Biomedical subjects

B Greer

Publications and source records attributed to B Greer.

At least 19 recordsLinked to original sources

PubMed2006

The effect of age on clinical/pathologic features, surgical morbidity, and outcome in patients with endometrial cancer.

OBJECTIVE: To evaluate the effect of age on clinical/pathologic features, surgical morbidity, and outcome in patients with endometrial cancer. METHODS: All women with surgically treated endometrial cancer at the University of Washington in Seattle, Washington between January 1990 and January 2000 were eligible; 396 patients underwent retrospective chart review. Statistical analysis was performed by SPSS. Median follow-up time was 33 months (range, 1 to 120 months). RESULTS: Age was < 45 years in 15% of patients, between 46 and 64 years in 47% of patients, and > 65 years in 38% of patients. Younger patients were statistically more obese than older patients (Body Mass Index of 40.3 kg/m2 vs. 35.3 kg/m2 vs. 31.0 kg/m2, P < 0.001). Intraoperatively, there were no differences between the three groups in the percentage of patients with lymph node sampling, operative time, blood loss, or complications. Postoperatively, older patients had more wound infections (P = 0.002), more cardiac events (P = 0.001), and more episodes of ileus (P = 0.025). Evaluation of pathology revealed that patients < 45 years old were statistically more likely to have endometrioid histology, grade I tumors, and stage IA disease. Women over age 65 were significantly more likely to have papillary serous histology, grade 3 tumors, and stage IC as compared to the younger patients. A subset analysis of patients > 75 years of age showed an increase in the percentage of patients with papillary serous histology (22% vs. 3%, P = 0.055), grade 3 disease (42% vs. 16%, P < 0.001), and stage IC disease (21% vs. 3%, P = 0.001) when compared to patients < 45 years old. Evaluation of endometrioid tumors only revealed a similar pattern of deeper myometrial invasion and higher tumor grade as age increased. CONCLUSIONS: Younger patients with endometrial cancer are generally more obese, with lower grade, lower stage disease, and with more favorable histologic cell types. Despite this, approximately a quarter have stage II-IV disease and 9% have positive lymph nodes. The older patients represent a dramatically different subset of patients. They are more likely to have aggressive papillary serous histology, higher grade tumors, and advanced stage disease. Age should be a consideration in appropriate referrals to gynecologic oncologists.

Adult↗

PubMed2006

Effects of sub-chronic exposure to naturally occurring N-terminally truncated metabolites of glucose-dependent insulinotrophic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), GIP(3-42) and GLP-1(9-36)amide, on insulin secretion and glucose homeostasis in ob/ob mice.

Glucose-dependent insulinotrophic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are important enteroendocrine hormones that are rapidly degraded by an ubiquitous enzyme dipeptidyl peptidase IV to yield truncated metabolites GIP(3-42) and GLP-1(9-36)amide. In this study, we investigated the effects of sub-chronic exposure to these major circulating forms of GIP and GLP-1 on blood glucose control and endocrine pancreatic function in obese diabetic (ob/ob) mice. A once daily injection of either peptide for 14 days had no effect on body weight, food intake or pancreatic insulin content or islet morphology. GLP-1(9-36)amide also had no effect on plasma glucose homeostasis or insulin secretion. Mice receiving GIP(3-42) exhibited small but significant improvements in non-fasting plasma glucose, glucose tolerance and glycaemic response to feeding. Accordingly, plasma insulin responses were unchanged suggesting that the observed enhancement of insulin sensitivity was responsible for the improvement in glycaemic control. These data indicate that sub-chronic exposure to GIP and GLP-1 metabolites does not result in physiological impairment of insulin secretion or blood glucose control. GIP(3-42) might exert an overall beneficial effect by improving insulin sensitivity through extrapancreatic action.

Animals↗

PubMed2004

Comparative effects of GLP-1 and GIP on cAMP production, insulin secretion, and in vivo antidiabetic actions following substitution of Ala8/Ala2 with 2-aminobutyric acid.

The two major incretin hormones, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP), are currently being considered as prospective drug candidates for treatment of type 2 diabetes. Interest in these gut hormones was initially spurred by their potent insulinotropic activities, but a number of other antihyperglycaemic actions are now established. One of the foremost barriers in progressing GLP-1 and GIP to the clinic concerns their rapid degradation and inactivation by the ubiquitous enzyme, dipeptidyl peptidase IV (DPP IV). Here, we compare the DPP IV resistance and biological properties of Abu8/Abu2 (2-aminobutyric acid) substituted analogues of GLP-1 and GIP engineered to impart DPP IV resistance. Whereas (Abu8)GLP-1 was completely stable to human plasma (half-life >12 h), GLP-1, GIP, and (Abu2)GIP were rapidly degraded (half-lives: 6.2, 6.0, and 7.1 h, respectively). Native GIP, GLP-1, and particularly (Abu8)GLP-1 elicited significant adenylate cyclase and insulinotropic activity, while (Abu2)GIP was less effective. Similarly, in obese diabetic (ob/ob) mice, GIP, GLP-1, and (Abu8)GLP-1 displayed substantial glucose-lowering and insulin-releasing activities, whereas (Abu2)GIP was only weakly active. These studies illustrate divergent effects of penultimate amino acid Ala8/Ala2 substitution with Abu on the biological properties of GLP-1 and GIP, suggesting that (Abu8)GLP-1 represents a potential candidate for future therapeutic development.

Adenylyl Cyclases↗

PubMed2004

Lys9 for Glu9 substitution in glucagon-like peptide-1(7-36)amide confers dipeptidylpeptidase IV resistance with cellular and metabolic actions similar to those of established antagonists glucagon-like peptide-1(9-36)amide and exendin (9-39).

The incretin hormone glucagon-like peptide-1(7-36)amide (GLP-1) has been deemed of considerable importance in the regulation of blood glucose. Its effects, mediated through the regulation of insulin, glucagon, and somatostatin, are glucose-dependent and contribute to the tight control of glucose levels. Much enthusiasm has been assigned to a possible role of GLP-1 in the treatment of type 2 diabetes. GLP-1's action unfortunately is limited through enzymatic inactivation caused by dipeptidylpeptidase IV (DPP IV). It is now well established that modifying GLP-1 at the N-terminal amino acids, His(7) and Ala(8), can greatly improve resistance to this enzyme. Little research has assessed what effect Glu(9)-substitution has on GLP-1 activity and its degradation by DPP IV. Here, we report that the replacement of Glu(9) of GLP-1 with Lys dramatically increased resistance to DPP IV. This analogue, (Lys(9))GLP-1, exhibited a preserved GLP-1 receptor affinity, but the usual stimulatory effects of GLP-1 were completely eliminated, a trait duplicated by the other established GLP-1-antagonists, exendin (9-39) and GLP-1(9-36)amide. We investigated the in vivo antagonistic actions of (Lys(9))GLP-1 in comparison with GLP-1(9-36)amide and exendin (9-39) and revealed that this novel analogue may serve as a functional antagonist of the GLP-1 receptor.

Adenylyl Cyclases↗

PubMed2004

N-terminal His(7)-modification of glucagon-like peptide-1(7-36) amide generates dipeptidyl peptidase IV-stable analogues with potent antihyperglycaemic activity.

Glucagon-like peptide-1(7-36)amide (GLP-1) possesses several unique and beneficial effects for the potential treatment of type 2 diabetes. However, the rapid inactivation of GLP-1 by dipeptidyl peptidase IV (DPP IV) results in a short half-life in vivo (less than 2 min) hindering therapeutic development. In the present study, a novel His(7)-modified analogue of GLP-1, N-pyroglutamyl-GLP-1, as well as N-acetyl-GLP-1 were synthesised and tested for DPP IV stability and biological activity. Incubation of GLP-1 with either DPP IV or human plasma resulted in rapid degradation of native GLP-1 to GLP-1(9-36)amide, while N-acetyl-GLP-1 and N-pyroglutamyl-GLP-1 were completely resistant to degradation. N-acetyl-GLP-1 and N-pyroglutamyl-GLP-1 bound to the GLP-1 receptor but had reduced affinities (IC(50) values 32.9 and 6.7 nM, respectively) compared with native GLP-1 (IC(50) 0.37 nM). Similarly, both analogues stimulated cAMP production with EC(50) values of 16.3 and 27 nM respectively compared with GLP-1 (EC(50) 4.7 nM). However, N-acetyl-GLP-1 and N-pyroglutamyl-GLP-1 exhibited potent insulinotropic activity in vitro at 5.6 mM glucose (P<0.05 to P<0.001) similar to native GLP-1. Both analogues (25 nM/kg body weight) lowered plasma glucose and increased plasma insulin levels when administered in conjunction with glucose (18 nM/kg body weight) to adult obese diabetic (ob/ob) mice. N-pyroglutamyl-GLP-1 was substantially better at lowering plasma glucose compared with the native peptide, while N-acetyl-GLP-1 was significantly more potent at stimulating insulin secretion. These studies indicate that N-terminal modification of GLP-1 results in DPP IV-resistant and biologically potent forms of GLP-1. The particularly powerful antihyperglycaemic action of N-pyroglutamyl-GLP-1 shows potential for the treatment of type 2 diabetes.

Animals↗

PubMed2003

The effect of body mass index on clinical/pathologic features, surgical morbidity, and outcome in patients with endometrial cancer.

OBJECTIVE: To evaluate the effect of body mass index (BMI) on clinical/pathologic features, surgical morbidity, and outcome in patients with endometrial cancer. METHODS: All women with surgically treated endometrial cancer at the University of Washington in Seattle, Washington, between 1 January 1990 and 1 January 2000 were eligible; 439 patients were identified and 43 were excluded due to incomplete medical records; 396 patients underwent retrospective chart review. Statistical analysis was performed by SPSS. Median follow-up time was 27 months (range, 1 to 120 mo). RESULTS: Mean BMI was 34 (range, 15 to 69). BMI was <30 in 40.7% of patients, 30 to 40 in 32.3%, and >40 in 27.0%. Clinically, patients with a BMI of >40 were more likely to have hypertension, diabetes, and pulmonary disease. Those patients with a BMI of >40 had statistically longer operating times (209 vs. 159 min) and more blood loss (604 vs. 324 ml) than patients with a BMI of <30. However, there was no difference between the three groups in number of lymph nodes removed, units of blood transfused, length of hospital stay, number of intensive care unit (ICU) days, or intraoperative complications. Postoperatively, patients with a BMI of >40 were more likely to have a wound separation than thinner patients. Pathologically, patients with a BMI of >40 were more likely to have endometrioid histology, lower stage disease, and lower grade tumors than women with a BMI of <30. However, 11.3% of patients with lymph node sampling and a BMI of >40 had positive lymph nodes and 23% were stage II or higher. Forty-two patients (10.6%) recurred. There were no postoperative deaths, and there was no difference in survival between the three groups. CONCLUSIONS: Patients with a BMI of >40 frequently have favorable stage I endometrial cancers. However, approximately a quarter of these patients have evidence of cervical or extrauterine disease. This study confirms that surgical staging can be performed adequately and safely in morbidly obese patients with no difference in length of hospital stay, number of ICU days, intraoperative or postoperative complications.

Adult↗

PubMed2003

Novel dipeptidyl peptidase IV resistant analogues of glucagon-like peptide-1(7-36)amide have preserved biological activities in vitro conferring improved glucose-lowering action in vivo.

Although the incretin hormone glucagon-like peptide-1 (GLP-1) is a potent stimulator of insulin release, its rapid degradation in vivo by the enzyme dipeptidyl peptidase IV (DPP IV) greatly limits its potential for treatment of type 2 diabetes. Here, we report two novel Ala(8)-substituted analogues of GLP-1, (Abu(8))GLP-1 and (Val(8))GLP-1 which were completely resistant to inactivation by DPP IV or human plasma. (Abu(8))GLP-1 and (Val(8))GLP-1 exhibited moderate affinities (IC(50): 4.76 and 81.1 nM, respectively) for the human GLP-1 receptor compared with native GLP-1 (IC(50): 0.37 nM). (Abu(8))GLP-1 and (Val(8))GLP-1 dose-dependently stimulated cAMP in insulin-secreting BRIN BD11 cells with reduced potency compared with native GLP-1 (1.5- and 3.5-fold, respectively). Consistent with other mechanisms of action, the analogues showed similar, or in the case of (Val(8))GLP-1 slightly impaired insulin releasing activity in BRIN BD11 cells. Using adult obese (ob/ob) mice, (Abu(8))GLP-1 had similar glucose-lowering potency to native GLP-1 whereas the action of (Val(8))GLP-1 was enhanced by 37%. The in vivo insulin-releasing activities were similar. These data indicate that substitution of Ala(8) in GLP-1 with Abu or Val confers resistance to DPP IV inactivation and that (Val(8))GLP-1 is a particularly potent N-terminally modified GLP-1 analogue of possible use in type 2 diabetes.

Amino Acid Substitution↗

PubMed2001

Identification of the region of non-Abeta component (NAC) of Alzheimer's disease amyloid responsible for its aggregation and toxicity.

The non-beta-amyloid (Abeta) component of Alzheimer's disease amyloid (NAC) and its precursor alpha-synuclein have been linked to amyloidogenesis in several neurodegenerative diseases. NAC and alpha-synuclein both form beta-sheet structures upon ageing, aggregate to form fibrils, and are neurotoxic. We recently established that a peptide comprising residues 3-18 of NAC retains these properties. To pinpoint the exact region responsible we have carried out assays of toxicity and physicochemical properties on smaller fragments of NAC. Toxicity was measured by the ability of fresh and aged peptides to inhibit the reduction of the redox dye 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) by rat pheochromocytoma PC12 cells and human neuroblastoma SHSY-5Y cells. On immediate dissolution, or after ageing, the fragments NAC(8-18) and NAC(8-16) are toxic, whereas NAC(12-18), NAC(9-16) and NAC(8-15) are not. Circular dichroism indicates that none of the peptides displays beta-sheet structure; rather all remain random coil throughout 24 h. However, in acetonitrile, an organic solvent known to induce beta sheet, fragments NAC(8-18) and NAC(8-16) both form beta-sheet structure. Only NAC(8-18) aggregates, as indicated by concentration of peptide remaining in solution after 3 days, and forms fibrils, as determined by electron microscopy. These findings indicate that residues 8-16 of NAC, equivalent to residues 68-76 in alpha-synuclein, comprise the region crucial for toxicity.

Acetonitriles↗

PubMed2000

Adjuvant therapy for high-risk, early stage cervical cancer.

The identification of various pathologic risk factors after primary surgical management of early stage cervical cancer portends a higher rate of relapse and decreased survival. Historical attempts to improve outcome focused mainly on the use of adjuvant pelvic radiation, with limited success overall. Analysis of patterns of failure after radical hysterectomy led to better stratification of patients into risk groups and incorporated testing of systemic agents in those considered at high risk of distant failure. Two recently reported randomized, clinical trials have greatly advanced our understanding of the role of postoperative therapy in cervix cancer. In patients with positive nodes, the use of combined adjuvant chemotherapy and radiation significantly improves relapse-free survival and overall survival, compared with radiation alone. For node-negative patients with other primary tumor risk features, pelvic radiation significantly improves relapse-free survival, compared with no further therapy. An observed improvement in survival for irradiated patients awaits statistical confirmation after maturation of the data. Further improvements in adjuvant therapy for high risk, early stage cervical cancer will come from enhanced definition of prognostic variables, better patient selection, and refinements in both local and systemic therapies.

Combined Modality Therapy↗

PubMed2000

Occupational Exposure in Nuclear Medicine and PET.

Purpose: With the increasing use of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) for scanning in oncology in our center, a radiation dose survey was performed to determine the impact on staff exposure. Conventional nuclear medicine procedures such as gallium scan, bone scans, and sestamibi cardiac scans are used for comparative purposes.Procedure: Patients were measured using a hand-held radiation monitor (Victoreen 450-P) at various distances and times that replicate typical patient contact scenarios in the Diagnostic Imaging Department.Results: We present our findings from the survey and the implications these have on staff radiation exposure. The data suggest that emerging oncologic techniques such as PET, high dose gallium-67, and high dose Tl-201 do not represent a significantly greater occupational radiation hazard than conventional nuclear medicine procedures.

Journal Article↗

PubMed2000

Regulation of adiposity by dietary calcium.

Recent data from this laboratory demonstrate that increasing adipocyte intracellular Ca(2+) results in a coordinated stimulation of lipogenesis and inhibition of lipolysis. We have also noted that increasing dietary calcium of obese patients for 1 year resulted in a 4.9 kg loss of body fat (P<0.01). Accordingly, we tested the possibility that calcitrophic hormones may act on adipocytes to increase Ca(2+) and lipid metabolism by measuring the effects of 1, 25-(OH)(2)-D in primary cultures of human adipocytes, and found significant, sustained increases in intracellular Ca(2+) and a corresponding marked inhibition of lipolysis (EC(50) approximately 50 pM; P<0.001), suggesting that dietary calcium could reduce adipocyte mass by suppressing 1,25-(OH)(2)-D. To test this hypothesis, we placed transgenic mice expressing the agouti gene specifically in adipocytes on a low (0.4%) Ca/high fat/high sucrose diet either unsupplemented or with 25 or 50% of the protein replaced by non-fat dry milk or supplemented to 1.2% Ca with CaCO(3) for 6 wk. Weight gain and fat pad mass were reduced by 26-39% by the three high calcium diets (P<0.001). The high calcium diets exerted a corresponding 51% inhibition of adipocyte fatty acid synthase expression and activity (P<0.002) and stimulation of lipolysis by 3. 4- to 5.2-fold (P<0.015). This concept of calcium modulation of adiposity was further evaluated epidemiologically in the NHANES III data set. After controlling for energy intake, relative risk of being in the highest quartile of body fat was set to 1.00 for the lowest quartile of Ca intake and was reduced to 0.75, 0.40, and 0.16 for the second, third, and fourth quartiles, respectively, of calcium intake for women (n=380;P<0.0009); a similar inverse relationship was also noted in men (n=7114; P<0.0006). Thus, increasing dietary calcium suppresses adipocyte intracellular Ca(2+) and thereby modulates energy metabolism and attenuates obesity risk.

Adipocytes↗

PubMed1998

Uterine papillary serous carcinoma: evaluation of long-term survival in surgically staged patients.

OBJECTIVE: Earlier studies have demonstrated that the uterine papillary serous carcinoma (UPSC) variant of endometrial carcinoma has a high recurrence rate, even when disease is apparently confined to the uterus. The current study evaluated survival in patients with surgically staged UPSC. METHODS: Patients with UPSC were identified from surgical pathology files and charts were retrospectively reviewed. Only patients who had undergone a TAH-BSO, lymph node dissection, and peritoneal cytology were included. RESULTS: The FIGO stages of the 36 patients were 12 Stage I (4 IA, 4 IB, 4 IC), 2 Stage IIB, 13 Stage III (5 IIIA, 8 IIIC), and 9 Stage IV. Of the 14 Stage I/II patients, 6 did not receive adjuvant therapy, 5 received whole pelvic radiation (WPXRT), and 3 received whole abdominal radiation therapy (WART); after a median follow-up interval of 50 months only 2 (14%) of these Stage I/II patients have developed a recurrence. Both of the recurrences were in Stage IC patients who received radiation; 1 recurred in the radiation field. Of the 5 Stage IIIA patients, 3 patients declined therapy and 2 were treated with WART; 3 patients, including the 2 who received radiation therapy, are alive without disease. Of the 8 Stage IIIC patients, 2 declined postoperative therapy, 2 received WART, and 4 received WPXRT with an extended field to include paraaortic nodes. Four of the 6 Stage IIIC patients treated with curative intent are without evidence of disease and 1 died of unrelated causes after a median follow-up interval of 48 months. Both of the Stage IIIC patients who declined treatment recurred. Of the 9 patients with Stage IV disease, 8 have died of disease. CONCLUSION: Women with UPSC have a good prognosis when surgical staging confirms that disease is confined to the uterus (Stage I/II). Surgical findings can also be used to tailor adjuvant radiation treatments. Further study is required to define the optimal treatment for women with metastatic UPSC.

Aged↗

PubMed1997

A retrospective review of paclitaxel-associated gastrointestinal necrosis in patients with epithelial ovarian cancer.

Seven patients with gastrointestinal necrosis following paclitaxel chemotherapy are reported. Four of seven patients had platinum refractory disease, while 3/7 patients received primary paclitaxel therapy. Complications occurred 5 to 16 days following paclitaxel therapy. The most common clinical presentation was fever (7/7 patients), neutropenia (6/7 patients), and abdominal pain (6/7 patients). All seven patients developed gastrointestinal necrosis following the first cycle of paclitaxel chemotherapy. The exact mechanism by which this complication occurs is poorly understood. We postulate that gastrointestinal necrosis may be the result of a direct drug effect on the gastrointestinal epithelium and might involve a synergistic interaction between compromised bowel and paclitaxel-induced mitotic arrest. We observe that the incidence of gastrointestinal necrosis in patients with platinum refractory disease is 4 of 108 patients (3.7%). The incidence of this complication in patients receiving primary paclitaxel at our institution is 3 of approximately 128 patients (2.3%). Eighteen cases to date have been identified in the literature. A high index of suspicion of this complication should be considered for patients presenting with neutropenic fever and abdominal pain following paclitaxel chemotherapy.

Adult↗

PubMed1997

Telomerase activation in cervical cancer.

It has been hypothesized that infection with high-risk human papillomaviruses (HPVs), in conjunction with other cellular events, plays a critical role in the development of cervical cancer. Activation of telomerase, a ribonucleoprotein enzyme complex that synthesizes telomere repeats, has been associated with acquisition of the immortal phenotype in vitro and is commonly observed in human cancers. In this study, we have examined 10 high-grade cervical cancers for telomerase activity and for the presence of HPV. Telomerase activity was detected in all of the cancers but in none of the paired histopathologically normal uterine tissues or in normal cervical epithelium. Analysis of these same tissues for HPV nucleic acids by polymerase chain reaction (PCR) using primers from the HPV L1 and E6 open reading frames demonstrated that 7 of 10 cancers were positive for HPV, 3 for HPV type 16 (HPV-16), and 4 for HPV-18. In one case, HPV-16 was detected in histopathologically normal uterine tissue, the same type as that detected in the cancer from the same patient. HPV DNA was not detected in 3 of 10 cancers. These results indicate that telomerase activation is common in high-grade cervical cancers and suggests that telomerase activity may be a useful diagnostic marker for the disease.

Adenocarcinoma↗

PubMed1995

Dear NICU....

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Home Nursing↗

PubMed1989

Papanicolaou smear screening interval and risk of cervical cancer.

The efficacy of Papanicolaou smear screening intervals of longer than 1 year is uncertain. Ninety-two symptomatic cases of invasive cervical cancer diagnosed between 1978-1983 in western Washington were identified with a population-based tumor registry. Using a random-digit-dialing technique, 178 controls from the same geographic area were selected. A structured telephone interview was used to ascertain screening history and risk factors for cervical cancer. The mean interval between papanicolaou smears in the 10 years preceding diagnosis (cases) or the reference date (controls) was calculated. The risk of squamous cell cervical cancer was increased 3.9 times (95% confidence interval 1.2-12.3) for women with Papanicolaou smears at 3-year intervals compared with women with annual screening. For women who had not had a Papanicolaou smear in the preceding 10 years, this risk increased 12.3 times (95% confidence interval 2.5-60.6). For screening intervals of 2 years, the risk of cervical cancer (all cell types) was not increased (relative risk 1.01; 95% confidence interval 0.43-2.37). The presence of well-known risk factors for cervical cancer did not modify these results. These data suggest an increasing risk of cervical cancer if Papanicolaou smear screening intervals exceed 2 years.

Adult↗

PubMed1983

Dermatofibrosarcoma protuberans of the vulva.

An unusual case of vulvar sarcoma, histologically identified as dermatofibrosarcoma protuberans, is presented together with a summary of current information regarding this lesion.

Female↗

PubMed1979

(15S)-15 methyl prostaglandin F2 alpha levels in amniotic fluid and blood in second trimester abortions.

A single intra-amniotic injection of (15S)-15 methyl prostaglandin F2 alpha (THAM) was used to induce second trimester abortion in five patients. Serial levels of (15S)-15 methyl prostaglandin F2 alpha were subsequently measured in amniotic fluid and plasma by radioimmunoassay. The slow removal of this drug from the amniotic fluid was documented. Plasma levels of (15S)-15 methyl prostaglandin F2 alpha increased fourfold to sevenfold after clinical rupture of the membranes in three patients, supporting the fact that prostaglandins are well absorbed from the vagina. Because this analogue of prostaglandin can cause marked peripheral bronchoconstriction when administered systemically, it is best to avoid its use in patients with a history of asthma.

Abortion, Induced↗