Delayed childbearing--are there any risks?

OBJECTIVE: To determine whether women delivering their first child at age 35 years or older are at increased risk of adverse (non-genetic) pregnancy outcomes. DESIGN AND SETTING: A cross-sectional analytic study of singleton deliveries in Northern Sydney Area Health Service (NSAHS) hospitals. PARTICIPANTS: All women aged > or = 20 years delivering their first child between 1 January 1990 and 31 December 1991. MAIN OUTCOME MEASURES: Obstetric complications and procedures, type of delivery and neonatal outcomes. RESULTS: Compared with women aged 20-29 years, women delivering their first child at > or = 35 years were at increased risk of pre-existing maternal hypertension (adjusted odds ratio [OR], 3.5; 95% confidence interval [CI], 1.7-7.0), antepartum haemorrhage (adjusted OR, 2.4; 95% CI, 1.6-3.7), preterm delivery (33-36 weeks) (adjusted OR, 2.0; 95% CI, 1.5-2.8) and breech presentation (adjusted OR, 1.8; 95% CI, 1.3-2.4). Women aged > or = 35 years were also substantially more likely to have an operative delivery, induced labour and/or epidural anaesthesia. Neither these women nor their infants were at increased risk of pregnancy-induced hypertension, gestational diabetes, threatened premature labour, postpartum haemorrhage, very preterm delivery (< or = 32 weeks), perinatal death, low Apgar scores or the need for neonatal resuscitation. CONCLUSIONS: Women who delay the birth of their first child face some increased risks, but these risks, for the most part, are manageable in the context of modern obstetric care.     

Clinical factors useful in predicting aortic valve structure in patients > 40 years of age with isolated valvular aortic stenosis

A number of reports have described the frequency of coronary arterial narrowing in patients with valvular aortic stenosis. No published reports have examined the structure of the stenotic aortic valve in adults and related the valve structure to variables, including coronary arterial narrowing, useful in predicting that structure. One hundred eighty-eight patients having aortic valve replacement for isolated valvular aortic stenosis were studied. All patients were > 40 years of age at the time of aortic valve replacement, all had coronary angiograms preoperatively, and of 182 patients (97%) measurements of serum total cholesterol had been obtained and 184 (98%) had body mass index calculated. The structure of the operatively excised valve was classified as unicuspid or bicuspid (congenitally malformed), or tricuspid aortic valve. A logistic regression model was developed that found 4 factors (age, serum total cholesterol, angiographic coronary artery disease and body mass index) to be predictive of aortic valve structure: (1) Patients with at least 3 or all 4 factors high or present (i.e., age > 65 years, serum total cholesterol > 200 mg/dl, body mass index > 29 kg/m2 and coronary artery disease) had a low probability (10 to 29%) of having a congenitally malformed valve; (2) patients with at least 3 or all 4 factors low or absent (i.e., age < or = 65 years, serum total cholesterol < or = 200 mg/dl, body mass index < or = 29 kg/m2, and no coronary artery disease) had a high probability (72 to 90%) of having a congenitally malformed valve.(ABSTRACT TRUNCATED AT 250 WORDS)     

Oral health of children undergoing allogeneic bone marrow transplantation

BACKGROUND: Mixed bone marrow chimerism reliably produces donor-specific transplantation tolerance for a variety of solid organ and cellular grafts. We used a rat heterotopic tracheal transplant model for chronic rejection to investigate whether mixed chimerism could successfully prevent obstructive airway disease. METHODS: Mixed allogeneic chimeras were prepared by reconstituting lethally irradiated Wistar-Furth (WF) recipients with a mixture of 5 x 10(6) T-cell-depleted syngeneic (WF) and 100 x 10(6) T-cell-depleted allogeneic (ACI) bone marrow cells (ACI + WF --> WF). Mixed chimerism was present in all animals 28 days after bone marrow transplantation. Donor-specific, syngeneic, or major histocompatibility complex (MHC)-disparate allogeneic tracheas were implanted in recipient's omentum and removed for histologic analysis 30 to 150 days after transplantation. RESULTS: At 30 days after implantation, median luminal obstruction grades (0=none, 4=complete) of syngeneic and allogeneic tracheas were 0 and 4, respectively. Donor-specific (ACI) tracheas implanted in chimeric (ACI + WF --> WF) recipients were remarkably free of obstruction (median luminal obstruction grade=0 at 150 days) and had excellent preservation of respiratory epithelium. Third-party F344 tracheas implanted in chimeric recipients developed progressive luminal obstruction (grade 2 at 30 days, grade 3 at 90 days). CONCLUSIONS: Mixed allogeneic chimerism induces donor-specific tolerance and prevents development of the characteristic fibroproliferative obstructive lesion of bronchiolitis obliterans in a rat heterotopic tracheal transplant model. Excellent preservation of tracheal structure and morphology was achieved across major and minor histocompatibility barriers.     

Elevated N-myristoyl transferase activity is reversed by sodium orthovanadate in streptozotocin-induced diabetic rat

N-Myristoyl transferase (NMT) is the enzyme that covalently modifies several proteins important in signal transduction. Streptozotocin-induced diabetes resulted in a 2-fold increase in NMT activity from rat liver as compared to control animals. Administration of sodium orthovanadate to the diabetic rats reduced the activity of the NMT to 75-120% of the control values. Elevated NMT activity was observed with both cAMP-dependent protein kinase-derived and pp60src-derived peptide substrates. No significant change in the apparent Km was observed with the cAMP-dependent protein kinase-derived peptide substrate. Unlike in rat brain, in all conditions highest NMT activity was observed in the particulate fraction of rat liver.     

Selective inhibition of primary acute myeloid leukaemia cell growth by lovastatin

The insulin receptors from erythrocytes of 50 patients with non-insulin-dependent diabetes mellitus were tested for their ability to autophosphorylate. The assay was performed by a new enzyme-linked immunosorbent assay system that used monoclonal anti-insulin receptor antibodies absorbed to microtiter plates as a first antibody and polyclonal antiphosphotyrosine antibody as a labeled second antibody. By this assay, 3 patients were identified with defects in their insulin receptor kinase, although their defects appeared heterogeneous. Patient 1 had 85% less maximal autophosphorylation with a normal ED50 (1.6 x 10(-9) M insulin). Patient 2, who had polycystic ovary disease, had a 49.2% decrease in maximal autophosphorylation of insulin receptors, and the ED50 was shifted to the right (5.6 x 10(-8) M). Patient 3 with acanthosis nigricans had a normal maximal autophosphorylation, but the ED50 shifted to the right (2.9 x 10(-8) M). The mechanisms for the diversity detected in this assay is not known, but this technique has sufficient specificity and sensitivity to be used to screen for insulin-resistant patients who have a lack of kinase activity.     

CD4-mediated and CD8-mediated cytotoxic and proliferative immune responses to Toxoplasma gondii in seropositive humans

Both CD4+ and CD8+ cytotoxic T lymphocytes (CTL) are part of the human immune response to Toxoplasma gondii infection. To further our understanding of Toxoplasma immunity, we investigated factors influencing stimulation of CD4+ or CD8+ human T. gondii-specific immune cells. Both antigen-pulsed and Toxoplasma-infected antigen-presenting cells (APC) induced cell proliferation. Toxoplasma-infected APC elicited strong proliferation of CD4+ cells, but little or no proliferation of CD8+ cells, unless high antigen loads were used. Toxoplasma-infected APC stimulated specific cytotoxicity poorly or not at all, owing to death of stimulated cultures, whereas antigen-pulsed APC strongly elicited specific cytotoxicity. Cytotoxicity elicited by either type of APC resided exclusively in CD4+ T cells in polyclonal cultures. Thus, Toxoplasma-infected APC elicited stronger CD4-mediated than CD8-mediated cell proliferation and generated CD4+ CTL more readily than CD8+ CTL. Nonetheless, specific CD8+ memory cells were demonstrated, and rare CD8+ Toxoplasma-specific CTL were subcloned. Fixed Toxoplasma-infected APC (which induce CD8+ CTL) also elicited cell proliferation, but polyclonal cultures stimulated with these infected APC did not die. Unfixed Toxoplasma-infected APC strongly inhibited phytohemagglutinin-induced cell proliferation, whereas fixed APC did not. These data suggested that infected APC were inhibitory or lethal to some immune cells. Further investigations into interactions between immune cells and Toxoplasma-infected cells likely will help elucidate factors involved in the immunopathogenesis of Toxoplasma infection. As other intracellular parasites, including Plasmodium spp. and Leishmania spp., also elicit CD4+ CTL, such work may help establish paradigms governing immunity to intracellular parasites.     

Interferon-induced upregulation and cytoplasmic localization of Myc-interacting protein Nmi

Production of toxins A and B by Clostridium difficile is enhanced in a defined medium with biotin-limited conditions. In the present study compounds inhibitory to enhanced toxin production by a C. difficile strain were examined. Increases in biotin concentration from 0.05 nM to 50 nM accelerated growth and inhibited enhanced toxin production. Asparagine, glutamic acid and glutamine (10 mM) showed an effect on growth and toxin production similar to that of biotin. Lysine (10 mM) suppressed growth and inhibited toxin production. Addition of these toxin-inhibitory compounds within an incubation period of 2 days inhibited the enhanced toxin production, but later addition showed only slight inhibition of toxin production. Amino acids contained in the defined medium under the biotin-limited conditions were actively utilised in the presence of the three toxin-inhibitory amino acids, but in the presence of lysine, amino-acid utilisation was suppressed. Different mechanisms of action of these toxin-inhibitory molecules, which may be divided into excess biotin, asparagine-glutamic acid-glutamine group, and lysine, are discussed.