NovaSure impedance controlled endometrial ablation: long-term follow-up results

STUDY OBJECTIVE: A 7-year follow-up evaluation of the safety, efficacy, and long-term outcome of endometrial ablation when using the NovaSure system in patients with menorrhagia secondary to abnormal uterine bleeding (AUB). DESIGN: Prospective, single-arm study (Canadian Task Force classification II-1). SETTING: St. Imre Teaching Hospital, Budapest, Hungary. PATIENTS: Seventy-five premenopausal women with menorrhagia secondary to AUB. INTERVENTIONS: Endometrial ablation using the NovaSure System without the use of endometrial pretreatment. MEASUREMENTS AND MAIN RESULTS: Loss of menstrual blood was measured using pictorial blood loss assessment chart diaries. Treatment times, complications, and rate of surgical re-interventions were recorded. No intra or postoperative complications were noted. Median follow-up period at the time was 7.8 years (range 6-8.6 years). The proportion of patients with fewer than 7 and 7 or more years of follow-up was 28.8% and 71.2%, respectively. The median treatment time was 92 seconds (range 40-120 seconds). At 7-year follow-up, 97.1% of evaluable patients reported amenorrhea. However, all patients (100%, actuarial rate: 97% with 95% CI [83%-100%]) experienced a successful reduction in bleeding to normal levels or less. Six of 75 patients underwent hysterectomy, and one of 75 had a repeat ablation representing a total of 92% (95% CI: 83%-96%) avoidance of additional surgery during the follow-up period. CONCLUSIONS: Clinical results demonstrate that the use of NovaSure System is safe and effective, with a low rate of surgical re-intervention at 7-year follow-up.     

Polymorphisms of the TNF-alpha gene and risk of celiac disease in T1DM children

BACKGROUND: Type 1 diabetes mellitus (T1DM) and celiac disease (CD) frequently occur together. Previous reports suggested that the (-308)A variant of the tumor necrosis factor-alpha (TNF-alpha) gene is associated either with T1DM or with CD. The aim of our study was to determine whether (-308)A and (-238)A allelic variants of the TNF-alpha gene might have any impact on the risk of CD in T1DM children. METHODS: Three hundred and one T1DM children were enrolled to the study. The presence of CD was screened with IgA endomysial antibodies (EMA) test. Jejunal biopsy was performed to confirm CD. TNF-alpha-308 and -238 genetic variants were tested using the method of restriction fragment length polymorphism. RESULTS: The prevalence of CD in the enrolled diabetic children was 6.3% (19 out of 301 children). The frequency of the (-308)A TNF-alpha variant was similar in the CD and the non-CD groups, exceeding the Hungarian healthy reference value. The number of (-238)A allele carriers was higher in the CD (4/19) than in the non-CD group (17/277) (p < 0.05). CONCLUSIONS: Our study is limited by the small number of CD patients. On the basis of our findings, carriers of TNF (-308)A allele do not seem to have an increased risk for CD in T1DM. The association between TNF-alpha(-238)A allele carrier state and CD requires further investigation.     

Predominance of null mutations in ataxia-telangiectasia

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder involving cerebellar degeneration, immunodeficiency, chromosomal instability, radiosensitivity and cancer predisposition. The responsible gene, ATM, was recently identified by positional cloning and found to encode a putative 350 kDa protein with a Pl 3-kinase-like domain, presumably involved in mediating cell cycle arrest in response to radiation-induced DNA damage. The nature and location of A-T mutations should provide insight into the function of the ATM protein and the molecular basis of this pleiotropic disease. Of 44 A-T mutations identified by us to date, 39 (89%) are expected to inactivate the ATM protein by truncating it, by abolishing correct initiation or termination of translation, or by deleting large segments. Additional mutations are four smaller in-frame deletions and insertions, and one substitution of a highly conserved amino acid at the Pl 3-kinase domain. The emerging profile of mutations causing A-T is thus dominated by those expected to completely inactivate the ATM protein. ATM mutations with milder effects may result in phenotypes related, but not identical, to A-T.      

Lymphocyte Calcium Influx Characteristics and their Modulation by Kv1.3 and IKCa1 Channel Inhibitors in Healthy Pregnancy and Preeclampsia

Citation Toldi G, Stenczer B, Treszl A, Kollár S, Molvarec A, Tulassay T, Rigó J, Vásárhelyi B. Lymphocyte calcium influx characteristics and their modulation by Kv1.3 and IKCa1 channel inhibitors in healthy pregnancy and preeclampsia. Am J Reprod Immunol 2011; 65: 154–163 Problem Calcium handling of T lymphocytes is altered in healthy pregnancy (HP) and preeclampsia (PE) compared to non‐pregnant (non‐P) women. We compared the activation‐elicited calcium influx in T lymphocytes in HP, PE and non‐P women and tested its alteration upon inhibition of Kv1.3 and IKCa1 potassium channels. Method of study The alteration of calcium influx was measured in major T‐lymphocyte subsets of 9 non‐P, HP and PE women with flow cytometry with or without treatment of cells with potassium channel inhibitors. Results The elicited calcium response was lower in HP compared to non‐P. In HP, calcium influx was sensitive to potassium channel inhibition in CD8 and Th1, but not in Th2 cells. In PE, calcium influx and its sensitivity to inhibition were comparable to non‐P. Conclusion There is a characteristic pattern of calcium influx in T lymphocytes and its sensitivity to potassium channel inhibition in HP that is missing in PE, raising the notion that T‐lymphocyte calcium handling may have a role in the characteristic immune status of HP.     

Glomus tympanicum chemodectomas: radiographic and clinical characteristics

Glomus tympanicum chemodectomas are benign neoplasms that develop from normal glomus bodies located along the Jacobson (tympanic) nerve in the middle ear. The medical charts and radiographic studies of 55 patients with these tumors were reviewed. Women outnumbered men in a ratio of 3.5:1, and the patients' average age when they initially reported symptoms was 52 years. Tinnitus, ear pulsations, and diminished hearing were the most frequent symptoms. No patient had a second chemodectoma, and none of seven patients who were tested had elevated neuroendocrine compounds. Review of the radiographic examinations showed that direct coronal, thin-section computed tomography (CT) was the most sensitive means of demonstrating glomus tympanicum chemodectomas. Magnification angiography was also a sensitive diagnostic study, typically depicting a trapezoidal, hypervascular, middle-ear mass that appeared initially in the middle-to-late arterial phase and quickly disappeared in the venous phase. Differentiation from an aberrant internal carotid artery is critical to prevent arterial biopsy.     

Human erythrocyte antigens: II. The In(Lu) gene regulates expression of an antigen on an 80-kilodalton protein of human erythrocytes

We have previously shown that a murine monoclonal antibody (A3D8) identifies a human erythrocyte protein antigen whose expression is regulated by the Lutheran inhibitor [In(Lu)] gene. In the present study, we demonstrated by immunoprecipitation and Western blot techniques that the antigen defined by A3D8 was on an 80-kD erythrocyte membrane protein. A second 170-kD protein was coprecipitated with the 80-kD protein but failed to show antigen activity by Western blot analysis. The 170-kD protein, when analyzed by sodium dodecyl sulfate- polyacrylamide gel electrophoresis in two dimensions, was composed of 50- and 30-kD disulfide-linked subunits. In(Lu) Lu[a-b-) erythrocytes differed from Lu(a+b+) or Lu(a-b+) erythrocytes in that In(Lu) deoxycholate erythrocyte membrane extracts contained trace amounts of immunoprecipitable 80-kD protein compared with detergent-solubilized erythrocyte membrane extracts prepared from Lu(a+b+) or Lu(a-b+) subjects.     

The formation of Ca++-dependent complexes of platelet membrane glycoproteins IIb and IIIa in solution as determined by crossed immunoelectrophoresis

Triton X-100 soluble proteins from 125I-labeled human platelets were studied by crossed immunoelectrophoresis employing a multispecific rabbit antibody raised against whole normal platelets. Emphasis was placed upon an analysis of immunoprecipitates containing 125I-labeled major membrane glycoproteins, and in particular, a prominent immunoprecipitate containing a glycoprotein antigen (s) previously designated as protein 16. SDS-polyacrylamide gel electrophoresis of protein 16 precipitated by a monospecific alloantibody. IgG L . . . , confirmed the presence of both glycoproteins IIb and IIIa. 125I-IgG L . . . , at concentration below that capable of precipitating protein 16 by itself, bound specifically to the precipitate containing protein 16 produced by the multispecific rabbit antibody. No other precipitates formed by the rabbit antibody contained either glycoprotein IIb or IIIa. When platelet proteins, incubated with optimum concentrations of ethylenediamine tetraacetic acid (EDTA) or ethyleneglycol bis (B- aminoethylether) NN1-tetraacetic acid (EGTA), were electrophoresed against the rabbit antibody, previously unobserved immunoprecipitates that contained either free glycoprotein IIb or free glycoprotein IIIa were detected. Upon readdition of excess Ca++, but not Mg++, to the same protein samples, a single immunoprecipitate containing both glycoproteins was once again observed. It is thus demonstrated that glycoproteins IIb and IIIa can form Ca++-dependent complexes (protein 16) in Triton X-100 extracts of normal platelets. The potential significance of the reversible association of these glycoproteins to normal platelet function is discussed.     

Mathematical three-dimensional solid modeling of biventricular geometry

The characterization of regional myocardial stress distribution has been limited by the use of idealized mathematical representations of biventricular geometry. State-of-the-art computer-aided design and engineering (CAD/CAE) techniques can be used to create complete, unambiguous mathematical representations (solid models) of complex object geometry that are suitable for a variety of applications, including stress-strain analyses. We have used advanced CAD/CAE software to create a 3-D solid model of the biventricular unit using planar geometric data extracted from anex vivo canine heart. Volumetric analysis revealed global volume errors of 4.7%, −1.3%, −1.6%, and −1.1% for the left ventricular cavity, right ventricular cavity, myocardial wall, and total enclosed volumes, respectively. Model errors for 34 in-plane area and circumference determinations (mean ±SD) were 5.3±6.7% and 3.8±2.7%. Error analysis suggested that model volume errors may be due to operator variability. These results demonstrate that solid modeling of theex vivo biventricular unit yields an accurate mathematical representation of myocardial geometry which is suitable for meshing and subsequent finite element analysis. The use of CAD/CAE solid modeling in the representation of biventricular geometry may thereby facilitate the characterization of regional myocardial stress distribution.     

Intracranial circulation: pulse-sequence considerations in three- dimensional (volume) MR angiography

The technique and feasibility of magnetic resonance (MR) angiography of intracranial vessels were studied in 35 healthy volunteers. Variations in image orientation, repetition time (TR), and flip angle were evaluated to determine their effects on flow-related enhancement. Gradient modifications--including echo time (TE), motion compensation, bandwidth, and field of view--were also studied in an effort to reduce motion-induced phase shifts. Results indicated that a FISP (fast imaging with steady precession) sequence with a TR of 50 msec, TE of 15 msec, velocity compensation in the read and section-select directions, acceleration compensation in the read direction, anisotropic volume, and a 1.25-mm partition thickness produced three-dimensional angiographic MR images that were accurate and reproducible in the depiction of the major intracranial vessels. Difficulties with field of view, persistent signal void secondary to higher-order motion, and spatial resolution remain major problems requiring additional study.