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Is there an ectopic secretion of monomeric calcitonin in the human being?

INTRODUCTION: Persistent detectable calcitonin (CT) values can be frequently observed after treatment of medullary thyroid carcinomas (MTCs). Apart from residual C cells or incomplete tumor extirpation, ectopic CT production should be taken into account. CT determination in patients without MTC and after total thyroidectomy should reveal to what extent, apart from the C cells, other neuroendocrine cells show a relevant CT production. OBJECTIVES: The objective of this study was to find out whether ectopic CT production can be detected using an assay specifically recognizing the monomeric form of CT. METHODS: The CT serum values were obtained from 94 healthy individuals and 64 patients who had undergone total thyroidectomy and radioiodine therapy because of follicular or papillary carcinoma. RESULTS: In the group of thyroidectomized patients, the CT values were below the detection limit of the assay. In the tested patients, there was neither a physiological (C cell) nor a pathological (MTC cell) secretion of monomeric CT. CONCLUSION: A relevant ectopic monomeric CT production could be excluded because the patients were without detectable CT concentration. For this reason, postoperative CT concentrations of the monomeric form in MTC patients can be traced either to remaining C cells or to tumor cells. For a differentiation of these two possibilities further diagnostics is necessary.

Adult↗

Ectopic pregnancy: current clinical trends.

During the 16 year period ending in November, 1978, 191 cases of ectopic pregnancy were managed at the University of Virginia Hospital. The overall incidence was 1/126 deliveries but during the last 3 years of the study the incidence was 1/60 deliveries. Only 56 patients have had a subsequent conception. Thirteen have had a recurrent ectopic implantation. Only 36 women (23.7% of those available for follow-up) have had subsequent term pregnancies. Ectopic pregnancy continues to be a major gynecologic problem and the potential for subsequent fertility is poor.

Adult↗

Conservative treatment of ectopic pregnancy with methotrexate.

Six subjects with distal ampullary ectopic pregnancies were treated with four doses of intravenous methotrexate (1.0 mg/kg) followed by four doses of leucovorin (0.1 mg/kg, intramuscularly). The diagnosis was established in all cases by laparoscopy following sonography and radioimmunoassay for serum beta subunit of human chorionic gonadotropin. Subjects were followed with daily quantitative serum beta-human chorionic gonadotropin radioimmunoassay and sonography. Five of the six subjects experienced resolution of their ectopic pregnancy without additional surgical treatment. One subject underwent salpingectomy following treatment. Morbidity also included three patients with mild stomatitis or gastritis, and two patients had transient elevations of serum transaminase levels. Two patients had protracted courses and received blood transfusions. The most abrupt response and most uncomplicated courses were experienced in the three subjects with initial human chorionic gonadotropin levels below 1000 mIU/ml. This preliminary experience suggests that methotrexate may be an effective alternative for the treatment of early ectopic pregnancy.

Adolescent↗

Serial human chorionic gonadotropin determinations by fluoroimmunoassay for differentiation between intrauterine and ectopic gestation.

A new means for differentiation between ectopic and early intrauterine pregnancy--the human chorionic gonadotropin score--is described. The score relates the rate of serum hCG rise per day to the initial human chorionic gonadotropin level. The positive predictive value for ectopic pregnancy was 94.7%, based on human chorionic gonadotropin scores from 41 women with increasing human chorionic gonadotropin levels in the range of 10 to 4000 IU/L. The method may be useful for identification of ectopic pregnancy in a category of women in whom ultrasonography is of limited diagnostic value.

Chorionic Gonadotropin↗

Laboratory and clinical comparison of a rapid versus a classic progesterone radioimmunoassay for use in determining abnormal and ectopic pregnancies.

A rapid, solid-phase, nonextraction progesterone kit (n = 36) was compared with an established extraction method, liquid phase tritium radioimmunoassay for progesterone (n = 79). Logistic regression of the rapid method over the extraction method gave a correlation coefficient of r = 0.968. Logistic regression gave a discriminatory zone (abnormal vs normal pregnancy) of 22.58 ng/ml by the rapid method compared with 15 ng/ml for the extraction method (log Y = 0.253 + 0.936 log X). Similar sensitivity (100% and 100%), specificity (63% and 59%), and predictive values of positive and negative tests (positive predictive value = 91% and 75%, negative predictive value = 100% and 100%) were found using a discriminatory level of 15 and 20 ng/ml for the extraction method (n = 79) and rapid method (n = 76), respectively. Clinically, curettage for patients with values less than these discriminatory zones would have given unacceptable rates for termination of a potentially normal pregnancy (38%). Clinical comparison of abnormal (ectopic or abortion) and normal (term pregnancy) outcomes in two populations of women presenting with first-trimester bleeding revealed that progesterone levels would accelerate the workup in only a small percentage (27%, 15 of 56) of patients with ectopic pregnancies. The rate of ruptured ectopic pregnancies in the observed patients was similar (20%, 3 of 15) to studies using progesterone levels prospectively. Therefore in this retrospective analysis progesterone levels would have given no greater benefit than conventional management.

Abortion, Spontaneous↗

Management of the ectopic ACTH syndrome due to thoracic carcinoids.

The association of a bronchial or thymic carcinoid as a source for the ectopic production of adrenocorticotropic hormone (ACTH) has been reported since 1957, with approximately 72 cases in the literature. These patients are characterized by young age, long duration of Cushing's syndrome because of the inability to find the ectopic source, and a high incidence of hypophysectomy or adrenalectomy without curing the disease. A substantial number of patients, upon discovery of the thoracic ectopic source, are also found to have malignant carcinoid tumors with lymph node metastases. Fifteen patients have been explored for a presumed intrathoracic source of ACTH at our institution since 1983 and 14 carcinoids (13 bronchial, one thymic) have been resected. Seventy-one percent (10/14) of the patients appear cured with normal plasma ACTH levels 5 to 57 months after resection, despite a 50% incidence of positive lymph node disease. Management of these patients demands an aggressive evaluation to prevent unnecessary adrenalectomy or hypophysectomy and to allow earlier resections before these potentially curable malignancies metastasize. When the tumor is discovered, thorough exploration and complete lymph node mapping with resection must be performed.

ACTH Syndrome, Ectopic↗

Surgical treatment for ectopic atrial tachycardia.

Atrial tachycardia is an infrequent but potentially dangerous arrhythmia which often determines cardiac enlargement. Surgical ablation of the arrhythmia is effective and safe, provided a careful atrial mapping is performed and the surgical technique is tailored to the individual focus location. Eight patients underwent surgical ablation of ectopic atrial tachycardia between 1977 and 1990. Different techniques were adopted for each patient according to the anatomical location of the focus and possibly associated arrhythmias. Whenever possible, a closed heart procedure was chosen. In 1 patient a double focal origin was found and treated by separate procedures. In 1 patient with ostium secundum atrial septal defect and atrial flutter, surgical isolation of the right appendage and the ectopic focus was performed. In all patients ectopic atrial tachycardia was ablated with maintenance of the sinoatrial and atrioventricular nodal function as well as internodal conduction. In follow-up up to December 1991, no recurrency was recorded.

Adolescent↗

Contraception and the risk of ectopic pregnancy: a meta-analysis.

The current knowledge of the association between contraceptive methods and the risk of ectopic pregnancy was evaluated by means of a meta-analysis. Case-control and cohort studies published between 1978 and 1994 in English, French, German and Dutch were retrieved by a search in Medline, a hand-search on recent medical journals and cross-references. Papers reporting on the association between contraceptives and ectopic pregnancy were judged according to predefined entrance criteria concerning selection of control groups, and retractability of raw data enabling the calculation of crude odds ratios. Common Odds Ratios (COR) and 95% confidence intervals were calculated if homogeneity was not rejected. Twelve case-control studies and one cohort study were detected. CORs could be calculated for current and past use of oral contraceptives, past IUCD use and tubal sterilization. All assessed contraceptives protect against ectopic pregnancy. Women becoming pregnant after sterilization or while currently using an IUCD are at an increased risk. The IUCD is the only contraceptive method associated with an increased risk after discontinuation of its use.

Case-Control Studies↗

Serum specific protein 1 and beta-human chorionic gonadotropin concentrations in patients with suspected ectopic pregnancies.

To determine the predictive value of serum specific protein 1 (SP1) and beta-human chorionic gonadotropin (beta-hCG) in the diagnosis of ectopic pregnancy, blood was sampled from 82 patients referred for suspected early extrauterine pregnancies. Serum concentrations of SP1 and beta-hCG were determined by EIA and RIA. All patients with early pregnancies had detectable SP1 and beta-hCG levels. An intrauterine pregnancy was found in six patients, and an ectopic pregnancy was confirmed by surgical explorations in 32 of these women. The remaining 40 women had other non-pregnancy related complaints. In all pregnant patients, the beta-hCG RIA and SP EIA determinations were also found positive. This study demonstrates the high predictive value of serum SP1 and beta-hCG determinations with an acceptable sensitivity and specificity in the diagnosis of suspected early ectopic pregnancies. In addition, the practicability and the easy performance of the enzymoimmunometric SP1 determination renders this test superior over the radioimmunoassay for beta-hCG determination.

Chorionic Gonadotropin↗

Production of "ectopic" vasoactive intestinal peptide-like immunoreactivity in normal human chromaffin cell cultures.

Vasoactive intestinal peptide-like immunoreactivity (VIPLI) is not detectable in normal adult human chromaffin cells in vivo, but was demonstrated in cultured chromaffin cells from two normal adults after 22 days in vitro. Cellular content of VIPLI was markedly increased in the presence of nerve growth factor, which also stimulated neurite outgrowth. Catecholamine content decreased in the same cultures, and was not regulated in parallel with VIPLI. The amounts of VIPLI in normal human chromaffin cells in culture are comparable to those previously reported in human pheochromocytoma cell cultures. Theoretical models have attributed production of ectopic peptides by pheochromocytomas and other tumors to "immaturity" of tumor cells. Our findings, however, indicate that neither neoplasia nor cellular immaturity is a prerequisite for ectopic peptide production. Ectopic neuropeptides produced by normal chromaffin cells which undergo neuronal differentiation are of potential clinical importance in patients receiving autologous chromaffin cell transplants for Parkinsons' disease.

Adrenal Medulla↗

Fertility and ectopic pregnancy.

In a retrospective analysis of 226 patients with ectopic pregnancy, 22% had been sterilized or were using contraceptives. Of the 168 parous women, only 57% had one or more normal pregnancies prior to the ectopic pregnancy. 30% have subsequently become pregnant (2--12 yr later), 8% have had a repeat ectopic pregnancy, and 16% have had a successful pregnancy.

Female↗

Measurements of hCG and PAPP-A in uncommon types of ectopic gestation.

Seven out of 54 women with ectopic gestation had uncommon features such as extra-tubal implantation or multiple intratubal pregnancy. Depressed levels (less than 10th centile) or apparent absence of circulating human chorionic gonadotrophin (hCG) and pregnancy-associated plasma protein A (PAPP-A) were seen respectively in 5 and 7 of 7 women studied. Normal levels of hCG were seen in two women, one with an abdominal and one with an angular pregnancy. These data suggest that the synthesis of placental proteins in ectopic pregnancies is independent of the site of implantation and the number of embryos. Measurements of maternal levels of the 2 placental proteins seem to be applicable as auxiliary diagnostic tests for ectopic pregnancy, regardless of the site of implantation.

Chorionic Gonadotropin↗

Antibodies to Chlamydia trachomatis in women with infertility, pelvic inflammatory disease and ectopic pregnancy.

Sixty-three women admitted to the gynecological ward at the University Hospital, Linköping, were studied for the presence of antibodies to Chlamydia trachomatis. 48% of infertile women, 78% of women with ectopic pregnancy and 44% of women with pelvic inflammatory disease had higher titer (greater than or equal to 1:128) IgG/IgA/IgM antibodies to C. trachomatis. Among 55 healthy pregnant women, used as controls, 13% had this high antibody titer. Among 30 women with a titer of greater than or equal to 1:128, 33% of previous conceptions resulted in ectopic pregnancy and 31% resulted in child birth. The corresponding figures among women with no antibodies to C. trachomatis were 12% and 60%, respectively. The prevalence of IgA antibodies varied from 22% to 38% in women with pelvic inflammatory disease, ectopic pregnancy or infertility. The results indicate the importance for C. trachomatis in development of sequelae to lower genital tract infections in women.

Antibodies, Bacterial↗

Tubal histopathology in ectopic pregnancies.

A histopathologic study in eighty six patients with ectopic pregnancy and in eighty six control patients was undertaken to evaluate the association between ectopic pregnancy and tubal pathology in our population. Fifty six (65%) and nine (10.4%) cases with chronic salpingitis (CS) were diagnosed in the study group and in the control group, respectively. This difference was statistically significant (p < 0.001). Twelve of 56 cases with chronic salpingitis were salpingitis isthmica nodosa (SIN) and no patient with SIN was observed in the control group. SIN was always concomittant with chronic salpingitis in our study. Based on these findings, we concluded that chronic salpingitis and SIN have an important role in the etiology of ectopic pregnancy in our population and SIN is significantly associated with chronic salpingitis.

Endometriosis↗

Treatment of the small unruptured ectopic pregnancy: a cost analysis of methotrexate versus laparoscopy.

OBJECTIVE: To compare the economic costs between two strategies for management of the small unruptured ectopic pregnancy: initial treatment with methotrexate versus initial treatment with laparoscopic salpingostomy. METHODS: We assumed that both treatment strategies would result in identical clinical outcomes: resolution of the ectopic pregnancy without maternal mortality or long-term morbidity. Based on a literature review, estimates were derived for the likely clinical outcomes of a single injection of methotrexate (50 mg/m2) and for the likely clinical outcomes of the laparoscopy strategy. A range of values was evaluated for the initial success rate of each strategy and varying assumptions made about the type of treatment modality used for initial treatment failures. Direct medical costs of each strategy were estimated based on actual reimbursement rates of a third-party payer for the components of each strategy. The treatment strategies were compared in best-case/worst-case scenarios to determine the potential range of differences in costs between the two strategies. RESULTS: The cost of the methotrexate strategy ranged from $438 to $1390, and the cost of laparoscopic salpingostomy ranged from $2506 to $2974; therefore, the methotrexate strategy was less costly than laparoscopy, with a cost difference ranging from $1124 (best-case laparoscopy-worst-case methotrexate scenario) to $2536 (worst-case laparoscopy-best-case methotrexate scenario). Sensitivity analyses demonstrated that initial therapy with methotrexate was less costly over a wide range of probability and cost estimates. CONCLUSION: Initial methotrexate is a cost-effective alternative to laparoscopic salpingostomy in the treatment of the small unruptured ectopic pregnancy.

Costs and Cost Analysis↗

The expression of major histocompatibility complex antigens by trophoblast in ectopic tubal pregnancy.

The reactivity of the various trophoblast populations found in ectopic fallopian tube pregnancy with established trophoblast-reactive markers and monoclonal antibodies to MHC antigens has been studied. In ectopic tubal pregnancy fetal trophoblast shows an identical reaction pattern with these antibodies to that seen in intrauterine pregnancy, suggesting that ectopic implantation is not related to an inherent immunological abnormality of fetal trophoblast. However, from this and other studies, it appears that extravillous trophoblast displays an unusual class I MHC antigenic structure. This observation may explain the ability of class I MHC--bearing fetal trophoblast--to survive both in the uterus and at an abnormal implantation site.

Antibodies, Monoclonal↗

Atrial ectopic activity and atrial fibrillation/flutter after coronary artery bypass surgery. A case-base study controlling for confounding from age, beta-blocker treatment, and time distance from operation.

To evaluate the impact of ectopic atrial activity and cardiac autonomic function for development of atrial fibrillation or flutter we studied 128 consecutive patients undergoing elective coronary artery bypass grafting. The patients were Holter monitored during a 96-h postoperative period. Autonomic balance was estimated by heart rate variability measurement. Thirty-eight (30%) patients developed sustained atrial fibrillation or flutter. Holter recordings were analyzed in a case-base design matching for age, beta-blocker treatment, and time elapsed after the operation. The number of supraventricular ectopic beats/h was increased (P < 0.01) in the case group during each of the last 7 h before onset of atrial fibrillation or flutter. Episodes of supraventricular tachycardia 62% vs. 26%; cases vs. controls (P = 0.007), episodes of non-sustained atrial fibrillation 29% vs. 0% (P = 0.0009), and episodes of non-sustained atrial flutter 15% vs. 0% (P = 0.05) were significant predictors of atrial fibrillation or flutter. Mean heart rate/h was increased in each of the 24 h preceding the arrhythmia. However, indexes of autonomic heart function did not differ significantly between groups. Patients developing atrial fibrillation or flutter after coronary artery bypass surgery present 'warning' atrial arrhythmias: numerous supraventricular ectopic beats, paroxysmal supraventricular tachycardia, and episodes of nonsustained atrial fibrillation and flutter.

Adrenergic beta-Antagonists↗