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Maternal serum alpha-fetoprotein levels in triplet and quadruplet pregnancy.

Maternal serum alpha-fetoprotein (AFP) levels were higher in six triplet pregnancies and three quadruplet pregnancies than in control singleton pregnancies matched for maternal age, parity and time of gestation at which the serum sample was taken. Between 12 and 23 weeks of pregnancy, the average AFP levels among the triplet pregnancies was three times that found in the singleton pregnancies, and the level in the quadruplet pregnancies was even higher. Maternal serum AFP levels appear to be associated with the number of fetuses in utero.

Female

Quadruplet hallucinations. Phenotypic variations of a schizophrenic genotype.

This article provides an in-depth analysis of hallucinations in monozygous quadruplets concordant for schizophrenia. Since all four are genetically identical, deviations among them with regard to various aspects of hallucinations probably represent the effects that nongenetic factors can produce in hallucinating schizophrenics. Concordance probably represent the effects of genetic factors. We present here findings based on this research strategy, and a brief review of the literature on hallucinations.

Adult

Anaesthetic considerations in caesarean section for quadruplets.

A case of a caesarean delivery with epidural analgesia of a term parturient with quadruplets is presented. Maternal considerations of hypotension, respiratory embarrassment and aspiration of gastric content and foetal considerations of prematurity and impaired placental function are discussed relative to the use of general anaesthesia or epidural analgesia.

Adult

Successful management of quadruplet pregnancy in a perinatal unit.

A case of quadruplet pregnancy is outlined and the management is described to demonstrate the application of monitoring and therapeutic procedures currently available for a multifetal pregnancy. Recording of the nonstressed fetal heart rate, ultrasound monitoring and glucocorticoid stimulation of pulmonary biochemical maturity were done. A successful outcome was achieved with a combined obstetric-neonatal approach and the experience of a perinatal unit.

Adult

A Unified Mechanism of +1 Ribosomal Frameshifting.

Ribosomes decode 3-nucleotide codons and move in 1-codon increments to maintain the messenger RNA (mRNA) frame thereby accurately producing the encoded protein. In special cases, including viral genomes and regulatory cellular proteins, frameshifting occurs to expand the coding repertoire of an mRNA to make more than one protein. How these frameshifting events are induced and regulated is an active area of research. Here, we discuss recent progress in the understanding of +1 frameshifting (+1FS), during which the ribosome shifts by 1 mRNA nucleotide in the 3' direction. Structural and biochemical studies yielded insights into +1FS induced by mRNA slippery sequences and transfer RNA (tRNA) stem-loop expansion or modifications. tRNAs with an additional anticodon nucleotide are explored as a biotechnology tool for expanding the genetic code in an approach termed quadruplet decoding. We revisit the challenges of the quadruplet decoding model, discuss +1FS scenarios in bacteria and eukaryotes, and propose a unifying structural mechanism for +1FS.

Frameshifting, Ribosomal

Paediatric preparation for multiple premature births.

We describe the managment of 2 sets of pre-term quadruplets born to 2 women pregnant concurrently following the induction of ovulation with gonadotrophin. Careful antenatal planning was necessary to provide for each of the 8 pre-term infants a standard of neonatal medical and nursing care comparable to that normally available for singleton pre-term infants.

Adult

Pharyngeal lecithin/sphingomyelin ratios in newborn infants.

Lecithin/sphingomyelin ratios were measured on hypopharyngeal secretions from newborn infants within 6 h of birth. L/S ratios of 1.8 or less correlated with the development of the idiopathic respiratory-distress syndrome. Low L/S ratios were more common in the shorter gestation infants, and there was a predominance of L/S ratios of more than 1.8 above 32 weeks' gestation. In multiple births, the first-born of triplets and quadruplets had higher L/S ratios than those subsequently born. This may indicate a link between fetal lung maturation and the onset of labour.

Birth Order

An hypothesis for high multiple pregnancies after clomiphene.

A triplet and a quadruplet pregnancy following induction of ovulation with clomiphene are described; in each patient secondary amenorrhoea followed oral contraceptive use and several anovulatory or inadequate menstrual cycles had occurred on initial clomiphene therapy. Conception occurred in the first cycle after increasing drug dosage or the addition of human chorionic gonadotrophin (HCG) to the treatment regimen. We suggest, in explanation of these pregnancies, that repeated suboptimal stimulation of the ovaries as a result of clomiphene therapy develops several follicles to a critical stage; a subsequent greater ovulatory stimulus allows for synchronous development of several large follicles and multiple ovulation.

Adult

Responses to exercise in the pregnant pygmy goat.

Pregnant Pygmy goats were trained to walk on a treadmill up a 10 degree grade at a rate of 1.5 mile/hr for 10 min. Hemodynamic measurements were made in duplicate during late pregnancy and postpartum, at rest and after 3 min of exercise. All kids were weighed within 12 hr of delivery to assess the effect of exercise on fetal growth. Pulse rate, cardiac output and oxygen consumption were higher during pregnancy than postpartum, at rest and also during exercise. Stroke volume increased significantly with exercise. Peripheral vascular resistance (pvr) at rest was lower during pregnancy than postpartum, and decreased significantly during exercise, especially in pregnancy. Exercise was associated with a fall in arterial P(CO2) during pregnancy and postpartum. In goats, as in humans, the increased oxygen demands of pregnancy, during exercise and at rest, are met by an increased cardiac output rather than by increased peripheral oxygen extraction. The individual birth weights of twins, triplets and quadruplets from Pygmy goats who were exercised during late pregnancy were smaller than birth weights of matched newborns from control animals.

Animals

Combined tubal and multiple intrauterine pregnancies following ovulation induction.

An infertile woman who conceived after human menopasual gonadotropin-induced ovulation experienced ovarian hyperstimulation and a quintuplet gestation--an ectopic and a quadruplet intrauterine pregnancy. The intrauterine pregnancy was confirmed by B-scan ultrasonography about the time that the tubal pregnancy was ruptured. Salpingectomy did not interfere with the intrauterine pregnancy, but in spite of a cervical cerclage the patient developed premature labor after about 26 weeks of gestation.

Adult

Analysis of multiple birth rates in Japan. 1. Secular trend, maternal age effect, and geographical variation in twinning rates.

Mean twin, triplet, and quadruplet birth rates in Japan from 1951 to 1968 were 6.41, 0.056, and 0.00094 per 1,000, respectively. In 1974 the corresponding figures were 5.83, 0.059, and 0.00329. No quintuplets were born in the former period, but a set was born in the latter year, the rate being 0.47 per million. From 1955 to 1966 the MZ twinning rate increased slightly, but decreased thereafter. This increase was limited to live-born MZ twins, particularly in the higher maternal age groups. The DZ twinning rate declined in the entire period, particularly in higher maternal age groups. This decline appeared to be essentially limited to fetal deaths. Among live births the MZ twinning rate underwent a nearly linear increase with maternal age, whereas the DZ twinning rate attained a mode in the maternal age group 35--39 years. The MZ and the DZ twinning rates among fetal deaths by maternal age had unimodal distributions with modes in maternal age groups 25--29 and 30--34 years, respectively. As to the DZ twinning rate, a geographical cline was noted, with a high rate in the northeast of Japan; the rate was positively correlated with latitude, which also positively correlated with the presence of multiple births among relatives. A negative but nonsignificant correlation was seen between the DZ twinning rate and the proportion of mothers treated with ovulation-inducing hormone. The proportion was higher in mothers of unlike-sexed twins than in those of like-sexed twins and in mothers of triplets than in those of twins. An association between DZ twinning rate and age-specific fertility per married woman is suggested to exist among higher maternal age groups in the northeast part of Japan in earlier years.

Adult

Treatment Decisions in Multiple Myeloma.

Revolutions in transplantation and targeted and immune therapies have transformed multiple myeloma from a disease with an associated survival of a few years into one for which functional cure is an emerging goal. This abundance of effective therapies has created clinical complexity. Here we provide a practical framework, anchored in trial evidence and informed by emerging biologic discoveries, for the navigation of treatment decisions across the disease spectrum. We outline how cytogenetic and genomic risk stratification, functional fitness, and measurable residual disease status individualize therapy in newly diagnosed disease, in which quadruplet induction therapy is now standard and the role of autologous transplantation is being reevaluated. Regarding relapse, we address the sequencing of B-cell maturation antigen-directed chimeric antigen receptor (CAR) T cells, bispecific antibodies, and antibody-drug conjugates, emphasizing T-cell fitness and multiantigen targeting to counter exhaustion and antigen escape. We also consider early interception in high-risk smoldering myeloma. Throughout, we underscore that enrollment of patients in clinical trials should be considered in order to ensure continued progress.

Humans