Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Birth Limiting”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 253 records · Page 14Linked to original sources
PubMed1999

Geographical variation in rate of schizophrenia in rural Ireland by place at birth vs place at onset.

This study examined geographical variation in rate of occurrence of schizophrenia by place at birth vs place at onset, among a rural Irish catchment area population of unusual stability and socioeconomic homogeneity. Within a catchment area of 21,520 persons, all cases of schizophrenia were sought using current inpatient and outpatient records and key informants active in the community. Suspected cases were interviewed personally and diagnosed using DSM-III-R criteria. Place at birth and place at onset of psychosis were specified among the 32 District Electoral Divisions constituting the study region. For the 72 cases ascertained, an unremarkable overall prevalence rate/morbid risk obscured substantial and significant geographical variations therein between District Electoral Divisions. Particularly after controlling for high-density families, men demonstrated prominent geographical variation both by place at birth and by place at onset, with most men remaining unmarried and becoming ill at their place of birth; conversely, women demonstrated prominent variation by place at birth but more limited variation by place at onset, despite more frequent transitions from the parental home to the marital home before onset. Even when cases changed their location before the onset of psychosis, geographical variation in rate of occurrence of schizophrenia remained associated more strongly with factors related to the place of their birth.

Adult↗
PubMed2001

[Prevention of congenital toxoplasmosis in France. Risk assessment. Results and perspectives of prenatal screening and newborn follow up].

In France, a national program for the prevention of congenital toxoplasmosis has been set up 25 years ago. This program is here presented and discussed in details. It is based on a decision tree well defined, with pre and/or per gravidic serological screening with several different tests, completed, if necessary, by ultrasounds examinations of the fetus, biomolecular tests (PCR) on amniotic fluid, and by clinical, biological, and radiological surveillance of neo-nates. The purpose of this prevention program is to: 1/identify nonimmune young women and limit their contamination risk during pregnancy by appropriate counseling on hygiene and diet; 2/screen and treat per gravidic toxoplasmosis as early as possible so as to prevent or limit transmission to the fetus and its consequences. 3/in utero diagnose and treat infestation of the fetus; 4/diagnose and treat asymptomatic congenital toxoplasmosis in neonates, to prevent risks of reactivation and late complications, especially ocular. Such a prevention program has a cost validated by the prevalence of acquired toxoplasmosis in adults in France (over 50% of the population) and by the yearly incidence of congenital toxoplasmosis (at least 0.1% of births according to the best hypothesis). These 6 to 700 congenital toxoplasmosis cases per year may be compared to the 6 to 7,000 per gravidic seroconversions which could lead to fetal contamination if no preventive measures are taken. Nevertheless, as it is often the case in the field of prevention, it is very difficult to statistically assess the efficacy of this program even though several arguments show that it allows to eliminate the most serious toxoplasmosis, sources of serious handicaps at birth, and to limit the frequency of late complications (especially retino-choroiditis) of asymptomatic infections in neonates. The position of European countries varies as to prevention of congenital toxoplasmosis. Some countries (Austria, Belgium) have national prevention programs similar to the French one, whereas others have set up only limited programs or set up no systematic prevention. These differences may be accounted for by the different frequencies of toxoplasmic risk. It seems mandatory to forget all dogmatism and not to stick to a strictly statistical approach for a disease with not only medical but also social and human consequences.

Female↗
PubMed2000

Lack of selective developmental neurotoxicity in rat pups from dams treated by gavage with chlorpyrifos.

Pregnant Sprague-Dawley rats were given chlorpyrifos (O:, O-diethyl-O:-[3,5,6-trichloro-2-pyridinyl] phosphorothioate; CPF) in corn oil by gavage from gestation day 6 (GD 6) through lactation day 10 (LD 10) at dosages of 0, 0.3, 1, or 5 mg/kg/day in a developmental neurotoxicity study that conformed to U.S. Environmental Protection Agency 1991 guidelines. GD 0 was the day when evidence of mating was observed and postnatal day 0 (PND 0) was the day of birth. Toxicity was limited to the highest dosage level (5 mg/kg/day) and, in the dams, consisted of muscle fasciculation, hyperpnea, and hyperreactivity. A nonsignificant overall trend toward weight gain and feed consumption was also observed in the high-dosage dams, with a statistically significant Group x Time interaction for reduced weight gain in the 5-mg/kg/day group near the end of gestation. Although many developmental indices were normal, pups from high-dosage dams had increased mortality soon after birth, gained weight more slowly than controls, and had several indications of slightly delayed maturation. The early deaths and delayed maturation were attributed to maternal toxicity, though a possible contributing role of direct pup toxicity in delayed development cannot be eliminated. In spite of the apparent delay in physical development, high-dosage pups tested just after weaning had normal learning and memory as tested on a T-maze spatial delayed-alternation task. Habituation, a primitive form of learning, was tested in 2 tasks (motor activity and auditory startle) and was not affected. No overt effects were noted in either dams or pups at 1 or 0.3 mg/kg/day. Based on these data, chlorpyrifos produced maternal and developmental toxicity in the 5-mg/kg/day-dosage group. There was no evidence of selective developmental neurotoxicity following exposure to chlorpyrifos.

Administration, Oral↗
PubMedDate not supplied

Dynamic patterned expression of orphan nuclear receptor genes RORalpha and RORbeta in developing mouse forebrain.

As a step toward using two closely related members of the nuclear receptor family, RORalpha and RORbeta, as markers and tools for genetic manipulations in mouse forebrain, we have used in situ hybridization to analyze their expression from E10.5 to P7. At later embryonic and early postnatal ages, RORalpha expression in dorsal thalamus is mainly limited to robust expression throughout the principal sensory nuclei. RORbeta is expressed in a similar set of dorsal thalamic nuclei as RORalpha, but exhibits a more limited expression within the principal sensory nuclei. RORalpha is expressed as early as E12.5 in dorsal thalamus by presumptive ventroposterior neurons, whereas RORbeta expression is not detected until later embryonic ages. RORbeta is highly expressed in embryonic neocortex, and exhibits strongly graded rostrocaudal and lateromedial patterns of expression. Over the first postnatal week, the graded expression of RORbeta gradually acquires a disjunctive pattern largely restricted to layers 4 and 5 of the primary sensory areas. In contrast, very weak RORalpha expression is first detected in the neocortex just around birth, and is limited to the middle layer of the cortical plate of the putative somatosensory area. Later, a limited and very weak RORalpha expression is evident mainly in layer 4 of more caudal areas. To determine whether patterned retinal input is required for the proper postnatal expression and patterning of RORalpha and RORbeta, we performed neonatal bilateral enucleations. We did not detect any significant differences between normal and enucleated mice in expression in visual areas. Although TCA input may be required for proper regulation of the postnatal expression of RORalpha and RORbeta, these findings suggest that aspects of the dynamic postnatal expression and patterning of these genes are regulated independently of patterned visual activity relayed by geniculocortical afferents. The patterned expression of RORalpha in dorsal thalamus suggests that this gene locus may be useful to genetically modify the development of dorsal thalamus and thalamocortical projections.

Animals↗
PubMed2005

Assisted reproductive technologies and birth outcomes: overview of recent systematic reviews.

Several systematic reviews have been published recently on birth outcomes of infants conceived through assisted reproductive technologies (ART), compared with infants conceived spontaneously. These outcomes include perinatal mortality, preterm birth, low birthweight and birth defects. Methodological limitations of many of the individual studies (including small sample size, potential for bias in ascertainment of outcomes and considering singletons and multiples together) were obviated in these reviews by excluding studies where methods were considered inadequate, by conducting meta-analyses using data from all methodologically sound studies (small and large) and by examining singletons separately. Overall, the reviews indicate few differences between outcomes in ART twins compared with twins conceived spontaneously. However, in singleton ART infants, there are around two-fold increases in risk of perinatal mortality, low birthweight and preterm birth, about a 50% increase in small for gestational age and a 30-35% increase in birth defects, compared with singletons conceived spontaneously. Couples considering ART should be counselled about the increased risk of adverse outcomes. Epidemiologists, in conjunction with clinical and laboratory colleagues, should now focus on large, methodologically sound studies with long-term follow up that seek to identify the reasons for these increased risks and their long-term consequences, whether they are associated with particular technologies and causes of infertility, and how they might be reduced.

Birth Weight↗
PubMed2005

Development of the blood and muscle oxygen stores in gray seals (Halichoerus grypus): implications for juvenile diving capacity and the necessity of a terrestrial postweaning fast.

To successfully transition from nursing to foraging, phocid seal pups must develop adequate diving physiology within the limited time between birth and their first independent foraging trip to sea. We studied the postpartum development of oxygen stores in gray seals (Halichoerus grypus, n=40) to better understand the ontogeny of diving capacity in phocids. Hemoglobin (Hb), hematocrit (Hct), blood volume (BV), and myoglobin (Mb) levels in newborn (3 d postpartum [DPP]) and newly weaned (17+/-0.4 DPP) pups were among the lowest measured across age classes. During the pups' terrestrial postweaning fast (PWF), Hb, Hct, mass-specific BV, and Mb increased by 28%, 21%, 13%, and 29%, respectively, resulting in a 35% increase in total body mass-specific oxygen stores and a 23% increase in calculated aerobic dive limit (CADL). Although Hb and Hct levels at the end of the PWF were nearly identical to those of yearlings, total body mass-specific oxygen stores and CADL of weaned pups departing for sea were only 66%-67% and 32%-62%, respectively, of those for yearlings and adult females. The PWF represents an integral component of the physiological development of diving capacity in phocids; however, newly independent phocids still appear to have limited diving capabilities at the onset of foraging.

Analysis of Variance↗
PubMed2001

Paternal contribution to birth weight.

STUDY OBJECTIVE: Understanding causes of variation in birth weight has been limited by lack of sufficient sets of data that include paternal birth weight. The objective was to estimate risks of low birth weight dependent on parental birth weights and to estimate father-mother-offspring correlations for birth weight to explain the variability in birth weight in terms of effects of genes and environmental factors. DESIGN: A family design, using trios of father-mother-firstborn child. SETTING: The complete birth population in Norway 1967-98. PARTICIPANTS: 67 795 families. MAIN RESULTS: The birth weight correlations were 0.226 for mother-child and 0.126 for father-child. The spousal correlation was low, 0.020. The relative risk of low birth weight in the first born child was 8.2 if both parents were low birth weight themselves, with both parents being above 4 kg as the reference. The estimate of heritability is about 0.25 for birth weight, under the assumption that cultural transmission on the paternal side has no effect on offspring prenatal growth. CONCLUSIONS: Paternal birth weight is a significant and independent predictor of low birth weight in offspring. The estimate of the heritability of birth weight in this study is lower than previously estimated from data within one generation in the Norwegian population.

Adult↗
PubMed1998

Should fewer premature infants be screened for retinopathy of prematurity in the managed care era?

OBJECTIVE: To determine appropriate upper limits for gestational age and birth weight when screening infants for retinopathy of prematurity (ROP). DESIGN: Retrospective survey. SETTING: Tertiary neonatal intensive care nursery. PATIENTS: Seven hundred seven infants born July 1, 1990 to June 30, 1996 and screened for ROP according to the 1988 to 1996 American Academy of Pediatrics guidelines. OUTCOME MEASURES: Maximum stage of ROP with respect to birth weight and gestational age. RESULTS: No ROP more than Stage 1 was observed in infants with gestational ages >/=32 weeks or birth weights >/=1500 g. All cases of threshold and Stage 4 ROP were confined to infants with gestational ages </=30 weeks or birth weights <1200 g. CONCLUSIONS: The latest American Academy of Pediatrics screening guidelines for ROP are discretionary for infants with birth weights >1500 g or gestational ages >28 weeks. If ROP screening is limited to infants with birth weights of </=1500 g, 34.2% fewer infants would require screening compared with the previous <1800 g recommendation, while missing no cases of ROP more than Stage 1. A gestational age cut-off of </=28 weeks, however, is less desirable, and could potentially miss several infants with more advanced retinopathy (including Stage 4). If ROP screening criteria were instead modified to include infants of gestational ages <32 weeks, the number of patients requiring screening could be reduced 29.1% compared with the previous recommendation of <35 weeks, again without missing any cases of ROP more than Stage 1. Use of such a screening strategy (birth weight <1500 g or gestational age <32 weeks) is predicted to save in excess of 1.5 million dollars annually in the United States, while missing no cases of ROP more than Stage 1.

Birth Weight↗
PubMedDate not supplied

Birth setting for low-risk pregnancies. An analysis of the current literature.

This article reviews the literature on birth settings for women with low-risk pregnancies. Methodological issues of the existing research include nonrandom designs, small samples, selection differences, data limitation, and confounding bias. Studies for four birth sites are summarized: the home, freestanding birth centers, in-hospital birthing centers or birthing rooms, and traditional hospital settings. Despite the methodological limitations, nontraditional birth settings present advantages for low-risk women as compared with traditional hospital settings: lower costs for maternity care, and lower use of childbirth procedures, without significant differences in perinatal mortality.

Confounding Factors, Epidemiologic↗
PubMed1997

Fetal pulmonary development: the role of respiratory movements.

The lung develops before birth as a collapsible, liquid-filled, organ. Throughout the later stages of gestation the fetal lungs are maintained at a level of expansion that is considerably greater than the level achieved as a result of passive equilibration between lung recoil and the chest wall. Fetal breathing movements (FBM) are a feature of normal fetal life and, as such, are used clinically in the assessment of fetal wellbeing. By opposing lung recoil, FBM help to maintain the high level of lung expansion that is now known to be essential for normal growth and structural maturation of the fetal lungs. During 'apnoeic' periods between successive episodes of FBM, active laryngeal constriction has the effect of opposing lung recoil by resisting the escape of lung liquid via the trachea. The prolonged absence or impairment of FBM is likely to result in a reduced mean level of lung expansion which can lead to hypoplasia of the lungs. There is clinical evidence, disputed by some, that the absence of FBM exacerbates the effects of other factors that are associated with lung hypoplasia, such as premature rupture of fetal membranes and oligohydramnios. Even in the absence of such factors, prolonged or repeated reductions or abolition of FBM may contribute to impairments of fetal lung development; FBM can be inhibited by fetal hypoxaemia, hypoglycaemia, maternal alcohol consumption, maternal smoking, intra-amniotic infection and maternal consumption of sedatives or narcotic drugs. Abnormal growth of the fetal lungs has relevance for postnatal respiratory health as it is now recognised that there may be only a limited capacity after birth for the restoration of normal pulmonary architecture following impaired intra-uterine lung development.

Animals↗
PubMed1996

Intraalveolar bubbles and bubble films. I. formation and development during the first 48 hours of extrauterine life in rabbits.

BACKGROUND: Aeration of mature lungs at birth depends on formation of intraalveolar bubbles and bubble films (Scarpelli 1978. Pediatr. Res., 12:1070-1076). Bubbles establish immediately structural stability and pulmonary gas exchange. Given that air spaces are cleared in minutes of fetal liquid (the initial substrate for bubble formation), in formation possible beyond this period? If so, is this related to early development of pulmonary function and structure? METHODS: Mature, spontaneously breathing rabbit pups at 1-10 min and 1, 3, 8, 24, and 48 h after vaginal birth were anesthetized, trachea was occluded at "resting volume" (approximately functional residual capacity), and lungs were rapidly exposed to preserve in vivo intrapulmonary status. The entire lung was examined by stereomicroscopy. Other determinations included resting volume, lung wet weight, volume-pressure curves, histological sections, lung dry weight, tissue hydroxyproline (OH-Pro), and lavage phospholipids (PL). Bubble mobility in situ was tested. Bubbles were released into bathing liquid by incision of peripheral units and monitored over time. RESULTS: Pup activity and gross appearance of the lungs, together with septal thinning, secondary septal development, clearance of intraluminal liquid, increasing tissue OH-Pro, and PL distribution indicated normal postnatal development. Each aerated unit examined at resting volume (all lobes, all ages) contained intraalveolar bubbles. Transition to free gas exclusively in conducting airways and bubbles/bubble films in peripheral gas exchange units occurred within 1 h. Bubbles appeared to be exclusively within alveoli at 4 h and thereafter. Bubbles persisted and new bubbles were formed during subsequent inflation to maximal volume and deflation to atmospheric pressure (P0). Volume of intact lungs at P0 was maintained by the counterforce of rigid bubble films against tissue retraction. When bubbles were released either at resting volume or at P0, the bubble-free loci became airless. Constant size and stability of released bubbles support preferential incorporation of surfactants into bubble films and constant "near-zero surface tension" (Scarpelli 1978. Pediatr. Res., 12:1070-1076). CONCLUSIONS: We show the ubiquitous presence of intraalveolar bubbles and bubble films in vivo throughout the first 48 h of postnatal life. Bubble film rigidity sustains aeration and prevents collapse, while low surface tension of the films facilitate liquid removal from the air spaces. Bubbles in situ are stable and, within apparent limits, mobile; after birth they are quickly restricted to the alveolar spaces, leaving airways bubble free.

Air↗
PubMed1993

A review of risk scoring for preterm birth.

Risk scoring is a quantitative method used to screen populations to identify persons at increased risk of developing a specific adverse health outcome. Risk scoring for preterm birth has taken the form of a simple additive score with risk factors based on clinical experience to sophisticated multivariable risk models using a large number of factors from several domains. It appears that our attempts at defining an effective risk scoring method for preterm birth have been unsuccessful. The positive predictive values (the percent of women defined as high risk that actually go on to have a preterm birth) have been relatively low (20% to 30%) and vary depending on the population studied. Several difficulties with risk scoring for preterm birth are identified. The biggest limitation of current efforts at screening for preterm birth is our ignorance of the causes of preterm birth. The role of recently defined risk factors, of the potential for synergistic relationship between risk factors, and of physician or hospital factors needs to be evaluated. Epidemiologic evidence is suggestive that preterm birth can be subclassified into preterm labor, preterm rupture of the membranes, and medically induced preterm births; however, substantial problems with misclassification, detection bias, and questionable biologic feasibility argue that these subgroups need to be validated before they can be used with confidence. Careful attention should also be paid to the statistical and methodologic limitations of risk scoring. Unless a single risk factor for a disease outcome has a relative risk over 5 and is very prevalent in the population (more than 25%), most of the disease cases will not have the risk factor. It may be unrealistic, however, to think that a single risk factor will adequately define women at high risk for preterm birth. Therefore in the future, if several lesser risk factors can be identified, multivariate modeling may prove useful in defining a valid high-risk group. In addition, attention should be paid to ensure that the risk factor assessment tools obtain accurate information and are easily reproducible among different health care providers. The reduction of preterm birth in France that occurred over a decade was accompanied by radical social changes in the ways in which the population and government perceived pregnancy and childbirth. In addition to universal access to prenatal care, population-based social changes to liberalize pregnancy leave policies and a commitment to supporting women during pregnancy were the focus of the government's commitment to reducing preterm birth.(ABSTRACT TRUNCATED AT 400 WORDS)

Discriminant Analysis↗
PubMed2002

A new mouse model for autosomal recessive polycystic kidney disease.

In the course of large-scale mutagenesis studies, we discovered a mutant that provides a new mouse model for human autosomal recessive polycystic kidney disease. Animals homozygous for this mutation, T(2;10)67Gso, present evidence of grossly cystic renal and hepatic tissue at birth and a limited survival time of 3-4 days. The recessively expressed phenotype is associated with inheritance of a reciprocal translocation involving mouse chromosomes 2 and 10. Here we describe the pathology and phenotype of this new mutation. The mapping of the chromosomal breakpoint to the 1.0-cM critical region defined for another mouse autosomal recessive polycystic kidney disease model, juvenile congenital polycystic kidney disease (jcpk), led us to undertake the complementation testing that confirmed T(2;10)67Gso and jcpk are allelic. Because of the strong resemblance between the phenotype associated with these mouse mutations and early childhood polycystic kidney disease, and because of advantages offered by reciprocal translocations for gene mapping and cloning, T(2;10)67Gso should prove a valuable asset for studies concerning this fatal disease.

Animals↗
PubMed1988

Obstetric analgesia and infant outcome in monkeys: infant development after intrapartum exposure to meperidine or alfentanil.

Infant monkeys (Macaca mulatta) exposed to narcotic analgesics during labor after treatment of dams were evaluated for growth and development over a 14-week period. Ten infants exposed to meperidine (2 mg/kg maternal dose) or alfentanil (0.1 mg/kg maternal dose) were compared with seven controls whose dams received no analgesic. No group differences in weight gain or body growth were observed. Alfentanil-exposed infants appeared to have a higher incidence of infections requiring veterinary treatment. Measures of spontaneous activity showed a significantly higher incidence of immature rest pattern (laying) in the alfentanil group associated with lower overall locomotor activity relative to controls. Meperidine-exposed infants had a generally higher overall level of locomotor activity than controls that was statistically significant at 11 weeks of age. Alfentanil-exposed animals were impaired in performance of a simple cognitive task (object constancy) at 2 to 3 months of age and meperidine-exposed infants showed a similar nonsignificant trend. Gross and fine motor maturations were similar to those of controls. Thus, in this situation, the impact of obstetric analgesic treatment was demonstrable for several months after birth in some limited areas.

Alfentanil↗
PubMed1988

Microtubule-associated proteins characteristic of embryonic brain are found in the adult mammalian retina.

We have used monoclonal antibodies against each of the major mammalian brain microtubule-associated proteins (MAPs), MAP1, MAP2, MAP3, MAP5, and tau, to study the timing of appearance and the cytological distribution of these proteins during the development of the rat retina. Western blots of adult rat retina reveal MAPs that are characteristic of embryonic brain, i.e., MAP5 and the low-molecular-weight forms of MAP2 (MAP2c) and tau (juvenile tau). At the onset of neuronal differentiation within the embryonic retina, MAP5, MAP3, MAP2c, and tau are found in the perikarya or extending axons of ganglion cells. High-molecular-weight MAP2, a dendrite marker, does not appear in the retina until the second day of postnatal development, when ganglion cell dendrites ramify within the inner plexiform layer. MAP1, which is characteristic of adult brain, does not appear in the retina until 1 week after birth, and is limited to ganglion cells and their processes. In the adult retina, MAP5 and MAP2c are concentrated within the inner segments and cell bodies of photosensitive cells, whereas tau is found in horizontal cells and more internal cell layers. Since photosensitive cells are unique among retinal neurons in their constant regeneration of their primary processes, the photoreceptive outer segments, both MAP5 and MAP2c appear not only to be involved in events associated with the embryonic differentiation and growth of neurites, but also in process regeneration in adult neurons that maintain some embryonic characteristics.

Age Factors↗
PubMed2005

Intertwin time interval: how it affects the immediate neonatal outcome of the second twin.

OBJECTIVE: Customarily 30 minutes is used as the upper limit of intertwin birth times. This study was conducted to define factors that influence the immediate neonatal outcome of the second twin and to assess whether a valid cutoff time is evident. STUDY DESIGN: We evaluated all live born viable vaginal twin deliveries (144) between November 1997 and December 2003. The relationship between intertwin birth time and neonatal outcome was then evaluated continuously and in 15 to 30-minute intervals. RESULTS: In multivariate analysis, only intertwin birth time predicted umbilical cord pH. Arterial/venous pH decreased linearly at a rate of 0.00063 and 0.00081 U/min. Venous pH was significantly lower in later 15-minute intervals compared with earlier ones (P = .002), and in patients delivering before or after a 30-minute cutoff (7.31 vs 7.26, P = .012). CONCLUSION: Our study confirmed that longer intertwin birth time is associated with a continuous slow decline in umbilical cord pH. However, the small differences in pH were not large enough to impact clinical management.

Apgar Score↗
PubMedDate not supplied

[Formation of a cohort of opiate addicts through linkage of confidential records].

The need to combine several files in order to create a cohort of opiate addicts, sufficiently large for the analysis of its mortality, requires use of the probabilistic method of record linkage. This study is a preliminary phase in which two sub-files of the Hospital del Mar (Barcelona) Register of toxicological emergencies are linked. This phase served to adapt probabilistic record linkage to our files, develop computer programs, define agreement criteria, and evaluate the validity and performance of the method. In order to safeguard confidentiality, identification variables were limited to sex, birth date and three initial letters from each surname. The automated probabilistic linkage was seen to be feasible, valid and efficient; in contrast to deterministic approaches, sensitivities and specificities above 95% were obtained with visual reviewing of under 5% of the records. Difficulties encountered during the process are discussed.

Cohort Studies↗
PubMed1999

Multiple high cell dose injections of normal marrow into newborn jaundiced mice dramatically prolong life despite transient repopulation.

Jaundiced (ja/ja) mice have a severe hemolytic anemia caused by deficiency of the erythroid cytoskeletal protein beta-spectrin. Unless they are transfused, 99% of the mutant mice die after birth. Here, we test a new therapy involving multiple, high cell dose marrow injections into newborn non-ablated recipients. The ja/ja and normal newborn mice were injected intravenously with a total of 8.7 x 10(6) genetically marked +/+ marrow cells/g body weight. Donor and host red blood cells were quantified and the status of the recipients monitored. The jaundiced but not the normal recipients had up to 57% replacement with donor red cells by 9 weeks. The treatment significantly increased red cell counts and extended the average lifespan to 5 months beyond that previously reported for ja/ja mice transfused at birth. Replacement was limited to red cells. The donor cells disappeared in three of five mutant mice alive beyond 27 weeks. Marrow from a 48-month-old ja/ja recipient no longer positive for donor cells was injected into a secondary host. The recipient acquired the blood phenotype of the primary ja/ja host. The possibility that the marker was not well tolerated following multiple cell injections was investigated in normal adult mice injected with a total of 5.3 x 10(6) marrow cells/g body weight. Recipients became chimeric (>38% donor red and white cells) long-term (>12 months). The results indicate donor stem cells (a) prolong life in the jaundiced mice, but (b) do not survive long-term when injected into newborn mice. We conclude that destructive mechanisms may not be limited to ja/ja red cells.

Animals↗