Biomedical subjects

S W Leung

Publications and source records attributed to S W Leung.

At least 19 recordsLinked to original sources

PubMed2006

Three-dimensional conformal radiotherapy for the treatment of arteriovenous shunting in patients with hepatocellular carcinoma.

The objective of this study is to evaluate the efficacy of radiotherapy for the treatment of arteriovenous shunting (AVS) in patients with hepatocellular carcinoma (HCC). Between November 1997 and April 2005, 20 HCC patients with AVS were referred to our department for radiotherapy. The radiation was delivered with 10-15 MV X-ray given 5 days per week at 2 approximately 2.5 Gy per fraction. Total doses ranged from 45 to 64 Gy (median dose 60 Gy). The patients were followed up with color Doppler sonography. When non-invasive imaging suggested obliteration, X-ray angiography was performed to verify the results. Four of the 20 AVS proved to be completely obliterated at X-ray angiography in 1.9, 2.8, 1.8 and 2.9 months after radiotherapy. One of the remaining 16 showed obvious regression on Doppler sonography 0.5 months after radiotherapy, but X-ray angiography was not performed to verify the result. Radiation-related hepatic failure did not occur during the follow-up period. In conclusion, radiotherapy is a treatment alternative for AVS in HCC patients and gives patients with poor prognosis the chance to receive further transcatheter arterial embolization.

Adult↗

PubMed2006

A randomised trial of carbetocin versus syntometrine in the management of the third stage of labour.

OBJECTIVE: Syntometrine is an effective uterotonic agent used in preventing primary postpartum haemorrhage but has adverse effects including nausea, vomiting, hypertension and coronary artery spasm. Carbetocin is a newly developed long-acting oxytocin analogue that might be used as an uterotonic agent. We compare the efficacy and safety of intramuscular (IM) carbetocin with IM syntometrine in preventing primary postpartum haemorrhage. DESIGN: Prospective, double-blinded, randomised controlled trial. SETTING: Delivery suite of a university-based obstetrics unit. POPULATION: Women with singleton pregnancy achieving vaginal delivery after and throughout 34 weeks. METHODS: Three hundred and twenty-nine eligible women were randomised to receive either a single dose of 100 microgram IM carbetocin or 1 ml IM syntometrine (a mixture of 5 iu oxytocin and 0.5 mg ergometrine) at the end of second stage of labour. MAIN OUTCOME MEASURES: Difference in haemoglobin drop measured 2 days after delivery between the two groups. RESULTS: There was no difference in the drop of haemoglobin concentration within the first 48 hours between the two groups. The incidence of additional oxytocic injections, postpartum haemorrhage (blood loss > or = 500 ml) and retained placenta were also similar. The use of carbetocin was associated with significant lower incidence of nausea (relative risk [RR] 0.18, 95% confidence interval [CI] 0.04-0.78), vomiting (RR 0.1, 95% CI 0.01-0.74), hypertension 30 minutes (0 versus 8 cases, P < 0.01) and 60 minutes (0 versus 6 cases, P < 0.05) after delivery but a higher incidence of maternal tachycardia (RR 1.68, 95% CI 1.03-3.57). CONCLUSIONS: IM carbetocin is as effective as IM syntometrine in preventing primary postpartum haemorrhage after vaginal delivery. It is less likely to induce hypertension and has a low incidence of adverse effect. It should be considered as a good alternative to conventional uterotonic agents used in managing the third stage of labour.

Adult↗

PubMed2004

Molecular epidemiology of the novel coronavirus that causes severe acute respiratory syndrome.

BACKGROUND: Severe acute respiratory syndrome (SARS) is a newly emerged disease caused by a novel coronavirus (SARS-CoV), which spread globally in early 2003, affecting over 30 countries. We have used molecular epidemiology to define the patterns of spread of the virus in Hong Kong and beyond. METHODS: The case definition of SARS was based on that recommended by WHO. We genetically sequenced the gene for the S1 unit of the viral spike protein of viruses from patients with SARS in Hong Kong (138) and Guangdong (three) in February to April, 2003. We undertook phylogenetic comparisons with 27 other sequences available from public databases (Genbank). FINDINGS: Most of the Hong Kong viruses (139/142), including those from a large outbreak in an apartment block, clustered closely together with the isolate from a single index case (HKU-33) who came from Guangdong to Hong Kong in late February. Three other isolates were genetically distinct from HKU-33 in Hong Kong during February, but none of these contributed substantially to the subsequent local outbreak. Viruses identified in Guangdong and Beijing were genetically more diverse. INTERPRETATION: The molecular epidemiological evidence suggests that most SARS-CoV from the outbreak in Hong Kong, as well as the viruses from Canada, Vietnam, and Singapore, are genetically closely linked. Three viruses found in Hong Kong in February were phylogenetically distinct from the major cluster, which suggests that several introductions of the virus had occurred, but that only one was associated with the subsequent outbreak in Hong Kong, which in turn spread globally.

Canada↗

PubMed2004

Retained products of gestation in miscarriage: an evaluation of transvaginal ultrasound criteria for diagnosing an "empty uterus".

OBJECTIVE: The purpose of this study was to compare clinical outcomes of conservative management versus surgical evacuation of retained products of gestation after misoprostol treatment for first trimester spontaneous miscarriage using less restrictive transvaginal ultrasound criteria for diagnosing "empty uterus," which were managed conservatively. STUDY DESIGN: This was a prospective, randomized, controlled trial. RESULTS: Forty-six patients who had sonographic features previously regarded as significant retained products of gestation after misoprostol treatment, ie, homogenous intrauterine dimension of more than 11 cm 2 in combined transverse and sagittal plane, or those with heterogeneous intrauterine contents were consented to randomization. The short-term complication rates of those managed conservatively were significantly higher than surgical evacuation ([9/24] 37.5% vs [0/21] 0%, P < .05). CONCLUSION: Our previously reported transvaginal ultrasound criteria of homogenous intrauterine dimension of less than 11 cm 2 in combined transverse and sagittal planes for defining "empty uterus," which requires no further treatment, cannot be "relaxed" without incurring additional complications.

Abortifacient Agents, Nonsteroidal↗

PubMed2004

Case study: a decade of changes in a small environmental engineering graduate program.

For a small graduate program in environmental engineering in a rural state in the US, it is important for the program curriculum to stay in the mainstream. While resident student enrollment is approaching a steady level, international student enrollment increases steadily, this is due in part to the out-of-state tuition waiver provided to the students. Part-time students are a significant part of the program, these students have special needs that are different from traditional full-time students that must be taken into consideration in program planning. A small program provides an attentive atmosphere for students' learning, but it also has problems that a larger program would not encounter, such as competitiveness, personal conflicts, program identity, etc. Despite success in the past, the program is likely to merge with other related programs in the university during times of budget restrictions.

Adult↗

PubMed2001

Functional analysis of the hydrophobic patch on nuclear transport factor 2 involved in interactions with the nuclear pore in vivo.

Nuclear transport factor 2 (NTF2) is a small homodimeric protein that interacts simultaneously with both RanGDP and FxFG nucleoporins. The interaction between NTF2 and Ran is essential for the import of Ran into the nucleus. Here we use mutational analysis to dissect the in vivo role of the interaction between NTF2 and nucleoporins. We identify a series of surface residues that form a hydrophobic patch on NTF2, which when mutated disrupt the NTF2-nucleoporin interaction. Analysis of these mutants in vivo demonstrates that the strength of this interaction can be significantly reduced without affecting cell viability. However, cells cease to be viable if the interaction between NTF2 and nucleoporins is abolished completely, indicating that this interaction is essential for the function of NTF2 in vivo. In addition, we have isolated a dominant negative mutant of NTF2, N77Y, which has increased affinity for nucleoporins. Overexpression of the N77Y protein blocks nuclear protein import and concentrates Ran at the nuclear rim. These data support a mechanism in which NTF2 interacts transiently with FxFG nucleoporins to translocate through the pore and import RanGDP into the nucleus.

Active Transport, Cell Nucleus↗

PubMed2001

Linear accelerator based radiosurgery as a salvage treatment for skull base and intracranial invasion of recurrent nasopharyngeal carcinomas.

Nasopharyngeal carcinoma is a common disease entity in Taiwan. It can spread in the prestyloid, retrostyloid compartments, parapharyngeal space, and skull base, and induce paralysis of cranial nerves. We have treated more than 1,500 cases in the past 14 years. Since 1994, we have treated 11 cases of nasopharyngeal carcinomas with skull base invasion by linear accelerator-based stereotactic radiosurgery. There were six male and five female patients. The mean age was 48.4 years. Seven patients had symptoms of low cranial nerves. For these patients, conformal radiotherapy plus brachytherapy was used for the masses beyond the skull base. Stereotactic radiosurgery with a dose of 10 Gy to 19 Gy for one treatment was used for the masses invading the skull base. Eight patients died in follow-up periods from 5 months to 2 years 7 months. Approximately half of patients revealed good response of tumor to radiosurgery. Two patients demonstrated no response of tumors to radiosurgery. Stereotactic radiosurgery may be an adjuvant treatment for recurrent nasopharyngeal carcinomas with skull base and intracranial invasion.

Adult↗

PubMed2001

Clinical characteristics of outpatients at a psycho-oncology clinic in a radiation oncology department.

BACKGROUND: Psychosocial care in cancer medicine has become increasingly important. The first psychiatric consultation-liaison (C-L) outpatient clinic in Taiwan was established in a department of radiation oncology in a medical center in Oct. 1998. METHODS: From October 1998 through January 2000, 121 patients were referred for psychosocial evaluation. Six referred patients were excluded because of cerebral complications of malignant disease or coincidental psychiatric disorder. The remaining 115 patients were referred because of psychological problems related to their malignant disease. These patients were divided into 'depression related disorder' and 'anxiety related disorder' groups according to psychiatric standard diagnoses. The records of these referred patients were retrospectively analyzed based on the psychiatric diagnoses. RESULTS: The outpatient utilization rate for psychiatric consultation escalated from 0% to 5.92% after the C-L clinic was established. Patients with nasopharynx, breast, and head and neck cancer had higher referral, rates (over 10%) than patients with other types of cancer. There were significant differences in major subjective psychiatric problems and psychological reactions between patients with psychiatric diagnosis and those without psychiatric diagnosis. Cancer patients who were diagnosed with 'depression related disorder' visited this clinic more times than those with 'anxiety related disorder'. The former received antidepressant drugs more frequently than the latter. There were also more multiple visits in the former group than the latter group. CONCLUSION: Locating a C-L clinic in a radiation oncology department improves access to psychiatric evaluation, early detection and continuous intervention can then be offered to cancer patients with anxiety or depression, especially those with 'depression related disorder'.

Adult↗

PubMed2000

Concomitant boost radiation therapy for inoperable non-small-cell lung cancer: preliminary report of a prospective randomized study.

PURPOSE: The radiation therapy results for patients with inoperable non-small-cell lung cancer (NSCLC) have been disappointing. Tumor dose escalation using concomitant boost technique (CBT) has been shown to improve local control in a few prospective studies. This trial was carried out to prospectively assess the radiation response and acute toxicity of CBT in comparison to the conventional treatment technique (CTT). METHODS AND MATERIALS: Ninety-seven consecutive eligible patients were entered in this prospective clinical trial between November 1994 and February 1998. Patients were randomized to receive either CBT (43 patients) or CTT (54 patients) radiation therapy. These patients either refused chemotherapy or were judged as unsuitable for chemotherapy. Patients in the CBT group received 46.8 Gy in 26 fractions using large fields that encompassed the gross and occult disease. A concomitant boost of 18.2 Gy (0.7 Gy per fraction) was delivered to the gross disease using small fields with 1.5-cm margins. The small fields were treated concurrently with the large fields and the total dose to the tumor area was 65 Gy in 26 fractions. Patients in the CTT group received 70.8 Gy in 38 fractions. The acute toxicity between each group was compared. The response rate was analyzed and compared by treatment group, gender, age, stage, histology, initial Karnofsky performance score (KPS), severity of acute toxicity, and maximum body weight loss (MBWL) during treatment course. RESULTS: The demographic parameters such as sex, age, and stage were evenly distributed in each treatment group. The majority of these patients had Stage IIIA and IIIB disease. Overall median treatment times were 39 days for the CBT group of patients and 62 days for the CTT group. No treatment-related mortality was found. There were 2 patients in the CTT group with acute RTOG Grade 3 lung toxicity, and no Grade 3 lung or esophageal toxicity was observed in CBT group. The response rates, assessed by radiographic images, were 69.8% and 48.1% for the CBT and CTT patients, respectively. Univariate and multivariate analysis revealed that patients in the CBT group, patients with better KPS, and patients with more severe acute toxicity had a higher response rate. CONCLUSION: This study demonstrates that concomitant boost radiation therapy is tolerable, and produces a superior response rate than conventional radiation therapy for patients with inoperable NSCLC. The length of treatment was reduced from 38 to 26 treatment days, almost a 30% reduction.

Adult↗

PubMed2000

Oral glutamine to alleviate radiation-induced oral mucositis: a pilot randomized trial.

PURPOSE: To evaluate the influence of oral glutamine on radiation-induced oral mucositis in the radiotherapy of head and neck cancer. METHODS AND MATERIALS: From July 1997 through June 1998, 17 patients with head and neck cancer receiving primary or adjuvant irradiation were randomized to either glutamine suspension (16 g in 240 ml normal saline) (n = 8) or placebo (normal saline) (n = 9) arm. Patients were instructed to swish the test solutions (30 ml) four times per day. All patients received half-mouth irradiation at least. Patients were treated 1.8 Gy per fraction daily, 5 days a week. We evaluated the grading of oral mucositis daily fraction at each day of treatment until 45 Gy/25 fractions. World Health Organization (WHO) step analgesic medication and body weight change were compared between the two arms. RESULTS: The duration of objective oral mucositis > or = Grade 1 (p = 0.0097), Grade 2 (p = 0.0232), and Grade 3 (p = 0.0168) was shorter in the glutamine arm. Mean maximum grade of objective oral mucositis was less severe in the glutamine arm (1.6 vs. 2.6) (p = 0.0058). Glutamine did not reduce the duration and severity of subjective oral mucositis except for duration > or = Grade 3 (p = 0.0386). In the analysis of mean maximum WHO step of analgesic medication, there was no statistical difference (p = 0.5374) between the two arms. Mean body weight change was also not significantly different (p = 0.8070). CONCLUSIONS: Oral glutamine may significantly reduce the duration and severity of objective oral mucositis during radiotherapy. It may shorten the duration of > or = Grade 3 subjective mucositis.

Administration, Oral↗

PubMed2000

Dermatofibrosarcoma protuberans: treatment results of 35 cases.

BACKGROUND AND PURPOSE: This study evaluates the treatment results of patients with dermatofibrosarcoma protuberans. PATIENTS AND METHODS: Between August 1987 and July 1998, 35 consecutive patients with pathologically proved dermatofibrosarcoma protuberans received surgery with or without radiation therapy. Their treatment results were analyzed retrospectively. RESULTS: The patient ages ranged from 5 to 67 years (median 37 years). There were 24 males and 11 females. The anatomic sites of tumor were: trunk in 21, extremity in eight, and head and neck region in six. The maximal dimension of tumor ranged from 1.5 to 25 cm. Surgery techniques included local excision and wide excision with or without graft or flap. Adjuvant radiation therapy was given to 11 patients, with a dose ranging from 46 to 68 Gy (one pre-operative, ten post-operative). At a median follow-up of 50 months (range 11-131 months), there were 11 patients (nine patients without radiation therapy) who developed local failure. Salvage therapy (excision with or without radiation therapy) was given to all of them, and ten achieved disease control. Some patients had treatment-related moderate cosmetic or functional problems. CONCLUSIONS: Dermatofibrosarcoma protuberans is a malignancy of a high cure rate, and adjuvant radiation therapy can reliably decrease the local recurrence rate and prevent mutilation and functional deficit caused by repeated surgery.

Adolescent↗

PubMed2000

Acetylcholine-mediated relaxation in rat thoracic aorta is enhanced following acute exposure to physiological concentrations of 17beta-estradiol.

We investigated the effects of short-term exposure to low concentrations of 17beta-estradiol on vasorelaxation using an in vitro rat thoracic aortic ring preparation. Supraphysiological levels of 17beta-estradiol directly relaxed phenylephrine-contracted rings. Although acute incubation (20 min) with 1-100 nM of the female sex hormone did not have any significant effect on phenylephrine-contracted rings, relaxation evoked by acetylcholine was significantly potentiated. In contrast, calcium ionophore A23187-elicited endothelium-dependent relaxation as well as cromakalim- and sodium nitroprusside-mediated endothelium-independent relaxation was unchanged following the same regime with 17beta-estradiol. These results demonstrate that short-term treatment with physiologically relevant levels of 17beta-estradiol, which on their own have no effect, enhances endothelium-dependent relaxation by acetylcholine. The vascular effects observed herein may partly account for some of the improved acute vasodilatory responses reported with 17beta-estradiol on blood flow in humans.

Acetylcholine↗

PubMed2000

Differential effects of 17beta-estradiol and testosterone on the contractile responses of porcine coronary arteries.

1. We investigated the effects of short-term exposure to physiological levels of 17beta-estradiol and testosterone on vasocontractile responses in porcine coronary artery rings. 2. Concentration-response curves to endothelin-1, 5-hydroxytryptamine, the thromboxane analogue U46619 and KCl were constructed in endothelium-intact and endothelium-disrupted artery rings. 3. Thirty minutes exposure to 17beta-estradiol (1 and 30 nM) significantly attenuated vasoconstriction to endothelin-1, 5-hydroxytryptamine and U46619. Conversely, the same concentrations of testosterone significantly potentiated responses elicited by these contractile agents. These inhibitory effects of 17beta-estradiol and enhancing actions of testosterone on contractions were endothelium-independent. KCl-mediated contractions were unaffected by the presence of either sex hormones. 4. The oestrogen receptor antagonists, tamoxifen (10 microM) and ICI 182,780 (10 microM), were unable to reverse the inhibitory influence 1 nM 17beta-estradiol had on the agonist-mediated contractile responses. Similarly, the androgen receptor antagonists, flutamide (10 microM) and cyproterone acetate (10 microM), failed to affect the potentiating activities of 1 nM testosterone. The alteration in vasoconstrictive responses observed following acute exposure to either 1 nM 17beta-estradiol and 1 nM testosterone were apparent even in the presence of the protein synthesis inhibitor cycloheximide (10 microM) and the transcription inhibitor actinomycin D (10 microM). 6. In conclusion, we report a unique type of sex hormone action on the coronary vasculature. These events occur at low nanomolar concentrations of 17beta-estradiol and testosterone, are insensitive to conventional sex hormone receptor antagonists, are not blocked by de novo protein synthesis inhibitors and have rapid time-courses that are uncharacteristic of classical genomic activities.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed2000

Diagnostic usefulness of telomerase activity in nasopharyngeal carcinoma.

Telomeres are specialized structures at the ends of eukaryotic chromosomes which are composed of simple repetitive G-rich hexameric sequences. Activation of telomerase, a ribonucleoprotein that synthesizes telomeric DNA, is found in most malignant tumors. However, little data is available concerning the correlation between telomerase activity and NPC (nasopharyngeal carcinoma). In this study, telomerase activation was determined using the TRAP (telomerase repeat amplification protocol) assay in 62 nasopharyngeal biopsies (25 NPC, 25 non-malignant nasopharyngeal lymphoid tissues, 12 post-irradiated nasopharyngeal tissues). The results showed that strong telomerase activity was present in both NPC and non-malignant nasopharyngeal biopsies. Post-irradiated nasopharyngeal samples had a significantly lower telomerase activity than NPC and non-malignant nasopharyngeal lymphoid tissues. It is well known that nasopharyngeal tissue is infiltrated by numerous lymphocytes, which might retain telomerase activity. Therefore, the finding that the telomerase activation was lowest in post-irradiated nasopharyngeal tissues is reasonable because of the destruction of activated lymphocytes and NPC by radiation. NPC biopsies with positive lymph node involvement exhibited higher levels of telomerase compared to those without lymph node involvement. Our data indicate a positive association between telomerase activity and tumor potential for lymphatic spreading in limited local tumors. In addition, telomerase activity may be useful as a diagnostic marker in the detection of tumor cells in recurrent NPC, but not in primary NPC.

Adolescent↗

PubMed2000

Conformal radiation therapy for hepatoma with portal vein thrombosis.

A 43-year-old male patient was diagnosed as having hepatocellular carcinoma with portal vein thrombosis and arterioportal shunts. Three-dimensional conformal radiation therapy (3DCRT) with high focal dose was given to the left portal venous area. Shrinkage of the tumour and thrombus, disappearance of the arterioportal shunts and restoration of the hepatopedal flow of the portal vein was noted 3 months after treatment. The patient received further transarterial embolisation and achieved successful tumour control. No serious complications were encountered. 3DCRT is technically feasible and effective to treat a small volume of liver tissue with a high dose of radiation in this advanced disease.

Adult↗

PubMed2000

Cardiac L-type calcium channel alpha 1-subunit is increased by cyclic adenosine monophosphate: messenger RNA and protein expression in intact bone.

L-type calcium channels have been identified previously in both osteoblast-like osteosarcoma cell lines and primary cultures of osteoblasts using numerous techniques such as patch clamp recording, drug inhibited 45Ca2+ uptake, and Fura-2 measurements, but intact bone has not been investigated. Using reverse-transcription polymerase chain reaction (RT-PCR) we found that the three major isoforms of the alpha 1-subunit of L-type calcium channels, (alpha 1C, alpha 1D, and alpha 1S) are present in RNA extracted from ROS 17/2.8 osteosarcoma cells, rat femur, and rat skull. Sequencing of most of the alpha 1C-subunit from rat femur and ROS cells revealed that the splice variants in osteosarcoma cells and intact bone differ, but there are no unique sequence variations compared with those found in other tissues. Northern blot analysis of ROS cell RNA indicated that cyclic adenosine monophosphate (cAMP), but not 1 alpha, 25-dihydroxyvitamin D3, increased the messenger RNA (mRNA) of the alpha 1C-subunit. Western blot of ROS cell lysates revealed a band of more then 220 kDa, the amount of which increased in cells treated with cAMP. Using confocal microscopy combined with immunohistochemistry in ROS cells, intact bone, and cartilage, we found that the alpha 1C-subunit of this channel is expressed in osteoblasts and chondrocytes suggesting this channel may be a pathway for signal transduction in intact tissue, because it is in osteosarcoma cell lines and primary osteoblasts grown in tissue culture.

Animals↗

PubMed1999

Computed tomography findings of bony regeneration after radiotherapy for nasopharyngeal carcinoma with skull base destruction: implications for local control.

PURPOSE: To evaluate the response of bony destruction (BD) of the skull base following radiotherapy in nasopharyngeal carcinoma (NPC) and investigate the implications of bony regeneration (BR) on local control and its related factors. METHODS AND MATERIALS: Ninety patients with NPC with skull base destruction clearly demonstrated on computed tomography (CT) were reviewed. These patients have completed the prescribed treatment and received regular CT follow-up. A total of 338 sets of CT images of the head and neck were reviewed. The tumor response and the appearance of BR in the previous destructive part of the skull base were recorded and analyzed. The tumor response was divided into complete, partial, or no response. BR was defined as recalcification or sclerotic change with partial or complete healing in the previous osteolytic bony defect. Local failure was confirmed either by pathological or merely by imaging studies showing progression of tumor in consecutive radiological pictures. RESULTS: The distribution of specific sites of bony destruction (BD) in these patients included the sphenoid bone (68%), paracavernous sinus area (48%), petrous apex (47%), clivus (44%), pterygoid plates (20%), and others (7%). The CT showed 57 patients (63%) had BR. All were observed within 1 year after treatment. Sixty-two patients (69%) had complete tumor response after treatment. Analyzed by logistic regression method, tumor response after treatment was found to have a statistically significant correlation with BR (p = 0.0004). Most BR (55/57) was demonstrated in patients with complete tumor response. The 3-year actuarial local control rate was 54 % in these patients. The local control was quite different in the comparison of patients with BR versus those with persistent BD (77% vs. 21%, p < 0.0001). Multivariate analysis showed that patients with complete tumor response or with BR on imaging had statistically better local control than those without either of the two findings (p < 0.05). CONCLUSION: Appearance of BR at previous destructive skull base following radiotherapy for NPC patients could be clearly demonstrated on CT. Bony regeneration significantly correlated with treatment response and local control. Although the underlying significance of BR was unknown, to predict the outcome after treatment, the appearance of BR shown on CT may imply the complete eradication of tumor in this area.

Adolescent↗

PubMed1999

Short-term exposure to physiological levels of 17 beta-estradiol enhances endothelium-independent relaxation in porcine coronary artery.

OBJECTIVES: While alterations in cholesterol and lipoprotein profiles partly account for menopause being a risk factor for coronary heart disease, recent studies have suggested that 17 beta-estradiol may have vascular effects. Our aims were to study the short-term effects of 17 beta-estradiol on vascular function in isolated porcine coronary artery rings. Concomitantly, we sought to determine if physiological concentrations of 17 beta-estradiol could acutely potentiate relaxation RESULTS: 17 alpha- and 17 beta-estradiol at pharmacological (> 1 microM) concentrations produced relaxation in U46619-pre-contracted porcine coronary artery rings. Relaxation evoked by 17 beta-estradiol was not reversed by the estrogen receptor antagonists tamoxifen and ICI 182780. Following 20 min exposure to a physiological concentration of 17 beta-estradiol (1 nM), which on its own had no effect, relaxation elicited by cromakalim, levcromakalim and sodium nitroprusside, but not bradykinin or calcium ionophore A23187, were significantly enhanced. This potentiating action was also insensitive to tamoxifen and ICI 182780. Our data provide evidence for an acute indirect relaxant action of 17 beta-estradiol and suggest that it may be via a tamoxifen- and ICI 182780-insensitive estrogen receptor. While this response was only observed at pharmacological concentrations, the potentiation of cromakalim, levcromakalim and sodium nitroprusside relaxation was evident in the presence of a physiological concentration (1 nM) of 17 beta-estradiol. CONCLUSIONS: These results demonstrate that short-term exposure to 17 beta-estradiol, at concentrations that have no effect on their own, can enhance vasorelaxation. These vascular effects may partly account for some of the acute effects of 17 beta-estradiol on blood flow.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗