Uteroplacental vascular involvement in recurrent spontaneous abortion

In the present study, we assessed the ability of increasing doses of intranasal calcitonin to suppress urinary deoxypyridinoline cross-link (DPD), a specific biochemical marker of bone resorption, in early postmenopausal women. Subjects consisted of 30 healthy Thai women within 5 years of postmenopause, randomly assigned to 50, 100, or 200 IU of intranasal calcitonin 5 days/week for 3 months. Calcium supplementation by calcium carbonate capsules at 750 mg of elemental calcium per day was given to all subjects. Twenty four-hour urine for DPD and creatinine assays was collected at baseline, 1 month, and 3 months after treatment. All DPD values were corrected with urinary creatinine before analyses. Data were expressed as mean +/- SEM. DPD decreased significantly 1 month after intranasal calcitonin treatment (P < 0.01). However, at 3 months, DPD increased when compared with the values at 1 month (P < 0.01), suggesting that there may be a reduction in the suppression of bone resorption after prolonged calcitonin therapy. Using a stepwise multiple regression model to address whether dosage and DPD at baseline influence the response to intranasal calcitonin, it was found that DPD suppression after intranasal calcitonin was not related to dosage but was strongly associated with baseline DPD (P < 0.0001). Suppression of bone resorption in early postmenopausal women by intranasal calcitonin is determined more by the state of bone turnover at baseline than the dosage of calcitonin.     

Ultrasonographic characteristics of lipoma of the soft tissues

This study includes 72 subjects with 90 soft tissue lipomas examined with high-resolution US. Forty-one lipomas were found in subcutaneous fat tissue, 29 in superficial muscles, 1 in the inguinal channed and 1 in the retroperitoneum. All the lesions were studied for: site, position in the body, number, shape, outline, size, echotexture, echogenicity and US beam transmission beyond the lesion. Sixty-seven lipomas were slightly ovalar (93%), 53 had regular margins (73.6%) and 21 exhibited a poorly- or well-defined capsule (29.2%). Twenty-two per cent of lipomas was homogeneous, 54.2% was slightly inhomogeneous and the extant 23.6% was inhomogeneous. Forty-five lesions were hypoechoic (62.5%), 13 hyperechoic (18.1%), 10 isoechoic (13.9%) and 4 exhibited a mixed echostructure (5.5%). In 24 cases (33.3%) sound was transmitted better through lipoma than through surrounding soft tissues. Posterior US beam attenuation was observed in one case (1.4%). Fifty-one lipomas (70.9%) exhibited the typical "striped" pattern, i.e., inner hyperechoic bands parallel to the skin. The clinical diagnosis of lipoma is based on patients' clinical history and on the palpation of a soft, well-defined and mobile mass. The US findings of an ovalar, well-defined, sometimes capsulated and, most important, "striped" mass, suggest the diagnosis of lipoma. Indeed, in our opinion, this pattern is characteristic of lipoma and represents the US appearance of its fibrous stroma. Therefore, we recommend US as the first-step method in the study of lipomas.     

Embryotoxic factors and recurrent spontaneous abortions]

The contributions of amino acids to the overall osmotic activity of cyst fluids were sought in this comparative study of fluids from the cysts of autosomal dominant polycystic disease (ADPKD) and gross cystic disease of the breast (GCDB). Fluids (n = 18) from 18 women with GCDB and from 8 patients with ADPKD (n = 25), grouped on the basis of sodium concentrations, were analyzed for potassium, chloride, protein, and osmolality by routine methods and for amino acids by reversed-phase high-pressure liquid chromatography. Similarities between kidney and breast cyst fluids included relative isosmolality, a wide range of sodium concentrations, an inverse relationship between sodium and potassium concentrations, higher concentrations of amino acids in low-sodium fluids, and significant correlations between sequential concentrations of amino acids in cyst fluids versus blood and some of its components. Therefore, cyst fluids in ADPKD and GCDB share compositional characteristics, and amino acids, possibly of blood protein origin, accumulate in small but osmotically significant amounts in some, particularly low-sodium, cysts of kidney and breast.     

Chlamydial serologic studies and recurrent spontaneous abortion

OBJECTIVE: Our purpose was to investigate the putative association between immunoglobulin G antibodies to Chlamydia trachomatis and recurrent spontaneous abortions. STUDY DESIGN: Sera from 106 idiopathic recurrent aborters and 81 of their partners were tested for immunoglobulin G antichlamydial antibodies by whole inclusion immunofluorescence and compared with 3890 sera from a general antenatal population. Positive sera were further investigated by microimmunofluorescence to determine species (Chlamydia trachomatis, Chlamydia pneumoniae, Chlamydia psittaci) specificity. RESULTS: Twenty-six (24.5%) of women with recurrent spontaneous abortions had immunoglobulin G antichlamydial antibodies compared with 28 (34.6%) of their partners (chi 2 2.25, p < 0.05) and 788 (20.3%) of the general antenatal population (chi 2 1.16, p < 0.05), and the incidence of antibody positivity showed no trend with increasing number of previous abortions. Fourteen women with recurrent spontaneous abortions had antibodies to Chlamydia trachomatis, 12 to Chlamydia pneumoniae. The prevalence of antibodies to C. trachomatis did not differ significantly between women with recurrent spontaneous abortions and their partners, but the male partners had a significantly (p = 0.005) higher prevalence of Chlamydia pneumoniae antibodies. Chlamydial antibody seropositivity did not correlate with subfertility or subsequent pregnancy outcome. CONCLUSION: There is no association between immunoglobulin G antibodies to Chlamydia trachomatis and recurrent spontaneous abortion.     

Endocrine factors associated with recurrent spontaneous abortion

The role of endocrine factors as a cause of recurrent spontaneous abortion is controversial. Diabetes mellitus and thyroid disease do not represent a significant risk factor for recurrent pregnancy loss. Luteal-phase defect has been questioned because there are no accurate methods for diagnosis and no convincing evidence of correction with treatment exists. The corpus luteum is an unusual endocrine gland, highly diverse in function and important for successful reproduction in all mammalian species. Much controversy exists about the luteal function in humans and how defects in luteal function affects reproduction. Disagreement has been due to lack of accurate diagnosis and controlled studies to determine whether correction of the luteal-phase defect is worthwhile when treating female reproductive problems. The donor egg recipient model from assisted reproductive technology programs has shown that corpus luteum function can be replaced by estrogen and progesterone administration. The mechanism by which these steroids stimulate a uterus to be receptive to implantation of the embryo is not known. Several proteins produced by the endometrium are candidate markers for uterine receptivity. Further work needs to be done to correlate these markers with subsequent pregnancy outcome. A noninvasive marker for uterine receptivity is ultrasonographic evaluation of the endometrium. Although the sensitivity of this test is high (100%), its specificity is low (only 20% to 60%).     

Anticardiolipin antibody in recurrent spontaneous aborting and fertile women

OBJECTIVE: To determine the association between the presence of anticardiolipin antibody and a history of recurrent spontaneous abortion. STUDY DESIGN: Clinical controlled study. LOCATION: Department of Gynecology and Obstetrics-University of Campinas (UNICAMP). SUBJECTS: 52 individuals with recurrent spontaneous abortion were included in Group 1 and 104 individuals with at least one live born child in Group 2. Elapsed time from last delivery to blood sampling varied from six months to two years. METHOD: Between November 1993 and November 1994, patients' blood samples were screened for anticardiolipin antibody by ELISA, as described by Triplett, Barna and Unger (1993). ANALYSIS: Chi-square and Fisher's Exact tests were used for statistical analysis. Student's "t" test was used to compare the means. RESULTS: There was no statistical difference in the presence of the anticardiolipin antibody between Group 1 (zero and 2.9%) and Group 2 (7.7 and 5.8%). CONCLUSION: There was no association between the presence of anticardiolipin antibody and recurrent spontaneous abortion.     

The effects of kainic acid in rats with spontaneous recurrent seizures

1. Rats with spontaneous recurrent seizures (SRS) were obtained by injection of kainic acid (KA; 10 mg/kg SC) to drug-naive rats that regularly developed wet-dog shakes followed by complex partial seizures and status epilepticus. Three to five weeks later, the rats with manifest SRS were selected. 2. The SRS rats were challenged with KA (10 mg/kg SC). The seizures induced in SRS rats by KA were similar to SRS regarding their clinical stage and duration (mean duration of seizures: 44 sec and 43 sec, respectively). The frequency of seizures was, however, increased compared with the frequency of SRS in control, vehicle-treated SRS rats (mean frequency of seizures: 12.9 and 0.4 per 3 hr, respectively). The KA-induced seizures in SRS rats differ behaviorally from KA-induced seizures in naive rats-namely, neither wet-dog shakes nor the status epilepticus could be induced. 3. Repeated injection of an equal dose of KA, applied to the SRS rats 1 day after the previous KA challenge, did not induce seizures. The loss of seizure susceptibility to KA was only temporary, as shown after a 7-day drug-free period, when the repeated injection of KA regained its seizure-triggering capacity. 4. The results indicate that reactivity to the seizure-inducing agent kainic acid changes in rats with spontaneous recurrent seizures.     

Ultrasonographic cross-sectional characteristics of muscles of the head and neck

OBJECTIVE: Computed tomography and magnetic resonance imaging are the common techniques for evaluating cross-sectional areas and volumes of human jaw muscles. Because computed tomography has the disadvantage of showing cumulative biological effects and because MRI poses a problem in terms of clinical availability and cost, the purpose of this study was to determine whether ultrasonography could be used to measure local linear cross-sectional dimensions of muscles of the head and neck. STUDY DESIGN: In 46 patients with signs and symptoms of temporomandibular disorders, the anterior temporalis, anterior masseter, deep masseter, anterior digastric, posterior digastric, and sternocleidomastoid muscles were measured bilaterally by ultrasonography to assess linear local cross-sectional dimensions. Measurements were made in 2 sessions with a time interval of at least 5 minutes. Data were analyzed for reliability and variability through use of the intraclass correlation coefficient (ICC) and the repeatability coefficient (RC). To assess local muscle asymmetry patterns, the absolute asymmetry index was used, with the mean maximum muscle diameters of the respective right and left sides calculated from 3 consecutive measurements. RESULTS: Satisfactory visualization of muscles was obtained in 93.8% of 1104 imaging procedures. For the ultrasound measurements there was a significant difference in local cross-sectional dimensions between the first and second sessions for the anterior temporalis muscle only (P < .01). Acceptable intrarater reliabilities were obtained for the deep masseter (ICC = 0.92), anterior digastric (ICC = 0.91), and sternocleidomastoid (ICC = 0.86) muscles, whereas evaluation of the posterior digastric (ICC = 0.74), anterior masseter (ICC = 0.72), and anterior temporalis (ICC = 0.70) muscles was associated with moderate reliability. Variability of repeated measurements was found to be acceptable for the anterior temporalis (RC = 0.32 mm) and posterior digastric (RC = 0.48 mm) muscles. Analysis of muscle site-related local cross-sectional dimensions showed a significant difference between the right and left sides for the deep masseter muscle only (P < .05). The study population investigated revealed mean asymmetry indices ranging from 5.3% for the anterior digastric muscle to 8.7% for the deep masseter muscle. CONCLUSIONS: Ultrasonography may prove to be a reliable diagnostic technique for the evaluation of cross-sectional dimensions and areas of muscles of the head and neck.     

Intrapartum management of multiple gestations

The proper intrapartum management of multiple gestations continues to be debated in the obstetric community. Ultrasonography is key in this management, through its initial assessment of the fetuses in the labor and delivery suite, observations of the second twin after the first has delivered, and its role in external cephalic version. The proper route of delivery requires further investigation for each combination of twin presentations and estimated fetal weights. It is recommended that the nonvertex second twin that is greater than 24 weeks' gestational age and fewer than 1700 g estimated fetal weight should have an attempt made at ECV and, if unsuccessful, a cesarean section should be performed. In the nonvertex second twin weighing greater than 1700 g, ECV or assisted breech extraction is appropriate. It is believed that all triplet gestations should be delivered abdominally. The use of intravenous nitroglycerin for uterine relaxation in multiple gestations is still experimental but may prove to be useful in the abdominal delivery of the nonvertex fetus. Further research is required to elucidate the most critical issues associated with the labor and delivery management of multiple gestations.     

Intravenous immunoglobulin therapy for recurrent spontaneous abortion: a meta-analysis

The aim of this paper was to identify the mechanism/s responsible of the antimetastatic effect of a single low dose of cyclophosphamide (Cy), previously demonstrated by us in the rat lymphoma LTACB. No direct cytotoxic antimetastatic activity of Cy could be proved. In vitro treatment of L-TACB cells with mafosfamide did not alter their invasiveness or their motility. The adoptive transfer of splenocytes from Cy-treated tumor-bearing rats, together with L-TACB cells inhibited their metastatic growth. The single low dose Cy treatment of T-immunodeficient nude mice did not show the antimetastatic effect on L-TACB observed in immunocompetent mice. An inhibition of the metastatic ability due to immunomodulation by Cy is proposed.     

A cytogenetic study of 514 Chinese couples with recurrent spontaneous abortion

OBJECTIVE: To study the role of chromosomal aberration in the causation of recurrent spontaneous abortion (RSA) in Chinese population. METHODS: A total of 514 Chinese couples with 2 or more spontaneous abortions at less than 24 weeks of gestation were included. For each proband, a minimum of 13 metaphases were analyzed by G-banding. Additional cells (usually 50-100 cells) were screened when mosaicism was suspected. Chi 2 test was used to compare the number and frequency of couples with and without balanced translocation with respect to whether liveborn was present or absent. Chi 2 test for trend was used to show whether a correlation existed between the occurrence of balanced translocation and the number of spontaneous abortions at ascertainment. RESULTS: The overall incidence of chromosome anomaly was 51 out of 514 (9.92%). Chi 2 test for trend analysis showed that the chance of one member of a couple being a balanced carrier increased with the number of spontaneous abortions. The chance of finding translocation in couples with liveborn was higher than that in couples without liveborn, but the difference was not statistically significant. We also found that pericentric inversion 9 did not play an important role in the causation of recurrent abortion. CONCLUSIONS: Cytogenetic analysis is indicated in couples with 2 or more spontaneous abortions and the chance of finding chromosomal aberration increases with the number of abortions at the time of ascertainment.     

Atypical presentation of preeclampsia in high-order multifetal gestations

OBJECTIVE: To describe our experience with preeclampsia in high-order multifetal gestations. METHODS: Records for all triplet and quadruplet pregnancies delivered after 24 weeks' gestation from January 1988 through June 1994 were reviewed. All patients were treated with bed rest from 20 weeks' gestation onward and received corticosteroids weekly beginning at 24 weeks. Tocolytics were used as needed. RESULTS: Twenty-one triplet and eight quadruplet pregnancies were studied. The mean gestational age at delivery was 32.3 and 27.9 weeks, and mean birth weights were 1547 and 1028 g, respectively. Seventeen of 29 patients developed preeclampsia, 14 of the 21 triplet mothers and three of the eight quadruplet mothers. Among 16 patients who were delivered for preeclampsia, only eight had blood pressure (BP) elevation before delivery, whereas ten had epigastric pain, visual disturbances and/or headache; nine had elevated liver enzyme levels; and seven had low platelet counts. Only three patients had proteinuria, and only six had edema. Five women developed the syndrome of hemolysis, elevated liver enzymes, and low platelets postpartum, all of whom had normal BP before delivery. Two patients developed preeclampsia after delivery. A total of 95 infants were delivered, all by cesarean, of whom 93 (98%) survived. CONCLUSION: Preeclampsia is common in high-order multifetal gestations and often presents in an atypical manner. Hypertension is not always the presenting sign, and symptoms consistent with severe preeclampsia and abnormal laboratory values predominate.     

Vulnerability and plasticity of the GABA system in the pilocarpine model of spontaneous recurrent seizures

Several similarities exist between the alterations observed in the chronic pilocarpine model of recurrent seizures in the rat and those found in human temporal lobe epilepsy. The present studies are focused on changes in the GABA system in this model. Following the initial pilocarpine-induced seizures, a substantial loss of glutamic acid decarboxylase (GAD) mRNA-containing neurons has been found in the hilus of the dentate gyrus (Obenaus et al., J. Neurosci., 13 (1993) 4470-4485), and, recently, a loss of GAD mRNA-labeled neurons has also been found in stratum oriens of CA1. Yet numerous other GABA neurons remain within the hippocampal formation, and there appear to be multiple compensatory changes in these neurons. Labeling for GAD65 mRNA and associated protein is substantially increased in the remaining GABA neurons at 2-4 months after the initial seizure episode. Such increased labeling suggests that the remaining GABA neurons are part of a functional circuit and may be responding to the need for increased activity. Alterations also occur in at least one subunit of the GABA-A receptor. Labeling for the alpha(5) subunit mRNA is substantially decreased in CA1 and CA2 of pilocarpine-treated rats during the chronic, seizure-prone period. These findings emphasize the complexity of changes in the GABA system and indicate a need for evaluating the functional consequences of each of the changes. The initial loss of specific groups of GABA neurons could be a critical first step in the gradual development of epileptiform activity. While many of the subsequent changes in the GABA system may be considered to be compensatory, significant deficits of GABAergic function could remain.     

Lack of association between antiphospholipid antibodies and first-trimester spontaneous abortion: prospective study of pregnancies detected within 21 days of conception

OBJECTIVE: To determine the role of antiphospholipid antibodies and anticardiolipin antibodies in first-trimester losses, addressing experimental pitfalls that preclude excluding the possibility that these antibodies reflect merely the selection bias of studying couples only after they have already experienced losses. DESIGN: Given that retrospective studies cannot exclude the possibility that such antibodies arise as a result of the fetal death, blood samples were obtained either before pregnancy or very early in pregnancy. Sera were obtained within 21 days of conception. SETTING: Multicenter university-based hospitals (National Institute of Child Health and Human Development collaborative study). PATIENT(S): Subjects for the current study were 93 women who later experienced pregnancy loss (48 diabetic; 45 nondiabetic), matched 2:1 with 190 controls (93 diabetic and 97 nondiabetic) who subsequently had normal live-born offspring. INTERVENTION(S): Sera from these 283 women were analyzed for antiphospholipid antibodies by enzyme immunoassay. In 260 of the 283 women (87 with pregnancy losses; 173 with live-born infants), sera were also available to perform assays for anticardiolipin antibodies by enzyme immunoassay. MAIN OUTCOME MEASURE(S): Pregnancy losses. RESULT(S): No association was observed between pregnancy loss and the presence of antiphospholipid antibodies or anticardiolipin antibodies. Levels of antiphospholipid antibodies were 6-19 PL/mL in 62.4% of the pregnancies that ended in losses and > or = 20 PL/mL in 5.4%; among pregnancies resulting in live-born infants, the percentages were 56.8% and 6.8%, respectively. Of the pregnancies that ended in a loss, 5.7% had anticardiolipin antibodies > or = 16 GPL/mL, compared with 5.2% of those ending in a live birth. CONCLUSION(S): This prospective study suggests that anticardiolipin antibodies and antiphospholipid antibodies are not associated with an increased risk for first-trimester pregnancy loss.     

Natural killer cell cytotoxicity and paternal lymphocyte immunization in women with recurrent spontaneous abortions

Although cardiac function is depressed during endotoxic shock, it remains controversial whether the ventricular contractility and structure are altered during sepsis. To resolve this issue, rats were subjected to polymicrobial sepsis by cecal ligation and puncture (CLP). At 2, 5, and 10 h after CLP (i.e., the early, hyperdynamic stage of sepsis) or 20 h after CLP (the late, hypodynamic stage of sepsis, based on the depressed tissue perfusion), in vivo left ventricular contractility parameters such as maximal rate of the left ventricular pressure increase (+dP/dtmax) and decrease (-dP/dtmax), maximal rate of "pressure-normalized" change in ventricular pressure (dP/dtmax/P), and ventricular peak systemic pressure were determined using a Digi-Med Heart Performance Analyzer. In additional groups of animals, ultrastructure of the cardiac muscle in the left ventricle was examined at 5, 10, or 20 h after CLP, using a transmission electron microscope. The results indicate that +dP/dtmax and dP/dtmax/P increased significantly at 2-10 h after CLP. The values of -dP/dtmax and ventricular peak systemic pressure increased significantly at 2 and 5 h after the onset of sepsis, respectively. These in vivo ventricular contractility parameters, however, were not significantly different from shams at 20 h after CLP. Ultrastructural examination showed that enlarged T-tubules were prominent during the hyperdynamic stage of sepsis, which was correlated with the increased cardiac contractility. Although focal and moderate hypertrophy as well as expanded intermyocyte junctions could be observed occasionally, myocardial cells did not appear to be compromised at 20 h after CLP. Thus, the transition from the hyperdynamic to hypodynamic circulation during sepsis does not appear to be due to any depression in myocardial function because cardiac contractility and structure are not compromised even during the late, hypodynamic stage of sepsis. However, further investigation is required to determine whether cardiac function is depressed at the terminal stage of polymicrobial sepsis.