A micro-RNA signature associated with race, tumor size, and target gene activity in human uterine leiomyomas

Human uterine leiomyomas (ULMs) are the most common neoplasms of women. Many genes are dysregulated in ULMs and some of this dysregulation may be due to abnormal expression of micro-RNAs (miRNAs). In this study, 55 ULMs and matched myometrium were collected from 41 patients for microarray-based global miRNA expression analysis. Of 206 miRNAs examined, 45 miRNAs were significantly up- or down-regulated in ULMs in comparison to the matched myometrium (P < 0.001). The top five dysregulated miRNAs in ULMs are the let-7 family, miR-21, miR-23b, miR-29b, and miR-197. Four polycistronic clusters of miRNAs were either up- or down-regulated, but not in a mixed pattern, indicative of coordinated regulation of these miRNAs. Significance analysis revealed that subsets of miRNAs were strongly associated with tumor sizes and race. By prediction analysis we identified some important tumorigenic genes previously identified in ULMs that may be targeted by the dysregulated miRNAs. HMGA2 was identified as one of target genes of the let-7 family of miRNAs and has been found to be suppressed by let-7 in vitro. This article contains Supplementary material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat.     

Detection of genomic deletions of PKP2 in arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited myocardial disease that predominantly affects the right ventricle and is associated with ventricular arrhythmias that may lead to sudden cardiac death. Mutations within at least seven separate genes have been identified to cause ARVC, however a genetic culprit remains elusive in approximately 50% of cases. Although negative genetic testing may be secondary to pathogenic mutations within undiscovered genes, an alternative explanation may be the presence of large deletions or duplications involving known genes. These large copy number variants may not be detected with standard clinical genetic testing which is presently limited to direct DNA sequencing. We describe two cases of ARVC possessing large deletions involving plakophilin‐2 (PKP2) identified with microarray analysis and/or multiplex ligation‐dependent probe amplification (MLPA) that would have been classified as genotype negative with standard clinical genetic testing. A deletion of the entire coding region of PKP2 excluding exon 1 was identified in patient 1 and his son. In patient 2, MLPA analysis of PKP2 revealed deletion of the entire gene with subsequent microarray analysis demonstrating a de novo 7.9 Mb deletion of chromosome 12p12.1p11.1. These findings support screening for large copy number variants in clinically suspected ARVC cases without clear disease causing mutations following initial sequencing analysis.     

Management of ovarian cysts with aspiration and methotrexate injection

PURPOSE: To evaluate prospectively ultrasonography (US)-guided cyst aspiration and methotrexate injection in the management of simple and endometriotic ovarian cysts in selected patients. MATERIALS AND METHODS: Authors obtained informed patient consent and approval from hospital ethics committee. Study included 162 female patients (aged 15-77 years) with simple or endometriotic ovarian cysts (3.0-10.6 cm) at a tertiary hospital. Criteria for inclusion in the study were (a) persistence of the cyst for at least 6 months, (b) benign appearance of the cyst at US, and (c) normal serum CA-125 level measurement before the procedure. Authors performed transabdominal aspiration of the cysts with direct US guidance and injection of methotrexate (30 mg). Cytologic examination was performed in all cases. Follow-up US was performed at 1, 3, and 6 months. If the cyst persisted, the procedure could be repeated. Main outcome measure was resolution or persistence of cysts. chi(2) Test or Mantel-Haentszel chi(2) tests for univariate analysis and multiple logistic regression were used for multivariate statistical analysis. RESULTS: Of 162 patients, 148 were available for follow-up. Malignant cells were not found in any of the cases at cytologic examination. At follow-up US, cysts had disappeared in 124 patients (83.8%) and persisted in 24 (16.2%). Cyst diameter proved to be a significant prognostic factor for cyst resolution (P = .01). No major complications were observed. Patients received neither analgesia nor antibiotics. CONCLUSION: US-guided transabdominal aspiration of cyst fluid and subsequent methotrexate injection appears to be an alternative treatment for both simple and endometriotic ovarian cysts in selected cases.     

Acid fog-induced bronchoconstriction. The role of hydroxymethanesulfonic acid

Hydroxymethanesulfonate (HMSA), the bisulfite (HSO3-) adduct of formaldehyde (CH2O), is a common constituent of California acid fogs. HMSA, most stable in a fog pH range of 3 to 5, dissociates at 6.6, the pH of the fluid lining human airways. The dissociation of inhaled HMSA should theoretically generate sulfur dioxide and CH2O, both of which have bronchoconstrictor potential. Thus, we hypothesized that HMSA may have a specific bronchoconstrictor effect independent of its strength as an acid. To determine whether HMSA has such an effect, 19 subjects with mild to moderate asthma were studied using two different protocols. Initially, a mouthpiece study was performed in which 9 subjects, on 2 separate days, inhaled five aerosols containing either sequentially increasing concentrations (0, 30, 100, 300, and 1000 microM) of HMSA in 50 microM sulfuric acid (H2SO4) or 50 microM H2SO4 alone. The subjects inhaled each aerosol for 3 min during tidal breathing at rest. Specific airway resistance (SRaw) was measured before and after each 3-min exposure. There were no significant differences in the mean changes in SRaw among the various aerosol exposures. To confirm this lack of bronchoconstrictor effect of HMSA, we then performed a chamber study in which 10 freely breathing, intermittently exercising subjects were exposed to fog containing either 1 mM HMSA in 5 mM H2SO4 or 5 mM H2SO4 alone for 1 h. SRaw was measured before, during, and at the end of the 1-h exposure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Midwives' knowledge of,attitudes towards and experiences of caring for women with intellectual disability during pregnancy and childbirth: A cross-sectional study in Sweden

Objective

to investigate midwives' knowledge of, attitudes towards and experiences of caring for women with intellectual disability (ID) during pregnancy and childbirth.

Design/setting

a cross-sectional study among six hundred midwives working at antenatal care and labour wards in Sweden.

Results

more than four out of five (81.5%) midwives had experience of caring for women with ID. Almost all midwives (97.1%) reported that caring for women with ID is different from caring for women without ID. Almost one-half (47.3%) had not received any education about pregnancy and delivery of women with ID, and a majority of the midwives (95.4%) requested evidence-based knowledge of women with ID in relation to childbirth. High proportion (69.7%) of the midwives were of the opinion that women with ID cannot satisfactorily manage the mother role, and more than one-third (35.7%) of the midwives considered that women with ID should not be pregnant and give birth at all. Most midwives partly/totally agreed that children of women with ID should grow up with their parents supported by the social authorities, but nearly one-fifth (19.1%) partly/totally agreed that the children should grow up in foster care.

Conclusions

even if the majority of midwives had experience of caring for women with ID, they were uncertain about how to adapt and give advice and they needed more knowledge about these women. Some midwives had negative attitudes towards childbearing among women with ID. Health Service providers should encourage midwives to update their knowledge and provide supportive supervision in midwifery care for women with ID.     

T2 values in the human brain: comparison with quantitative assays of iron and ferritin

Magnetic resonance (MR) imaging with a whole-body imager was performed in 10 fresh, unfixed whole human brains selected randomly from cadavers. All subjects were neurologically intact before death. T2 time constants were measured within the caudate nucleus, putamen, globus pallidus, cortical gray matter, subcortical white matter, and optic radiation. These regions were then excised, and T2 values were measured again with a 1.5-T MR spectrometer. Quantitative assays of iron, ferritin, and protein from these areas were then performed. Iron concentration varied significantly among brain regions, whereas ferritin and protein concentrations were constant among brain regions and among individuals. Neither iron nor ferritin concentration showed any consistent correlation with T2 values. Histologic examination of brain micro-sections with iron- and ferritin-specific stains of demonstrated poor correlation with biochemical assays of ferritin and iron concentrations. Results indicate that T2 values correlate poorly with iron and ferritin concentrations found in neurologically intact brains.     

Complete orbit and forehead reconstruction using a free latissimus dorsi flap and MEDPOR implants

BACKGROUND: Reconstruction of enormous composite defects of the face in the presence of meningitis is a difficult problem. We present a case of a 29-year-old man with a huge, posttraumatic bone and soft tissue defect of the upper half of the left side of the face (orbit-zygoma-frontal-partial temporal bones), frontal lobe of the brain, and enucleated eye with intact facial skin. METHODS: An initial reconstruction using cement was complicated by multiple episodes of meningitis. In a multiple-stage procedure, we used a free latissimus dorsi muscle flap to re-construct the soft tissue defect and control the infection, a complete left orbit and frontal MEDPOR implant for the bone defect, and also an orbital sphere MEDPOR implant for the eyeball. RESULTS: In a 2-year follow-up, no infection was observed, and the cosmetic result is satisfactory. CONCLUSION: The combination of free flap and MEDPOR implants demonstrates an alternative method for reconstruction of complicated facial defects.     

Efficacy of tolterodine in preventing urge incontinence immediately after prostatectomy

Purpose: Urgency and urge incontinence are frequently observed after prostatectomy. Although symptoms ameliorate within a relatively short time, they usually cause significant stress and anxiety to the patient as far as their duration is concerned. Aim of our study was to determine the efficacy of tolterodine in preventing urgency and urge incontinence after catheter removal in patients that underwent prostatectomy for benign prostate hyperplasia. Patients and methods: Twenty-seven patients with moderate/severe lower urinary tract symptoms due to benign prostatic enlargement, scheduled for prostatectomy, were randomised into two groups, Group A (14 pts) received tolterodine 2 mg b.i.d starting the day of surgery, while group B patients received no such treatment. Tolterodine treatment was discontinued 15 days after catheter removal. All patients completed the International Prostatic Symptom Score (IPSS) and the International Continence Society (ICS-BPH) forms the day before surgery, and three times more, one, fifteen and thirty days after catheter removal. Results: Pre-operative total 1PSS and frequency of urgency/urge incontinence as determined by questions 3 and 4 of the ICS-BPH questionnaire were equally distributed between groups. Tolterodine was well tolerated and no adverse effects were reported. Post-operative IPSS and QoL scores did not differ between groups. However, the frequency of urge incontinence both the first day and fifteen days after catheter removal was significantly lower in the tolterodine group (16.6% vs. 69.2%, p=0.004 and 8.3% vs. 38.4%, p=0.039, respectively). Conclusion: Tolterodine was well tolerated in all patients and had a beneficial effect regarding the postoperative urge incontinence. Trials of a larger scale could determine which patients would benefit more, especially according to the presence of storage lower urinary tract symptoms prior to surgery.