Diagnosis of multiple pregnancy.

A study was made of 94 sets of twins born during 1975-8. Nine of these sets had not been diagnosed before labour started. Of the others, 75 were diagnosed as a result of clinical suspicion and 10 were diagnosed unexpectedly during the antenatal period, nine by ultrasonic examination. Thus, while ultrasonic examination has substantially reduced the incidence of undiagnosed twins, a fifth of all patients who had ultrasonography performed in the presence of a twin pregnancy were reported on at least one occasion to have a singleton pregnancy. Ultrasonography must be performed at least twice, therefore, before a multiple pregnancy can be confidently excluded.     

Birthweight discordance in multiple pregnancy.

This paper reviews several aspects of discordant growth in multiple pregnancies. Discordant growth is not a chance event and therefore several patterns can be discerned. About 75% of twins exhibit < 15% discordance (concordant), 20% are 15-25% (mildly) discordant, and about 5% are more than 25% (severely) discordant. Higher frequencies and increased severity are seen among triplets. Five observations regarding discordance became generally accepted: (a) not all discordant pairs are similar; (b) the larger the discordance level the greater is the risk for an adverse outcome; (c) discordant growth does not necessarily represent growth restriction; (d) a discordance level may have a different clinical implication in different gestational ages; and (e) the smaller fetuses in severely discordant pairs are at disproportionate risk for neonatal mortality. Mild discordance may represent a normal variation between sibs whereas severely discordant pairs often exhibit patterns of growth restriction. Not infrequently, discordance may represent an adaptation to the limited intrauterine space in order to increase gestational age.     

Loss in higher multiple pregnancy and multifetal pregnancy reduction.

From early pregnancy into childhood, higher multiples have much higher rates of mortality, whether from spontaneous abortion, the 'vanishing twin' syndrome, fetal or infant death. Many parents must cope with the death of one baby whilst the siblings remain critically ill or later become disabled and yet there grief is often underestimated. Little is known about the long term feelings of parents who choose to have a multifetal pregnancy reduction (MFPR). Most say they made the right decision but also that there was insufficient respect for their loss. They are often anxious about what, if anything, to tell the survivors and how they might react. Long term follow-up studies of the children as well as the parents are needed. Meanwhile parents who chose to have a MFPR must be given more information and ongoing support.     

The role of ultrasound in analytical derivatizations

Ultrasound is a type of energy that until recently was rarely used for analytical purposes. In recent years, work in chemical and industrial fields alerted analytical chemists to the great potential of ultrasonic energy to accelerate or improve different steps of the analytical process. One of these steps is derivatization: depolymerization, redox, hydrolysis, esterification, alkylation and complex formation are examples of derivatization reactions, all of which are significantly improved with the aid of ultrasound. This review discusses the valuable characteristics of ultrasound and its influence on a number of derivatization reactions is discussed in this review.     

The role of HLA-G in human pregnancy

Pregnancy in mammals featuring hemochorial placentation introduces a major conflict with the mother's immune system, which is dedicated to repelling invaders bearing foreign DNA and RNA. Numerous and highly sophisticated strategies for preventing mothers from rejecting their genetically different fetus(es) have now been identified. These involve production of novel soluble and membrane-bound molecules by uterine and placental cells. In humans, the placenta-derived molecules include glycoproteins derived from the HLA class Ib gene, HLA-G. Isoforms of HLA-G saturate the maternal-fetal interface and circulate in mothers throughout pregnancy. Uteroplacental immune privilege for the fetus and its associated tissues is believed to result when immune cells encounter HLA-G. Unequivocally demonstration of this concept requires experiments in animal models. Both the monkey and the baboon express molecules that are similar but not identical to HLA-G, and may comprise suitable animal models for establishing a central role for these proteins in pregnancy.     

Maternal serum alpha-fetoprotein levels in multiple pregnancy.

Maternal serum alpha-fetoprotein (AFP) levels were higher in 10 twin pregnancies and one triplet pregnancy than in 22 control singleton pregnancies matched for maternal age, parity, and the time of gestation at which the serum sample was taken. In twin pregnancies the average AFP levels were double those found in singleton pregnancies and the level in the triplet pregnancy was even higher. Raised maternal serum AFP values due to multiple pregnancy should not cause unnecessary amniocentesis in the diagnosis of anencephaly or spina bifida if an ultrasound investigation is routinely performed first.     

The role of multiple somatic point mutations in metastatic progression.

To test the hypothesis that the ability to metastasize is determined by multiple point mutations during the expansion of a neoplastic clone, a mathematical model for sequential mutations was derived. Development of the metastatic phenotype was attributed to the mutation of a specific group of genes. The average tumor size was estimated for when a cell should manifest a set number of these mutated genes. In a tumor of 10(9) cells subject to 10(-6) mutations/gene per generation, only one of these genes, on average, should have mutated. To explain the multiplicity of changes associated with the metastatic phenotype, genetic variation at rates greater than 10(-3) variations/gene per generation seems necessary. Possible mechanisms for this variation involve gene amplification, chromosomal aneuploidy, and altered gene regulation rather than point mutation.     

Early pregnancy assessment with transvaginal ultrasound scanning.

OBJECTIVE: To establish normal parameters in early pregnancy through transvaginal ultrasonography so that gestational age can be determined and to correlate the sonographic findings with serum human chorionic gonadotropin (hCG) levels calibrated against the first international reference preparation standard. SETTING: Infertility clinic. PATIENTS: Thirty-five women with normal intrauterine pregnancy. INTERVENTIONS: Serial measurement of the serum hCG level and the diameter of the gestational sac through transvaginal ultrasonography. MAIN RESULTS: The gestational sac could not be visualized when the hCG level was less than 1100 IU/L. The average growth rate of the sac was 0.9 mm/d. The threshold values for sac diameter, serum hCG level and gestational age below which the yolk sac was not visible were 3.7 mm, 1900 IU/L and 36 days respectively; the corresponding values above which the yolk sac was always visible were 6.7 mm, 5800 IU/L and 40 days. The threshold values below which cardiac activity was not visible were 8.3 mm, 9200 IU/L and 41 days respectively, and the corresponding values above which cardiac activity was always visible were 14.0 mm, 24,000 IU/L and 46 days. The mean gestational ages and the 95% confidence and prediction intervals were tabulated so that measurement of the gestational sac diameter could be used to estimate gestational age early in normal pregnancy. CONCLUSIONS: Transvaginal ultrasonography enables detection of an intrauterine sac and reliable estimation of gestational age on the basis of sac dimensions before an embryo can be seen.     

The role of antibodies in multiple sclerosis

B cells, plasma cells, and antibodies are commonly found in active central nervous system (CNS) lesions in patients with multiple sclerosis (MS). B cells isolated from CNS lesions as well as from the cerebrospinal fluid (CSF) show signs of clonal expansion and hypermutation, suggesting their local activation. Plasma blasts and plasma cells maturating from these B cells were recently identified to contribute to the development of oligoclonal antibodies produced within the CSF, which remain a diagnostic hallmark finding in MS. Within the CNS, antibody deposition is associated with complement activation and demyelination, indicating antigen recognition-associated effector function. While some studies indeed implied a disease-intrinsic and possibly pathogenic role of antibodies directed against components of the myelin sheath, no unequivocal results on a decisive target antigen within the CNS persisted to date. The notion of a pathogenic role for antibodies in MS is nevertheless empirically supported by the clinical benefit of plasma exchange in patients with histologic signs of antibody deposition within the CNS. Further, such evidence derives from the animal model of MS, experimental autoimmune encephalomyelitis (EAE). In transgenic mice endogenously producing myelin-specific antibodies, EAE severity was substantially increased accompanied by enhanced CNS demyelination. Further, genetic engineering in mice adding T cells that recognize the same myelin antigen resulted in spontaneous EAE development, indicating that the coexistence of myelin-specific B cells, T cells, and antibodies was sufficient to trigger CNS autoimmune disease. In conclusion, various pathological, clinical, immunological, and experimental findings collectively indicate a pathogenic role of antibodies in MS, whereas several conceptual challenges, above all uncovering potential target antigens of the antibody response within the CNS, remain to be overcome.     

The role of oxytocin in mating and pregnancy

The hormone oxytocin (OT) is released both centrally and peripherally during and after mating. Although research in humans suggests a central role in sexuality, the most reliable findings to date involve peripheral activation. This review will discuss these results and will particularly focus on understanding the most recent findings from fMRI data and the effects of exogenous peripheral OT administration. We will then consider hypotheses of the roles played by central and systemic OT release as well as their control and modulation in the female, summarizing recent findings from animal research. Finally, we will discuss the contribution of OT to the initiation of pregnancy in rodents. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior.     

The role of intravascular ultrasound imaging in vascular brachytherapy

Intracoronary brachytherapy has recently emerged as a new therapy to prevent restenosis. Initial experimental work was achieved in animal models and the results were assessed by histomorphometry. Initial clinical trials used angiography to guide dosimetry and to assess efficacy. Intravascular ultrasound (IVUS) permits tomographic examination of the vessel wall, elucidating the true morphology of the lumen and transmural components, which cannot be investigated on the lumenogram obtained by angiography. This paper reviews the use of IVUS in the clinical studies of brachytherapy conducted to date. IVUS allows clinicians to make a thorough assessment of the remodeling of the vessel and appears to have a major role to play in facilitating understanding of the underlying mechanisms of action in this emerging field. The authors propose that state-of-the-art IVUS techniques should be employed to further knowledge of the mechanisms of action of brachytherapy in atherosclerotic human coronary arteries.     

Prevention of multiple pregnancy during ovulation induction.

Gonadotrophin ovulation induction is currently used for a heterogeneous group of ovulation disorders and unexplained infertility. In the United States it is reported that multiple pregnancy rates of greater than 30% occur as a result of ovulation induction, most commonly after controlled ovarian hyperstimulation and intrauterine insemination. Treatment strategies to reduce the incidence of multiple pregnancies on ovulation induction programs can be targeted to reducing multiple follicular development and subsequent ovulation by a more aggressive cancellation policy, follicle reduction by fine needle aspiration or conversion to IVF; or dealing with the problem of multiple gestation after it has occurred (i.e., multifetal pregnancy reduction). The procedures and abilities exist to resolve this problem. What is needed are appropriate treatment guidelines and well constructed trials to demonstrate that higher order multiple pregnancies can be substantially reduced and/or eliminated without compromising a couple's chances to conceive.     

A multiple pregnancy register in the north of England.

A regional population-based Multiple Pregnancy Register was established in 1998, with the aim of collecting detailed information on multiple pregnancies to enable research into mortality and morbidity in multiples. Multiple pregnancies are notified to the Register as soon as they are detected, irrespective of whether they resulted in a spontaneous abortion, termination of pregnancy or registered birth. Nine hundred and twenty-six twin pregnancies were recorded during 1998-99, giving a twinning rate of 14.8 per 1000 maternities (rate at birth 13.0 per 1000 maternities). Sixty one per cent of twin pregnancies were detected before 13 weeks of gestation. Chorionicity was determined in 82.6% of 849 twin maternities with at least one stillbirth or livebirth. The fetal loss rate before 24 weeks of gestation was 10.5% (194/1852). The perinatal and infant mortality rates were 40.6 per 1000 births and 32.6 per 1000 livebirths respectively. A prospective Multiple Pregnancy Register not only allows monitoring of trends in multiple birth rates and mortality, but also etiological research and long-term follow-up studies.     

The role of circulating miRNAs in multiple myeloma

Multiple myeloma(MM) is a common malignant hematological disease. Dysregulation of micro RNAs(mi RNAs) in MM cells and bone marrow microenviroment has important impacts on the initiation and progression of MM and drug resistance in MM cells. Recently, it was reported that MM patient serum and plasma contained sufficiently stable mi RNA signatures, and circulating mi RNAs could be identified and measured accurately from body fluid. Compared to conventional diagnostic parameters, the circulating mi RNA profile is appropriate for the diagnosis of MM and estimates patient progression and therapeutic outcome with higher specificity and sensitivity. In this review, we mainly focus on the potential of circulating mi RNAs as diagnostic, prognostic, and predictive biomarkers for MM and summarize the general strategies and methodologies for identification and measurement of circulating mi RNAs in various cancers. Furthermore, we discuss the correlation between circulating mi RNAs and the cytogenetic abnormalities and biochemical parameters assessed in multiple myeloma.