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S Robinson

Publications and source records attributed to S Robinson.

At least 91 records · Page 5Linked to original sources
PubMed2001

Vaccine-elicited V3 loop-specific antibodies in rhesus monkeys and control of a simian-human immunodeficiency virus expressing a primary patient human immunodeficiency virus type 1 isolate envelope.

Vaccine-elicited antibodies specific for the third hypervariable domain of the surface gp120 of human immunodeficiency virus type 1 (HIV-1) (V3 loop) were assessed for their contribution to protection against infection in the simian-human immunodeficiency virus (SHIV)/rhesus monkey model. Peptide vaccine-elicited anti-V3 loop antibody responses were examined for their ability to contain replication of SHIV-89.6, a nonpathogenic SHIV expressing a primary patient isolate HIV-1 envelope, as well as SHIV-89.6P, a pathogenic variant of that virus. Low-titer neutralizing antibodies to SHIV-89.6 that provided partial protection against viremia following SHIV-89.6 infection were generated. A similarly low-titer neutralizing antibody response to SHIV-89.6P that did not contain viremia after infection with SHIV-89.6P was generated, but a trend toward protection against CD4+ T-lymphocyte loss was seen in these infected monkeys. These observations suggest that the V3 loop on some primary patient HIV-1 isolates may be a partially effective target for neutralizing antibodies induced by peptide immunogens.

AIDS Vaccines↗
PubMed2001

Chemokine GRO1 and the spatial and temporal regulation of oligodendrocyte precursor proliferation.

Oligodendrocyte precursor proliferation is precisely regulated spatially and temporally during development to allow optimal myelination of the central nervous system (CNS). We propose that a paracrine regulatory pathway involving the chemokine GRO1 and platelet-derived growth factor (PDGF) permit local control of precursor proliferation in the brain. GRO1, PDGF, and their receptors act synergistically to precisely regulate oligodendrocyte precursor proliferation in vitro and in vivo in the rat CNS. The nature of the paracrine regulatory loop with astrocyte and neuronal GRO1 expression in a pattern that is closely correlated with PDGF alpha R(+) oligodendrocyte precursors suggests that the GRO1/PDGF regulatory mechanism provides local control of oligodendrocyte precursor proliferation during development.

Aging↗
PubMed2001

Prospective study of recovery following neonatal brachial plexus injury.

The prognosis for recovery from brachial plexus injury sustained at or before birth is generally favorable. However, roughly 10% of these infants remain profoundly weak and later exhibit functional disability in the affected arm. Early identification of these at-risk infants would be helpful in selecting patients for surgical management. In our prospective study, 80 infants with brachial plexus injury were examined on a monthly basis. Complete recovery occurred in 53 (66%); in 9 (11%), mild weakness persisted. In each child, recovery to antigravity strength in the biceps, triceps, and deltoid was noted by 6 months of age. Moderate arm weakness persisted in 7 children (9%); none had antigravity strength in the deltoid at age 6 months. Eleven children (14%) had severe permanent weakness (mean follow-up: 4.4 years). At age 6 months, these individuals exhibited at best 2/5 strength proximally and typically 0-1/5 strength in the wrist and finger extensors. Our results demonstrate that detailed strength testing up to 6 months of age predicts not only complete recovery of neonatal brachial plexus injury but also those children destined for long-term severe disability.

Birth Injuries↗
PubMed2001

Estrogen receptor (ER)alpha and ERbeta exhibit unique pharmacologic properties when coupled to activation of the mitogen-activated protein kinase pathway.

The rapid, nongenomic effects of estrogen are increasingly recognized as playing an important role in several aspects of estrogen action. Rapid activation of the mitogen-activated protein kinase (MAPK) signaling pathway by estrogen is among the more recently identified of these effects. To explore the role of estrogen receptors (ERs) in mediating these effects, we have transfected ER-negative Rat-2 fibroblasts with complementary DNA clones encoding either human ERalpha or rat ERbeta and examined their ability to couple to activation of MAPK in response to 17beta-estradiol (17beta-E(2)) and other ligands. For both receptors, addition of E(2) resulted in a rapid phosphorylation of MAPK. Activation of MAPK in ERalpha-transfected cells was partially and completely blocked by the antiestrogens tamoxifen and ICI 182,780, respectively. In ERbeta-transfected cells, MAPK activation was less sensitive to inhibition by tamoxifen and ICI 182,780. We have also observed that, in this model system, a membrane-impermeable estrogen (BSA-E(2)) and 17alpha-E(2) were both able to activate MAPK in a manner similar to E(2) alone. Here also, ICI 182,780 blocked the ability of BSA-E(2) to activate MAPK through ERalpha, but failed to block ERbeta-mediated effects. BSA-E(2) treatment, however, failed to activate nuclear estrogen-response-element-mediated gene transcription. These data show that these nuclear ERs are necessary for estrogen's effects at the membrane. This model system will be useful in identifying molecular interactions involved in the rapid effects mediated by the ERs.

Animals↗
PubMed2001

Neonatal bone mass: influence of parental birthweight, maternal smoking, body composition, and activity during pregnancy.

Evidence is accumulating that intrauterine growth and development may influence an individual's risk of osteoporosis in later adult life. To examine maternal and paternal influences on intrauterine skeletal growth, we used dual-energy X-ray absorptiometry to measure the neonatal bone mineral content (BMC) and bone mineral density (BMD) of 145 infants born at term. Independently of the infant's duration of gestation at birth, the birthweights of both parents and the height of the father were positively correlated with neonatal whole body BMC. Women who smoked during pregnancy had infants with a lower whole body BMC and BMD; overall, there was a 7.1-g (11%) average difference between whole body BMC of infants whose mothers did and did not smoke during pregnancy (p = 0.005). Women with thinner triceps skinfold thicknesses (reflecting lower fat stores) and those who reported a faster walking pace and more frequent vigorous activity in late pregnancy also tended to have infants with a lower BMC and BMD (p values for BMC; 0.02, 0.03, and 0.05, respectively). Maternal thinness and faster walking pace but not maternal smoking or parental birthweight also were associated with lower bone mineral apparent density (BMAD). The influences on skeletal growth and mineralization were independent of placental weight, a marker of the placental capacity to deliver nutrients to the fetus. These observations point to a combination of genetic and intrauterine environmental influences on prenatal skeletal development and suggest that environmental modulation, even at this early stage of life, may reduce the risk of osteoporosis in adulthood.

Absorptiometry, Photon↗
PubMed2001

Immunogenicity of Ly5 (CD45)-antigens hampers long-term engraftment following minimal conditioning in a murine bone marrow transplantation model.

Various techniques are available for distinguishing donor from host cells evaluating the efficacy of conditioning regimen for experimental bone marrow transplantation (BMT). Techniques include the use of extracellular immunological markers, such as Ly5 (CD45), and intracellular biochemical markers, such as glucose-phosphate-isomerase (Gpi). Because Ly5 is an extracellular protein, the disparity between donor (Ly5.1) and host (Ly5.2) antigens may induce a weak immune response whereas with Gpi, no immune response is expected. This difference may be of particular concern in experimental transplantation approaches that use minimal conditioning such as low-dose total body irradiation (TBI). Such mild conditioning may not induce the immunosuppression required to overcome host rejection of Ly5 disparate cells. To compare the relative engraftment of Ly5.1 and Gpi-1(a) donor marrow, B6 (Gpi-1(b)/Ly5.2) mice were irradiated with low-level TBI (0-6 Gy) and transplanted with several bone marrow (BM) doses (2 x 10(6)-5 x 10(7) cells). At 8, 26, and 52 weeks post-BMT, the level of donor engraftment was measured using flow cytometry (Ly5) or Gpi-electrophoresis. Lower engraftment levels were found in mice transplanted with Ly5 congenic BM in groups given low-dose TBI (< or = 4 Gy) and/or low doses of BM cells (BMC) (2 x 10(6)). However, when higher TBI or BMC doses were used, similar engraftment levels were found, suggesting sufficient immune suppression to allow equal engraftment of both sources of BM. These data suggest that even a minor phenotypic disparity between donor and host, such as Ly5, may necessitate high-dose TBI to prevent rejection. The combination of low-dose TBI or other nonmyeloablative conditioning strategies with small numbers of BMC may lead to reduced engraftment when extracellular immunological markers such as Ly5 are used for transplantation studies. Therefore, small immunological differences must be considered when using the Ly5 marker for engraftment.

Animals↗
PubMed2001

[Temporomandibular joint pain: radiological diagnosis].

Pain in the temporomandibular joint is often the result of internal derangement, other causes are traumatic, functional or inflammatory processes. Conventional radiography is indicated in case of suspected trauma or for specialised preoperative measurements to plan the treatment of various facial dysplasias. MRI and CT should be used in the context with the results of clinical investigation and of axiography to differentiate the various functional and morphological abnormalities of this joint.

Diagnosis, Differential↗
PubMed2000

In vivo CAMPATH-1H prevents graft-versus-host disease following nonmyeloablative stem cell transplantation.

A novel nonmyeloablative conditioning regimen was investigated in 44 patients with hematologic malignancies. The median patient age was 41 years. Many of the patients had high-risk features, including 19 patients with a previous failed transplant. Recipient conditioning consisted of CAMPATH-1H, 20 mg/day on days -8 to -4; fludarabine, 30 mg/m(2) on days -7 to -3; and melphalan, 140 mg/m(2) on day -2. Thirty-six recipients received unmanipulated granculocyte colony-stimulating factor-mobilized peripheral blood stem cells from HLA-identical siblings, and 8 received unmanipulated marrow from matched unrelated donors. GVHD prophylaxis was with cyclosporine A alone for 38 patients and cyclosporine A plus methotrexate for 6 sibling recipients. Forty-two of the 43 evaluable patients had sustained engraftment. Results of chimerism analysis using microsatellite polymerase chain reaction indicate that 18 of 31 patients studied were full-donor chimeras while the other patients were mixed chimeras in one or more lineages. At a median follow-up of 9 months (range 3 to 29 months), 33 patients remain alive in complete remission or with no evidence of disease progression. Seven patients relapsed or progressed post-transplantation, and 4 of them subsequently died. Four patients died of regimen-related complications. There were no cases of grades III-IV acute GVHD. Only 2 patients developed grade II acute GVHD, and only 1 had chronic GVHD. The estimated probability of nonrelapse mortality was 11%. Although longer follow-up is needed to establish the long-term remission rates, this study demonstrates that this nonmyeloablative preparative regimen is associated with durable engraftment, minimal toxicity, and low incidence of GVHD.

Adolescent↗
PubMed2000

Elevated levels of the chemokine GRO-1 correlate with elevated oligodendrocyte progenitor proliferation in the jimpy mutant.

The dysmyelinating mutant jimpy (jp) arises from a point mutation in the mouse gene encoding proteolipid protein and is characterized by severe dysmyelination attributable to oligodendrocyte death. This mutant was used to investigate the regulation of oligodendrocyte progenitor proliferation in the postnatal spinal cord. At postnatal day 18, jp spinal cord contained a three- to eightfold greater number of proliferating oligodendrocyte progenitor cells than did wild-type (wt) spinal cord. Increased proliferation in jp spinal cord was accompanied by a twofold increase in the number of progenitor cells. Semiquantitative reverse transcriptase-PCR revealed no change in the level of mRNA encoding the platelet-derived growth factor A, transforming growth factor-beta, or insulin-like growth factor-I, all of which have been implicated as regulators of proliferation and differentiation of oligodendrocyte progenitor cells. There was, however, a 17-fold increase in the level of mRNA encoding the chemokine GRO-1 and a 5- to 6-fold increase in GRO-1 protein in the jp spinal cord. Double immunofluorescence labeling revealed elevated levels of GRO-1 in reactive astrocytes in jp spinal cord white matter. In vitro studies indicated that extracts from jp spinal cord stimulated oligodendrocyte progenitor proliferation. Furthermore, removal of GRO-1 from jp extracts by immunoprecipitation reduced the proliferation of progenitor cells to a level similar to that achieved by wt extracts. These findings suggest a novel mechanism by which proliferation of oligodendrocyte progenitor cells is regulated in the postnatal spinal cord in response to insult.

Animals↗
PubMed2000

Genetic variation of basal iron status, ferritin and iron regulatory protein in mice: potential for modulation of oxidative stress.

Toxic and carcinogenic free radical processes induced by drugs and other chemicals are probably modulated by the participation of available iron. To see whether endogenous iron was genetically variable in normal mice, the common strains C57BL/10ScSn, C57BL/6J, BALB/c, DBA/2, and SWR were examined for major differences in their hepatic non-heme iron contents. Levels in SWR mice were 3- to 5-fold higher than in the two C57BL strains, with intermediate levels in DBA/2 and BALB/c mice. Concentrations in kidney, lung, and especially spleen of SWR mice were also greater than those in C57BL mice. Non-denaturing PAGE of hepatic ferritin from all strains showed a major holoferritin band at approximately 600 kDa, with SWR mice having > 3-fold higher levels than C57BL strains. SDS PAGE showed a band of 22 kDa, mainly representing L-ferritin subunits. A trace of a subunit at 18 kDa was also detected in ferritin from SWR mice. The 18 kDa subunit and a 500 kDa holoferritin from which it originates were observed in all strains after parenteral iron overload, and there was no major variation in ferritin patterns. Although iron uptake studies showed no evidence for differential duodenal absorption between strains to explain the variation in basal iron levels, acquisition of absorbed iron by the liver was significantly higher in SWR mice than C57BL/6J. As with iron and ferritin contents, total iron regulatory protein (IRP-1) binding capacity for mRNA iron responsive element (IRE) and actual IRE/IRP binding in the liver were significantly greater in SWR than C57BL/6J mice. Cytosolic aconitase activity, representing unbound IRP-1, tended to be lower in the former strain. SWR mice were more susceptible than C57BL/10ScSn mice to the toxic action of diquat, which is thought to involve iron catalysis. If extrapolated to humans, the findings could suggest that some people might have the propensity for greater basal hepatic iron stores than others, which might make them more susceptible to iron-catalysed toxicity caused by oxidants.

Absorption↗
PubMed2000

Short-acting beta 2 agonists for stable chronic obstructive pulmonary disease.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a chronic condition characterised by progressive airflow limitation that is at most partially reversible. Despite the lack of reversibility patients often report symptomatic improvement with short-acting beta 2 bronchodilator medications. They are used on either an "as required" or a "regular plus as required basis" and they may be used in conjunction with other bronchodilator medicines such as ipratropium and methylxanthines. These medicines are used in the management of both stable and acute exacerbations of COPD. This review examined the effect of short-acting beta 2 bronchodilators given by inhalation in stable COPD. OBJECTIVES: To determine the clinical effect and assess the adverse effects of inhaled short-acting beta 2 agonist bronchodilators compared with placebo in stable COPD. SEARCH STRATEGY: Only randomised controlled trials (RCTs) were considered. RCTs were identified using the Cochrane Airways Group database (CENTRAL). In addition, the reference lists of review articles and RCTs retrieved in full were searched for other potentially relevant citations. SELECTION CRITERIA: Only trials with adult patients with stable COPD, as defined by internationally accepted guidelines (ATS, ERS or BTS) were included in this review. All trials had a minimum duration of 7 days of regular treatment with short-acting beta 2 bronchodilators given by inhalation and compared with placebo. Data from trials where beta 2 agonists were used alone or in combination with other medicines (e.g. ipratropium bromide) were used only if there was a direct comparison between beta 2 bronchodilator alone and placebo. DATA COLLECTION AND ANALYSIS: Outcomes were analysed as continuous or dichotomous outcomes, using standard statistical techniques. For continuous outcomes, the weighted mean difference (WMD) and 95% confidence intervals were calculated and for dichotomous outcomes, the odds ratio was calculated with 95% confidence intervals by Peto's methods. Funnel plots were used to test for publication bias. MAIN RESULTS: Thirteen studies were included in this review. Most had small sample sizes and some of the sutides used very short-acting outdated compounds. All the studies used a cross-over design and were of high quality. Spirometry done at the end of study period was measured after administration of treatment (post-bronchodilator) which showed both FEV1 (0.150 L/min, 95%CI: 0. 02-0.28) and FVC (0.310 L, 95%CI: 0.00-0.62) to improve significanly but slightly when compared to placebo. A few studies measured FRC, airway resistance or conductance at the end of the study period. In all cases these measurements were done several hours after treatment, and no significant differences (p>0.05 in all cases) were found between the bronchodilator and placebo groups. Walking test Large increases in 6MW distance was observed in two studies, however one study did not show any positive improvements. There was a large increase in the 12MW distance as shown by one study. Due to the small number of studies reporting this outcome no significant differences were found in the walking distance between the bronchodilator and placebo groups. Peak Flow Rate Both morning (36. 04 L/min; 95%CI: 0.80-71.27) and evening (36.68 L/min; 95%CI: 2. 47-70.89) PEFR were significantly higher during active treatment than during placebo. Symptoms Breatlessness was measured on various scales therefore data that were presented in a suitable form were combined using standardized means for inclusion in the analysis. A significant improvement (-0.33; 95%CI: -0.58 to -0.07 with p=0.01) in the breathlessness score was observed during treatment with beta-2 agonist when compared to placebo. Cough was reported to improve significantly (data not usable) during treatment with beta2 agonist in one study but not in two others. A non-significant decrease in sputum production was reported by Wilson 1980, however four other studies reported no

Administration, Inhalation↗
PubMed2000

Behaviour, body composition and diet in adolescent girls.

The purpose of the study was to examine the relationships between patterns of behaviour, body composition and diet in adolescent girls. A group of 328 14 to 16-year-old girls at school in Southampton, U. K. completed a questionnaire about their behaviour and lifestyle, and had their heights, weights and skinfold thicknesses measured. Of these girls, 286 also provided dietary information. Socially independent girls were more likely to smoke, and less likely to eat breakfast and meals with family. They consumed more snacks, chocolate and soft drinks. Girls who were dissatisfied with their weight dieted and exercised, watched less television and spent less of their money on food. Dissatisfaction with weight was strongly related to body mass index. The odds of being a dieter, an indication of dissatisfaction with weight, increased with every unit increase in body mass index, so that girls with a body mass index of 24 kg/m(2)and over were 19 times more likely to diet than those with a body mass index of 19 kg/m(2)or less. Girls who were less satisfied with their weight reported lower energy intakes but ate more green vegetables and brown bread than other girls. The eating habits of the girls were therefore influenced by the extent of their social lives and by their satisfaction with their weight.

Adolescent↗
PubMed2000

Apical plasma membrane mispolarization of NaK-ATPase in polycystic kidney disease epithelia is associated with aberrant expression of the beta2 isoform.

Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disease of the kidney, characterized by cystic enlargement of renal tubules, aberrant epithelial proliferation, and ion and fluid secretion into the lumen. Previous studies have shown abnormalities in polarization of membrane proteins, including mislocalization of the NaK-ATPase to the apical plasma membranes of cystic epithelia. Apically located NaK-ATPase has previously been shown to be fully functional in vivo and in membrane-grown ADPKD epithelial cells in vitro, where basal-to-apical (22)Na transport was inhibited by application of ouabain to the apical membrane compartment. Studies were conducted with polymerase chain reaction-generated specific riboprobes and polyclonal peptide antibodies against human sequences of alpha1, alpha3, beta1, and beta2 subunits of NaK-ATPase. High levels of expression of alpha1 and beta1 messenger RNA were detected in ADPKD and age-matched normal adult kidneys in vivo, whereas beta2 messenger RNA was detected only in ADPKD kidneys. Western blot analysis and immunocytochemical studies showed that, in normal adult kidneys, peptide subunit-specific antibodies against alpha1 and beta1 localized to the basolateral membranes of normal renal tubules, predominantly thick ascending limbs of Henle's loop. In ADPKD kidneys, alpha1 and beta2 subunits were localized to the apical epithelial cell membranes, whereas beta1 was distributed throughout the cytoplasm and predominantly in the endoplasmic reticulum, but was not seen associated with cystic epithelial cell membranes or in cell membrane fractions. Polarizing, renal-derived epithelial Madin Darby canine kidney cells, stably expressing normal or N-terminally truncated chicken beta1 subunits, showed selective accumulation in the basolateral Madin Darby canine kidney cell surface, whereas c-myc epitope-tagged chicken beta2 or human beta2 subunits accumulated selectively in the apical cell surface. Similarly, human ADPKD epithelial cell lines, which endogenously expressed alpha1 and beta2 NaK-ATPase subunits, showed colocalization at the apical cell surface and coassociation by immunoprecipitation analysis. These results are consistent with a model in which the additional transcription and translation of the beta2 subunit of NaK-ATPase may result in the apical mislocalization of NaK-ATPase in ADPKD cystic epithelia.

Animals↗
PubMed2000

Obstetric risks of pregnancy in women less than 18 years old.

OBJECTIVE: To quantify the age-related risks of adverse outcome during pregnancy in women less than 18 years old. METHODS: We analyzed data from 341,708 completed singleton pregnancies in the North West Thames region between 1988 and 1997. Pregnancy outcomes were compared by age at delivery in women less than 18 years old (n = 5246) and 18-34 years old (n = 336,462); women 35 years old or older (n = 48,658) were excluded. Data are presented as percentages of women less than 18 and 18-34-year-old women, with adjusted odds ratios (OR) and 99% confidence intervals (CI). RESULTS: Pregnancy in women less than 18 years old was associated with increased risk of preterm labor before 32 weeks' gestation (OR 1.41, CI 1.02, 1.90), maternal anemia (OR 1.82, CI 1.63, 2.03), chest infection (OR 2.70, CI 1.21, 6.70), and urinary tract infection (OR 1.60, CI 1.11, 2.31), but less obstetric intervention. Operative vaginal delivery (OR 0. 46, CI 0.41, 0.56), elective cesarean (OR 0.47, CI 0.35, 0.65), or emergency cesarean (OR 0.45, CI 0.38, 0.53) were all less likely in women aged less than 18 years. Women less than 18 years old were no more likely to have stillbirths (OR 0.75, CI 0.42, 1.34) or small-for-gestational-age infants (OR 0.95, CI 0.82, 1.09) than women aged 18-34 years. CONCLUSION: Pregnant women less than 18 years old were more likely to deliver preterm than older women. In most other respects they have less maternal and perinatal morbidity and were more likely to have normal vaginal deliveries.

Adolescent↗
PubMed2000

Neuronal-glial interactions and behaviour.

Both neurons and glia interact dynamically to enable information processing and behaviour. They have had increasingly intimate, numerous and differentiated associations during brain evolution. Radial glia form a scaffold for neuronal developmental migration and astrocytes enable later synapse elimination. Functionally syncytial glial cells are depolarised by elevated potassium to generate slow potential shifts that are quantitatively related to arousal, levels of motivation and accompany learning. Potassium stimulates astrocytic glycogenolysis and neuronal oxidative metabolism, the former of which is necessary for passive avoidance learning in chicks. Neurons oxidatively metabolise lactate/pyruvate derived from astrocytic glycolysis as their major energy source, stimulated by elevated glutamate. In astrocytes, noradrenaline activates both glycogenolysis and oxidative metabolism. Neuronal glutamate depends crucially on the supply of astrocytically derived glutamine. Released glutamate depolarises astrocytes and their handling of potassium and induces waves of elevated intracellular calcium. Serotonin causes astrocytic hyperpolarisation. Astrocytes alter their physical relationships with neurons to regulate neuronal communication in the hypothalamus during lactation, parturition and dehydration and in response to steroid hormones. There is also structural plasticity of astrocytes during learning in cortex and cerebellum.

Animals↗
PubMed2000

An assessment of chloramphenicol and thiamphenicol in the induction of aplastic anaemia in the BALB/c mouse.

The potential of the antibiotics chloramphenicol succinate (CAPS) and thiamphenicol (TAP) to induce aplastic anaemia in the female BALB/c mouse was investigated. CAPS was administered at 2000 mg/kg, and TAP at 850 mg/kg, daily by gavage, for 17 days. At 1, 13, 22, 41, 98 and 179 days after the final dose of each antibiotic, mice (n = 4 or 5) were sampled for haematological examination and haematopoietic stem cell assays. Both CAPS and TAP induced significant reductions in red blood cell count, haematocrit and haemoglobin values at day 1 post dosing; counts of colony-forming units-erythroid and colony-forming units-granulocyte-macrophage, were similarly significantly decreased at this time. All these reduced parameters returned towards normal at days 13 and 22. At days 41, 98 and 179, results for all haematological values and stem cell assays in both CAPS- and TAP-treated mice compared with the controls; there was no evidence of a reduction in peripheral blood values or bone marrow parameters at the later sampling points, as would be expected in a developing or overt bone marrow aplasia. We therefore consider that the administration of CAPS and TAP, which have been associated with the development of aplastic anaemia in man, induce a reversible anaemia, but not a chronic bone marrow aplasia, when given at haemotoxic dose levels for 17 days in the BALB/c mouse.

Anemia, Aplastic↗
PubMed2000

The prevalence of polycystic ovaries in women with a history of gestational diabetes.

OBJECTIVE: Women with a history of gestational diabetes mellitus (GDM) and women with polycystic ovary syndrome (PCOS) both demonstrate abnormalities in insulin action and secretion, and both are at increased risk of developing type 2 diabetes. To determine whether these similarities reflect a common pathophysiological basis, we examined the prevalence of ultrasound-based polycystic ovarian morphology in a large multiethnic group of women with a history of GDM and a group of women who had normal glucose tolerance during pregnancy. PATIENTS AND DESIGN: We studied 91 women with previous GDM (48 European, 20 South Asian, 10 Afro-Caribbean and 13 of other or mixed ethnicity) and 73 normoglycaemic control women (56 European, one South Asian, 14 Afro-Caribbean and two of other or mixed ethnicity), a median (interquartile range) of 20 (11-36) and 29 (17-49) months postpartum, respectively. A detailed history was taken, and the prevalence of PCO morphology on ultrasound scan was assessed. Fasting lipids, insulin, glucose status, gonadotrophins and testosterone were measured. Estimates of beta-cell function (%B) and insulin sensitivity (%S) were derived using the HOMA algorithm. RESULTS: Women with previous GDM had higher fasting glucose (5.4 (4. 8-6.0) vs. 4.7 (4.4-5.0) mmol/l, P<0.0001) and features reminiscent of syndrome X: higher BMI (26.4 (22.8-31.4) vs. 23.8 (21. 0-27.5) kg/m2, P = 0.002), waist/hip ratio (0.82 (0.79-0.88) vs. 0. 77 (0.73-0.81), P<0.0001), fasting insulin (165 (68-299) vs. 54 (24-156) pmol/l, P<0.0001), triglycerides (1.1 (0.8-1.6) vs. 0.8 (0.6-1.1) mmol/l, P<0.0001) and lower insulin sensitivity (%S) (27 (16-62) vs. 86 (34-139)%, P<0.0001) compared to control women. The prevalence of PCO was higher in the previous GDM group than in the control subjects (47/91 (52%) vs. 20/73 (27%), chi2 = 9.86, P = 0. 002 overall, odds ratio 2.7, P = 0.007 by logistic regression allowing for ethnicity). There was no difference in any metabolic parameter between the post-GDM PCO group and the post-GDM normal ovaries group, but irregular cycles were more prevalent in the PCO group (22/47 (47%) vs. 9/44 (21%), chi2 = 7.03, P = 0.008). CONCLUSIONS: We found a higher prevalence of polycystic ovarian morphology in women with a history of gestational diabetes. Among the women with previous gestational diabetes, irregular cycles were more prevalent in the PCO group than in the women with normal ovarian morphology, but no other differences in endocrine or metabolic parameters were detected. These findings confirm an association between PCO and gestational diabetes and suggest that women with gestational diabetes display metabolic abnormalities irrespective of ovarian morphology.

Blood Glucose↗