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Spot overlapping in two-dimensional maps: a serious problem ignored for much too long.

In the analysis of a neuroblastoma xenograft implanted in mice using two-dimensional maps, some 85 proteins were found to be up- or down-regulated (out of a total of 264 detected by a medium-sensitivity colloidal Coomassie stain). When these spots were eluted and analysed by mass spectrometry in a quadrupole time of flight mass spectrometer, a number of spots were found to be envelopes of different polypeptide chains. Out of a total of 74 proteins identified, 52 (71%) were found to be singlets, 14 (19%) were doublets, 6 (8%) were triplets, 1 was a quadruplet and 1 a quintuplet. Analysis of the DeltapI and DeltaMr of all species contained in a single gel segment eluted helped point out potential errors in protein identification. This was a unique case, in that very minute bioptic sample loads were applied to the gel. In normal cases, where sample loads of ca. 1 mg of total protein are applied and typically at least 1000 spots are visualised, the singlets will be the minority, rarely exceeding 30% of all spots analysed. The experimental data on the abundance of overlapping spots were in excellent agreement with theoretical data calculated on the basis of the statistical theory of spot overlapping, originally proposed by Davis and further developed by some of the authors. Ways and means for minimizing spot overlap and visualising a greater number of spots in a two-dimensional map are discussed.

Adrenal Gland Neoplasms↗

High-throughput simultaneous determination of plasma water deuterium and 18-oxygen enrichment using a high-temperature conversion elemental analyzer with isotope ratio mass spectrometry.

This paper presents a high-throughput method for the simultaneous determination of deuterium and oxygen-18 (18O) enrichment of water samples isolated from blood. This analytical method enables rapid and simple determination of these enrichments of microgram quantities of water. Water is converted into hydrogen and carbon monoxide gases by the use of a high-temperature conversion elemental analyzer (TC-EA), that are then transferred on-line into the isotope ratio mass spectrometer. Accuracy determined with the standard light Antartic precipitation (SLAP) and Greenland ice sheet precipitation (GISP) is reliable for deuterium and 18O enrichments. The range of linearity is from 0 up to 0.09 atom percent excess (APE, i.e. -78 up to 5725 delta per mil (dpm)) for deuterium enrichment and from 0 up to 0.17 APE (-11 up to 890 dpm) for 18O enrichment. Memory effects do exist but can be avoided by analyzing the biological samples in quintuplet. This method allows the determination of 1440 samples per week, i.e. 288 biological samples per week.

Administration, Oral↗

The maternal and neonatal outcome of high order gestation at King Abdulaziz University Hospital.

OBJECTIVE: To review the outcome of high-order gestations at King Abdulaziz University Hospital (KAUH). METHODS: A retrospective chart review of all high order multiple pregnancy delivered at KAUH. The ante partum and postpartum complications and the neonatal outcome had been studied. RESULTS: Thirty-six triplets, five quadruplets, and one set of quintuplets delivered during the period (1985-2005). The mean maternal age was 28.5 +/- 5 years. The mean gestational age at delivery was 33.9 +/- 2.5 weeks. The maternal complications included: first trimester bleeding 7 (15.4%), pre-eclampsia 5(19.2%), gestational diabetes 2 (3.8%), anemia 12 (23.1%), and preterm labor 29 (65.4%). Of 133 fetuses there were three stillbirths, seven neonatal deaths, six early neonatal deaths, and one late neonatal death, and all died because of extreme low birth weight. Fifteen babies had low APGAR score of < 7 at 5 min. Three babies had congenital anomalies. CONCLUSION: The outcome of high order gestations at our center is comparable to others, prematurity and extreme low birth weight being major determinants.

Female↗

Management of multifetal pregnancies: sixteen years' experience at the Sloan Hospital for Women.

An analysis is made of the management and outcome of 35 pregnancies involving triplets, quadruplets, and quintuplets. Bed rest does not seem to increase the gestational age at the time of delivery but definitely improves the fetal outcome. Administration of betamethasone as early as 24 to 26 weeks' gestation to enhance pulmonary maturity is recommended. Cesarean section is the best mode of delivery if the obstetrician is not confident enough with vaginal maneuvers. The rate in this series was 42%. An experienced medical and nursing staff is mandatory for the successful management of multifetal gestations.

Abortion, Spontaneous↗

Selective termination: clinical experience and residual risks.

Assisted reproductive technologies have aided thousands of couples, but complications have resulted in multifetal pregnancies creating a bitter irony for infertility patients. In an effort to increase the rate of intact survival, we have successfully performed transabdominal first-trimester selective termination procedures on 22 pregnancies including one octuplet, five quintuplet, twelve quadruplet, and four triplet gestations. There have been eight sets of twins, and two singletons delivered, seven twin pregnancies are ongoing, and one early and four late losses of pregnancies. With experience we now counsel as to a high likelihood of a technically successful procedure, but we still have concerns for late losses. We have tried to balance the arguments about the direct harms of performing selective termination and the obstetric risks of not performing selective termination. We believe that selective termination should not be considered a "social" procedure. Our data do not yet make clear whether one, two, or three is the optimal number of embryos to leave. Therefore, on the basis of both current obstetric risk factors and ethical reasoning we will continue to support our protocol of optimally leaving twins.

Abortion, Induced↗

First-trimester transabdominal multifetal pregnancy reduction: a report of two hundred completed cases.

OBJECTIVE: Multifetal pregnancy reduction has been proposed as a way to reduce the risk of preterm delivery in women who conceive three or more fetuses. This communication presents the outcome of 200 consecutive multifetal pregnancies in which reduction to a smaller number of fetuses was accomplished. STUDY DESIGN: All of the procedures were performed in the first trimester by the transabdominal injection of potassium chloride into the thoraces of those fetuses that underwent feticide. All of the pregnancies have been completed and outcome data have been obtained in every case. RESULTS: At the time of the procedure 88 women had triplets, 89 had quadruplets, 16 had quintuplets, and 7 had from 6 to 9 fetuses. These pregnancies were reduced to 189 sets of twins, 5 sets of triplets, and 6 singletons. Reductions to triplets were done at the patient's request, and reductions to singletons were only done for medical indications. There were no cases of chorioamnionitis or other maternal complications attributable to the procedure. A total of 181 women were delivered of one or more live infants after 24 weeks' gestation, and 19 (9.5%) lost all of their fetuses before that time. The mean gestational age for all women delivered after 24 weeks was 35.7 weeks. The mean gestational age at delivery varied inversely with the initial number of fetuses, from 36.1 weeks for women who presented with triplets to 33.8 weeks for those who had 6 or more fetuses, and this trend was statistically significant. Sixteen of the 19 complete pregnancy losses occurred > 4 weeks after the reduction procedure had been performed. The loss rates were 7.9% for those who presented with 3 or 4 fetuses, 12.5% for those with 5, and 42.9% for those with > or = 6. This trend was statistically significant. Two neonates died in the first week of life and one died at 10 months of age as a consequence of the sequelae of severe prematurity. Only two surviving infants have shown evidence of chronic morbidity related to early delivery, and all of the others are developing normally. CONCLUSION: The incidence of intrauterine growth retardation was not increased over that anticipated in a population of twins.

Abortion, Induced↗

Time structure and stimulus dependence of precisely replicating patterns present in monkey cortical neuronal spike trains.

Evidence is presented on the parameters that affect the occurrence of precisely replicating patterns of neural discharge present as 'hidden' patterns in individual neuronal discharge trains of the visual cortical cells of the rhesus monkey in response to precisely controlled stimuli described in our previous publication. Using the All-Interval analytical paradigm we demonstrate: (1) that precisely replicating patterns are present in numbers that cannot be generated through continuous, smoothly varying probability distributions of interspike intervals; (2) that the records contain very large numbers of precisely replicating patterns--doublets, triplets, quadruplets, quintuplets and hextuplets of pulses; (3) that triplet-antitriplet pairs and symmetrical quadruplets are also present in improbable numbers; (4) that different stimuli generate different triplets; (5) and that the first order decay constant of capacity to generate specific precise patterns is a direct function of the number of events making up the patterns and thus that a temporary memory of the occurrence of a pattern exists following the presentation of a stimulus. It is concluded that such patterns of pulses are almost certainly coded symbols related to visual information; that such symbols are sufficiently precise in their replication to permit them to be decoded through spatial summation mechanisms and finally that the ability to generate and the capacity to store such symbols are probably present in the brain as related and coordinated complexes of specific facilitated synapses. Some properties of a proposed model for the production and decoding of such patterns are presented and discussed as are specific mechanisms through which neural networks may implement such functions. Finally, existing and further experimental tests of the mechanisms proposed are outlined.

Animals↗

Invasive techniques for fetal diagnosis in multiple pregnancy.

During a 12-year period, a variety of fetal diagnostic techniques were performed in 112 twin, 3 triplet and 1 quintuplet pregnancies, respectively. Tissues sampled included amniotic fluid, fetal blood and chorionic villi. Two spontaneous abortions occurred and one case of twins was stillborn. Four selective feticides were performed in twins for specific indications and four healthy surviving infants were delivered. It is concluded that fetal diagnosis in multiple pregnancy is safe and accurate without significant perinatal morbidity and mortality.

Female↗

Karyotypic variation of cells from murine thymic lymphomas during short-term culture.

The present study examined the balance in the proportion of cells with either trisomy 15 or a diploid chromosome complement during short-term culture in vitro. Neonatal CFW/D mice were given an intrathymic injection of an endogenous virus (DMBA-LV) isolated from a DMBA-induced thymic lymphoma. The thymus was removed at the terminal leukemic stage, and the cells from each enlarged thymus were cultured in quintuplet. At 0, 6, 12, 24, and 48 hr, cultures were given colcemid for 2 hr prior to harvesting for chromosome examination. The analyzed lymphomas can be divided into three groups according to the characteristics of their stem lines and sidelines, as revealed by direct chromosome preparation (0 hr). Two groups consisted of lymphomas carrying a stem line with either trisomy 15 (group 1) or a diploid karyotype (group 2). A third group (group 3) consisted of lymphomas with a mixture of an abnormal stem line and sidelines. Chromosome analysis of cultures at subsequent times showed that there were fluctuations in the proportion of cells characterized as either stem line or sideline in all tumors at different times during culture. The initial sideline in group 1 tumors had a diploid complement. Although the proportion of the diploid cells increased in 5 of the 6 tumors following either 24 or 48 hr in culture, cells with a diploid karyotype remained as a sideline throughout the culture period. Similarly, the two tumors analyzed in group 2 showed that the initial sideline that contained trisomy 15 increased temporarily to become the stem line following 6 or 12 hr in culture. Group 3 tumors showed a slight variation in the proportion of cells with an abnormal stem line or sideline during culture. Considering all the data from the 10 tumors, 7 tumors had cells with a diploid karyotype, and, although the proportion of cells with this karyotype increased (4 tumors) or persisted (3 tumors) during 48 hr in culture, it remained as a sideline and was not overgrown by trisomy 15 stem line.

Animals↗

Two hundred ninety consecutive cases of multifetal pregnancy reduction: comparison of the transabdominal versus the transvaginal approach.

OBJECTIVE: The purpose of this study was to compare the performance of the transabdominal versus the transvaginal route for the multifetal pregnancy reductions. STUDY DESIGN: Two hundred ninety consecutive cases of multifetal pregnancy reduction were reviewed. Two hundred three reductions (70.0%) were done transabdominally; 75 cases (25.9%) were done transvaginally, and 12 cases (4.1%) used both routes. The indications for the transvaginal route were extreme obesity, abdominal scars, or if the lower fetus could not be reached transabdominally. Two hundred seventy-one women were delivered of live born babies after 24 weeks (group 1). Nineteen cases had pregnancy losses </=24 weeks (group 2). RESULTS: The complete pregnancy loss rate was 6.5% (19/290 cases). Total pregnancy loss rates of multifetal pregnancy reduction were 3.5% (7/203 reductions) for the transabdominal route and 13.3% (10/75 reductions) for the transvaginal route ( P = .004). Overall pregnancy losses were 4.8% for starting with twins, 6.6% for starting with triplets, 1.8% for starting with quadruplets, 14.3% for starting with quintuplets, and 14.3% with starting numbers of >/=6 fetuses. For finishing numbers, total pregnancy losses were 5.1% for ending with a singleton infant, 6.6% for ending with twins, and 0% for ending with triplets. Significant differences in complete pregnancy loss were observed between transabdominal and transvaginal routes for starting with triplets (2.7% for transabdominal versus 16.7% for transvaginal; P = .006) and for finishing with a single fetus (0% for transabdominal versus 20% for transvaginal; P < .004). CONCLUSION: The multifetal pregnancy reduction success rate was higher with the transabdominal route compared with the transvaginal route. Significant differences in favor of the transabdominal route were observed for starting with triplets or finishing with a single fetus. The transvaginal route should be reserved only for cases in which the transabdominal approach is hard or impossible to perform. The performance of the procedure at 12 to 13 weeks of gestation enables structural evaluation of the fetuses before reduction.

Adult↗

Early and simple determination of chorionic and amniotic type in multifetal gestations in the first fourteen weeks by high-frequency transvaginal ultrasonography.

OBJECTIVE: Our aim was to determine the chorionic and amniotic types in multifetal pregnancies with transvaginal ultrasonography at > or = 14 weeks' gestation. STUDY DESIGN: Two hundred twelve multifetal pregnancies were scanned transvaginally at or before 14 weeks' gestation. The number of fetuses and the chorionic and amniotic type were determined ultrasonographically. Of the 212 patients, 54 were delivered at our institution, and 43 of these 54 had pathologic evaluation of the placenta. Ultrasonographic and pathologic correlation of the chorionic and amniotic type was assessed in this group. RESULTS: Ultrasonographic evaluation of the 212 pregnancies demonstrated 64 twin, 87 triplet, 41 quadruplet, 18 quintuplet, 1 sextuplet, and 1 septuplet gestation. Nine of the twin pregnancies were monochorionic-diamniotic; two of the triplets were dichorionic-triamniotic, and four of the quadruplets were trichorionic-quadraamniotic. In the 43 patients with both ultrasonographic and pathologic assessment, there were 40 twins, five of which were monochoronic diamniotic type. All three triplets were trichorionic-triamniotic type. In all 43 transvaginal ultrasonography correctly predicted the chorionic and amniotic type as determined by the pathologic findings. CONCLUSIONS: Transvaginal ultrasonography at < or = 14 weeks can easily and accurately determine the chorionic and amniotic type in multifetal pregnancies.

Amnion↗

Multifetal pregnancy reduction: evaluation of fetal growth in the remaining twins.

OBJECTIVE: Our purpose was to study fetal growth after reduction of high-order multiple gestations to twins. STUDY DESIGN: Birth weight and gestational age data were collected for 236 triplet and greater multiple pregnancies reduced to twins (113 triplets, 89 quadruplets, and 34 quintuplets or above) and was compared with those of a control group of unreduced twins. RESULTS: Rates of intrauterine growth restriction per pregnancy were significantly different between the nonreduced and all categories of reduced multifetal pregnancies. The incidence of intrauterine growth restriction was 19.4% in the nonreduced twins, 36.3% in pregnancies reduced from triplets, 41.6% in pregnancies reduced from quadruplets, and 50% from higher-order multiple gestations. There was a statistically significant trend toward increasing frequency of intrauterine growth restriction with increasing starting fetal number (p = 0.04). The increase in intrauterine growth restriction was primarily accounted for by twin pairs with only one growth-restricted newborn. CONCLUSION: Multifetal pregnancy reduction does not reduce the incidence of intrauterine growth restriction in the remaining fetuses to that of nonreduced twins.

Birth Weight↗

Multifetal pregnancy reduction is not associated with an increased risk of intrauterine growth restriction, except for very-high-order multiples.

OBJECTIVE: Our purpose was to investigate whether multifetal pregnancies reduced to twins have an increased risk of intrauterine growth restriction and discordant birth weight. STUDY DESIGN: This retrospective cohort study investigated the rates of birth weight discordance > 20% and intrauterine growth restriction using both twin and singleton birth weight curves in 441 twin deliveries after multifetal pregnancy reduction (233 reduced from triplets, 156 from quadruplets, and 52 from quintuplets or greater) compared with 136 nonreduced dichorionic twins. RESULTS: No significant difference was found in the frequency of birth weight discordance and in the overall incidence of intrauterine growth restriction by both twin and singleton birth weight curves when pregnancies that underwent multifetal pregnancy reduction were compared with the control group. There was, however, an almost twofold increase in the rate of intrauterine growth restriction in pregnancies with a starting fetal number of 5 or more (23.1%) compared with that in those reduced from triplets or quadruplets (12.1%) when the twin curve standard was used (P = .03). This difference disappeared when these groups were compared with a singleton nomogram. CONCLUSION: This study suggests that multifetal pregnancy reduction is not associated with an increased risk of intrauterine growth restriction unless the starting fetal number is > or = 5. This finding provides a further rationale to avoid transferring excessive numbers of preembryos after in vitro fertilization.

Birth Weight↗

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↗

Assisted reproductive technologies: estimates of their contribution to multiple births and newborn hospital days in the United States.

OBJECTIVE: Estimate the contribution of assisted reproductive technology (ART) in the United States to multiple gestation births and newborn hospital days. DESIGN: Analysis of successful ART conceptions occurring during 1990 to 1991 compared with vital statistics. Newborn hospital days are estimated from the 1990 National Hospital Discharge Survey. SETTING: The American Fertility Society and the Society for Assisted Reproductive Technology registry. PATIENTS: Infants delivered from ART. INTERVENTIONS: Assisted reproductive technology. MAIN OUTCOME MEASURES: Number of multiple gestation infants and newborn hospital days. RESULTS: Approximately 12,327 live-born infants were delivered from ART conceptions during 1990 to 1991, representing 22.2% of all live-born triplet, 17.3% of quadruplet, and 11.4% of quintuplet infants born in the United States. The number of newborn hospital days attributed to ART infants was 87,135 days. Between the periods 1972 through 1974 and 1990 through 1991, the rate of triplet and higher order multiple gestation infants per 100,000 white live births increased by 191%, with 38% due to ART conceptions and 30% to increased childbearing among older women. CONCLUSIONS: Assisted reproductive technology contributed 22% of U.S. triplet and higher order multiple births during 1990 to 1991.

Female↗

Selective reduction.

Multifetal pregnancy reduction continues to be controversial. Attitudes about MFPR have not, in our experience, followed a simple "pro-choice/pro-life" dichotomy. As far back as the mid to late 1980s, opinions about the subject were varied. Even then, when much less was known about the subject, opinions did not always parallel the usual pro-choice/theological boundaries. We believe that the real debate over the next 5 to 10 years will not be whether or not MFPR should be performed with triplets or more. The fact is that MFPR does improve those outcomes. A serious debate will emerge over whether or not it is appropriate to offer MFPR routinely for twins, even natural ones, for whom the outcome is commonly considered "good enough." Our data suggest that reduction of twins to a singleton improves the outcome of the remaining fetus. No consensus on appropriateness of routine 2-1 reductions is ever likely to emerge. The ethical issues surrounding MFPR will always be controversial. Over the years, much has been written on the subject. Opinions will always vary from outraged condemnation to complete acceptance. No short paragraph could do justice to the subject other than to state that most proponents do not believe this is a frivolous procedure but do believe in the principle of proportionality ie, therapy to achieve the most good for the least harm). Over the past 15 years, MFPR has become a well-established and integral part of infertility therapy and attempts to deal with the sequelae of aggressive infertility management. In the mid 1980s, the risks and benefits of the procedure could only be guessed. We now have clear and precise data on the risks and benefits of the procedure and an understanding that the risks increase substantially with the starting and finishing number of fetuses in multifetal pregnancies. The collaborative loss rate numbers (ie, 4.5% for triplets, 8% for quadruplets. 11% for quintuplets, and 15% for sextuplets or more) seem reasonable to present to patients for the procedure performed by an experienced operator. Our experiences and anecdotal experiences from other groups suggest that less experienced operators have worse outcomes. Pregnancy loss is not the only poor outcome. The other main issue with which to be concerned is very early premature delivery, where there is an increasing rate of poor outcomes correlated with the starting number. The finishing numbers are also critical, with twins having the best outcomes for cases starting with three or more. Triplets and singletons do not do as well. We hope that MFPR will become obsolete as better control of ovulation agents and assisted reproductive technologies make multifetal pregnancies uncommon.

Female↗

Prediction of patients with higher order multifetal pregnancy at risk for postpartum pulmonary edema.

OBJECTIVE: This retrospective study aims to verify the factors for the development of maternal pulmonary edema in higher order multifetal pregnancy. STUDY DESIGN: We analyzed medical profiles of a total of 13 triplet, quadruplet and quintuplet pregnancies for the years 1992 through 1997. Some treatments were applied in attempts to promote these multifetal pregnancies. All underwent cesarean section, two of which developed pulmonary edema within a few hours of delivery. There had been no evidence for the development of pulmonary edema antepartum. RESULTS: In the patients affected by pulmonary edema, postoperative values of PaO2/FIO2<250 mmHg showed close association to a value perioperative fluid loading index (FLI)>0; the index consists of an intraoperative fluid balance and preoperative infusion volume within 24 h prior to surgery. Two patients with postoperative pulmonary edema had a perioperative FLI>0, whereas the others had values 0 may have a much higher risk for postoperative pulmonary edema, suggesting the predictive role of the perioperative FLI value.

Adult↗

Adaptation to various environments and resistance to disease of the Improved Boer goat.

The Improved Boer Goat is a remarkable small-stock ruminant that possesses distinctive qualities enabling it to excel as an efficient red meat producer. It is early maturing, reaching a mean maximum weight of approximately 62kg at 3.5 years of age on natural pasture under extensive grazing conditions. It boasts high fecundity, with approximately 2.09 kids born per doe kidded. A relatively large proportion of does ( approximately 33%) have triplets, whilst the occurrence of kids born as quadruplets and quintuplets have also been documented. The Boer goat is predominantly a browser, enabling it to convert shrub and bush into red meat, thereby playing a supplementary role to other farm stock in increasing meat production per unit area, rather than being in competition with them. As a browser, the goat is also extremely useful and effective in combatting undesirable bush encroachment. In addition, it appears to be fairly resistant towards certain diseases which are normally contracted by other small stock, such as sheep. Lastly, Boer goats produce red meat of high quality which is hardly distinguishable from that of mutton or lamb as far as flavour is concerned, provided animals are slaughtered at a relatively young age.

Journal Article↗