Antigen Expression by Cells Near the Maternal-Fetal Interface

ABSTRACT: The purpose of the present study was to evaluate the potential for immunologic interaction between the mother and fetus by documenting 1) fetal and maternal cell histocompatibility antigen (HLA) expression and 2) populations of immunologically relevant cells near the maternal-fetal interface through all stages of normal pregnancy. Mesenchymal cells in extraembryonic tissues demonstrated a gradual and progressive development of both class I and class II HLA, with class I expression preceding class II. Coordinated development of expression of two subclasses of class II HLA-D, HLA-DR and HLA-DQ, by fetal mesenchymal cells was noted. In adjacent tissue, maternal decidual cells were strongly class I HLA positive; but in contrast to fetal cells, expression of HLA-D subclasses was discoordinate. HLA-DR was present throughout gestation but HLA-DQ expression was detectable only in second and third trimester tissues. Immunologically relevant cells were present in both fetal and maternal tissues. The major leukocyte population and the major class II-bearing cell type at the maternal-fetal interface was of monocyte/macrophage lineage. T and B lymphocytes were present only in very low densities (1–3% of all cells), whereas at all stages of gestation, macrophages were present in high density in both the fetal mesenchyme (14–25%) and in maternal decidua (27–32%). Documentation of class I and class II HLA expression and the cell types available to participate in immunologic events at the maternal-fetal interface may assist in understanding the immunologic basis of the maternal-fetal relationship during successful pregnancy.     

Elevated Amniotic Fluid Interleukin-6 Levels During the Early Second Trimester Are Associated With Greater Risk of Subsequent Preterm Delivery

PROBLEM: Subclinical intra-amniotic infection is often associated with preterm delivery and may precede it by several weeks. We tested the hypothesis that Interleukin-6 (IL-6) may be elevated in the midtrimester amniotic fluid of pregnancies destined to deliver preterm. METHODS: A historical cohort study was designed to compare the amniotic fluid (AF) concentrations of IL-6 at 14–20 weeks in a group of women subsequently delivering at ≤ 34 weeks (n = 13) with those of women delivering at term (n = 166). Included were singleton gestations with no evidence of fetal structural or chromosomal abnormalities, or maternal conditions known to be associated with preterm delivery (n = 179). Levels of IL-6 were measured by immunoassay and correlated with demographic and pregnancy outcome information. Statistical analysis included correlation, one-way ANOVA after log-transformation, contingency tables, logistic regression, and receiver operator characteristic (ROC) curve analysis. RESULTS: There was an inverse correlation between AF IL-6 levels at 15–20 weeks and gestational age at delivery (r = ?0.16, P = 0.03). Women delivering at ≤ 34 weeks had significantly higher median AF IL-6 levels (570 pg/ml versus 330 pg/ml, P < 0.0001), rate of African American race (50% versus 12%, P = 0.004), and of infants with birth weights < 10th centile (31% versus 7%, P = 0.02) than women delivering at ≥ 37 weeks. Logistic regression analysis showed that IL-6 was independently associated with PTD at ≤ 34 weeks after controlling for race and birth weight centiles (P = 0.039). CONCLUSIONS: AF IL-6 at 15–20 weeks can identify patients at risk for PTD at ≤ 34 weeks, suggesting that a portion of PTD cases have inciting events that take place during the early second trimester. CAPSULE: Midtrimester amniotic fluid IL-6 concentrations are significantly higher in women subsequently delivering preterm at ≤34 weeks compared with those delivering at term.     

Tissue Magnesium Levels and the Arrhythmic Substrate in Humans

Magnesium and Arrhythmias. Introduction: Magnesium deficiency has been implicated in the pathogenesis of sudden death, but the investigation of arrhythmic mechanisms has been hindered by difficulties in measuring cellular tissue magnesium stores.
Methods and Results: To see if magnesium deficiency is associated with a propensity toward triggered arrhythmias, we measured tissue magnesium levels and QT interval dispersion (as an index of repolarization dispersion) in 40 patients with arrhythmic complaints. Magnesium was measured in sublingual epithelium using X-ray dispersive analysis. QT interval dispersion was assessed on 12-lead surface F-XCs in all patients, and programmed stimulation was performed in 28. The sublingual epithelial magnesium level ([Mg]_i), but the not the serum level, correlated Inversely with QT interval dispersion in 40 patients (r = 0.58, P < 0.0.5); in 12 patients undergoing repeat testing on therapy, the change in magnesium also correlated inversely with the change in QT dispersion (r = 0.61, P < 0.05). Patients with left ventricular ejection fractions > 40% had significantly higher tissue magnesium and lower QT dispersion (34.5 ± 0.5 mEq/L, 81 ± 8 msec) than those with left ventricular ejection fractious < 40% (32.7 ± 0.5 mEq/L, P < 0.01, and 114 ± 9 msec, P < 0.05). There was no difference in either [Mg]_i, or QT dispersion in the 16 patients with inducible monomorphic ventricular tachycardia versus the 12 noninducible patients.
Conclusion: Reduced tissue magnesium stores may represent a significant risk factor for arrhythmias associated with abnormal repolarization, particularly in patients with poor left ventricular systolic function, but may not represent a risk for excitable gap arrhythmias associated with a fixed anatomic substrate (e.g., monomorphic ventricular tachycardia).     

Vasopressin Secretion in the DIDMOAD (Wolfram) Syndrome

SUMMARY The diabetes insipidus which accompanies the DIDMOAD (Wolfram)Syndrome is thought to be hypothalamic in origin, though noformal study of vasopressin secretion in the syndrome has beenpublished, and some data in the literature suggest arenal tubulardefect. We have studied vasopressin secretion in seven patientswith the Wolfram /DIDMOAD syndrome during three dymatic stimuli:an Osmotic Stimulus (hypertonic Saline infusion), hypoglycaemia(insulin tolerance test) and a baroregulatory stimulus (trimetaphaninfusuion). Hypertonic saline infusion demonstrated three patientsto have complete and four to have partial hypothalamic diabetesinsipidus; administration of (per nasal) desmopressin excludednephrogenic diabetes insipidus in all seven patients. Insulinhypoglycaemia failed to stimulate vasopressin release, but trimetaphan-inducedhypotension produced significant though subnormal rises in plasmavasopressin in three patients with partial diabetes insipidus,though it produced a negligible rise and no rise in plasma vasopressinin two patients with complete diabetes insipidus. The data suggest a much greater frequency of hypothalamic diabetesinsipidus in the Wolfram/DIDMOAD syndrome than is reported,but did not identify nephrogenic diabetes insipidus. The absenceof vasopressin responses to non-osmotic stimuli in patientswith complete diabetes insipidus suggests global lack of vasopressinsecreting neurones, rather than an isolated osmoreceptor defector selective vasopressin secreting neuronal loss, as the lesionproducing diabetes insipidus in the DIDMOND syndr     

ICD Implantation via Thoracoscopy without the Need for Sternotomy or Thoracotomy

After development of the technique in mongrel dogs, implantable cardioverter defibrillator (ICD) patch and sensing lead implanlation was attempted via thoracoscopy, without sternotomy or thoracotomy, in three patients. Two large titanium mesh defibrillator patches and two "screw-in" epicardial sensing leads were applied without difficulty in each of two patients. In a third patient, satisfactory placement of the defibrillator patches could not be achieved via thoracoscopy, necessitating thoracotomy. Defibrillation threshold (DFT), cardioversion energy requirement (CER), and rate and morphology signals in those patients with successful thoracoscopic implantation were comparable to those achieved by open technique. We conclude that ICD patch and sensing lead implantation via thoracoscopy is feasible.