Safety and efficacy of advanced atrial pacing therapies for atrial tachyarrhythmias in patients with a new implantable dual chamber cardioverter-defibrillator

OBJECTIVES: This study evaluated the safety and efficacy of atrial pacing therapies for the treatment and prevention of atrial tachycardia (AT) or atrial fibrillation (AF) in a new dual chamber implantable cardioverter defibrillator (ICD). BACKGROUND: Patients with an ICD may also experience AT or AF that is amenable to pace termination. METHODS: The efficacy of atrial antitachycardia pacing (ATP) therapies for atrial tachycardia or atrial fibrillation (AT/AF) was determined in 151 patients after implantation of a GEM III AT ICD (Medtronic Inc., Minneapolis, Minnesota). The percentage of episodes successfully terminated was adjusted for multiple episodes per patient. RESULTS: A total of 717 of 728 (96%) episodes classified as AT or AF were judged to be appropriate detections. By device classification, atrial ATP terminated 187 of 383 (40% adjusted) episodes classified as AT compared with 65 of 240 episodes classified as AF (26% adjusted, p = 0.013). Atrial Ramp or Burst+ ATP terminated 184 of 378 episodes of AT (39% adjusted), whereas 50-Hz Burst pacing therapy terminated only 12 of 109 episodes of AT (12% adjusted) and 65 of 240 episodes of AF (26% adjusted). If efficacy was defined as termination of AT/AF within 20 s of delivery of the pacing therapy, ATP therapies terminated 139 of 383 (32% adjusted) episodes of AT compared with 34 of 240 episodes of AF (15% adjusted, p = 0.003). Efficacy was dependent on AT cycle length. Frequent transitions between AT and AF predicted inefficacy of atrial ATP (p < 0.001). Ventricular proarrhythmia secondary to atrial ATP was not observed. CONCLUSIONS: Atrial ATP therapies terminate many episodes of AT without ventricular proarrhythmia. The addition of 50-Hz Burst pacing has minimal efficacy for AT/AF.     

Nonpalpable testes in young boys: evaluation with MR imaging

A prospective evaluation of magnetic resonance (MR) imaging for localization of a nonpalpable testis was performed in 24 boys aged 11 months to 6 years. Definitive surgical follow-up was obtained for 15 nonpalpable testes in 14 patients who form the basis of this study. MR imaging correctly indicated the unilateral absence of a testis in six of seven patients prospectively and all seven patients retrospectively. Surgically localized undescended testes were identified with MR imaging in five of eight cases prospectively and seven of eight cases retrospectively. Like scrotal testes, undescended testes were hypointense to fat on sequences with a short repetition time (TR) and echo time (TE) in all cases, and hyperintense or isointense to fat on long TR/TE sequences in all but two cases. Inguinal testes were located along the course of a linear low-signal-intensity structure that extended to the scrotum, which may represent the remnant of the gubernaculum testis. A low-signal-intensity band through the testis, presumably the mediastinum testis, was seen in five of the undescended testes. Although MR imaging can often be used to localize a nonpalpable testis, currently MR is not sensitive enough to allow complete exclusion of the diagnosis of an undescended testis; thus failure to localize a testis with MR imaging should not defer laparoscopy or surgical exploration when indicated.     

Cutaneous reaction to contrast material

Two children are described who developed an apparent cutaneous contact reaction to contrast material in urine. Both children had undergone uneventful voiding cystourethrography with diatrizoate meglumine injection USP 18% followed by intravenous urography with diatrizoate meglumine injection USP 60%. Approximately 1 hour after urography cutaneous bullae and surrounding erythema of the buttocks (one case) or foreskin (one case) were noted. This reaction resembled a superficial chemical burn.     

Oxidized guanine lesions and hOgg1 activity in lung cancer

In humans, the oxidatively induced DNA lesion 8-hydroxyguanine (8-oxoG) is removed from DNA by hOgg1, a DNA glycosylase/AP lyase that specifically incises 8-oxoG opposite cytosine. We analysed the expression of hOGG1 mRNA in 18 lung cancer and three normal cell lines. Although hOGG1 was overexpressed in most cell lines, 2/18 (11.1%) showed a lower hOGG1 mRNA and protein expression (approximately 80% decrease) relative to normal cell lines. Liquid chromatography/mass spectrometry analysis showed increased levels of 8-oxoG in the two cell lines with the lowest hOGG1 mRNA expression. We examined the ability of nuclear and mitochondrial extracts to incise 8-oxoG lesion in cell lines H1650 and H226 expressing lower hOGG1 mRNA and H1915 and H1975 with higher than normal hOGG1 mRNA expression. Both nuclear and mitochondrial extracts from H1915 and H1975 cells were proficient in 8-oxoG removal. However, both cell lines with the lowest hOGG1 mRNA expression exhibited a severe reduction in 8-oxoG incision in both nuclear and mitochondrial extracts. Under-expression of hOGG1 mRNA and hOgg1 protein was associated with a decrease in mitochondrial DNA repair in response to oxidative damaging agents. These results provide evidence for defective incision of 8-oxoG in both nuclear and mitochondria of H1650 and H226 lung cancer cell lines. These results may implicate 8-oxoG repair defects in certain lung cancers.     

Determining the position and size of the subthalamic nucleus based on magnetic resonance imaging results in patients with advanced Parkinson disease

OBJECT: The subthalamic nucleus (STN) is a target in surgery for Parkinson disease, but its location according to brain atlases compared with its position on an individual patient's magnetic resonance (MR) images is incompletely understood. In this study both the size and location of the STN based on MR images were compared with those on the Talairach and Tournoux, and Schaltenbrand and Wahren atlases. METHODS: The position of the STN relative to the midcommissural point was evaluated on 18 T2-weighted MR images (2-mm slices). Of 35 evaluable STNs, the most anterior, posterior, medial, and lateral borders were determined from axial images, dorsal and ventral borders from coronal images. These methods were validated using histological measurements in one case in which a postmortem examination was performed. The mean length of the anterior commissure-posterior commissure was 25.8 mm. Subthalamic nucleus borders derived from MR imaging were highly variable: anterior, 4.1 to -3.7 mm relative to the midcommissural point; posterior, 4.2 to 10 mm behind the midcommissural point; medial, 7.9 to 12.1 mm from the midline; lateral, 12.3 to 15.4 mm from the midline; dorsal, 0.2 to 4.2 mm below the intercommissural plane; and ventral, 5.7 to 9.9 mm below the intercommissural plane. The position of the anterior border on MR images was more posterior, and the medial border more lateral, than its position in the brain atlases. The STN was smaller on MR images compared with its size in atlases in the anteroposterior (mean 5.9 mm), mediolateral (3.7 mm), and dorsoventral (5 mm) dimensions. CONCLUSIONS: The size and position of the STN are highly variable, appearing to be smaller and situated more posterior and lateral on MR images than in atlases. Care must be taken in relying on coordinates relative to the commissures for targeting of the STN.     

Increased matrix metalloproteinase-2 activity induced byTGF-β1 in duct cells of human salivary gland is associated with the development of cyst formation in vivo

Proteolytic enzyme activity has been shown to be important for cyst formation. In this study, we constructed a cyst-like structure in vivo and analyzed molecular mechanisms involved in the development of the lesion. When SV40-immortalized duct cells of normal human salivary gland (NS-SV-DC) were treated with TGF-βl at a concentration of 1 ng/ml or 5 ng/ml followed by co-inoculation with Matrigel into the backs of nude mice, they formed large cysts containing fluid when 5 ng/ml of TGF-βl was used. Analysis of the fluid demonstrated high MMP activity. Immunohistochemical staining exhibited strong reactivity with anti-MMP-2 antibody in TGF-pl (5 ng/ml)-treated NS-SV-DC. Northern blot analysis indicated that the expression of TGF-β1 and MMP-2 mRNAs in ceils was greatly enhanced by treatment with 5ng/ml TGF-βl. These findings suggest that the in vivo cyst formation by TGF-βl-treated cells is associated with continuous induction of MMP-2 activity.     

Evaluation of hospitalized infants and young children with bronchiolitis - a multi centre study

Four hundred and twenty nine young children with bronchiolitis admitted consecutively in different hospitals of Bangladesh were evaluated. Three hundred and forty eight children studied for their putative risk factors, clinical profile, management and the outcome. Both cases and controls were examined for respiratory syncytial virus (RSV) antibody status. The diagnosis of bronchiolitis was made on the basis of first attack of wheeze in previously healthy children below two years of age. Detailed history including the possible risk factors, the management and daily follow-up on the ward and the outcome at discharge were documented through a structured questionnaire. Chest x-ray was done in each case to find out the radiological changes. Blood of 266 patients and 30 controls were studied for RSV IgM and IgG antibody by ELISA. There were 66% male and 34% female children. The median age of the children was 3.0 months and 82.7% were below 6 months of age. Most of the babies were born term (88%), with ABW (73%), by normal vaginal delivery (88%). Exclusive or predominant breast-feeding were given in 72% cases. The location of the patient was rural in 55% cases. Around half of the parents were illiterate or slightly educated (up to 5 years schooling) fathers 46.5% and mothers 56% and majority of the parents were poor (74%). In 52% cases the number of family members in one room were four or more. Half of the parents (52%) were smokes and there was atopy in 26.5% families. The clinical features of bronchiolitis were mostly cough (99%), respiratory distress (97%), feeding difficulty (93%) and fast breathing (96%) (median RR 68/min). Fever (1000F or more) was in only 33% cases, though parents complained in 90% cases. All children (100%) had wheeze and crackles in lungs in 96% cases. Liver could be palpable in 83% and spleen in 42% cases. Important radiological features were increased translucency (96%), increased interstitial markings (87%), hyperinflation (75%) and streaky densities (61%). In 69.6% cases TLC was 12,000 or less and only 15% with a neutrophil fraction greater than 60%. Children were positive for IgM antibody in 43.6% cases and both IgM and IgG in 5.3% cases. The main modalities of treatment were antibiotics (99%) (Ampicillin, 76%), oxygen therapy (83%), nebulised salbutamol (76%) and intravenous fluid (51%). The median duration of hospital stay was 4 days. Most of the children were discharged with improvement (96%) with 2% mortality. Not a single case was diagnosed as bronchiolitis in hospitals outside Dhaka. Cefrtiaxone (72.5%) and parenteral steroids (70.5%) were the mainstay of therapy there.     

High-throughput molecular analysis of urine sediment for the detection of bladder cancer by high-density single-nucleotide polymorphism array

The detection of urothelial malignancies remains challenging. The majority of patients diagnosed with bladder cancer require life-long surveillance for disease recurrence. Monitoring strategies rely predominantly on invasive endoscopic techniques, which are inconvenient and uncomfortable. Multiple in vitro diagnostic technologies have been developed to supplant the contemporary standard of care. The U.S. Food and Drug Administration has approved several assays, but [because of inferior performance characteristics (low sensitivity and specificity)] these tests have not made a significant impact on practice, to date. We sought to develop a test for bladder cancer with better performance characterization detection based on a novel molecular approach. Matched urine and peripheral blood lymphocyte samples were obtained before surgery from 31 patients with bladder cancer (10 pTa, 4 pT1, and 17 pT2>or). DNA from these samples was subjected to allelic imbalance analysis using HuSNP chips and was validated in parallel with microsatellite analysis for loss of heterozygosity and microsatellite instability. Peripheral blood lymphocyte and urine DNA obtained from 14 individuals without clinical evidence of genitourinary malignancy served as controls. Thirty-one of 31 (100%) urine DNA samples from patients with bladder tumors were found to have 24 or more single-nucleotide polymorphism (SNP) DNA alterations. In general, SNP alterations were more common in urine samples from pT2>or tumors than pTa or pT1 tumors. SNP alterations were not identified in nine normal control subjects and in four of five patients with hematuria. These data support the noninvasive HuSNP chip assay in urine DNA as a valuable tool for the detection of bladder cancer (on a high-throughput-automated platform).