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Biomedical subjects

J E Buster

Publications and source records attributed to J E Buster.

At least 55 records · Page 3Linked to original sources

Improved sensitivity and specificity of a single measurement of serum progesterone over serial quantitative beta-human chorionic gonadotrophin in screening for ectopic pregnancy.

The sensitivity and specificity of a single serum progesterone measurement was compared against two beta-human chorionic gonadotrophin (HCG) measurements 48 h apart in screening for abnormal pregnancy, i.e. ectopic pregnancy, completed or incomplete abortion. Of 1120 patients in the first trimester presenting with a positive urinary pregnancy test, 116/1120 (10.4%) had an ectopic pregnancy, 755/1120 (67.4%) had ultrasonographically confirmed intra-uterine pregnancies, and 249/1120 (22.2%) had abnormal intra-uterine pregnancies documented as complete, incomplete or missed abortions. Of the ectopic pregnancies, 113/116 (97.4%) had a serum progesterone level less than 25 ng/ml while 516/755 (68.3%) viable intra-uterine pregnancies had a serum progesterone level greater than or equal to ng/ml. Of the 1120 patients screened, 402 (35.9%) had both a serum progesterone and two HCG measurements and were eligible for inclusion in this study. Setting a cut-off of 25 ng/ml, the sensitivity and specificity of a single serum progesterone measurement was then compared against two serial HCG measurements, utilizing receiver operating characteristic curves. This analysis demonstrated that a single serum progesterone measurement was significantly more sensitive (P less than 0.05) than two HCG measurements in screening for an abnormal pregnancy. In some patients, a single serum progesterone makes possible the diagnosis of ectopic pregnancy 2 days earlier than two HCG determinations because a second blood sample was not required. We conclude that a single serum progesterone measurement should be added to serial HCG determinations as a standard diagnostic screening test for ectopic pregnancy.

Chorionic Gonadotropin↗

Postmenopausal steroid replacement with micronized dehydroepiandrosterone: preliminary oral bioavailability and dose proportionality studies.

OBJECTIVES: Because dehydroepiandrosterone may protect against neoplasia, osteoporosis, and cardiac disease, we investigated the bioavailability of oral micronized dehydroepiandrosterone, anticipating its adjunctive use in postmenopausal steroid replacement. STUDY DESIGN: Eight postmenopausal women randomly received either a placebo or 150 or 300 mg of oral micronized dehydroepiandrosterone in a lipid matrix. Serum dehydroepiandrosterone, dehydroepiandrosterone sulfate, testosterone, and estradiol were measured periodically over the 12 hours after each dose. All treatments, all doses, and mean serum dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone were compared with analysis of variance for repeated measures and Newman-Keuls a posteriori test of statistical significance. RESULTS: Mean peak steroid concentrations after 150 mg (300 mg) doses were dehydroepiandrosterone 1617 (2639) ng/dl, 7 (11.5)-fold above placebo; dehydroepiandrosterone S 1185 (1688) micrograms/dl, 14 (20)-fold above placebo; and testosterone 183 (311) ng/dl, 4 (7)-fold above placebo. Estradiol concentrations remained less than 20 pg/ml, but androgen concentrations rose by 1 hour and remained elevated through the twelfth hour. Peak androgen concentrations and areas under the curves exhibited proportionality with both doses. A testosterone radioimmunoassay with celite chromatography revealed a 300% overestimation for testosterone in the direct-assay method used in this study. Thus after appropriate readjustment maximum testosterone concentrations were observed consistently within physiologic premenopausal ranges after the 150 mg dose. CONCLUSIONS: Micronized dehydroepiandrosterone may provide a steroidal postmenopausal replacement that is adjunctive to estrogens and worthy of further investigation.

Administration, Oral↗

Superovulation fails to increase human blastocyst yield after uterine lavage.

Uterine lavage affords the potential for non-invasive human blastocyst recovery, with obvious potential for preimplantation genetic diagnosis. In an effort to duplicate in women the multiple blastocyst recovery per cycle that can be achieved in several other species, we initiated a programme in which fertile women underwent superovulation, followed by lavage and embryo collection. We superovulated 15 fertile women, aged 21-40, in 29 cycles using one of four regimens. Insemination was by either intercourse or artificial intracervical donor insemination with cryopreserved sperm from men of proven fertility. In 28 of 29 cycles, the uterus was lavaged daily for 1, 2, or 3 days between 5 and 10 days after human chorionic gonadotropin (hCG) administration or luteinizing hormone (LH) surge. Almost total fluid volume was recovered in every lavage. There were no retained pregnancies and no complications. Surprisingly, only two morulae, one blastocyst, and four unfertilized ova were recovered. Thus, alterations in ovulation induction, insemination timing, or lavage techniques must be contemplated in order to increase the blastocyst yield and thus fulfil the potential of uterine lavage for preimplantation diagnosis.

Adult↗

Low human chorionic somatomammotropin fails to predict spontaneous resolution of unruptured ectopic pregnancies.

Early diagnosis of EP allows conservative medical and surgical therapy but also commits a proportion of patients whose EP would spontaneously resolve to therapeutic intervention. This prospective study examined the feasibility of not treating those EPs whose hCS level was low. However, three of eight subjects with EP required therapy. Thus, a single hCS alone cannot be used to identify which EPs required no therapy.

Abortion, Spontaneous↗

Feasibility of semen collection and cryopreservation during chemotherapy.

Collection and cryopreservation of semen was undertaken in a 40-year-old man undergoing combination cyclophosphamide-doxorubicin-vincristine-prednisone chemotherapy for diffuse large cell lymphoma. Semen samples worthy of cryopreservation could be obtained through 39 days of therapy, with azoospermia observed after 70 days. Although pregnancy has not been attempted in the current case, reports by others suggest that normal outcomes can be expected with thawed semen collected during chemotherapy.

Adult↗

Suppression of circulating delta 4-androstenedione and dehydroepiandrosterone sulfate during oral glucose tolerance test in normal females.

Extending a series of previous investigations on the regulatory interaction of insulin and androgens, this study tests the hypothesis that the physiological insulinemia after oral glucose suppresses circulating dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEA-S), and androstenedione (delta 4A) delta 4 in normal women. Accordingly, seven normal weight, ovulatory women were randomized to receive first either a 75 g glucose dose or a sham control for diurnal rhythm consisting of distilled water at 1700 h. After this insulin stimulus, DHEA-S suppressed below sham control at 90 and 120 min (P less than 0.05) whereas delta 4A suppress at 60, 90, and 120 min (P less than 0.05). Furthermore, as serum insulin increased after glucose, DHEA-S (r2 = 0.351, P less than 0.05) and delta 4A (r2 = 0.314, P less than 0.05) decreased in an inverse linear relationship with insulin. There was no significant suppression below sham at any point in time for DHEA, testosterone, or cortisol. Thus, the endogenous serum insulin response after oral glucose in normal women is associated with suppression of serum DHEA-S and delta 4A with absence of testosterone and cortisol suppression.

Administration, Oral↗

Methotrexate treatment of unruptured ectopic pregnancy: a report of 100 cases.

In an ongoing clinical trial, 100 patients with an unruptured ectopic pregnancy of 3.5 cm or less in greatest dimension were treated with an outpatient protocol of methotrexate and citrovorum factor chemotherapy. Methotrexate and citrovorum were given on alternating days until the hCG titer had decreased by 15% on 2 consecutive days. The patients ranged in age from 16-40 years, gravidity from 1-8, and parity from 0-5. Twenty-three patients had a previous ectopic pregnancy. Of the 100 patients, 96 (96%) received methotrexate/citrovorum as primary therapy and four (4%) were treated for persistent hCG titers after a conservative surgical procedure. The tubal pregnancies of patient nos. 1-50 were confirmed by laparoscopy, whereas patient nos. 51-100 were diagnosed according to a nonlaparoscopic algorithm. Four patients of 100 failed medical therapy and required surgery. Of these, one had an ectopic pregnancy with cardiac activity, one ruptured after intercourse, and the remaining two cases had no specific identifiable risk factors. Of the ectopic pregnancies with cardiac activity, 80% were successfully treated. Five patients (5%) had methotrexate-related side effects, all after the fourth dose, but none required treatment for these side effects. Hysterosalpingograms done on 58 patients subsequently demonstrated tubal patency in 84.5% on the involved side. To date, 37 pregnancies have occurred in this group, of which 31 (89.2%) were intrauterine and four (10.8%) were recurrent ectopic pregnancies. We conclude that methotrexate/citrovorum is safe, effective, and helps to preserve reproductive performance when used as primary therapy for unruptured ectopic pregnancy and for treatment of persistent disease following a conservative surgical procedure.

Adolescent↗

Reproductive performance after methotrexate treatment of ectopic pregnancy.

The purpose of this study was to examine return of reproductive potential, hysterosalpingographic findings, and time to conception in patients treated with methotrexate and citrovorum factor for unruptured ectopic pregnancy. Fifty-seven patients with unruptured ectopic pregnancies less than 3.0 cm in greatest dimension were treated with methotrexate and citrovorum factor. The mean time from resolution of the ectopic pregnancy to return of menses was 26.0 (0 to 157) days. Forty-four patients were available for follow-up (2 to 15 months). Nineteen of 23 patients who had hysterosalpingograms demonstrated patency in the ipsilateral tube. Fourteen patients desired pregnancy; 11 of 14 (78.6%) were successful, with 10 of 11 (90.9%) having an intrauterine pregnancy, whereas one of 14 (9.1%) were extrauterine gestations. The mean time from first attempt to achieving pregnancy was 2.3 (1 to 4) months. We conclude that methotrexate and citrovorum factor treatment of unruptured ectopic pregnancy is associated with subsequent tubal patency and does not impair return of menses. Most importantly, the pregnancy rates after this form of therapy appear to be better than those achieved by traditional surgical methods, and are comparable to results after laparoscopic salpingostomy.

Adolescent↗

Differential modulation of ACTH-stimulated cortisol and androstenedione secretion by insulin.

Results of previous clinical studies suggested counter regulatory actions between insulin and DHEA(S). The present studies were performed using primary monolayer cultures of bovine fasciculata-reticularis cells to test the hypothesis that insulin directly affects adrenal androgen secretion. Although having no independent effect, insulin exhibited complex time- and concentration-specific actions on ACTH-stimulated secretion of both C21 (cortisol) and C19 (androstenedione) corticosteroids. In the presence of low concentrations (0.05-0.1 nM) of ACTH, cortisol secretion during a 2 h incubation was about 2-fold greater in the presence than in the absence of insulin (0.01-100 ng/ml). In the presence of a maximal concentration (10 nM) of ACTH, on the other hand, cortisol secretion was not affected by insulin at concentrations less than or equal to 0.1 ng/ml, but was decreased at higher insulin concentrations. ACTH-stimulated androstenedione secretion was not significantly affected by insulin during a short-term (2 h) incubation. During a prolonged (24 h) incubation, insulin produced a concentration-dependent inhibition of ACTH-stimulated cortisol secretion. At an insulin concentration of 100 ng/ml, ACTH (10 nM)-stimulated cortisol secretion declined to a level only 30% of that produced by ACTH alone. In contrast, insulin exhibited biphasic effects on the secretion of androstenedione by cells maintained in the presence of ACTH for 24 h; an effect that was most dramatic in the presence of a maximal concentration of ACTH. At an insulin concentration of 0.1 ng/ml, androstenedione secretion by cells maintained in the presence of 10 nM ACTH was increased approximately 2.5-fold. At higher concentrations of insulin, ACTH-stimulated androstenedione secretion was inhibited to an extent comparable to that in cortisol secretion. The effects of insulin on ACTH-stimulated cortisol and androstenedione secretion could not be accounted for by changes in steroid degradation or a loss in 11 beta-hydroxylase activity. These results indicate that insulin interacts with ACTH to modulate the secretion of both C21 and C19 corticosteroids and that physiological concentrations (less than or equal to 1 ng/ml) of insulin may have a long-term effect to enhance selectively adrenal androgen secretion. These data are consistent with a servo mechanism between insulin and DHEA(S) in vivo and indicate that the correlations observed clinically result, at least in part, from a direct action of insulin to modulate the rate of adrenal androgen production.

Adrenal Glands↗

Nonsurgical diagnosis and treatment of tubal pregnancy.

These data suggest that EP can be diagnosed and safely treated medically with MTX using the scheme outlined with no laparoscopy. Laparoscopic removal can be reserved for those patients with large unruptured EP (greater than 3.0 cm; cardiac activity) or the individual who requires laparoscopy for diagnosis.

Clinical Protocols↗

Emergency department diagnosis of ectopic pregnancy.

STUDY OBJECTIVES: To assess the accuracy of the history and physical examination as compared to the addition of serum progesterone screening for ectopic pregnancy in women presenting to the emergency department. DESIGN: Prospective, consecutive case series, N = 2,157. SETTING: ED of the Regional Medical Center at Memphis, a publicly subsidized, 450-bed acute care hospital staffed by residents and faculty of the University of Tennessee, Memphis. TYPE OF PARTICIPANTS: All ED patients with a positive urine pregnancy test treated between January 1 and December 31, 1988. INTERVENTIONS: Screening history, physical examination, and serum progesterone (P) and quantitative human chorionic gonadotropin (hCG) titer. MEASUREMENTS: All discharged patients were given follow-up appointments within two weeks; those found to have a P less than 25 ng/mL were called to return for repeat hCG and transvaginal ultrasound. MAIN RESULTS: One hundred sixty-one of 2,157 patients (7.5%) with a positive urine pregnancy test were found to have an ectopic pregnancy. All but five had a P of less than 25 ng/mL (sensitivity, 97%); four of these were admitted for immediate surgery because of symptoms. Overall, the ED physician detected 89 of 161 ectopics (55.3%) on initial presentation, 53 (60%) of which were ruptured at the time of surgery. Seventy-two patients (44.7%) who were discharged but later found to have an ectopic pregnancy had benign clinical presentations, including 41 with vaginal bleeding. There were no statistically significant differences in the presenting symptoms of patients with unruptured ectopics compared with normal intrauterine pregnancies. All but one of the 72 discharged patients were noted the following day to have a progesterone of less than 25 ng/mL and contacted to return. Eight of these were found to have a ruptured ectopic at the time of surgery. Only 91 of 161 patients (56.5%) with ectopic pregnancy acknowledged one or more clinical risk factors on follow-up questioning. CONCLUSION: The standard history and physical examination, including those performed by gynecologic specialists, are insufficiently sensitive for early detection of unruptured ectopic pregnancy. EDs with a high incidence of ectopic pregnancy should strongly consider implementation of a universal progesterone screening program to decrease unnecessary patient morbidity and the risk of mortality from undiagnosed ectopic pregnancy.

Chorionic Gonadotropin↗

Genetic diagnosis of the preimplantation embryo.

Genetic diagnosis and therapy is well established in the antenatal period. The advancement of uterine and in vitro fertilization allow access to the early blastocyst. Simultaneously, laboratory techniques are being miniaturized to be sufficiently sensitive and specific for diagnosis with only a few cells. Thus genetic diagnosis and therapy may be extended from the antenatal patient to the antegravid patient. This article discusses the techniques of uterine lavage and in vitro fertilization as well as the diagnostic possibilities that this early embryonic period offers.

Blastomeres↗

Preventing ruptured ectopic pregnancy with a single serum progesterone.

Retrospective data on patients with documented ectopic pregnancies have demonstrated the potential usefulness of serum progesterone in decreasing the time to diagnosis. We report a prospective trial utilizing serum progesterone in the emergency department of a large city-county hospital. Sixty-seven ectopic pregnancies were document in the 582 patients screened; 54 (80.6%) had a progesterone level less than 15 ng/ml. Only one (1.5%) ruptured ectopic pregnancy was associated with a progesterone level greater than 25 ng/ml. There were 387 documented or presumed normal intrauterine pregnancies, 41 (10.6%) had progesterone concentrations of less than 15 ng/ml and 236 (61%) had a progesterone level greater than 25 ng/ml. We decreased minimum time of diagnosis from 48 to 72 hours to less than 24 hours by use of a progesterone screening protocol. During this time the percentage of ruptured ectopic pregnancies decreased from 79.2% to 38.8% (p less than 0.05). Because of its simple interpretation and 24-hour maximum delay, we conclude that the determination of serum progesterone should be used for ectopic pregnancy screening in all patients at risk for ectopic pregnancy, or at any time when the diagnosis is in question.

Algorithms↗

Failure to demonstrate significant antisperm antibodies in peritoneal fluid of patients with endometriosis.

Endometriosis, even in mild cases, decreases monthly fecundity. Immunologic disorders have been suggested as the mechanism. In light of possible increases in serum autoimmune antibodies, increased peritoneal macrophages, and increased sperm phagocytosis associated with this disease, we postulated that peritoneal fluid antisperm antibodies would be increased and might be the cause of increased sperm phagocytosis and its associated infertility. Peritoneal fluid, from 18 patients with endometriosis and 10 infertile controls, was tested with the antisperm antibody immunobead test validated for peritoneal fluid. One of 18 patients with endometriosis and none of 10 controls had antisperm antibodies present. Therefore, increased sperm phagocytosis is unlikely a result of peritoneal antisperm antibodies in endometriosis patients.

Antibodies↗

Rising human chorionic somatomammotropin predicts ectopic pregnancy rupture following methotrexate chemotherapy.

In the medical management of ectopic pregnancy, human chorionic somatomammotropin (hCS) proved to be a more sensitive indicator of continued trophoblastic activity than either beta-human chorionic gonadotropin (beta-hCG) or progesterone (P). In the authors' series of 21 women treated with methotrexate for ectopic pregnancies, only two ruptured. In both cases, hCS levels continued to rise during and after methotrexate treatment. Concomitantly, beta-hCG and P decreased in both of these patients. The authors thus interpret increasing hCS as a reflection of continued syncytiotrophoblast growth, signalling impending rupture. Furthermore, patients with levels of hCS less than 10 ng/ml may require neither medical nor surgical therapy.

Chorionic Gonadotropin↗

Predictive value of a single serum pregnancy associated plasma protein-A or progesterone in the diagnosis of abnormal pregnancy.

The value of a single measurement of serum levels of pregnancy associated plasma protein-A (PAPP-A) or progesterone (P4) in predicting abnormal gestations was assessed in 65 patients. P4 was greater than 20 ng/ml (mean +/- SEM 61.2 +/- 6.6 ng/ml, range 22.4-100.0 ng/ml) in all patients with normal intrauterine pregnancies (n = 21), and greater than 20 ng/ml (mean +/- SEM 8.5 +/- 3.9 ng/ml, range 0.1-68.8 ng/ml) in 16 out of 17 patients destined to abort spontaneously. Patients with ectopic gestations (n = 27) exhibited P4 values less than 20 ng/ml (mean +/- SEM 6.4 +/- 1.2 ng/ml, range 0.1-17.2 ng/ml). P4 levels in normal pregnancies were significantly higher (P = 0.001) than those of abnormal gestations. PAPP-A levels ranged from undetectable to 6448 mIU/ml in normal gestations. In 42 out of 44 abnormal pregnancies levels of PAPP-A were less than 100 mIU/ml, as were 7 out of 14 normal intrauterine pregnancies of less than 7 weeks gestational age. No ectopic demonstrated a value of PAPP-A greater than 50 mIU/ml and in 23 out of 27 ectopics, levels were undetectable. However, PAPP-A was less specific than P4 in correctly discriminating normal from abnormal gestations and exhibited lower positive and negative predictive values. It can be concluded therefore that a single PAPP-A measurement is of limited value in discerning normal from abnormal pregnancy prior to 8 weeks gestation. However, a single serum P4 is highly accurate and specific in detecting abnormal pregnancy, regardless of gestational age.

Female↗

Outpatient chemotherapy of unruptured ectopic pregnancy.

This report describes an individualized, reduced dose, methotrexate (MTX) and citrovorum factor (CF) treatment regimen for outpatient management of unruptured ectopic pregnancy (EP). One hundred sixteen laparoscopically documented EPs, the majority (90%) of whom were symptomatic, were diagnosed from an Emergency Department population. Eighty of 116 (69%) were unruptured, 37 (46.3%) of whom were eligible for MTX-CF chemotherapy. One patient refused chemotherapy. Thirty-four of the 36 (94.4%) patients treated with MTX-CF had complete resolution of their ectopics, whereas 2 experienced rupture after chemotherapy, 1 of them 23 days after MTX initiation. While there were no major chemotherapy-related side effects, 3 of the 36 (8.3%) patients experienced minor side effects. The authors conclude that: (1) individualized dosing of outpatient MTX-CF chemotherapy for symptomatic EP can be safely managed, even in an indigent population; (2) rupture can occur up to 23 days after chemotherapy initiation; (3) fetal cardiac activity is an absolute contraindication to chemotherapy; (4) chemotherapy in patients with symptoms is of limited value because the disease is too far advanced; therefore, it is essential that the diagnosis of EP be established before symptom onset; and (5) chemotherapy offers no significant immediate advantages to outpatient laparoscopic surgery. However, increasingly reliable nonlaparoscopic diagnosis will soon give wider application to this approach.

Adult↗