions of clinically used estrogens on human aortic SMC biology are mediated by estrogen receptors. We examined the effects of various clinically used estrogens in the presence and absence of ICI 182,780, an estrogen receptor antagonist, on cultured human aortic SMC DNA synthesis ([(3)H]thymidine incorporation), cellular proliferation (cell counting), cell migration (modified Boyden chamber), collagen synthesis ([(3)H]proline incorporation), and mitogen-activated protein kinase activity. FCS-induced DNA synthesis, cell proliferation, collagen synthesis, platelet-derived growth factor-induced SMC migration, and mitogen-activated protein kinase activity were significantly inhibited by physiological (10(-9) mol/L) concentrations of 17beta-estradiol and low concentrations (10(-8) to 10(-7) mol/L) of 17beta-estradiol, estradiol valerate, estradiol cypionate, and estradiol benzoate but not by estrone, estriol, 17alpha-estradiol, or estrone sulfate. The inhibitory effects of 17beta-estradiol and other inhibitory estrogens were completely reversed by 100 micromol/L ICI 182,780, and the rank-order potency of various estrogens to inhibit SMC biology matched their rank-order affinity for estrogen receptors. The inhibitory effects of estrogens on SMC biology are in part receptor-mediated. Because the cardioprotective effects of hormone replacement therapy are most likely mediated by modification of SMC biology, whether hormone replacement therapy protects a given postmenopausal woman against cardiovascular disease will depend partially on the affinity of the estrogen for estrogen receptors in vascular SMCs.

Aorta↗
PubMed2000

Estradiol inhibits smooth muscle cell growth in part by activating the cAMP-adenosine pathway.

Estradiol inhibits smooth muscle cell growth; however, the mechanisms involved remain unclear. Because estradiol stimulates cAMP synthesis and adenosine inhibits cell growth, we hypothesized that the conversion of cAMP to adenosine (ie, the cAMP-adenosine pathway) mediates in part the inhibitory effects of estradiol on vascular smooth muscle cell growth. To test this hypothesis, we examined the effects of estradiol (0.001 to 1 micromol/L) on serum-induced DNA, collagen, and total protein synthesis and cell number in the absence and presence of 1, 3-dipropyl-8-p-sulfophenylxanthine (10 nmol/L; A(1)/A(2) adenosine receptor antagonist), KF17837 (10 nmol/L; selective A(2) adenosine receptor antagonist), 8-cyclopentyl-1,3-dipropylxanthine (10 nmol/L; selective A(1) adenosine receptor antagonist), and 2', 5'-dideoxyadenosine (10 micromol/L; adenylyl cyclase inhibitor). Estradiol inhibited all measures of cell growth, and the concentration-dependent inhibitory curves for estradiol were shifted to the right (P<0.05) by 1,3-dipropyl-8-p-sulfophenylxanthine, KF17837, and 2',5'-dideoxyadenosine but not by 8-cyclopentyl-1, 3-dipropylxanthine. Moreover, the inhibitory effects of estradiol were enhanced by stimulation of adenylyl cyclase with forskolin and by inhibition of adenosine metabolism with erythro-9-(2-hydroxy-3-nonyl)adenine plus iodotubericidin (adenosine deaminase and kinase inhibitors, respectively). Estradiol also increased levels of cAMP and adenosine, and these effects were blocked by 2',5'-dideoxyadenosine (P<0.05). Our results support the hypothesis that estradiol stimulates cAMP synthesis and cAMP-derived adenosine regulates smooth muscle cell growth via A(2) adenosine receptors. Thus, the cAMP-adenosine pathway may contribute importantly to the antivasooclusive effects of estradiol.

Adenosine↗
PubMed2000

Cerebral MR venography: normal anatomy and potential diagnostic pitfalls.

BACKGROUND AND PURPOSE: MR venography is often used to examine the intracranial venous system, particularly in the evaluation of dural sinus thrombosis. The purpose of this study was to evaluate the use of MR venography in the depiction of the normal intracranial venous anatomy and its variants, to assess its potential pitfalls in the diagnosis of dural venous sinus thrombosis, and to compare the findings with those of conventional catheter angiography. METHODS: Cerebral MR venograms obtained in 100 persons with normal MR imaging studies were reviewed to determine the presence or absence of the dural sinuses and major intracranial veins. RESULTS: Systematic review of the 100 cases revealed transverse sinus flow gaps in 31% of the cases, with 90% of these occurring in the nondominant transverse sinus and 10% in the codominant transverse sinuses. No flow gaps occurred in the dominant transverse sinuses. The superior sagittal and straight sinuses were seen in every venogram; the occipital sinus was seen in only 10%. The vein of Galen and internal cerebral veins were also seen in every case; the basal veins of Rosenthal were present in 91%. CONCLUSIONS: Transverse sinus flow gaps can be observed in as many as 31% of patients with normal MR imaging findings; these gaps should not be mistaken for dural sinus thrombosis.

Adolescent↗
PubMed2000

Effect of voxel position on single-voxel MR spectroscopy findings.

BACKGROUND AND PURPOSE: Single-voxel MR spectroscopy is a widely used tool for evaluating brain tumors. Although extensive data are available on the MR spectral appearance of tumors, less is known about the effect of voxel position on the accuracy of single-voxel MR spectroscopy findings. The purpose of this study was to test the hypothesis that the accuracy of single-voxel MR spectroscopy in the categorization of lesions as either tumor or not tumor is dependent on voxel position. METHODS: Fifty single-voxel MR spectra acquired with a fully automated stimulated-echo spectroscopy sequence were reviewed retrospectively in 43 patients with new or previously treated intra-axial brain tumors. Spectra were analyzed for the presence of choline, creatine, N-acetylaspartate (NAA), and lipid/lactate. Choline/creatine and NAA/creatine peak area ratios were assessed qualitatively. Lesions were grouped into one of three categories on the basis of spectral pattern: tumor, not tumor, or indeterminate. Results of MR spectroscopy were compared with the final histopathologic diagnosis. RESULTS: Histologic confirmation was obtained in 19 patients; MR spectra were interpretable in 17 of those. MR spectra correctly categorized nine of 17 lesions (six tumor, three nontumor). All eight misdiagnosed lesions were tumors. When the MR spectroscopy voxel included the enhancing edge of the lesion, the spectra correctly categorized seven of eight lesions (four of five tumors and all three cases of radiation necrosis). When the MR spectroscopy voxel was positioned centrally within the lesion, the spectra correctly reflected histologic outcome in two of nine lesions (all tumors). CONCLUSION: The reliability of single-voxel MR spectroscopy findings is dependent on voxel position. Spectra obtained from voxels at the enhancing edge of a tumor more accurately reflect lesion histopathology than do spectra obtained from the lesion center, even if the centrally placed voxels contain solidly enhancing tissue.

Aspartic Acid↗