Killing of dsrA mutants of Haemophilus ducreyi by normal human serum occurs via the classical complement pathway and is initiated by immunoglobulin M binding

Previously, we showed that serum resistance in Haemophilus ducreyi type strain 35000HP required expression of the outer membrane protein DsrA because the isogenic dsrA mutant FX517 is highly serum susceptible. In this study, we confirmed this finding by construction of additional serum-susceptible dsrA mutants in more recently isolated serum-resistant strains. We also demonstrated that killing of dsrA mutants required an intact classical complement cascade but not the alternative or mannan-binding lectin pathways. Between 5- and 10-fold more purified human immunoglobulin M (IgM) but not IgG was deposited onto dsrA mutant FX517 than onto parent strain 35000HP, consistent with IgM initiation of the classical cascade. Depletion of IgM, but not IgG, from complement-intact serum inhibited killing of FX517. As predicted from the amounts of IgM bound, more of the individual complement components were bound by FX517 than by parent strain 35000HP. Examination of the binding of negative regulators of complement as an explanation for serum resistance indicated that parent strain 35000HP bound more C4 binding protein and vitronectin than FX517 but not factor H. However, the degree and pattern of complement component binding observed suggested that IgM binding to the serum-susceptible mutant FX517 was responsible for the activation of the classical pathway and the observed killing of FX517 as opposed to binding of negative regulators of complement by the serum-resistant parent. We speculate that an undefined neo-epitope, possibly carbohydrate, is exposed in the dsrA mutant that is recognized by naturally occurring bactericidal IgM antibodies present in human sera.     

Nickel and chromium levels in the saliva of a Saudi sample treated with fixed orthodontic appliances

AimThe aim of this study was to measure the amount of nickel (Ni) and chromium (Cr) released into the saliva of Saudi patients treated with fixed orthodontic appliances.Materials and methodsNinety salivary samples were collected in a cross-sectional manner. Forty samples were collected from patients (17 males, 23 females) with fixed orthodontic appliances after different periods of orthodontic treatment ranging from the first month and up to 32 months into treatment. The fixed orthodontic appliance consisted of 4 bands, 20 stainless steel brackets, and upper and lower nickel titanium or stainless-steel arch wires. The other 50 samples were collected from people without appliances (24 males, 26 females). Samples were analyzed using Inductive Coupled Plasma/Mass Spectrometry and Inductively Coupled Plasma Optical Emission Spectroscopy to measure Ni and Cr levels, respectively. Student’s t-test was used to compare Ni and Cr levels in the treated and untreated control groups.ResultsThe mean Ni level was 4.197 μg/L in the experimental group and 2.3 μg/L in the control group (p < 0.05). The mean Cr level was 2.9 μg/L in the experimental group and 3.3 μg/L in the control group (p < 0.05).ConclusionFixed orthodontic appliances resulted in a non-toxic increase in salivary levels of Ni, but no change in Cr levels. Duration of orthodontic treatment did not affect Ni and Cr levels in the saliva.     

Magnetic resonance imaging of the bone marrow in 3 patients with aplastic anemia

Bone marrow appearances in aplastic anemia are characterized by the abundance of fatty marrow that replaces normal functional marrow. The signal intensity of aplastic bone marrow in sagittal T1-weighted magnetic resonance images of the spine is bright, resembling that of subcutaneous fat and, in most cases, is not difficult to differentiate from normal age-related marrow changes. Three patients with aplastic anemia are described, and the correlation of magnetic resonance imaging of the spine with bone marrow trephine biopsy findings in these patients is portrayed. Magnetic resonance imaging is an accessible, non-invasive technique that allows sampling of a larger volume of bone marrow tissue and is especially useful in the detection of fatty marrow replacement of the normal functional marrow in aplastic anemia.     

Splenic complications of the sickling syndromes and the role of splenectomy.

PURPOSE: To analyze the authors' experience with splenectomy for sickling disorders and evaluate the indications, complications, and outcome. PATIENTS AND METHODS: Over a period of 10 years (1987-1997), 113 patients with sickling disorders (100 with sickle cell disease and 13 with sickle-beta-thalassemia) had splenectomy at the authors' hospital as part of their management. The indications for splenectomy were hypersplenism (26 patients), major splenic sequestration crisis (MSSC) (23 patients), minor recurrent splenic sequestration crisis (MRSSC) (50 patients), splenic abscess (12 patients), and massive splenic infarction (2 patients). RESULTS: Splenectomy in patients with sickle cell disease (SCD) and sickle-beta-thalassemia (S-beta-Thal) was beneficial in reducing their transfusion requirements and its attendant risks, eliminating the discomfort from mechanical pressure of the enlarged spleen, and avoiding the risks of acute splenic sequestration crisis. It also was curative for patients with splenic abscess and massive splenic infarction. Twenty-four patients with SCD (24%) had splenectomy and cholecystectomy caused by concomitant gallstones. There was no mortality, and the postoperative morbidity was 7%. CONCLUSIONS: With careful perioperative management, splenectomy is both safe and beneficial in a select group of patients with SCD and S-beta-Thal.     

The use of progesterone during pregnancy to prevent preterm birth

One of the most significant problems facing maternal and children health worldwide is preterm birth (PTB). Although strategies to increase the survival of premature infants have significantly improved in the past few decades, they have yet to be successful. Nine years ago, the use of progesterone in pregnancy was approved by the United States Food and Drug Administration (FDA) for PTB prevention. This paper reviews the recent evidence supporting the use of progesterone in pregnancy for PTB prevention and provides guidelines for its use in daily clinical practice. The guidelines address multiple current controversial areas regarding the prevention of PTB to aid physicians with their clinical decision-making practice, including the use in multifetal gestation, different formulations, safety in pregnancy, dose and route of administration.     

Pulmonary hypertension in congenital diaphragmatic hernia patients: Prognostic markers and long-term outcomes

Prenatal observed/expected lung–to-head ratio (O/E LHR) by ultrasound correlates with postnatal mortality for congenital diaphragmatic hernia (CDH) patients. The aim of this study is to determine if O/E LHR correlates with pulmonary hypertension (PH) outcomes for CDH patients.

Basal Subtype,as Approximated by Triple-Negative Phenotype,is Associated with Locoregional Recurrence in a Case–Control Study of Women with 0–3 Positive Lymph Nodes After Mastectomy

Purpose

Basal subtype, as approximated by the triple-negative phenotype (ER–PR–Her2?), has correlated with higher LRR in recent studies. Indications for postmastectomy RT (PMRT) in women with 0–3 positive lymph nodes remain unclear. We evaluated the importance of biologic subtype in a cohort of women with LRR after mastectomy.

Methods

We identified 22 women with 0–3 positive lymph nodes at our institution who were initially treated with mastectomy (without post-mastectomy radiation), suffered LRRs, and had paraffin-embedded tissue blocks from the primary mastectomy specimen available for staining. None of these women received PMRT. We case–control matched these to 29 women with 0–3 positive nodes who had mastectomy (no PMRT) and remained without evidence of disease at last follow-up and had available primary specimens for processing. We matched controls for age (±3 years) and follow-up duration (<5 year vs. more). Paraffin-embedded specimens were used to construct a triple-redundant tissue microarray. We used conditional logistic regressions to study the association between each predictor and LRR. Results were summarized based on odds ratio (OR).

Results

On univariate analysis, ER+, PR+, or the combination was strongly associated with lower odds of LRR. Basal subtype, as approximated by ER–PR–Her2? (TN), was associated with higher LRR (OR 8.5, p = 0.048). Use of chemotherapy also was associated with lower LRR (OR 0.126, p = 0.0073).

Conclusions

Our data are concordant with reports from others demonstrating that TN phenotype is associated with higher LRR and can be considered along with other predictors of LRR when selecting women for PMRT.