Activity of E2F-dependent promoters in bladder carcinoma cells and their use for tumour-specific targeting of p53-induced apoptosis

Inactivation of P53 and RB functions are crucial changes in bladder cancer (TCC). High-level re-expression of P53 elicits apoptosis in TCC cell lines, but also--as shown here--in normal uroepithelial cells. Compromised RB function is thought to cause increased activity of E2F-dependent promoters in carcinoma cells. Indeed, several, but not all E2F-dependent promoters were stronger in TCC lines than in normal cells, with the highest activities in cell lines lacking RB rather than p16INK4A. Re-expression of p53 from an E2F-dependent promoter suppressed clone formation and induced apoptosis in TCC lines as efficiently as expression from the stronger RSV-LTR or LINE-1 promoters. In normal cells, p53 expression from an E2F-dependent promoter was tolerated, whereas expression from both stronger promoters was lethal. Thus, specific E2F-dependent promoters allow adjustment of p53 expression to selectively induce apoptosis in TCC vs. normal uroepithelial cells. This approach could be useful in targeting apoptosis to TCC and other carcinomas lacking p53 and RB function.     

Systematic Review of Transabdominal Cerclage Placed via Laparoscopy for the Prevention of Preterm Birth

Preterm birth is the leading cause of neonatal mortality and morbidity. Multiple interventions are available to minimize this occurrence; however, despite current recommendations including medical management, cervical length screening, and transvaginal cerclage, a substantial number of women still experience preterm birth. For those patients, experts recommend transabdominal cerclage (TAC). In this systematic review, we compared 26 studies (1116 patients) of TAC placed via laparotomy (TAC-lap) and 15 studies (728 patients) of TAC placed via laparoscopy (TAC-lsc). There was no significant difference in overall neonatal survival between the TAC-lsc and TAC-lap groups (89.9% vs 90.8%, respectively; p?=?.80). When T1 losses were excluded, the neonatal survival rate was significantly higher for the TAC-lsc group (96.5% vs 90.1%; p?<?.01). In terms of obstetrical outcomes, the TAC-lsc group had a higher rate of deliveries at gestational age (GA)?>?34 weeks (82.9% vs 76%; p?<?.01) and a lower rate of deliveries at GA 23.0 to 33.6 weeks (6.8% vs 14.8%; p?<?.01). The TAC-lsc group also had fewer T2 losses (3.2% vs 7.8%; p?<?.01). TAC-lsc offers all the benefits of minimally invasive surgery with better obstetrical outcomes compared with TAC-lap.     

Optimizing in-kind drug donations for Tanzania-a case study

A questionnaire survey (QS) among stakeholders in Tanzania had shown that in-kind drug donations (DDs) are important to boost the drug supply system. Major problems were their insufficient quantity for sustainable treatment and the discrepancy between the needs of the recipients and the donors' supply. Objectives in this study were to discuss these findings and to learn from key informants (KIs) how to improve the DD process. Data were collected through KI interviews in 2001/2002.A 30% gap in drug supply has to be bridged by DDs. KIs confirmed the importance of the World Health Organisation and Tanzanian DD guidelines as a tool for good donation practice and emphasized the role of the government in their implementation. They requested that donors meet the recipient country's regulatory requirements. In contrast to QS respondents, KIs did not view DD quality as a minor problem, and proposed that DD quality should be adapted to the national quality assurance procedures. DD processes could be improved through (a) effective implementation of DD guidelines as an aid for decision-making and for quality assurance, (b) availability of data to improve communication between donors and recipients, (c) transparency between recipients and donors and (d) clearly defined accountability.     

Infantile hypertrophic pyloric stenosis: An association in twins?

BACKGROUND

The etiology of infantile hypertrophic pyloric stenosis (IHPS) remains a mystery. Some suspected risk factors include birth rank, maternal age, sex, family history and monozygosity in twins. Various theories attempt to explain the etiology of IHPS. Scientific research suggests that enteric neuronal damage and nitric oxide synthase dysfunction may be implicated, but the consensus is that environmental modification must exist to account for the variability in its occurrence.

METHOD

Four cases of concordant occurrences of IHPS in twins were examined to determine the history and outcome of IHPS development in twins. Three sets were dizygotic and one was monozygotic. Of the eight infants, three were female, including the one monozygotic pair. In all four cases, a time lag existed between the development of symptomatic onset of IHPS in twin A and twin B. In one set, sonographic confirmation, performed because of IHPS diagnosis in the twin sibling, occurred concurrently with onset of vomiting, leading to early surgery before fluid and electrolyte imbalances developed.

CONCLUSIONS

Despite the lack of agreement as to whether the cause of IHPS is genetic, environmental or both, the high concordance rate seen in twins is indisputable. Thus, the empirical evidence provides credence to consider examining the asymptomatic co-twin when one of the twins presents with IHPS.     

Voxel-based iterative sensitivity (VBIS) analysis: methods and a validation of intensity scaling for T2-weighted imaging of hippocampal sclerosis

Abnormalities in the brain generally manifest on MRI as changes in shape (morphometry) or changes in the nature of the tissue (signal intensity). Voxel Based Morphometry (VBM) is a whole brain quantitative way of assessing morphometric changes. Voxel Based Relaxometry (VBR) directly assesses signal intensity changes in quantitative maps of T2 relaxation time, but this requires specialised multiple-echo acquisition sequences that are not usually available at clinical sites. This paper introduces and assesses an objective voxel-based statistical method for evaluation of signal intensity in groups of routinely acquired qualitative images. We call the method Voxel-Based Iterative Sensitivity (VBIS) analysis. It adaptively optimises the relative global scaling of images to maximise sensitivity to regional effects. We apply and validate the method of analysis for T2-weighted images of the human brain. To validate the method, it was directly compared with VBR by extracting T2-weighted images of a single echo from multi-echo T2 relaxometry acquisitions from a group of 24 patients with left hemisphere hippocampal sclerosis and 97 healthy controls. Expected signal abnormalities in the patients were detectable with VBIS-T2, confirming the feasibility of the technique. This opens the door to the use of a voxel-based analysis approach on the vast amount of T2-weighted image data that has been and is being acquired on MRI scanners. When a quantitative modality is not available, VBIS can be an effective way to quantify differences between groups. We expect the method could also assist quantitative analysis of other qualitative modalities such as T1-weighted MRI, SPECT and CT.     

Cardiac Computed Tomography

Computed tomography (CT) has emerged in the past decade as an important tool in the evaluation of cardiac pathology, specifically in the diagnosis of coronary artery disease (CAD). This article will review the technique and role of CT and CT angiography (CTA) in modern cardiovascular care. CT techniques are described, as are the applications of CT in the assessment of CAD including both calcium scoring and CTA. Although CAD is the mainstay of cardiac CT, important noncoronary cardiac applications including the evaluation of cardiac function, masses, valvular disease, and pericardial disease, are reviewed as well. The nursing care of the patient undergoing CTA is reviewed as are future developments within this field.