Successful laparoscopic management of primary abdominal pregnancy

Overall, approximately 1% of ectopic pregnancies are abdominal pregnancies, which can be life-threatening even when surgical intervention with laparotomy is performed. We present a case in which abdominal pregnancy was successfully managed by operative laparoscopy. A 25 year old Japanese woman presented 6 weeks after her last menstruation with elevated basal body temperature, lower abdominal pain, and light vaginal bleeding. The urinary human chorionic gonadotrophin (HCG) concentration was 2137 IU/I, and laparoscopic findings (i.e. the implantation site was the posterior serosa of the uterus with normal adnexae) established a diagnosis of primary abdominal pregnancy. The gestational product was completely removed by laparoscopic surgery with no uncontrollable loss of blood. The urinary concentration of HCG declined rapidly and the patient made an uneventful recovery. Operative laparoscopy is a safe alternative for the management of appropriately selected patients with early abdominal pregnancy.     

Diagnostic reliability of vaginal ultrasound in ectopic pregnancy

The therapeutic approach to ectopic pregnancy (EP) has changed over the last decade. A prerequisite for a differentiated management is an early diagnosis of EP. This can be achieved by transvaginal sonography (TVS). The purpose of this study was to evaluate the accuracy of TVS in the diagnosis of EP. 184 patients with clinically suspected ectopic pregnancy were examined by TVS. In 103 cases suspicion of EP was confirmed, in 81 cases it was ruled out. All cases were evaluated by laparoscopy, D&C, serial HCG determinations or sonographic follow-up in case of an intrauterine pregnancy. Sensitivity of TVS in the diagnosis of EP was 96%, specificity 88%, the positive predictive value was 89%, the negative predictive value was 95%. Four cases with a false negative result at TVS were very early in pregnancy and were subjected to laparoscopy because of persistent high HCG values without demonstration of an intrauterine pregnancy. Five cases of sonographically confirmed ectopic pregnancies were missed by the first laparoscopy. These cases required intervention because of clinical symptoms and had low levels of HCG. TVS has a high diagnostic accuracy in the diagnosis of ectopic pregnancy.     

Transforming growth factor-alpha in human implantation trophoblast: immunohistochemical evidence for autocrine/paracrine function

Epidermal growth factor (EGF) and its receptor (EGF-R) have been demonstrated in human implantation sites. Transforming growth factor-alpha (TGF-alpha), a protein with extensive sequence homology to EGF and with equal affinity for the EGF-R, was localized immunohistochemically in early intrauterine and ectopic pregnancies. Within the same experiments, TGF-alpha immunostaining was more intense in ectopic than intrauterine pregnancies. In both groups, TGF-alpha immunostaining was moderate to intense in the syncytiotrophoblast (ST), light to moderate in the cytotrophoblast (CT), and moderate to intense in intermediate trophoblast (IT). In ST, TGF-alpha immunostaining localized to the cytoplasm and plasma membranes, including microvilli. No nuclear associated TGF-alpha was noted in ST. In CT, differential TGF-alpha immunostaining was noted between the villous and nonvillous CT. Villous CT demonstrated light to absent cytoplasmic TGF-alpha immunostaining with intense nuclear staining. In contrast, nonvillous CT revealed moderate to intense cytoplasmic staining without demonstrable nuclear staining. These results demonstrate the presence of immunoreactive TGF-alpha in all forms of trophoblast. The known presence of the EGF-R suggests an autocrine/paracrine role for TGF-alpha during human implantation.     

Plasma thymidine kinase activity in dogs with lymphoma and leukemia

Plasma thymidine kinase (TK) activity was evaluated as a plasma marker for canine lymphoma and leukemia. A tentative "cut-off" value was set at 6.0 U/l as the upper level of plasma TK based on the mean + 2SD of plasma TK activity in 13 clinically healthy dogs. The levels of plasma TK activity in all of the 20 dogs with lymphoma and leukemia were higher than the cut-off value, whereas those in dogs with lymphoma decreased in parallel with the reduction of the tumor mass after chemotherapy. These findings suggested that estimation of plasma TK activity can be used as a plasma marker for lymphoma and leukemia in the dog.     

The role of scientific societies

Ectopic pregnancy is one of the most common and dangerous complications of the early pregnancy period. Until now diagnosis has been late because major symptoms occur after tubal rupture and so only demolitive surgery has been possible. At present, with the appearance of ultrasound in obstetrics an earlier diagnosis of this pathology can be made before tubal rupture so medical treatment has become possible. We treated a series of twelve patients with early ectopic pregnancy (9 tubal and 3 with no localized site of implantation) with intramuscular 0.5 mg/kg methotrexate and oral 0.1 mg/kg of folic acid (Citrovorum Factor) on alternate days, in the attempt to reduce hospitalization and obtain more effective and safer medical management. We observed a fall in serum beta-HCG levels after one cycle of treatment in 11 out of 12 patients and after two cycles of therapy in the remaining case. Minimal side-effects were observed in four cases. Three pregnancies occurred after treatment before the advised interval time and ended in blighted ovum. Methotrexate systemic therapy can be considered an elective treatment and a sufficiently safe management in early unruptured ectopic pregnancy when a good clinical selection of patients is performed.     

Enhanced sensitivity of mdx mice to intramuscular injection of compound 48/80

Species-specific differences in the inflammatory response, specifically with regard to mast cells, have been proposed to explain the phenotypic variation among dystrophin-deficient humans, and mdx mice (Gorospe et al., 1994). To test this hypothesis we have intramuscularly injected a mast cell secretogogue into both dystrophin-negative mdx and dystrophin-positive normal mice. Mast cell activity was determined by measuring the activity of mast cell tryptase, while creatine kinase activity was used to determine the course of muscle damage in vivo. Area of damage around the injection site was measured at autopsy, and used as an indication of relative sensitivity to the secretogogue effect of compound 48/80. Mdx mice exhibited more damage in response to intramuscular injection than normal control mice. In addition, mdx mice showed a substantial increase in plasma tryptase activity, followed by a large increase in muscle creatine kinase activity. On the other hand, dystrophin-positive normal controls injected with 48/80 liberated little CK or tryptase activity. These results are consistent with the hypothesis that species-specific differences in mast cell activity, or sensitivity to mast cell products could account for the variation in pathology seen in dystrophin-deficient animals.     

A decision tree for the early diagnosis of acute myocardial infarction in nontraumatic chest pain patients at hospital admission

STUDY OBJECTIVE: To find an accurate algorithm for the diagnosis of acute myocardial infarction in nontraumatic chest pain patients on presentation to the emergency department. DESIGN: In a prospective clinical study, we compared the diagnostic performances of clinical symptoms, presenting ECG, creatinine kinase, creatine kinase MB activity and mass concentration, myoglobin, and cardiac troponin T test results of hospital admission blood samples. By classification and regression trees, a decision tree for the diagnosis of acute myocardial infarction was developed. SETTING: Emergency room of a Department of Internal Medicine (University Hospital). PATIENTS: One hundred fourteen nontraumatic chest pain patients (median delay from onset of chest pain to hospital admission, 3 h; range, 0.33 to 22): 26 Q-wave and 19 non-Q-wave myocardial infarctions, 49 patients with unstable angina pectoris, and 20 patients with chest pain caused by other diseases. MEASUREMENTS AND RESULTS: Of each parameter taken by itself, the ECG was tendentiously most informative (areas under receiver operating characteristic plots: 0.87 +/- 0.04 [ECG], 0.80 +/- 0.08 [myoglobin], 0.80 +/- 0.04 [creatine kinase MB mass], 0.77 +/- 0.04 [creatine kinase activity], 0.69 +/- 0.06 [clinical symptoms] 0.67 +/- 0.06 [creatine kinase MB activity], 0.67 +/- 0.05 [troponin T]). In patients presenting 3 h or less after the onset of chest pain, ECG signs of acute transmural myocardial ischemia were the best discriminator between patients with and without myocardial infarction. In patients presenting more than 3 h, however, creatine kinase MB mass concentrations (discriminator value, 6.7 micrograms/L) were superior to the ECG, clinical symptoms, and all other biochemical markers tested. This algorithm for diagnosing acute myocardial infarction was superior to each parameter by itself and was characterized by 0.91 sensitivity, a 0.90 specificity, a 0.90 positive and negative predictive value, and a 0.90 efficiency. CONCLUSIONS: We found an algorithm that could accurately separate the myocardial infarction patients from the others on admission to the emergency department. Therefore, this classifier could be a valuable diagnostic aid for rapid confirmation of a suspected myocardial infarction.     

Staff attitudes to oral health care. A comparative study of registered nurses, nursing assistants and home care aides

The diagnosis of early ectopic pregnancy remains challenging for the gynecologist. Although early detection of a suspected pregnancy has been facilitated by quantitative beta human chorionic gonadotropin studies and ultrasonography, a patient subgroup remains with an ambiguous presentation. In this group of patients, the clinician must rely on microscopic examination of products of conception in a uterine curettage specimen to rule out the presence of an extrauterine pregnancy. The presence of an implantation site, chorionic villi, or trophoblastic tissue in uterine curettage samples is conventionally held as definitive evidence of an intrauterine pregnancy. We present a series of four cases that challenge this convention. In these cases, chorionic villi or an implantation site were identified in uterine samples of pregnant women who each ultimately proved to have an ectopic pregnancy. If clinical suspicion is high, the finding of either chorionic villi or an implantation site should not preclude further workup of a possible ectopic pregnancy. In cases where only a few villi or a single chorionic villus are identified, other signs of intrauterine implantation such as intermediate trophoblastic cells, hyalinized vessels, and a fibrinoid matrix should be sought to establish firmly the diagnosis of an intrauterine pregnancy.     

Effects and mechanism of emodin and sandostatin on pancreatic ischemia in acute haemorrhagic necrotizing pancreatitis

We hypothesized that maternal serum levels of the isoenzyme creatine kinase (CK)-BB, which is highly expressed in the placenta, may be elevated during the early second trimester in gestations destined to deliver prematurely or of a small-for-gestational-age infant (birthweight below 10th percentile). To test this hypothesis, we compared maternal serum CK-BB levels and percentage of CK-BB over total CK, in 69 normal pregnancies (delivering at term of appropriate-for-gestational-age infants) with those of 25 cases complicated by preterm delivery at < or = 34 weeks (n = 14), of a small-for-gestational-age infant (n = 8), or both (n = 3). No differences were present in maternal serum CK BB levels between normal and complicated pregnancies. Moreover, no correlation was found between gestational age at delivery and CK BB levels (r = 0.03; p = 0.7).     

The contribution of assays for lymphocyte capping and creatine kinase to detection of the Becker-type dystrophy trait

Members of three unrelated families with the mild Becker type of muscular dystrophy were subjected to lymphocyte capping tests and measurements of serum creatine kinase activity. Both tests correctly identified all nine affected males, but only the capping test was abnormal in seven of eight obligate carriers. The number of capped cells in carriers and affected persons with the Becker-type dystrophy was generally intermediate between those observed for individuals with the Duchenne trait and normal controls, thus potentially aiding in the differential diagnosis between the two myopathies. The lack of sensitivity of measurements of serum creatine kinase activity in identifying carriers is further complicated by the difficulty of establishing reliable reference intervals for this enzyme in 204 healthy controls. Detailed directions for the performance of the capping test are presented.     

Is luteal function maintained by factors other than chorionic gonadotrophin in early pregnancy?

Women with ectopic pregnancy (n = 14) and early embryonic arrest ('blighted ovum') (n = 9) were studied 16 days after conception, at a time when they were asymptomatic and serum concentrations of beta-human chorionic gonadotrophin (HCG) were in the normal range and increasing at an apparently normal rate. Serum progesterone and oestradiol concentrations were compared with those from normal women matched for gestational age and serum beta-HCG concentration whose singleton intra-uterine pregnancies proceeded normally beyond 20 weeks. Mean serum progesterone concentrations were significantly lower in the women with ectopic pregnancies than in matched controls (P < 0.002); however, there was no difference in the serum progesterone concentrations between women with blighted ova and matched controls. Statistically significant differences were not seen in serum oestradiol concentrations between either group and matched controls. Similarly there was no difference in serum progesterone or oestradiol concentrations in 20 women who conceived ectopic pregnancies and 20 women conceiving blighted ovum pregnancies and their matched intra-uterine controls when conception followed ovarian stimulation. The low serum progesterone concentrations seen in ectopic pregnancy suggest that there is a specific and selective deficiency in progesterone synthesis, which implies that factors other than HCG may influence luteal function.     

Fetal cells in the peripheral blood of pregnant women express thymidine kinase: a new marker for detection

Fetal cells occur in maternal blood in a substantial proportion of normal pregnancies. Several different approaches have been used to detect and enrich these cells for non-invasive prenatal diagnosis. However, before these fetal cells can routinely be used for prenatal diagnosis, perfectly reproducible procedures for detection and enrichment need to be established. We found that these fetal cells express high intracellular levels of the DNA precursor pathway enzyme thymidine kinase. Since normal adult peripheral blood cells do not exhibit any thymidine kinase activity, this enzyme is a potent new marker to detect and enrich fetal cells from maternal blood. We further describe the first successful application of a cytofluorometric thymidine kinase assay to detect fetal cells in the maternal circulation by virtue of their high thymidine kinase activity.     

Cervical pregnancy: an obstetric emergency. A clinical case

Cervical implantation could develop in three different ways. The gestational sac can grow up to external os and interruption may simulate an abnormal menstruation. Theoretically the gestational sac could reach the uterine cavity, with a normal evolution of the pregnancy, even if the implantation of the placenta would be on internal uterine os. Lastly, the ectopic gestational sac developes all in cervical channel with an "obstetrical catastrophe". The incidence of cervical pregnancy presents great differences between authors, from 1:1,000 to 1:95,000 pregnancies; this is due to the variability of diagnostic criteria. A 36 year-old woman, para 1001, came to the emergency unit with painless vaginal bleeding. She was pregnant at 8 weeks of amenorrhoea, and previously undergone a cesarean section. The portio was swollen and bluewish, the external os was opened. The uterus was slightly increased, expecially in the peri-isthmic area; no adnexal mass. The urinary hCG was < 15,000 I.U. An ultrasound examination showed the endometrium in decidual transformation, without identification of embrional or extraembrional structures. The diagnosis was retained miscarriage. During the cervical dilatation, an impressive and uncontrollable haemorrhage occurred. It was decided to perform a total hysterectomy via laparotomy. The macroscopic examination of the uterus showed the cavity empty and the sopravaginal cervical area enlarged, invaded by an ectopic trophoblastic proliferation. The majority of obstetricians will never see a cervical pregnancy; the minority who has to treat this pathology wishes to have never seen one.     

Diagnosis of ectopic pregnancy--why we need a protocol

OBJECTIVE: To audit the management after instituting a screening programme for ectopic pregnancy in an institution with a protocol utilising ultrasound examination and serial human chorionic gonadotropin (hCG) and to examine the risk of missed diagnosis with deviation from the protocol. MATERIAL AND METHOD: A retrospective analysis of the management of 145 symptomatic patients in early pregnancies without intrauterine gestational sacs from ultrasound examinations, during the period April to June 1994 in Kandang Kerbau Hospital. Patients underwent serial hCG tests over 48 hours with or without repeat ultrasound scans before definitive treatment unless clinical indications for emergency surgery was necessary. RESULTS: There were 35 ectopic pregnancies (24%), 16 were viable intrauterine pregnancies (11%), 87 were non-viable pregnancies (60%) and 7 were of unknown outcome. There were much practice deviations from the protocol. Forty-four percent (64 cases) of the management decisions were made based on the initial clinical and ultrasound findings, and another 14% (21 cases) after a repeat assessment within the next day by either a repeat scan or serial serum hCG over one day. Among them, two of the 29 operated for suspected ectopic pregnancy were not ectopic (7%) and two of the 56 thought not to be ectopic, turned out to be ectopic (4%) (p < 10(-8)). Six percent (8 cases) defaulted after the initial assessments and one of them was found to be ectopic subsequently. Thirty percent (43 cases) adhered to the protocol. They had serial serum hCG done over two days. Seven of them requiring further repeats of serial serum hCG before management decisions were made. Four patients who were operated on were confirmed ectopic and 39 patients not operated on were not ectopic. Three percent (5 cases) were managed by serial hCG over 3 to 5 days and another 3% (4 cases) by repeating scan over one to two weeks without serial hCG. None of these was ectopic. The percentage change of hCG levels over two days gave indications of the likely diagnosis. CONCLUSION: Adhering to a protocol utilising the principle of ultrasound scan, serial hCGs and selective repeat ultrasound scans are highly recommended for the diagnosis of ectopic pregnancy. Any deviation from protocol is dangerous, with a 4% risk of missing an ectopic and a 7% risk of unnecessary operation for suspected ectopic pregnancy.     

'Inclusion body'-myositis

In 3 patients, a 72-year-old man, a 62-year-old man and a 73-year-old woman with weakness of respectively the quadriceps femoris, the finger flexors and the pharyngeal muscles, the diagnosis of 'inclusion body myositis' was made. This is a rare, slowly progressive skeletal muscle disorder which is more common in men and after the age of fifty. The activity of serum creatine kinase is often 2-5 times the highest normal value. The electromyogram pattern is myopathic, but can also display neuropathic changes (exclusively). Inclusion body myositis is often misdiagnosed, which can lead to an inappropriate treatment or approach. A frozen muscle biopsy is needed to make cryostat sections for demonstration of myositis with rimmed vacuoles.     

Increased plasma creatine kinase activity in rabbits: effect of systematically repeated blood sampling

Various physical, chemical and biological factors are involved in an increased plasma creatine kinase activity. Repeated blood sampling induced in all rabbits studied a reaction of similar pattern but of different intensity, expressed by a maximum of plasma CPK activity. The physiological origins of this variation of CPK activity seems to be, as seen in control animals, the consequence of emotional stress due to handling and possibly an additional stress due to the venepunctures.     

Ectopic pregnancy in women who use intrauterine contraceptive devices]

This study analyzes occurrence of ectopic pregnancies in women using intrauterine contraceptive devices. During a 5-year period, 1990-1994, 524 women with ectopic pregnancies underwent surgery at our Clinic, while 22 (4.2%) had intrauterine devices. At admission most patients had signs of heavy intraabdominal bleeding, so in 77.27% cases the diagnosis was made by punction of the Douglas area, and only in 9.09% by laparoscopy, that is other methods for early detection of diseases. Rupture of the fallopian tube occurred in 50% of patients, tubal abortions in 36.36% and ovarian pregnancies in 13.64%, whereas 18 salpingectomies and 4 adnexectomies were performed. Late diagnosis and impossibility of performing conservative operations on fallopian tubes are the consequence of disregarding the possibility of getting pregnant by the users of intrauterine devices themselves, as well as by physicians whose help is asked for after symptoms appear.     

Late complications after systemic methotrexate treatment of unruptured ectopic pregnancies: a report of three cases

BACKGROUND: The use of methotrexate (MTX) by systemic administration in the treatment of unruptured ectopic pregnancy has been reported as a safe and effective method. CASES: We report three cases (one hematosalpinx and two pelvic hematocoeles) of complications after the use of MTX in the treatment of unruptured ectopic pregnancies. All three cases came to our observation for pelvic pain, abnormal bleeding and a pelvic mass after an interval of 3-5 months, subsequent to the disappearance of symptoms and normalization of serum human chorionic gonadotropin beta-subunit (beta-hCG) levels. CONCLUSIONS: These findings suggest that: (a) such complications should be considered before selecting the mode of treatment for ectopic pregnancy; and (b) that an early ultrasonographic control should be performed after MTX treatment even when the decline in beta-hCG levels suggests a successful resolution. This would permit an early diagnosis of these late complications.     

Analysis of three hundred fifteen ectopic pregnancies treated with single-dose methotrexate

OBJECTIVES: The objective of this study was to review the largest single series of ectopic pregnancies treated with single-dose methotrexate reported to date. STUDY DESIGN: A review of 315 patients with unruptured ectopic pregnancies treated with single-dose methotrexate 50 mg/m2 from March 21, 1990, to March 1, 1997, was performed. RESULTS: Overall 287 patients were successfully treated with methotrexate for a success rate of 90.1%. Six patients electively withdrew and requested surgery within 1 week of starting therapy. Excluding withdrawals the overall success rate was 92.9%. Ten patients with an ectopic pregnancy > 3.5 cm but < or = 4 cm in size were treated for a 90% success rate. Forty-four patients with positive ectopic cardiac activity were treated with an 87.5% success rate. CONCLUSIONS: This large series indicates that single-dose intramuscular methotrexate for treatment of ectopic pregnancy is associated with an excellent overall success rate.     

Immunohistochemical identification of the receptor for urokinase plasminogen activator associated with fibrin deposition in normal and ectopic human placenta

The receptor for urokinase plasminogen activator (uPAR) is a key molecule in cell surface-directed plasminogen activation. uPAR binds urokinase plasminogen activator (uPA) and thereby focuses plasminogen activation on the cell surface. Plasmin dissolves fibrin deposits and facilitates cell migration during tissue repair processes by degrading the extracellular matrix. During human implantation and placental development, plasmin is considered important for both trophoblast migration/invasion and for fibrin surveillance. This study examined the expression of uPAR in normal and ectopic human placentae by immunohistochemistry. In first and third trimester normal placentae as well as in tubal ectopic placental tissues, a high uPAR expression was seen in the trophoblast associated with deposits of fibrin-type fibrinoid. Extravillous trophoblast of the basal plate, of the cell islands, and of the cell columns was also positive for uPAR in the first trimester whereas at term the expression of the protein was decreased. Moreover, uPAR immunostaining was observed in decidual cells throughout normal gestation and in endometrial tissues of patients with ectopic pregnancies. These findings suggest that uPAR participates in placental development and in trophoblast invasion particularly in the first trimester of pregnancy and that uPAR is involved in repair mechanisms of the trophoblast and fibrin surveillance.