Biomedical subjects

T J Moss

Publications and source records attributed to T J Moss.

At least 19 recordsLinked to original sources

PubMed2002

The effect of prenatal betamethasone administration on postnatal ovine hypothalamic-pituitary-adrenal function.

Prenatal exposure to glucocorticoids is associated with alterations in fetal growth and endocrine function. However, few studies have examined the effects of clinically relevant doses of glucocorticoids on postnatal hypothalamic-pituitary-adrenal (HPA) function. To determine the effects of maternal or fetal betamethasone administration (0.5 mg/kg maternal or estimated fetal weight) on postnatal HPA function at 6 months and 1 year postnatal age, pregnant ewes were randomized into the following treatment groups: no treatment (n=6); maternal saline (n=6); single maternal betamethasone (M1) (n=6); repeated maternal betamethasone (M4) (n=6); fetal saline (n=5); single fetal betamethasone (n=6) and repeated fetal betamethasone (F4) (n=6). Single injections were given at 104 days of gestation and repeated injections at 104, 111, 118 and 125 days. Lambs were born spontaneously and the ACTH and cortisol responses to i.v. corticotropin-releasing hormone (CRH) (0.5 microg/kg) plus arginine vasopressin (AVP) (0.1 microg/kg) were measured at 6 months and 1 year postnatally. At 6 months postnatal age, neither maternal nor fetal prenatal betamethasone administration altered significantly the ACTH and cortisol responses to CRH+AVP. However, in animals at 1 year postnatal age, a previous single injection of betamethasone to the mother (M1) resulted in significantly elevated basal and stimulated cortisol levels (P<0.05), without significant change in the ACTH response. In contrast, betamethasone administration to the fetus resulted in significantly attenuated ACTH responses to CRH+AVP at 1 year compared with control animals (P<0.05), but these were not associated with any significant changes in basal or stimulated cortisol levels. All control animals exhibited a significant increase in peak ACTH responses to CRH+AVP between 6 months and 1 year postnatal age (P<0.05). After prenatal betamethasone (F4, M4) the difference in peak ACTH response between animals at 6 months and 1 year postnatal age was abolished. We conclude that in sheep between 6 months and 1 year postnatal age, HPA function undergoes developmental changes that are influenced by prenatal glucocorticoid exposure. Furthermore, the effects of glucocorticoid on postnatal HPA responses may vary according to the time in gestation that the steroid was administered, and whether it was given directly into the fetal or maternal compartment.

Adrenocorticotropic Hormone↗

PubMed2001

The fetal placental hypothalamic-pituitary-adrenal (HPA) axis, parturition and post natal health.

A general characteristic of fetal endocrine maturation across different species is the enhanced activity of the fetal hypothalamic-pituitary-adrenal (HPA) axis during late gestation. Precocious activation of this axis may occur when the fetus is exposed to an adverse intra-uterine environment, such as hypoxemia. HPA development is associated with increased levels of ACTH(1-39) and adrenal corticosteroids (cortisol in sheep and human) in the fetal circulation, and increased expression of mRNA encoding corticotrophin releasing hormone (CRH) in the hypothalamus, proopiomelanocortin (POMC) in the pituitary, and key steroidogenic enzymes in the fetal adrenal. At term, increased levels of cortisol act on the placenta/trophoblast derived cells to increase expression of prostaglandin synthase Type II (PGHS-II). In human gestation, cortisol also decreases expression of 15-hydroxyprostaglandin dehydrogenase (PGDH) in chorionic trophoblast cells. Increased synthesis and decreased metabolism of prostaglandin (PG) results, during late gestation, in enhanced output of primary PG, which in turn increases the activity of 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) in the human fetal membranes. Increased chorionic 11 beta HSD-1 results in increased local generation of cortisol from cortisone, with further paracrine/autocrine stimulation of PG output. Increased fetal cortisol contributes to the maturation of organ systems required for postnatal extra-uterine survival. However, excessive levels of feto-placental glucocorticoid, derived from maternal administration of synthetic corticosteroids or sustained endogenous fetal cortisol production, results in intrauterine growth restriction. Fetal sheep, exposed to maternal betamethasone in late gestation, develop insulin resistance and exaggerated adrenal responses to HPA stimulation by 6-12 months postnatal life. Thus, the level of fetal HPA activity is crucial not only for determining gestation length, but may also predict pathophysiologic adjustments in later life.

Animals↗

PubMed2001

Dose and time response after intraamniotic endotoxin in preterm lambs.

Intraamniotic endotoxin causes chorioamnionitis, which is followed by improved fetal lung function after 4 d in fetal sheep. We evaluated 0.1 mg, 1 mg, 4 mg, and 10 mg endotoxin for inflammation and lung maturation effects after 7 d. Four and 10 mg endotoxin caused similar lung maturation and inflammation in the lung and chorioamnion. The number of neutrophils in cord blood and the inflammatory cells in alveolar lavage and fetal lung tissue increased in a dose-dependent manner. Lower endotoxin doses induced indicators of chorioamnionitis, lung and systemic inflammation without inducing lung maturation. Therefore, some degree of inflammation can occur without subsequent lung maturation. The inflammatory changes caused by 4 mg endotoxin were assessed after 5 h, 24 h, 72 h, and 7 d to discern local versus systemic inflammation after intraamniotic endotoxin. At 5 h active inflammatory cells were in the airways producing hydrogen peroxide, and interleukin-6 and -8 were increased in the cord blood indicating both lung and systemic responses. Cells recruited into the amniotic fluid produced proinflammatory cytokine mRNA for 7 d with no cytokine mRNA in chorioamnion, lung, or spleen after 72 h. The cells in the amniotic fluid may be a source of prolonged fetal exposure to proinflammatory cytokines.

Amniotic Fluid↗

PubMed2001

Ventilatory and arousal responses to respiratory stimuli of full term, intrauterine growth restricted lambs.

We aimed to determine the effect of intrauterine growth restriction (IUGR) on the control of breathing and arousal in sleeping postnatal animals. We measured ventilatory and arousal responses to respiratory challenges during sleep in normally grown (birthweight 5.17+/-0.48 kg) and IUGR (2.64+/-0.19 kg) full term lambs. During wakefulness, IUGR lambs had significantly lower arterial pH and higher Pa(CO(2)) levels. During quiet sleep, but not active sleep, end tidal CO(2) was elevated in IUGR lambs (P=0.08). During active and quiet sleep, minute ventilation (per kg body weight) was significantly higher in IUGR lambs than controls. Ventilatory responses to hypercapnia and/or hypoxia were not different between control and IUGR lambs during active and quiet sleep but end tidal CO(2) at arousal was consistently higher in IUGR lambs; other indices of arousal were not affected by IUGR. Our findings suggest IUGR lambs require an elevated level of ventilation to maintain respiratory homeostasis and that alterations in lung function are likely consequences of IUGR.

Animals↗

PubMed2001

Antenatal glucocorticoids and growth: single versus multiple doses in animal and human studies.

In recent years, many clinicians have prescribed repeated courses of glucocorticoids to pregnant women at risk of early preterm birth. The published literature has provided reassurance from randomized controlled trials that single-course treatment improves postnatal lung function without deleterious consequences, but we do not yet have data from randomized trials designed specifically to investigate the effects of repeated courses. Data from animal studies have, for many years, provided evidence that prenatal exposure to glucocorticoids restricts fetal growth and, more recently, has suggested a role in programming the individual to adult disease. Multivariate analyses from non-randomized cohorts have also suggested associations between repeated treatments and reduced birth weight, but we await results from randomized controlled trials currently in progress to provide more definitive answers. Regardless of any effect on growth, the possibility that adult health and disease may be programmed by fetal exposure to glucocorticoids will ensure our need to balance the ability of these agents to improve newborn survival with the potential consequences in later life.

Animals↗

PubMed2001

The interactive effects of endotoxin with prenatal glucocorticoids on short-term lung function in sheep.

OBJECTIVE: Previously we have shown that neonatal lung function in sheep after preterm birth is profoundly enhanced by intra-amniotic injection of endotoxin, with a magnitude at least equal to that induced by maternal betamethasone administration. This study investigated the effects of betamethasone on lung maturation and growth in the presence of inflammation by treating sheep with both maternal intramuscular betamethasone and intra-amniotic endotoxin injections. STUDY DESIGN: Time-mated pregnant ewes at 118 days' gestation were allocated at random to receive maternal intramuscular or intra-amniotic saline solution injection (n = 10), maternal intramuscular betamethasone injection (0.5 mg/kg; n = 7), intra-amniotic endotoxin injection (20 mg Escherichia coli B055;B5; n = 11) by ultrasonographic guidance, or both betamethasone and endotoxin injections (n = 7). The lambs were delivered abdominally at 125 days' gestation (term is 150 days' gestation), and the neonates were ventilated for 40 minutes before postmortem examination. RESULTS: Combined treatment with betamethasone and endotoxin resulted in significantly greater improvements in neonatal lung function than occurred after treatment with either agent alone, and this effect was not accompanied by a further increase in surfactant levels. The reduction in birth weight that is seen after maternal betamethasone treatment was not seen when this treatment was combined with endotoxin. Endotoxin treatment resulted in inflammatory responses in cord blood and alveolar wash, and these responses were not inhibited by betamethasone treatment. There were no pregnancy losses. CONCLUSION: Both intra-amniotic endotoxin injection and maternal intramuscular betamethasone injection promoted fetal lung maturation. When these treatments were combined, there were additive effects on short-term postnatal lung function but not on surfactant levels. Endotoxin negated the growth restriction in sheep caused by maternal betamethasone treatment. These findings provide evidence that the lung maturation induced by glucocorticoids and that induced by endotoxin are mediated by different mechanisms.

Acute-Phase Reaction↗

PubMed2001

Breast tumor contamination of PBSC harvests: tumor depletion by positive selection of CD34(+) cells.

BACKGROUND: Positive selection of CD34(+) cells may reduce or eliminate tumor cells contaminating PBSC harvests of breast cancer (BrCa) patients. However, to assess tumor purging accurately methods may be needed that are of higher sensitivity than standard immunocytochemistry (ICC) assays. METHODS: BrCa-cell depletion, resulting from CD34(+) cell selection, was evaluated using a novel, highly sensitive assay based upon immunomagnetic enrichment with ICC detection in 36 BrCa patients undergoing highdose chemotherapy with autologous PBSC support. RESULTS: The prevalence of BrCa-cell contamination was significantly lower (P = 0.0078) in selected CD34(+) cell fractions (17/35, 49%) from apheresis collections compared with CD34(-) cell fractions (25/35, 71%). In 8/34 (24%) patients, BrCa cells were detected in CD34(-) cell fractions, but not in paired CD34(+) cell fractions. Significantly lower total numbers (P < 0.0005) of BrCa cells were enumerable in CD34(+) cell fractions compared with corresponding apheresis harvests. The median total BrCa-cell content of selected CD34(+) cell fractions with measurable contamination was 22 BrCa cells (range, 6-73 BrCa cells), compared with 3297 BrCa cells (range, 10-98 400 BrCa cells) in apheresis harvests. The median log depletion of BrCa cells achieved by positive CD34(+) cell selection in specimens with detectable contamination both before and after selection was 2.2 (range, 1.7-4.0). Total pre-selection BrCa cell number was significantly predictive (P = 0.004) of residual detectable post-selection contamination. DISCUSSION: Positive CD34(+) cell selection is an effective tumor purging strategy. The prevalence of PBSC contamination in BrCa patients is substantially higher than formerly appreciated.

Adult↗

PubMed2001

Programming effects in sheep of prenatal growth restriction and glucocorticoid exposure.

Our aim was to determine the postnatal effects of single and repeated glucocorticoid injections during late gestation. Repeated (104, 111, 118, 125 days) or single (104 days) injections of betamethasone or saline were given to the ewe or by ultrasound guided injection to the fetus (term 150 days). Lambs were born spontaneously and studied at 3 and 6 mo and 1 yr of age. Arterial pressure was measured at each age, and we performed intravenous glucose tolerance tests at 6 mo and 1 yr. Repeated maternal, but not single maternal or fetal, betamethasone injections prolonged gestation, reduced weight at birth and 3 mo, and was associated with low arterial pressure at 3 mo but not at 6 mo and 1 yr. Glucose metabolism was altered in all betamethasone treatment groups, regardless of the number or route of injections. Our data demonstrate that glucocorticoid-induced fetal growth restriction is associated with a transient reduction in postnatal arterial pressure, but glucocorticoid exposure with or without growth restriction alters glucose metabolism.

Aging↗

PubMed2000

Breast tumor contamination of peripheral blood stem cell harvests: increased sensitivity of detection using immunomagnetic enrichment.

Contaminating tumor cells in peripheral blood stem cell (PBSC) grafts infused for hematopoietic rescue after high-dose chemotherapy could potentially contribute to relapse in BrCa patients. To date the prevalence of PBSC contamination in BrCa patients, as determined by standard immuno-cytochemistry (ICC) assays, has generally been found to be relatively low. However, assay sensitivity may have an important impact on the ability to detect contamination. In this investigation a novel and highly sensitive BrCa cell assay using immunomagnetic enrichment with a panel of antiBrCa monoclonal antibodies (MAbs) and detection by ICC has been characterized. The immunomagnetic enrichment with ICC detection (IE-ICC) assay was directly compared with standard ICC in ability to detect BrCa contamination of PBSC specimens from patients with high-risk stage II/III and metastatic disease. The sensitivity of the IE-ICC assay was approximately 50-fold greater than that of standard ICC. As determined by standard ICC assay, BrCa cells were present in 1/14 patients (7%) and 2/26 (8%) specimens. In contrast, with IE-ICC assay the proportions of positive findings in patients (12/14, 86%) and specimens (19/26, 73%) were significantly higher (p = 0.001 and p < 0.0005, respectively). These preliminary findings suggest that the prevalence of PBSC contamination may be substantially higher than previously appreciated. Consequently, measures to reduce tumor contamination in the graft may have the potential to improve patient outcomes. Higher sensitivity assays such as the IE-ICC assay may play an important role in assessing the risks associated with tumor contamination and the effectiveness of tumor-purging approaches such as positive selection of CD34+ cells and in monitoring patient response to therapy.

Antibodies, Monoclonal↗

PubMed2000

Ventilatory and arousal responses of sleeping lambs to respiratory challenges: effect of prenatal maternal anemia.

We have examined the effects of exposure to chronic maternal anemia, throughout the final one-third of gestation, on postnatal ventilatory and arousal responses to hypoxia, hypercapnia, and combined hypoxia-hypercapnia in sleeping lambs. While resting quietly awake, lambs from anemic ewes had higher arterial PCO(2) levels than control animals during the first 2-3 postnatal wk, but pH, arterial PO(2), and arterial O(2) saturation were not different. During active and quiet sleep lambs from anemic ewes had higher end-tidal CO(2) levels than control animals when breathing room air and at the time of spontaneous arousal or when aroused by progressive hypercapnia or by combined hypoxia-hypercapnia. Ventilation and arterial O(2) saturation during uninterrupted sleep and ventilatory responsiveness to hypoxia (inspiratory O(2) fraction, 10%), progressive hypercapnia, and combined hypoxia/hypercapnia were not significantly affected by exposure to maternal anemia. Our findings show that maternal anemia results in elevated PCO(2) levels in the offspring. This effect may be due, at least in part, to altered pulmonary function.

Anemia↗

PubMed2000

Endotoxin-induced lung maturation in preterm lambs is not mediated by cortisol.

Antenatal exposure to glucocorticoids, amnionitis, intraamniotic interleukin (IL)-1alpha, or endotoxin can improve postnatal lung function after preterm delivery. The relationship between early lung maturation and the dose and duration of a proinflammatory stimulus has not been evaluated. The effects of proinflammatory stimuli on fetal plasma cortisol also have not been evaluated. We hypothesized that intraamniotic endotoxin would induce early lung maturation in fetal sheep without increasing fetal cortisol. Intraamniotic injections of 1, 4, 20, or 100 mg of Escherichia coli 055:beta5 endotoxin caused 2-fold increases in compliance, 4- to 5-fold increases in lung gas volumes, and 20-fold increases in alveolar saturated phosphatidylcholine (Sat PC) when given 7 d before preterm delivery at 125 d gestation. Animals treated with 20 mg endotoxin for treatment to delivery intervals of 5 h to 15 d had no significant elevations in cord plasma cortisol levels. Increases in Sat PC in lung tissue and alveolar washes were detected 2 d after endotoxin treatment and lung function improved 4 d after endotoxin treatment. Two doses of endotoxin given 3 and 7 d or 7 and 15 d before treatment resulted in lung maturation responses equivalent to single dose comparison groups without elevations in cortisol. Early lung maturation induced by intraamniotic endotoxin in fetal sheep occurred without an increase in fetal plasma cortisol, indicating that endotoxin promoted lung maturation by a mechanism independent of cortisol.

Amnion↗

PubMed2000

Human herpesvirus 8 open reading frame 26 and open reading frame 65 sequences from multiple myeloma patients: a shared pattern not found in Kaposi's sarcoma or primary effusion lymphoma.

Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus, has been implicated in the pathogenesis of Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), multicentric Castleman's disease, and recently multiple myeloma (MM). DNA sequence analyses of HHV-8 suggest that multiple HHV-8 strains exist. We extracted DNA from 24 patients with MM and 3 patients with monoclonal gammopathy of undetermined significance and compared HHV-8 open reading frames (ORFs) 26 and 65 sequences with those derived from patients with KS, PEL, and two HHV-8-positive PEL cell lines KS-1 and BC-1. ORF26 sequence data suggest that MM patients are consistently carriers of HHV-8 strain subtype C3. All MM patients also consistently revealed either a single bp deletion or substitution at position 112197 in ORF65. This unique alteration is not present in patients with KS or PEL or in PEL cell lines. It occurs in the portion of ORF65 that is known to be responsible for a serological response to HHV-8.

Amino Acid Sequence↗

PubMed1999

Clinical relevance of minimal residual cancer in patients with solid malignancies.

With the advent of new therapeutic modalities, the treatment options for oncologists can vary greatly depending upon the aggressiveness of the patient's cancer. Patients may receive no therapy, adjuvant therapy, aggressive adjuvant therapy (taxane based), monoclonal antibody therapy (e.g. Herceptin) or bone marrow transplantation. It is now mandatory to determine accurate prognostic patient profiles at diagnosis and during therapy to determine who would benefit most from a particular therapeutic regimen or to determine who should be shifted into more aggressive therapy. We now have ultra-sensitive methods of tumor cell detection that can determine the presence of minimal residual cancer (MRC) in marrow, stem cell product (SCP) and lymph node to help create these prognostic profiles. The author has conducted a critical review of the literature regarding the type of testing used to detect MRC, the incidence of MRC in marrow, SCP, and lymph node, and the clinical significance of MRC at diagnosis and during therapy. To date it is now clear that immunohistochemistry is a very useful diagnostic tool with adequate sensitivity to detect MRC. The presence of MRC at diagnosis in marrow and/or lymph node is associated with a poor prognosis for a number of disorders including breast cancer, neuroblastoma, gastrointestinal tumors, and lung cancer. In addition, the presence of MRC during therapy in marrow and/or SCP is associated with a very poor prognosis for patients with breast cancer. The use of testing for MRC in the patient provides prognostic information that may be of use to the oncologist.

Humans↗

PubMed1998

Frequent detection of tumor cells in hematopoietic grafts in neuroblastoma and Ewing's sarcoma.

Many poor-risk neuroblastomas and tumours of the Ewing's sarcoma family (ET) recur despite autologous transplants. Recurrence may be due to tumor cells contained in the BM harvests or PBSC harvests. The objectives of this prospective study were to: (1) determine the incidence and degree of tumor cell contamination in paired BM and PBSC harvests; and (2) determine the efficacy of tumor cell purging by immunomagnetic CD34+ cell selection. 198 samples from 11 consecutive patients with neuroblastoma or Ewing's sarcoma were analyzed. We assayed tumor contamination by RT-PCR assay for PGP 9.5, plus immunohistochemistry for neuroblastoma-specific antigens (the latter in neuroblastoma only). None of these patients had tumor cells detected in their BM by clinical histology immediately before BM or PBSC harvests. However, 82% of PBSC and 89% of backup BM harvests were contaminated with tumor by RT-PCR and/or immunocytochemistry assays. Unselected PBSC and BM harvests contained similar quantities of tumor cells (median, approximately 200000 cells). Cyclophosphamide plus G-CSF mobilization did not affect the incidence or level of contamination in PBSC harvests, as compared to blood obtained before mobilization. Immunomagnetic CD34+ cell selection depleted tumor cells by a median of 3.0 logs for PBSC, and 2.6 logs for BM harvests.

Adolescent↗

PubMed1998

Occult tumor contamination of hematopoietic stem-cell products does not affect clinical outcome of autologous transplantation in patients with metastatic breast cancer.

PURPOSE: To determine whether occult tumor contamination of autologous bone marrow or peripheral-blood progenitor cells (PBPC) influences clinical outcome after high-dose chemotherapy in patients with stage IV breast cancer. PATIENTS AND METHODS: We used an immunocytochemical assay capable of detecting one tumor cell in 5 x 10(5) hematopoietic cells to analyze bone marrow and/or PBPC collections obtained from 57 consecutive women with chemotherapy-sensitive metastatic breast cancer who received high-dose chemotherapy. The influence of occult tumor on time to progression, overall survival, and first site of recurrence (old or new) was studied. RESULTS: Twenty-three of 57 (40%) patients received bone marrow (n=6) or peripheral-blood progenitor collections (n=17) that contained microscopic cancer. Median time to progression and overall survival were 9 and 22 months in patients who did not receive infused tumor cells, compared with 10 and 24 months, respectively, in those who received occult tumor (P=not significant [NS]). Worse survival, but not time to progression, was observed in six patients who received > or = 2/100,000 tumor cells. Regardless of whether occult tumor was infused, the majority of relapses occurred in prior, rather than new sites of disease. Three patients who received stem-cell products contaminated by microscopic breast cancer remain free from progression at 21+, 47+, and 52+ months. CONCLUSION: Microscopic tumor was frequently detected by immunocytochemistry in hematopoietic stem-cell products, but did not predict for inferior treatment outcome in this cohort of patients with metastatic breast cancer. Quantitative information regarding infused tumor burden may have prognostic significance.

Bone Marrow Neoplasms↗

PubMed1998

Ventilatory responsiveness to progressive asphyxia during sleep in newborn lambs: effects of maternal anemia during pregnancy.

Our aim was to determine the effects of intrauterine compromise, induced by maternal anemia, on ventilatory responsiveness of the sleeping newborn to progressive asphyxia. We induced anemia in 6 sheep for the final third of pregnancy and studied their offspring for 2-3 weeks after birth. Lambs from anemic ewes were growth-restricted at birth; they and 6 control lambs were chronically instrumented soon after birth and underwent studies during which we determined ventilatory and arousal responsiveness to a progressive asphyxic stimulus during sleep. During quiet wakefulness, active sleep and quiet sleep, lambs from anemic ewes had elevated end-tidal CO2 levels (FECO2,%) compared to controls. Ventilatory responsiveness (i.e., gradient of relationship between minute ventilation and FECO2) was greater in quiet sleep than in active sleep for both groups of lambs but did not differ between the two groups in either active or quiet sleep. Lambs from anemic ewes had significantly higher FECO2 values than controls before arousing from either active or quiet sleep. Other indices of arousability (time to arousal, percent hemoglobin saturation at arousal) were not different between the two groups. Our results indicate that prenatal exposure to maternal anemia induces fetal growth restriction and elevates the CO2 'set-point' for normal ventilation. It does not, however, produce significant abnormalities in ventilatory responsiveness to progressive asphyxia during sleep.

Anemia↗

PubMed1997

Treatment of poor-risk neuroblastoma patients with high-dose chemotherapy and autologous peripheral stem cell rescue.

A single institutional pilot study was conducted in which 12 poor-risk neuroblastoma (NB) patients were uniformly treated with multi-agent induction chemotherapy followed by myeloablative consolidation chemotherapy and unpurged peripheral blood stem cell (PBSC) rescue. In addition to using standard criteria for evaluating response to induction chemotherapy, tumor cell contamination of the peripheral blood and/or bone marrow was analyzed in seven patients by immunocytology using a panel of five anti-NB monoclonal antibodies. Seven patients had morphologic evidence of bone marrow disease at the time of diagnosis, and two additional patients had tumor cells detected in bone marrow samples by immunocytology prior to the second cycle of chemotherapy. After three cycles of chemotherapy, two of the 12 patients continued to have evidence of bone marrow disease. Samples from 29 PBSC harvests collected from nine patients were also analyzed for the presence of contaminating tumor cells by immunocytology. In each case, the stem cells were found to be free of tumor. Eleven of the 12 patients underwent myeloablative therapy and PBSC rescue; five patients remain alive without disease progression, 28+ to 53+ months from diagnosis, and six patients have developed recurrent disease. We conclude that PBSCs can be successfully harvested from children with NB, and used for hematopoietic reconstitution following myeloablative chemotherapy. However, more effective therapy for poor-risk NB patients is still urgently needed.

Adult↗

PubMed1996

Prematurity alters hypoxic and hypercapnic ventilatory responses in developing lambs.

We have determined the effects of preterm birth on the postnatal development of ventilatory responses to progressive hypoxia and hypercapnia in awake lambs. Hypoxic and hypercapnic rebreathing tests were performed at weekly intervals in 5 preterm (born at 135 +/- 0.5 d) and 5 term (born at 146 +/- 0.2 d) lambs up to 6-7 weeks after birth. Term lambs were also studied at 25 weeks after birth. During rebreathing tests, we measured arterial PO2 and PCO2 and related them to minute ventilation (VI). Owing to variability in resting PAO2, hypoxic sensitivity was defined as the percentage increase in VI when PaO2 fell to 60% of resting values. Hypoxic sensitivities of preterm lambs did not change with age (68.9 +/- 24.4%), whereas values for term lambs more than doubled over the first 6 weeks (day 2, 73.9 +/- 15.8%; week 6, 227.4 +/- 24.9%) but returned to early postnatal values by week 25 (87.0 +/- 21.2%). Hypercapnic sensitivities (ml min-1 kg-1 mmHg CO2(-1) of preterm lambs were lower than those of term lambs between day 2 and week 2, but reached values in term lambs thereafter. We conclude that preterm birth abolishes the normal postnatal maturation of hypoxic ventilatory sensitivity, and temporarily depresses hypercapnic sensitivity.

Animals↗